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Banaskiewicz K, Treffalls R, Wilken S, Stonko DP, Morrison JJ. Performance of open versus endovascular approaches in swine modeling of acute mesenteric ischemia. Vascular 2025:17085381251339240. [PMID: 40285791 DOI: 10.1177/17085381251339240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
ObjectivesTraditionally, acute mesenteric ischemia studies are performed by utilizing an open superior mesenteric artery (SMA) occlusion, which is an invasive technique with potentially devastating effects. A new endovascular technique for SMA occlusion using a catheter-balloon system was designed and compared to the open SMA occlusion to test its efficacy and animal safety.MethodsAll animals underwent open instrumentation of the superior mesenteric vein (SMV) for blood flow monitoring. The animals were grouped into an open SMA occlusion technique group and an endovascular SMA occlusion group. The open SMA occlusion technique group involved exposure of the SMA via left medial visceral rotation with vascular clamping. In the endovascular group, an endovascular balloon was placed in the SMA and inflated to produce occlusion.ResultsComplete cessation of flow to the SMV was observed in the endovascular group, compared to the residual SMV flow in the open occlusion group. Following a 30-min post-occlusion period, the MAP in the endovascular group increased, compared to a decline of MAP in the open occlusion group.ConclusionsThis study indicates the endovascular technique provides a more potent SMA occlusion, with insignificant consequences on the overall health of the animal, in contrast to the open vascular clamping.
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Affiliation(s)
| | - Rebecca Treffalls
- Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN, USA
| | - Silvana Wilken
- Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN, USA
| | - David P Stonko
- Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA
| | - Jonathan J Morrison
- Division of Vascular and Endovascular Surgery, Mayo Clinic, Rochester, MN, USA
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Bao P, Zhang Z, Liang Y, Yu Z, Xiao Z, Wang Y, Yu Y, Liu W, Chen X, Huang Z, Su Y, Chen R, Ge J. Role of the Gut Microbiota in Glucose Metabolism During Heart Failure. Front Cardiovasc Med 2022; 9:903316. [PMID: 35859583 PMCID: PMC9289393 DOI: 10.3389/fcvm.2022.903316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/31/2022] [Indexed: 11/29/2022] Open
Abstract
Background Blood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure. Methods Thoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism. Results After microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group. Conclusion The gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.
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Affiliation(s)
- Pei Bao
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhiwei Zhang
- Reproductive Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yixiu Liang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- Key Laboratory of Viral Heart Diseases, Department of Cardiovascular Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ziqing Yu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- Key Laboratory of Viral Heart Diseases, Department of Cardiovascular Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zilong Xiao
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yucheng Wang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yong Yu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wen Liu
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xueying Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhenzhen Huang
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yangang Su
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- *Correspondence: Yangang Su
| | - Ruizhen Chen
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- Key Laboratory of Viral Heart Diseases, Department of Cardiovascular Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
- Ruizhen Chen
| | - Junbo Ge
- Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China
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Glancy B, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB. Mitochondrial lactate metabolism: history and implications for exercise and disease. J Physiol 2021; 599:863-888. [PMID: 32358865 PMCID: PMC8439166 DOI: 10.1113/jp278930] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 03/25/2020] [Indexed: 12/31/2022] Open
Abstract
Mitochondrial structures were probably observed microscopically in the 1840s, but the idea of oxidative phosphorylation (OXPHOS) within mitochondria did not appear until the 1930s. The foundation for research into energetics arose from Meyerhof's experiments on oxidation of lactate in isolated muscles recovering from electrical contractions in an O2 atmosphere. Today, we know that mitochondria are actually reticula and that the energy released from electron pairs being passed along the electron transport chain from NADH to O2 generates a membrane potential and pH gradient of protons that can enter the molecular machine of ATP synthase to resynthesize ATP. Lactate stands at the crossroads of glycolytic and oxidative energy metabolism. Based on reported research and our own modelling in silico, we contend that lactate is not directly oxidized in the mitochondrial matrix. Instead, the interim glycolytic products (pyruvate and NADH) are held in cytosolic equilibrium with the products of the lactate dehydrogenase (LDH) reaction and the intermediates of the malate-aspartate and glycerol 3-phosphate shuttles. This equilibrium supplies the glycolytic products to the mitochondrial matrix for OXPHOS. LDH in the mitochondrial matrix is not compatible with the cytoplasmic/matrix redox gradient; its presence would drain matrix reducing power and substantially dissipate the proton motive force. OXPHOS requires O2 as the final electron acceptor, but O2 supply is sufficient in most situations, including exercise and often acute illness. Recent studies suggest that atmospheric normoxia may constitute a cellular hyperoxia in mitochondrial disease. As research proceeds appropriate oxygenation levels should be carefully considered.
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Affiliation(s)
- Brian Glancy
- National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
- National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
| | - Daniel A. Kane
- Department of Human Kinetics, St. Francis Xavier University, NS B2G 2W5, Antigonish, Canada
| | | | - Matthew L. Goodwin
- Department of Orthopaedic Surgery, Washington University School of Medicine, Saint Louis, MO 63110, USA
| | - Wayne T. Willis
- College of Medicine, Department of Medicine, University of Arizona, Tucson, AZ 85724-5099, USA
| | - L. Bruce Gladden
- School of Kinesiology, Auburn University, Auburn, AL 36849-5323, USA
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Perioperative Fluid Accumulation Impairs Intestinal Contractility to a Similar Extent as Peritonitis and Endotoxemia. Shock 2019; 50:735-740. [PMID: 29251668 DOI: 10.1097/shk.0000000000001088] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
BACKGROUND Perioperative resuscitation with large amounts of fluid may cause tissue edema, especially in the gut, and thereby impairing its functions. This is especially relevant in sepsis where capillaries become leaky and fluid rapidly escapes to the pericapillary tissue. We assessed the effects of endotoxemia and peritonitis, and the use of high and moderate volume fluid resuscitation on jejunal contractility. We hypothesized that both endotoxemia and peritonitis impair jejunum contractility and relaxation, and that this effect is aggravated in peritonitis and with high fluid administration. METHODS Pigs were randomized to endotoxin (n = 16), peritonitis (n = 16), or sham operation (n = 16), and either high (20 mL/kg/h) or moderate volume (10 mL/kg/h) fluid resuscitation for 24 h or until death. At the end of the experiment, jejunal contractility and relaxation were measured in vitro using acetylcholine and sodium nitroprusside reactivity, and the effect of nitric oxide synthase inhibition (NOS-I) was assessed. RESULTS Mortality in the respective groups was 88% (peritonitis high), 75% (endotoxemia high), 50% (peritonitis moderate), 13% (endotoxemia moderate and sham operation high), and 0% (sham operation moderate volume resuscitation). Although gut perfusion was preserved in all groups, jejunal contractility was impaired in the two peritonitis and two endotoxemia groups, and similarly also in the sham operation group treated with high but not with moderate volume fluid resuscitation (model-fluid-contraction-interaction, P = 0.036; maximal contractility 136 ± 28% [average of both peritonitis, both endotoxemia and sham operation high-volume groups) vs. 170 ± 74% of baseline [sham operation moderate-volume group]). NOS-I reduced contractility (contraction-inhibition-interaction, P = 0.011) without significant differences between groups and relaxation was affected neither by peritonitis and endotoxemia nor by the fluid regimen. CONCLUSIONS Intestinal contractility is similarly impaired during peritonitis and during endotoxemia. Moreover, perioperative high-volume fluid resuscitation in sham-operated animals also decreases intestinal contractility. This may have consequences for postoperative recovery.
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Goodwin ML, Pennington Z, Westbroek EM, Cottrill E, Ahmed AK, Sciubba DM. Lactate and cancer: a "lactatic" perspective on spinal tumor metabolism (part 1). ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:220. [PMID: 31297385 DOI: 10.21037/atm.2019.02.32] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
Spine tumors are among the most difficult tumors to treat given their proximity to the spinal cord. Despite advances in adjuvant therapies, surgery remains a critical component of treatment, both in primary tumors and metastatic disease. Given the significant morbidity of these surgeries and with other current adjuvant therapies (e.g., radiation, chemotherapy), interest has grown in other methods of targeting tumors of the spine. Recent efforts have highlighted the tumor microenvironment, and specifically lactate, as central to tumorigenesis. Once erroneously considered a waste product that indicated hypoxia/hypoperfusion, lactate is now known to be at the center of whole-body metabolism, shuttling between tissues and being used as a fuel. Diffusion-driven transporters and the near-equilibrium enzyme lactate dehydrogenase (LDH) allow rapid mobilization of large stores of muscle glycogen in the form of lactate. In times of stress, catecholamines can bind muscle cell receptors and trigger the breakdown of glycogen to lactate, which can then diffuse out into circulation and be used as a fuel where needed. Hypoxia, in contrast, is rarely the reason for an elevated arterial [lactate]. Tumors were originally described in the 1920's as being "glucose-avid" and "lactate-producing" even in normoxia (the "Warburg effect"). We now know that a broad range of metabolic behaviors likely exist, including cancer cells that consume lactate as a fuel, others that may produce it, and still others that may change their behavior based on the local microenvironment. In this review we will examine the relationship between lactate and tumor metabolism with a brief look at spine-specific tumors. Lactate is a valuable fuel and potent signaling molecule that has now been implicated in multiple steps in tumorigenesis [e.g., driving vascular endothelial growth factor (VEGF) expression in normoxia]. Future work should utilize translational animal models to target tumors by altering the local tumor microenvironment, of which lactate is a critical part.
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Affiliation(s)
- Matthew L Goodwin
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Zach Pennington
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Erick M Westbroek
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Ethan Cottrill
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - A Karim Ahmed
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Daniel M Sciubba
- Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Strand-Amundsen RJ, Reims HM, Reinholt FP, Ruud TE, Yang R, Høgetveit JO, Tønnessen TI. Ischemia/reperfusion injury in porcine intestine - Viability assessment. World J Gastroenterol 2018; 24:2009-2023. [PMID: 29760544 PMCID: PMC5949714 DOI: 10.3748/wjg.v24.i18.2009] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 04/20/2018] [Accepted: 04/23/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate viability assessment of segmental small bowel ischemia/reperfusion in a porcine model.
METHODS In 15 pigs, five or six 30-cm segments of jejunum were simultaneously made ischemic by clamping the mesenteric arteries and veins for 1 to 16 h. Reperfusion was initiated after different intervals of ischemia (1-8 h) and subsequently monitored for 5-15 h. The intestinal segments were regularly photographed and assessed visually and by palpation. Intraluminal lactate and glycerol concentrations were measured by microdialysis, and samples were collected for light microscopy and transmission electron microscopy. The histological changes were described and graded.
RESULTS Using light microscopy, the jejunum was considered as viable until 6 h of ischemia, while with transmission electron microscopy the ischemic muscularis propria was considered viable until 5 h of ischemia. However, following ≥ 1 h of reperfusion, only segments that had been ischemic for ≤ 3 h appeared viable, suggesting a possible upper limit for viability in the porcine mesenteric occlusion model. Although intraluminal microdialysis allowed us to closely monitor the onset and duration of ischemia and the onset of reperfusion, we were unable to find sufficient level of association between tissue viability and metabolic markers to conclude that microdialysis is clinically relevant for viability assessment. Evaluation of color and motility appears to be poor indicators of intestinal viability.
CONCLUSION Three hours of total ischemia of the small bowel followed by reperfusion appears to be the upper limit for viability in this porcine mesenteric ischemia model.
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Affiliation(s)
- Runar J Strand-Amundsen
- Department of Clinical and Biomedical Engineering, Oslo University Hospital, Oslo 0424, Norway
- Department of Physics, University of Oslo, Oslo 0316, Norway
| | - Henrik M Reims
- Department of Pathology, Oslo University Hospital, Oslo 0424, Norway
| | - Finn P Reinholt
- Department of Pathology, Oslo University Hospital, Oslo 0424, Norway
| | - Tom E Ruud
- Institute for Surgical Research, Oslo University Hospital, Oslo 0424, Norway
- Department of Surgery, Baerum Hospital, Vestre Viken Hospital Trust, Drammen 3004, Norway
| | - Runkuan Yang
- Department of Emergencies and Critical Care, Oslo University Hospital, Oslo 0424, Norway
| | - Jan O Høgetveit
- Department of Clinical and Biomedical Engineering, Oslo University Hospital, Oslo 0424, Norway
- Department of Physics, University of Oslo, Oslo 0316, Norway
| | - Tor I Tønnessen
- Department of Emergencies and Critical Care, Oslo University Hospital, Oslo 0424, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway
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Ferguson BS, Rogatzki MJ, Goodwin ML, Kane DA, Rightmire Z, Gladden LB. Lactate metabolism: historical context, prior misinterpretations, and current understanding. Eur J Appl Physiol 2018; 118:691-728. [PMID: 29322250 DOI: 10.1007/s00421-017-3795-6] [Citation(s) in RCA: 245] [Impact Index Per Article: 35.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Accepted: 12/22/2017] [Indexed: 02/07/2023]
Abstract
Lactate (La-) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La- has often been erroneously viewed as simply a hypoxic waste product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La- in metabolism begin. The evidence for La- as a major player in the coordination of whole-body metabolism has since grown rapidly. La- is a readily combusted fuel that is shuttled throughout the body, and it is a potent signal for angiogenesis irrespective of oxygen tension. Despite this, many fundamental discoveries about La- are still working their way into mainstream research, clinical care, and practice. The purpose of this review is to synthesize current understanding of La- metabolism via an appraisal of its robust experimental history, particularly in exercise physiology. That La- production increases during dysoxia is beyond debate, but this condition is the exception rather than the rule. Fluctuations in blood [La-] in health and disease are not typically due to low oxygen tension, a principle first demonstrated with exercise and now understood to varying degrees across disciplines. From its role in coordinating whole-body metabolism as a fuel to its role as a signaling molecule in tumors, the study of La- metabolism continues to expand and holds potential for multiple clinical applications. This review highlights La-'s central role in metabolism and amplifies our understanding of past research.
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Affiliation(s)
- Brian S Ferguson
- College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA
| | - Matthew J Rogatzki
- Department of Health and Exercise Science, Appalachian State University, Boone, NC, USA
| | - Matthew L Goodwin
- Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA.,Huntsman Cancer Institute, Salt Lake City, UT, USA
| | - Daniel A Kane
- Department of Human Kinetics, St. Francis Xavier University, Antigonish, Canada
| | - Zachary Rightmire
- School of Kinesiology, Auburn University, 301 Wire Road, Auburn, AL, 36849, USA
| | - L Bruce Gladden
- School of Kinesiology, Auburn University, 301 Wire Road, Auburn, AL, 36849, USA.
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Sabroe JE, Ellebæk MB, Qvist N. Intraabdominal microdialysis - methodological challenges. Scand J Clin Lab Invest 2016; 76:671-677. [PMID: 27701896 DOI: 10.1080/00365513.2016.1233574] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2016] [Revised: 07/07/2016] [Accepted: 09/04/2016] [Indexed: 12/17/2022]
Abstract
Microdialysis is used for in vivo sampling of extracellular molecules. The technique provides a continuous and dynamic view of concentrations of both endogenous released and exogenous administered substances. Microdialysis carries a low risk of complications and has proven to be a safe procedure in humans. The technique has been applied in several clinical areas, including gastrointestinal surgery. Microdialysis may be used for studies of tissue metabolism, and the technique is also a promising tool for pharmacological studies of drug penetration into abdominal organ tissue and the peritoneal cavity. The clinical significance of intraabdominal microdialysis in postoperative monitoring of surgical patients has yet to be proven. In this review, we introduce the microdialysis technique, and we present an overview of theoretical and practical considerations that should be taken into account when using microdialysis in intraabdominal clinical research.
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Affiliation(s)
- Jonas E Sabroe
- a Department of Surgery , Odense University Hospital , Odense C , Denmark
| | - Mark B Ellebæk
- a Department of Surgery , Odense University Hospital , Odense C , Denmark
| | - Niels Qvist
- a Department of Surgery , Odense University Hospital , Odense C , Denmark
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Skoog P, Hörer T, Nilsson KF, Ågren G, Norgren L, Jansson K. Intra-abdominal Hypertension—An Experimental Study of Early Effects on Intra-abdominal Metabolism. Ann Vasc Surg 2015; 29:128-37. [DOI: 10.1016/j.avsg.2014.08.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Revised: 07/02/2014] [Accepted: 08/04/2014] [Indexed: 12/16/2022]
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Pynnönen L, Minkkinen M, Perner A, Räty S, Nordback I, Sand J, Tenhunen J. Validation of intraluminal and intraperitoneal microdialysis in ischemic small intestine. BMC Gastroenterol 2013; 13:170. [PMID: 24325174 PMCID: PMC3880346 DOI: 10.1186/1471-230x-13-170] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 12/05/2013] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GI-tract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia with higher sensitivity and specificity. METHODS IL and IP microdialysate lactate, pyruvate, glucose and glycerol were analysed from small intestine of pancreaticoduodenectomy patients before and after occluding the mesenteric vasculature and routine resection of a segment of small intestine. Ex vivo time sequences of microdialysate metabolites were described and ROC analyses after 0-30, 31-60, 61-90 and 91-120 minutes after the onset ischemia were calculated. RESULTS IL lactate to pyruvate ratio (L/P ratio) indicated ischemia after 31-60 minutes with 0.954 ROC AUC (threshold: 109) in contrast to IP L/P (ROC AUC of 0.938 after 61-90 minutes, threshold: 18). At 31-60 minutes IL glycerol concentration indicated ischemia with 0.903 ROC AUCs (thresholds: 69 μmol/l). IP glycerol was only moderately indicative for ischemia after 91-120 minutes with 0,791 ROC AUCs (threshold 122 μmol/l). After 31-60 minutes IL and IP lactate to glucose ratios (L/G ratio) indicated ischemia with 0.956 and 0,942 ROC AUCs (thresholds: 48,9 and 0.95), respectively. CONCLUSIONS The results support the hypothesis that intraluminal application of microdialysis and metabolic parameters from the small intestinal lumen indicate onset of ischemia earlier than intraperioneal microdialysis with higher sensitivity and specificity.
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Affiliation(s)
| | | | | | | | | | | | - Jyrki Tenhunen
- Critical Care Medicine Research Group, Department of Intensive Care Medicine, Tampere University Hospital, Tampere, Finland.
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Intraluminal intestinal microdialysis detects markers of hypoxia and cell damage in experimental necrotizing enterocolitis. J Pediatr Surg 2012; 47:1646-51. [PMID: 22974600 DOI: 10.1016/j.jpedsurg.2012.03.086] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2011] [Revised: 02/20/2012] [Accepted: 03/20/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND/PURPOSE Necrotizing enterocolitis (NEC) represents one of the gravest complications in premature infants and carries significant morbidity and mortality. There is a great need for improved diagnostic methods to reduce the severity and incidence of NEC. The aim of the study was to investigate if intraluminal microdialysis can detect intestinal ischemia in newborn rats with induced experimental NEC. METHODS The studies were performed on 1-day-old Sprague-Dawley rat pups. Experimental NEC was induced using hypoxia/reoxygenation treatment. Microdialysis catheters were rectally inserted and placed in the rectosigmoid part of the colon. Microdialysate levels of glucose, lactate, pyruvate, and glycerol were measured. Intestinal specimens were collected at the end of the experiments for microscopic evaluation. RESULTS Intraluminal microdialysis revealed signs of intestinal hypoxia and cellular damage, with a marked increase of lactate and glycerol. Microscopic evaluation confirmed intestinal damage in the NEC group. CONCLUSION Intraluminal microdialysis can detect intestinal hypoxic stress and mucosal cell membrane decay in a rat model of NEC. Intestinal intraluminal microdialysis is easily accessible through the rectum and may be a useful noninvasive complement to other methods in the assessment of NEC.
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Högberg N, Carlsson PO, Hillered L, Meurling S, Stenbäck A. Intestinal ischemia measured by intraluminal microdialysis. Scandinavian Journal of Clinical and Laboratory Investigation 2011; 72:59-66. [PMID: 22103734 DOI: 10.3109/00365513.2011.629307] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the possibility of detecting intestinal ischemia by intraluminal microdialysis and comparing the ileum and colon. METHODS The studies were performed on male Sprague-Dawley rats. In the first part of the study, microdialysis catheters were placed in the sigmoid part of the colon and in the subcutaneous adipose tissue. In the second part of the study, microdialysis catheters were placed in the lumen of the ileum and the colon. The infrarenal aorta was clamped proximal to the cranial mesenteric artery. Microdialysate levels of glucose, lactate, pyruvate and glycerol were measured. Intestinal specimens were removed at the end of the ischemic period for microscopic evaluation. RESULTS Intraluminal microdialysis could detect early signs of ischemic injury in the ileum, as well as in the colon, with a marked increase of lactate, lactate/pyruvate ratio and glycerol. The increased levels of intraluminal glycerol showed a positive correlation to prolonged ischemia and to higher degrees of intestinal damage. CONCLUSION Intraluminal measurement of glycerol is a good marker for intestinal ischemia. Intraluminal microdialysis in the colon is easily accessible through the rectum, and may prove to be a valuable clinical tool for diagnosing intestinal ischemia.
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Affiliation(s)
- Niclas Högberg
- Department of Women's and Children's Health, Division of Pediatric Surgery, Uppsala University Hospital, Uppsala, Sweden.
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Juel IS, Solligård E, Skogvoll E, Aadahl P, Grønbech JE. Lactate and glycerol released to the intestinal lumen reflect mucosal injury and permeability changes caused by strangulation obstruction. Eur Surg Res 2007; 39:340-9. [PMID: 17622777 DOI: 10.1159/000105132] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2007] [Accepted: 05/07/2007] [Indexed: 12/13/2022]
Abstract
BACKGROUND The present study evaluates whether microdialysis of glycerol and lactate reflects mucosal injury and permeability changes after strangulation obstruction of the pig small intestine. METHODS Strangulation obstruction was induced by tightening a rubber band around a small bowel loop until its venous pressure increased to a level just below diastolic aortic pressure (partial strangulation), or further until cessation of flow in the main feeding artery (total strangulation). Mucosal injury and permeability of marker molecules from blood to lumen and vice versa was compared to release of glycerol and lactate to the intestinal lumen. RESULTS Mucosal injury, hyperpermeability, and release of glycerol were more pronounced after total than after partial strangulation. In animals with partial strangulation there was a complete restitution of the surface epithelium, and luminal glycerol and lumen-to-blood permeability of polyethylene glycol 4000 remained low. Such animals showed a sustained elevation of lactate and blood-to-lumen permeability of fluorescein isothiocyanate dextran after 2 h of partial strangulation, but a decline to baseline levels of these parameters in animals with 1 h partial strangulation. CONCLUSION Microdialysis of lactate and glycerol in the intestinal lumen may be used to assess structural and functional changes of the intestinal mucosa after strangulation obstruction.
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Affiliation(s)
- I S Juel
- Department of Surgery, St. Olav University Hospital, Trondheim, Norway.
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Knuesel R, Takala J, Brander L, Haenggi M, Bracht H, Porta F, Jakob SM. Membrane microdialysis: Evaluation of a new method to assess splanchnic tissue metabolism. Crit Care Med 2006; 34:2638-45. [PMID: 16915109 DOI: 10.1097/01.ccm.0000239430.73826.23] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo. DESIGN A membrane-based microdialyzer was first validated in vitro. The same device was tested afterward in a randomized, controlled animal experiment. SETTING University experimental research laboratory. SUBJECTS Twenty-four Landrace pigs of both genders. INTERVENTIONS In vitro: Membrane microdialyzers were kept in warmed sodium lactate baths with lactate concentrations between 2 and 8 mmol/L for 10-120 mins, and microdialysis lactate concentrations were measured repeatedly (210 measurements). In vivo: An extracorporeal shunt with blood reservoir and roller pump was inserted between the proximal and distal abdominal aorta, and a microdialyzer was inserted intraperitoneally. In 12 animals, total splanchnic blood flow (measured by transit time ultrasound) was reduced by a median 43% (range, 13% to 72%) by activating the shunt; 12 animals served as controls. MEASUREMENTS AND MAIN RESULTS In vitro: The fractional lactate recovery was 0.59 (0.32-0.83) after 60 mins and 0.82 (0.71-0.87) after 90 mins, with no further increase thereafter. At 60 and 90 mins, the fractional recovery was independent of the lactate concentration. In vivo: Abdominal blood flow reduction resulted in an increase in peritoneal microdialysis lactate concentration from 1.7 (0.3-3.8) mmol/L to 2.8 (1.3-6.2) mmol/L (p = .006). At the same time, mesenteric venous-arterial lactate gradient increased from 0.1 (-0.2-0.8) mmol/L to 0.3 (-0.3 -1.8) mmol/L (p = .032), and mesenteric venous-arterial Pco2 gradients increased from 12 (8-19) torr to 21 (11-54) torr (p = .005). CONCLUSIONS Peritoneal membrane microdialysis provides a method for the assessment of splanchnic ischemia, with potential for clinical application.
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Affiliation(s)
- Rafael Knuesel
- Clinic for Intensive Care Medicine, University Hospital of Bern (Inselspital), Bern, Switzerland
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Sommer T. Microdialysis of the bowel: the possibility of monitoring intestinal ischemia. Expert Rev Med Devices 2006; 2:277-86. [PMID: 16288591 DOI: 10.1586/17434440.2.3.277] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Assessment of the intestinal circulation in a clinical setting still presents a significant diagnostic challenge. In patients suspected of having intestinal ischemia pre- or postoperatively, there is no clinically relevant marker which can determine whether the bowel is suffering from lack of oxygen or not. Microdialysis is a microinvasive technique that makes it possible to continuously detect tissue-specific metabolic changes. Recently, it has been demonstrated that intestinal ischemia can be detected and monitored continuously by the use of a microdialysis catheter placed in the proximity of the ischemic bowel. This review summarizes the clinical dilemma of intestinal ischemia and the latest experimental results using the microdialysis technique to detect critical perfusion in the small intestine. The possibility of using microdialysis in a clinical setting is outlined with the perspective of using it as a pre- or postoperative monitoring tool in relevant patients.
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Affiliation(s)
- Thorbjørn Sommer
- Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg DK-9000, Denmark.
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Krejci V, Hiltebrand L, Büchi C, Ali SZ, Contaldo C, Takala J, Sigurdsson GH, Jakob SM. Decreasing gut wall glucose as an early marker of impaired intestinal perfusion. Crit Care Med 2006; 34:2406-14. [PMID: 16878039 DOI: 10.1097/01.ccm.0000233855.34344.29] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of this study was to assess the microcirculatory and metabolic consequences of reduced mesenteric blood flow. DESIGN Prospective, controlled animal study. SETTING The surgical research unit of a university hospital. SUBJECTS A total of 13 anesthetized and mechanically ventilated pigs. INTERVENTIONS Pigs were subjected to stepwise mesenteric blood flow reduction (15% in each step, n = 8) or served as controls (n = 5). Superior mesenteric arterial blood flow was measured with ultrasonic transit time flowmetry, and mucosal and muscularis microcirculatory perfusion in the small bowel were each measured with three laser Doppler flow probes. Small-bowel intramucosal Pco2 was measured by tonometry, and glucose, lactate (L), and pyruvate (P) were measured by microdialysis. MEASUREMENTS AND MAIN RESULTS In control animals, superior mesenteric arterial blood flow, mucosal microcirculatory blood flow, intramucosal Pco2, and the lactate/pyruvate ratio remained unchanged. In both groups, mucosal blood flow was better preserved than muscularis blood flow. During stepwise mesenteric blood flow reduction, heterogeneous microcirculatory blood flow remained a prominent feature (coefficient of variation, approximately 45%). A 30% flow reduction from baseline was associated with a decrease in microdialysis glucose concentration from 2.37 (2.10-2.70) mmol/L to 0.57 (0.22-1.60) mmol/L (p < .05). After 75% flow reduction, the microdialysis lactate/pyruvate ratio increased from 8.6 (8.0-14.1) to 27.6 (15.5-37.4, p < .05), and arterial-intramucosal Pco2 gradients increased from 1.3 (0.4-3.5) kPa to 10.8 (8.0-16.0) kPa (p < .05). CONCLUSIONS Blood flow redistribution and heterogeneous microcirculatory perfusion can explain apparently maintained regional oxidative metabolism during mesenteric hypoperfusion, despite local signs of anaerobic metabolism. Early decreasing glucose concentrations suggest that substrate supply may become crucial before oxygen consumption decreases.
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Affiliation(s)
- Vladimir Krejci
- Department of Anesthesiology, Inselspital, Bern, Switzerland
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Schnoor J, Zoremba N, Korinth MC, Kochs B, Silny J, Rossaint R. Short-term elevation of intracranial pressure does neither influence duodenal motility nor frequency of bolus transport events: a porcine model. BMC Emerg Med 2006; 6:1. [PMID: 16433933 PMCID: PMC1368992 DOI: 10.1186/1471-227x-6-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2005] [Accepted: 01/25/2006] [Indexed: 11/18/2022] Open
Abstract
Background Patients with traumatic brain injuries and raised intracranial pressure (ICP) display biphasic response with faster gastric emptying during the early stage followed by a prolonged gastric transit time later. While duodenal contractile activity plays a pivotal role in transpyloric transit we investigated the effects of raised intracranial pressure on duodenal motility during the early phase. In order to exclude significant deterioration of mucosal blood supply which might also influence duodenal motility, luminal microdialysis was used in conjunction. Methods During general anaesthesia, 11 pigs (32–37 kg, German Landrace) were instrumented with both a luminal catheter for impedancometry and a luminal catheter for microdialysis into the proximal duodenum. Additionally, a catheter was inserted into the left ventricle to increase the intracranial pressure from baseline up to 50 mmHg in steps of 10 mmHg each hour by injection of artificial cerebrospinal fluid. At the same time, duodenal motility was recorded continuously. Duodenal luminal lactate, pyruvate, and glucose concentrations were measured during physiological state and during elevated intracranial pressure of 10, 20, 30, 40, and 50 mmHg in six pigs. Five pigs served as controls. Results Although there was a trend towards shortened migrating motor cycle (MMC) length in pigs with raised ICP, the interdigestive phase I–III and the MMC cycle length were comparable in the groups. Spontaneous MMC cycles were not disrupted during intracranial hypertension. The mean concentration of lactate and glucose was comparable in the groups, while the concentration of pyruvate was partially higher in the study group than in the controls (p < 0.05). This was associated with a decrease in lactate to pyruvate ratio (p < 0.05). Conclusion The present study suggests that a stepwise and hourly increase of the intracranial pressure of up to 50 mmHg, does not influence duodenal motility activity in a significant manner. A considerable deterioration of the duodenal mucosal blood flow was excluded by determining the lactate to pyruvate ratio.
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Affiliation(s)
- Joerg Schnoor
- Department of Anaesthesiology, University Hospital Aachen, Germany
| | - Norbert Zoremba
- Department of Anaesthesiology, University Hospital Aachen, Germany
| | | | - Bjoern Kochs
- Department of Anaesthesiology, University Hospital Aachen, Germany
| | - Jiri Silny
- Femu-Research Institute, University Hospital Aachen, Germany
| | - Rolf Rossaint
- Department of Anaesthesiology, University Hospital Aachen, Germany
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Gumaste UR, Joshi MM, Mourya DT, Barde PV, Shrivastav GK, Ghole VS. Alcohol dehydrogenase: A potential new marker for diagnosis of intestinal ischemia using rat as a model. World J Gastroenterol 2005; 11:912-6. [PMID: 15682493 PMCID: PMC4250609 DOI: 10.3748/wjg.v11.i6.912] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: Intestinal ischemia (Ii) is an abdominal emergency due to blockade of the superior mesenteric artery resulting in 60-100% mortality if diagnosed late. Changes in several biochemical parameters such as D (-)-lactate, Creatinine kinase isoenzymes and lactate dehydrogenase suggested for early diagnosis, lack specificity and sensitivity. Therefore a biochemical parameter with greater sensitivity needs to be identified.
METHODS: Wistar male rats were randomly assigned into two groups; control sham operated (n = 24) and ischemic test (n = 24) group. Superior mesenteric arterial occlusion was performed in the ischemic test group for 1 h. Alcohol dehydrogenase (ADH) was estimated in blood from portal vein, right ventricle of heart, dorsal aorta (DA) and inferior vena cava (IVC). The Serum glutamic acid pyruvate transaminase (SGPT) was also estimated in blood from portal vein and right ventricle of heart.
RESULTS: A significant increase (P<0.001) in the levels of ADH in both portal blood as well as heart blood of the test group (232.72±99.45 EU and 250.85±95.14 EU, respectively) as compared to the control group (46.39±21.69 EU and 65.38±30.55 EU, respectively) were observed. Similarly, increased levels of ADH were observed in blood samples withdrawn from DA and IVC in test animals (319.52±80.14 EU and 363.90±120.68 EU, respectively) as compared to the control group (67.68±63.22 EU and 72.50±58.45 EU, respectively). However, in test animals there was significant increase in SGPT in portal blood (P = 0.054) without much increase in heart blood.
CONCLUSION: Significant increase in the levels of ADH in portal and heart blood within 1 h of SMA occlusion without increase in SGPT in heart blood, suggests that the origin of ADH is from ischemic intestine and not from liver. Similarly, raised ADH levels were found in DA and IVC as well. IVC blood does represent peripheral blood sample. A raised level of ADH in test animals confirms it to be a potential marker in the early diagnosis of Ii.
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Affiliation(s)
- Upendra R Gumaste
- Division of Biochemistry, Department of Chemistry, University of Pune, Pune 411007, India
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19
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Sommer T, Larsen JF. Intraperitoneal and intraluminal microdialysis in the detection of experimental regional intestinal ischaemia. Br J Surg 2004; 91:855-61. [PMID: 15227691 DOI: 10.1002/bjs.4586] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The aim was to investigate the possibility of using intraluminal or intraperitoneal microdialysis to monitor regional intestinal ischaemia. METHODS Microdialysis catheters were inserted in the lumen, in and outside the intestinal wall, and in the peritoneum of each of ten pigs. Regional occlusive ischaemia was induced in 100 cm of jejunum. Levels of glucose, pyruvate, lactate and glycerol in the microdialysate were measured at 20-min intervals before and after induction of ischaemia. Systemic haemodynamics were monitored and laser Doppler flowmetry (LDF) recordings made in each of the intestinal segments. RESULTS Ischaemia caused a significant decrease in glucose level, and an increase in lactate and glycerol concentrations and lactate/pyruvate ratio, at all catheters, although glucose could not be detected by the intraluminal catheter. The metabolic changes occurred simultaneously and were statistically significant in almost all catheters after 100 min. LDF revealed a significant decrease in intestinal blood flow, but there was considerable individual variation. CONCLUSION Regional occlusive ischaemia in 100 cm of small intestine could be detected and monitored by means of a microdialysis catheter placed in the peritoneal cavity or the bowel lumen.
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Affiliation(s)
- T Sommer
- Department of Surgical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark.
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20
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Tenhunen J. Can we distinguish between different types of local perfusion/metabolic derangement by regional venous concentrations of intermediary energy substrates? Shock 2004; 22:191-2. [PMID: 15257097 DOI: 10.1097/01.shk.0000133597.80869.87] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Fröjse R, Lehtipalo S, Winsö O, Johansson G, Biber B, Arnerlöv C. Assessment of Graded Intestinal Hypoperfusion and Reperfusion Using Continuous Saline Tonometry in a Porcine Model. Eur J Vasc Endovasc Surg 2004; 28:79-88. [PMID: 15177236 DOI: 10.1016/j.ejvs.2004.02.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/09/2004] [Indexed: 10/26/2022]
Abstract
OBJECTIVE To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS Twelve barbiturate-anaesthetized female pigs. METHODS Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.
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Affiliation(s)
- R Fröjse
- Department of Surgical and Perioperative Sciences, Anesthesiology and Intensive Care, Umeå, University Hospital, Umeå, Sweden
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22
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Klaus S, Heringlake M, Bahlmann L. Bench-to-bedside review: microdialysis in intensive care medicine. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2004; 8:363-8. [PMID: 15469599 PMCID: PMC1065008 DOI: 10.1186/cc2882] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Microdialysis is a technique used to measure the concentrations of various compounds in the extracellular fluid of an organ or in a body fluid. It is a form of metabolic monitoring that provides real-time, continuous information on pathophysiological processes in target organs. It was introduced in the early 1970s, mainly to measure concentrations of neurotransmitters in animal experiments and clinical settings. Using commercial equipment it is now possible to conduct analyses at the bedside by collecting interstitial fluid for measurement of carbohydrate and lipid metabolites. Important research has been reported in the field of neurosurgery in recent decades, but use of metabolic monitoring in critical care medicine is not yet routine. The present review provides an overview of findings from clinical studies using microdialysis in critical care medicine, focusing on possible indications for clinical biochemical monitoring. An important message from the review is that sequential and tissue-specific metabolic monitoring, in vivo, is now available.
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Affiliation(s)
- Stephan Klaus
- Department of Anaesthesiology, Medical University of Luebeck, Luebeck, Germany
| | - Matthias Heringlake
- Department of Anaesthesiology, Medical University of Luebeck, Luebeck, Germany
| | - Ludger Bahlmann
- Department of Anaesthesiology, Medical University of Luebeck, Luebeck, Germany
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23
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Bäckström T, Liska J, Oldner A, Lockowandt U, Franco-Cereceda A. SPLANCHNIC METABOLISM DURING GUT ISCHEMIA AND SHORT-TERM ENDOTOXIN AND HEMORRHAGIC SHOCK AS EVALUATED BY INTRAVASAL MICRODIALYSIS. Shock 2004; 21:572-8. [PMID: 15167688 DOI: 10.1097/01.shk.0000127069.65490.65] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The splanchnic area is of considerable interest in different types of shock. To characterize the metabolic changes in the splanchnic region in response to different types of shock we used a model where shock-induced metabolic changes in the splanchnic region were studied by the use of intravasal microdialysis. 23 anesthetized domestic pigs were randomized into four groups: Group I, serving as controls (n = 5); Group II, mesenteric ischemia for 180 followed by 120 min of reperfusion (n = 5); Group III, endotoxin shock for 5 h (n = 5); and Group IV, hemorrhagic shock for 180 min followed by re-transfusion of shed blood (n = 8). Microdialysis catheters were placed in the left femoral artery, portal vein and a small ileal mesenteric vein. Samples of the perfusate were continuously collected in micro-vials and analyzed for glucose, lactate, pyruvate and glycerol. In gut ischemia and endotoxin shock the outflow-pattern of lactate, lactate/pyruvate ratio and glucose in the mesenteric vein differed significantly from controls and hemorrhage whereas an increase in glycerol was only noted in the ischemic group. The most prominent differences were detected in lactate/pyruvate ratio, a marker of tissue ischemia with the most pronounced changes during mesenteric ischemia/reperfusion. During endotoxin shock increases in microdialysate metabolites were only noted in the splanchnic region suggesting a specific vulnerability in the region. Studying the lactate/pyruvate ratio may provide additional information when interpreting increased blood lactate levels. In addition glycerol may prove to be a useful marker of splanchnic ischemia. Intravasal microdialysis represents a potentially useful method for monitoring regional metabolic events.
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Affiliation(s)
- Tobias Bäckström
- Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
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Solligård E, Juel IS, Bakkelund K, Johnsen H, Saether OD, Grønbech JE, Aadahl P. Gut barrier dysfunction as detected by intestinal luminal microdialysis. Intensive Care Med 2004; 30:1188-94. [PMID: 14991095 DOI: 10.1007/s00134-004-2173-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2003] [Accepted: 12/30/2003] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To evaluate the use of gut luminal microdialysis as a tool for monitoring ischaemic metabolites, particularly glycerol, as markers of intestinal dysfunction during and after intestinal ischaemia. DESIGN A randomised, controlled animal experiment. SETTING National laboratory animal centre. INTERVENTIONS In seven pigs the thoracic aorta was cross-clamped for 60 min followed by 2 h of reperfusion, while five pigs served as controls. MEASUREMENTS AND RESULTS Glycerol, lactate and glucose in the intestinal lumen and mucosa were measured by microdialysis. Intestinal tissue blood flow was determined by means of colour-labelled microspheres. To assess intestinal permeability, (14)C-polyethylene glycol 4000 (PEG-4000) was instilled in a jejunal segment and then measured in venous blood. Intestinal blood flow was reduced to 10% of baseline by aortic cross-clamping ( p=0.001) and returned to baseline during reperfusion. Intestinal luminal lactate increased during ischaemia and further increased during reperfusion. The increase was paralleled by augmented intestinal permeability; there was a significant correlation between luminal lactate and venous PEG-4000 ( r=0.89, p<0.01). Aortic cross-clamping caused a marked increase in intestinal mucosal glycerol concentrations, which correlated with luminal glycerol during both ischaemia and reperfusion ( r=0.85, p<0.01). CONCLUSION Microdialysis of lactate may be useful for monitoring intestinal ischaemia and reperfusion. Release of lactate into the intestinal lumen appears to be related to increased permeability. Intestinal luminal glycerol closely mirrored glycerol concentrations in the intestinal wall.
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Affiliation(s)
- Erik Solligård
- Department of Anaesthesiology and Intensive Care, St. Olav University Hospital, Norwegian University of Science and Technology, 7006 Trondheim, Norway.
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25
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Tenhunen JJ, Uusaro A, Kärjä V, Oksala N, Jakob SM, Ruokonen E. Apparent heterogeneity of regional blood flow and metabolic changes within splanchnic tissues during experimental endotoxin shock. Anesth Analg 2003; 97:555-563. [PMID: 12873953 DOI: 10.1213/01.ane.0000072703.37396.93] [Citation(s) in RCA: 36] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
UNLABELLED We conducted a randomized, controlled experiment of prolonged lethal endotoxin shock in pigs aiming at 1) simultaneously measuring perfusion at different parts of the gut to study the potential heterogeneity of blood flow within the splanchnic region; 2) studying the association among regional blood flows, oxygen supply, and different metabolic markers of perfusion; and 3) analyzing the association between histological gut injury and markers of perfusion and metabolism. The primary response to endotoxin was a decrease in systemic and splanchnic blood flow followed by hyperdynamic systemic circulation. Redistribution of blood flows occurred within the splanchnic circulation: superior mesenteric artery blood flow was maintained, whereas celiac trunk blood flow was compromised. Mucosal to arterial PCO(2) gradients did not reflect changes in total splanchnic perfusion, but they were associated with regional blood flows during the hypodynamic phase of shock. During hyperdynamic systemic circulation, PCO(2) gradients increased heterogeneously in the gastrointestinal tract, whereas luminal lactate increased only in the colon. Histological analysis revealed mucosal epithelial injury only in the colon. We conclude that markers of perfusion and metabolism over one visceral region do not reflect perfusion and metabolism in other splanchnic vascular areas. Intestinal mucosal epithelial injury occurs in the colon during 12 h of endotoxin shock while the epithelial injury is still absent in the jejunum. Hyperdynamic and hypotensive shock induces gut luminal lactate release in the colon but not in the jejunum. The association or causality between the mucosal epithelial injury and luminal lactate release remains to be elucidated. IMPLICATIONS Surrogate regional markers of tissue perfusion over one region do not reflect the state of perfusion over another. Therefore, regional metabolic monitoring (microdialysis) in multiple locations is needed. Although tonometry does not differentiate between macro-level regional perfusion defect and tissue injury, intestinal luminal microdialysis detects mucosal lactate release, which may be associated with epithelial injury. The degree of correlation or causality between the two remains to be evaluated.
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Affiliation(s)
- Jyrki J Tenhunen
- Departments of *Anesthesiology and Intensive Care, †Clinical Pathology, and ‡Surgery, Kuopio University Hospital, Kuopio, Finland
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Korth U, Krieter H, Denz C, Janke C, Ellinger K, Bertsch T, Henn C, Klein J. Intestinal ischaemia during cardiac arrest and resuscitation: comparative analysis of extracellular metabolites by microdialysis. Resuscitation 2003; 58:209-17. [PMID: 12909384 DOI: 10.1016/s0300-9572(03)00119-9] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
Intestinal ischaemia is a major complication of shock syndromes causing translocation of bacteria and endotoxins and multiple organ failure in intensive care patients. The present study was designed to use microdialysis as a tool to monitor intestinal ischaemia after cardiac arrest and resuscitation in pigs. For this purpose, microdialysis probes were implanted in pig jejunal wall, peritoneum, skeletal muscle and brain, and interstitial fluid was obtained during circulatory arrest (induced by ventricular fibrillation) and after return of spontaneous circulation (ROSC). Cardiac arrest for 4 min caused a prolonged (60 min) reduction of blood flow in jejunal wall, muscle and brain as determined by the ethanol technique. This was accompanied by cellular damage in heart muscle and brain as indicated by increased levels of troponin-I and protein S-100, respectively. Plasma levels of glucose, lactate and choline were increased at 15-60 min following cardiac arrest. In contrast, cardiac arrest induced a rapid but variable decrease of interstitial glucose levels in all monitored organs; this decrease was followed by an increase over baseline during reperfusion. In the intestine, lactate, glutamate and choline levels were increased during ischaemia and reperfusion for 60-120 min; intestinal and peritoneal samples yielded parallel changes of lactate levels. Brain and muscle samples showed similar changes as in intestinum and peritoneum except for glutamate, which was increased in brain but not in muscle. We conclude that intestinal ischaemia occurs as a consequence of cardiac arrest and resuscitation and can be monitored by in vivo microdialysis. Comparative analysis by multi-site microdialysis reveals that the intestine is equally or even more sensitive to ischaemia than brain or muscle.
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Affiliation(s)
- Ulrike Korth
- Faculty of Clinical Medicine Mannheim, Institute of Anesthesiology, University of Heidelberg, 68165 Mannheim, Germany
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27
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Klaus S, Heringlake M, Gliemroth J, Pagel H, Staubach K, Bahlmann L. Biochemical tissue monitoring during hypoxia and reoxygenation. Resuscitation 2003; 56:299-305. [PMID: 12628561 DOI: 10.1016/s0300-9572(02)00342-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Oxygen deficiency during critical illness may cause profound changes in cellular metabolism and subsequent tissue and organ dysfunction. Clinical treatment in these cases targets rapid reoxygenation to avoid a prolonged impaired synthesis of cellular high-energy phosphates (ATP). However, the effect of this therapeutic intervention on tissue metabolism has not been determined yet. Thus the present study was designed to determine the effects of hypoxia and reoxygenation with either room air or 100% oxygen on variables of interstitial metabolism in different tissues using in vivo microdialysis. Twenty-seven adult, male CD-rats (407-487 g; Ivanovas, Kisslegg, Germany) were studied during general anesthesia. Following preparation and randomization, rats were normoventilated for 45 min (FiO(2) 0.21), followed by induction of hypoxia (FiO(2) 0.1, 40 min) and reoxygenated for 50 min either with FiO(2) 1.0 (group 1, n=10) or FiO(2) 0.21 (group 2, n=10). Control animals (n=7) were ventilated with 21% oxygen during the observation period. Additional to invasive haemodynamic parameters, biochemical tissue monitoring was performed using CMA 20 microdialysis probes, inserted into muscle, subcutaneous space, liver, and the peritoneal cavity allowing analyses of lactate and pyruvate at short intervals. Hypoxia induced a significant reduction in mean arterial pressure (MAP) in group 1 and 2 compared with the control group (P<0.05) without any significant differences between both treatment groups. This was accompanied by a significant increase in blood lactate (10.5+/-3.1 mM (group 1) and 12.3+/-4.1 mM (group 2) vs. 1.5+/-0.3 mM (control); P<0.05) and severe metabolic acidosis (base excess (BE): -18.3+/-5 mM (1) and -17.3+/-7 mM (2) vs. -2.6+/-1.8 mM (control), P<0.05). During hypoxia, the interstitial lacate/pyruvate ratio in groups 1 and 2 increased to 455+/-199% (muscle), 468+/-148% (intraperitoneal), 770+/-218% (hepatic) and 855+/-432% (subcutaneous) (P<0.05 vs. control, respectively). No significant inter-organ or inter-group differences in interstitial dialysates were observed in the treatment groups, neither during hypoxia nor during reoxygenation. Our data suggest, that hypoxia induces comparable metabolic alterations in various tissues and that reoxygenation with 100% oxygen is not superior to 21% oxygen in restoring tissue metabolism after critical hypoxia.
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Affiliation(s)
- Stephan Klaus
- Department of Anaesthesiology, Medical University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
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Tenhunen JJ, Takala J. Intestinal luminal lactate in shock-marker for altered epithelial cellular metabolism? Intensive Care Med 2003. [DOI: 10.1007/s00134-002-1599-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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29
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Träger K, Radermacher P, Leverve X. The adrenergic coin: perfusion and metabolism. Intensive Care Med 2003; 29:150-3. [PMID: 12594579 DOI: 10.1007/s00134-002-1596-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2002] [Accepted: 09/20/2002] [Indexed: 10/22/2022]
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