Despite the high prevalence of neurological complications and mortality associated with extracorporeal cardiopulmonary resuscitation (ECPR), neurologically-focused animal models are scarce. Our objective is to review current ECPR models investigating neurological outcomes and identify key elements for a recommended model.

We searched PubMed and four other engines for animal ECPR studies examining neurological outcomes. Inclusion criteria were: animals experiencing cardiac arrest, ECPR/ECMO interventions, comparisons of short versus long cardiac arrest times, and neurological outcomes.

Among 20 identified ECPR animal studies (n = 442), 13 pigs, 4 dogs, and 3 rats were used. Only 10% (2/20) included both sexes. Significant heterogeneity was observed in experimental protocols. 90% (18/20) employed peripheral VA-ECMO cannulation and 55% (11/20) were survival models (median survival = 168 hours; ECMO duration = 60 minutes). Ventricular fibrillation (18/20, 90%) was the most common method for inducing cardiac arrest with a median duration of 15 minutes (IQR = 6-20). In two studies, cardiac arrests exceeding 15 minutes led to considerable mortality and neurological impairment. Among seven studies utilizing neuromonitoring tools, only four employed multimodal devices to evaluate cerebral blood flow using Transcranial Doppler ultrasound and near-infrared spectroscopy, brain tissue oxygenation, and intracranial pressure. None examined cerebral autoregulation or neurovascular coupling.

The substantial heterogeneity in ECPR preclinical model protocols leads to limited reproducibility and multiple challenges. The recommended model includes large animals with both sexes, standardized pre-operative protocols, a cardiac arrest time between 10-15 minutes, use of multimodal methods to evaluate neurological outcomes, and the ability to survive animals after conducting experiments.

State-of-the-art cardiopulmonary resuscitation (CPR) restores circulation with inconsistent blood-flow and pressure. Extracorporeal life support (ECLS) following CPR opens the opportunity for "controlled reperfusion". In animal experiments investigating CPR with ECLS, systemic anticoagulation before induced cardiac arrest is normal, but a major point of dispute, since preliminary heparinization in patients undergoing unwitnessed cardiac arrest is impossible. In this study, we investigated options for ECLS after an experimental 15 minutes normothermic cardiac arrest, without preceding anticoagulation, in pigs. Neurological recovery was assessed by a scoring system, electroencephalography and brain magnetic resonance imaging. Additionally, brain histology was performed on day seven after cardiac arrest. We demonstrated that preliminary heparin administration was not necessary for survival or neurological recovery in this setting. Heparin flushing of the cannulae seemed sufficient to avoid thrombus formation. These findings may ease the way to using ECLS in patients with sudden cardiac arrest.

Therapeutic hypothermia during cardiac arrest and after restoration of spontaneous circulation enables intact survival after prolonged cardiopulmonary cerebral resuscitation (CPCR). The effect of cooling during CPCR is not known. We hypothesized that mild to moderate hypothermia during CPCR would increase the rate of neurologically intact survival after prolonged cardiac arrest in dogs.

Randomized, controlled study using a clinically relevant cardiac arrest outcome model in dogs.

University research laboratory.

Twenty-seven custom-bred hunting dogs (19-29 kg; three were excluded from outcome evaluation).

Dogs were subjected to cardiac arrest no-flow of 3 mins, followed by 7 mins of basic life support and 10 mins of simulated unsuccessful advanced life support attempts. Another 20 mins of advanced life support continued with four treatments: In control group 1 (n = 7), CPCR was with normothermia; in group 2 (n = 6, 1 of 7 excluded), with moderate hypothermia via venovenous extracorporeal shunt cooling to tympanic temperature 27 degrees C; in group 3 (n = 6, 2 of 8 excluded), the same as group 2 but with mild hypothermia, that is, tympanic temperature 34 degrees C; and in group 4 (n = 5), with normothermic venovenous shunt. After 40 mins of ventricular fibrillation, reperfusion was with cardiopulmonary bypass for 4 hrs, including defibrillation to achieve spontaneous circulation. All dogs were maintained at mild hypothermia (tympanic temperature 34 degrees C) to 12 hrs. Intensive care was to 96 hrs.

Overall performance categories and neurologic deficit scores were assessed from 24 to 96 hrs. Regional and total brain histologic damage scores and extracerebral organ damage were assessed at 96 hrs. In normothermic groups 1 and 4, all 12 dogs achieved spontaneous circulation but remained comatose and (except one) died within 58 hrs with multiple organ failure. In hypothermia groups 2 and 3, all 12 dogs survived to 96 hrs without gross extracerebral organ damage (p < .0001). In group 2, all but one dog achieved overall performance category 1 (normal); four of six dogs had no neurologic deficit and normal brain histology. In group 3, all dogs achieved good functional outcome with normal or near-normal brain histology. Myocardial damage scores were worse in the normothermic groups compared with both hypothermic groups (p < .01).

Mild or moderate hypothermia during prolonged CPCR in dogs preserves viability of extracerebral organs and improves outcome.

To study the use of emergency department (ED) femoro-femoral cardiopulmonary bypass (CPB) in the resuscitation of medical cardiac arrest patients.

Prospective, uncontrolled trial.

Urban academic ED staffed with board-certified emergency physicians (EPs).

Ten patients with medical cardiac arrest unresponsive to standard therapy.

Femoro-femoral CPB instituted by EPs.

The time of cardiac arrest prior to CPB (mean+/-SD) was 32.0+/-13.6 min. The cardiac output while on CPB was 4.09+/-1.03 L/min with an average of 229+/-111 min on bypass. All 10 patients had resumption of spontaneous cardiac activity while on CPB. Seven of these were weaned from CPB with intrinsic spontaneous circulation. Of these, six patients were transferred from the ED to the operating room for cannula removal and vessel repair while the other patient died in the ED soon after discontinuing CPB. Mean survival was 47.8+/-44.7 h in the six patients leaving the ED. Although these patients had successful hemodynamic resuscitation, there were no long-term survivors.

CPB instituted by EPs is feasible and effective for the hemodynamic resuscitation of cardiac arrest patients unresponsive to advanced cardiac life support therapy. Future efforts need to focus on improving long-term outcome.

Standard external cardiopulmonary resuscitation (SECPR) frequently produces very low perfusion pressures, which are inadequate to achieve restoration of spontaneous circulation (ROSC) and intact survival, particularly when the heart is diseased. Ultra-advanced life support (UALS) techniques may allow support of vital organ systems until either the heart recovers or cardiac repair or replacement is performed. Closed-chest emergency cardiopulmonary bypass (CPB) provides control of blood flow, pressure, composition and temperature, but has so far been applied relatively late. This additional low-flow time may preclude conscious survival. An easy, quick method for vessel access and a small preprimed system that could be taken into the field are needed. Open-chest CPR (OCCPR) is physiologically superior to SECPR, but has also been initiated too late in prior studies. Its application in the field has recently proven feasible. Variations of OCCPR, which deserve clinical trials inside and outside hospitals, include 'minimally invasive direct cardiac massage' (MIDCM), using a pocket-size plunger-like device inserted via a small incision and 'direct mechanical ventricular actuation' (DMVA), using a machine that pneumatically drives a cup placed around the heart. Other novel UALS approaches for further research include the use of an aortic balloon catheter to improve coronary and cerebral blood flow during SECPR, aortic flush techniques and a double-balloon aortic catheter that could allow separate perfusion (and cooling) of the heart, brain and viscera for optimal resuscitation of each. Decision-making, initiation of UALS methods and diagnostic evaluations must be rapid to maximize the potential for ROSC and facilitate decision-making regarding long-term circulatory support versus withdrawal of life support for hopeless cases. Research and development of UALS techniques needs to be coordinated with cerebral resuscitation research.

This article reviews the critical resuscitations necessary during prehospital and emergency department treatment of cardiac arrest. Standard therapy for cardiac arrest rhythms is presented. Novel pharmacologic agents, types of cardiopulmonary resuscitation, and circulatory-assist devices are discussed.

In a previous cardiopulmonary resuscitation (CPR) study in swine, ventilation was associated with improved rate of return of spontaneous circulation (ROSC) compared with nonventilated animals, which had greater hypoxia and hypercarbic acidosis. We used the same model to determine the independent effect of hypoxia and hypercarbic acidosis on ROSC after cardiac arrest.

Laboratory model of cardiac arrest.

University teaching hospital laboratory.

Domestic swine (23 to 61 kg).

Twenty-four swine were randomly assigned to three groups receiving ventilation during CPR with 85% O2/15% N2 (control), 95% O2/5% CO2 (hypercarbia), or 10% O2/90% N2 (hypoxia). All animals had ventricular fibrillation for 6 min without CPR, then CPR with one of the ventilation gases for 10 min, then defibrillation. Animals without ROSC received epinephrine, 85% O2, CPR for another 3 min, and defibrillation.

During the tenth minute of CPR, the hypercarbic group had more mean (SD) arterial hypercarbia than the control group (PCO2, 47 +/- 6, compared with 34 +/- 6; p < 0.01), and greater mixed venous hypercarbia (PCO2, 72 +/- 14, compared with 59 +/- 8; p < 0.05), while mean arterial and mixed venous PO2 was not significantly different. The hypoxic group had significantly less mean arterial (43 +/- 9 compared with 228 +/- 103 mm Hg) and mixed venous (22 +/- 5 compared with 35 +/- 7 mm Hg) PO2 when compared with the control group (p < 0.01), while mean arterial and mixed venous PCO2 were not significantly different. Thus, the model succeeded in producing isolated hypercarbia without hypoxia in the hypercarbic group and isolated hypoxia without hypercarbia in the hypoxic group. The rate of ROSC was 6/8 (75%) for the control group, 1/8 (13%) for the hypercarbic group, and 1/8 (13%) for the hypoxic group (p < 0.02).

Both hypoxia and hypercarbia independently had an adverse effect on resuscitation from cardiac arrest. In this model with a prolonged interval of untreated cardiac arrest, adequate ventilation was important for resuscitation.

Epinephrine has been used in cardiac arrest to increase the low blood flow generated by standard CPR methods. Reperfusion with high flow such as that obtained with cardiopulmonary bypass (CPB) may obviate the need for or alter the dose of epinephrine after cardiac arrest. The objective of this study was to evaluate the effect of high-flow reperfusion after cardiac arrest with and without epinephrine on coronary perfusion pressure, defibrillation energy, restoration of spontaneous circulation (ROSC), and 2-hour survival after prolonged cardiac arrest.

Prospective, randomized, double-blind, placebo-controlled study using a canine model.

Thirty mongrel dogs were randomized to receive, after ventricular fibrillation cardiac arrest of 12 minutes' duration without CPR, placebo (n = 10), standard-dose epinephrine (.02 mg/kg) (n = 10), or high-dose epinephrine (.2 mg/kg) (n = 10) during reperfusion with CPB. Epinephrine or placebo was given with the start of CPB and then every 5 minutes, followed by countershock until ROSC or crossover at the fourth dose to high-dose epinephrine.

ROSC was achieved in the first 15 minutes of bypass in 10 of 10 dogs given high-dose epinephrine, in 9 of 10 given standard-dose epinephrine, and in 1 of 10 given placebo. After the crossover to high-dose epinephrine, ROSC was achieved in 8 of 10 dogs originally given placebo and the remaining animal given the standard dose of epinephrine. During early reperfusion, the high-dose group had a higher mean coronary perfusion pressure (high dose, 153 + 62 mm Hg; standard dose, 81 +/- 18 mm Hg; placebo, 51 +/- 15 mm Hg; P < .002) and a shorter mean ROSC time (high dose, 16.2 +/- 8 minutes; standard dose, 20.3 +/- 3.6 minutes; placebo, 27.9 +/- 3.2; P < .02) and required less defibrillation energy. CPB flow during ventricular fibrillation was 63% of baseline cardiac output in all three groups. Two-hour survival was 5 of 10 in the high-dose group, 8 of 10 in the standard-dose group, and 5 of 10 in the placebo group.

Restoration of high blood flow alone is insufficient to restore spontaneous circulation after prolonged cardiac arrest. Epinephrine, when administered early under high-flow conditions, increases coronary perfusion pressure, decreases defibrillation energy, and decreases time elapsed before ROSC. Higher doses of epinephrine under conditions of high-flow reperfusion do not improve 2-hour survival compared with standard-dose epinephrine.

Successful resuscitation of the brain requires unimpaired blood recirculation. The study addresses the question of the severity and reversibility of no-reflow after cardiac arrest.

Adult normothermic cats were submitted to 5, 15 and 30 min cardiac arrest by ventricular fibrillation. The extent of no-reflow was assessed in each cardiac arrest group after 5 min closed chest cardiac massage in combination with 0.2 mg/kg epinephrine or after successful resuscitation followed by 30 min recirculation.

Reperfusion of the brain was visualized by labelling the circulating blood with FITC-Albumin. Areas of no-reflow, defined as absence of microvascular filling, were identified by fluorescence microscopy at 8 standard coronal levels of forebrain, and expressed as percent of total sectional area. During cardiac massage, no-reflow affected 21 +/- 5%, 42 +/- 38% and 70 +/- 27% of forebrain after 5, 15 and 30 min cardiac arrest, respectively. After 30 min spontaneous recirculation following successful resuscitation of the heart, no-reflow significantly declined to 7 +/- 11% after 5 min cardiac arrest (p < 0.05) but persisted in 30 +/- 11% and 65 +/- 21% of forebrain after 15 and 30 min cardiac arrest, respectively (n.s.).

Our observations demonstrate that resuscitation of the heart by closed chest massage causes severe (and after prolonged cardiac arrest irreversible) no-reflow of the brain. This suggests that no-reflow is an important cause of post-resuscitation brain pathology.

The need for ventilation during the initial management of cardiac arrest is an important public health problem that is being debated. The present study was designed to determine whether ventilation affects return of spontaneous circulation from cardiac arrest in a swine model with an interval of untreated ventricular fibrillation of 6 minutes, as reported in witnessed out-of-hospital human cardiac arrest.

Twenty-four animals were randomly assigned to two groups: one that received ventilation during the first 10 minutes of chest compression and one that did not. Coronary perfusion pressure and minute ventilation were continuously recorded. Arterial and mixed venous blood gases were measured at intervals. Return of spontaneous circulation was defined prospectively as an aortic systolic blood pressure of > 80 mm Hg for > 5 minutes and was the primary outcome variable. All animals were anesthetized, paralyzed, and intubated. Ventricular fibrillation was induced and persisted for 6 minutes without chest compression, followed by mechanical chest compression for 10 minutes and then attempted defibrillation. Animals without return of spontaneous circulation were given epinephrine, ventilation, and chest compression for an additional 3 minutes. Defibrillation was again attempted, and animals were assessed for return of spontaneous circulation. There were no significant differences between the two groups in baseline prearrest mean cardiac index, coronary perfusion pressure, or arterial and mixed venous blood gases. However, after 9 minutes of chest compression, significant differences were noted between the ventilated and nonventilated groups. The nonventilated group had significantly (P < .05) lower mean arterial PO2 (38 +/- 17 mm Hg compared with 216 +/- 104 mm Hg) and higher PCO2 (62 +/- 16 mm Hg compared with 35 +/- 8 mm Hg), lower mixed venous PO2 (15 +/- 7 mm Hg compared with 60 +/- 7 mm Hg). Nine of 12 (75%) of the ventilated animals, and only 1 of 12 (8%) of the nonventilated animals had return of spontaneous circulation after cardiac arrest (P < .002).

In this animal model of cardiac arrest, ventilation was important for resuscitation. The importance of ventilation could be related to the prolonged duration of untreated ventricular fibrillation and the significantly greater hypoxia and hypercarbic acidosis found in the nonventilated animals.

To determine organ blood flow changes, relative to baseline, following cardiac arrest and resuscitation in a closed-chest cardiac arrest swine model using cardiopulmonary bypass to achieve reproducible return of spontaneous circulation (ROSC).

Following 10 min of ventricular fibrillation (VF), animals (n = 10) received low-flow cardiopulmonary bypass at 10 ml/kg/min from 10-15 min. At 15 min of VF, norepinephrine (0.12 mg/kg) was given and bypass flow increased to 50 ml/kg/min, followed by countershocks at 16 min. Following ROSC, cardiopulmonary bypass was immediately weaned off with norepinephrine support. Organ blood flows were determined during normal sinus rhythm, during reperfusion of VF and during the early post-ROSC period while off cardiopulmonary bypass support. Organ blood flows during the early ROSC period were compared with organ blood flow at baseline and during VF.

During early reperfusion of VF prior to any drug therapy, myocardial, cerebral and abdominal organ blood flows were all low. All animals achieved ROSC at 16.9 +/- 0.7 min and were weaned from bypass in < 5 min following ROSC. During the early post-ROSC period, blood flow to the myocardial, cerebral and adrenal vascular beds was significantly elevated relative to baseline. Simultaneously, blood flow to the kidneys, liver, spleen and lungs was reduced relative to baseline.

This low-flow bypass model produces reproducible high resuscitation rates and ROSC times. Early post-resuscitation organ blood flow is characterized by a selective hyperemia involving the cerebral, myocardial and adrenal vascular beds, in contrast to hypoperfusion of the pulmonary and mesenteric vascular beds.

The objective of this study was to determine the time limits of resuscitation following increasing intervals of untreated pulseless electrical activity using cardiopulmonary bypass as the resuscitation tool.

Prospective controlled laboratory investigation using a canine model of pulseless electrical activity.

20 mechanically ventilated mongrel dogs of either sex under Halothane anesthesia.

Pulseless electrical activity was produced by clamping the endotracheal tube. The ECG and hemodynamics were monitored until loss of pressure fluctuations by aortic catheter. Animals were then randomized to remain in untreated pulseless electrical activity for 10 min (Group I), 15 min (Group II) or 20 min (Group III). Following each interval, resuscitation was begun using fixed-flow closed-chest cardiopulmonary bypass (50 ml/kg/min) and an epinephrine infusion (4 micrograms/kg/min). Cardiopulmonary bypass was continued for 30 min or until return of spontaneous circulation. Following return of spontaneous circulation, animals were weaned from bypass and observed for 1 h.

Return of spontaneous circulation was achieved in 100% (7/7) Group I, 50% (3/6) Group II and 29% (2/7) Group III animals (P < or = 0.02, Group I vs. Group III). One-hour survival was achieved in 71% (5/7) Group I, 33% (1/3) Group II and 0% (0/2) Group III animals (P > 0.05). Coronary perfusion pressure, bypass flow and arterial blood gases during reperfusion were similar between groups.

Cardiopulmonary bypass is effective at restoring spontaneous circulation when used early in asphyxial pulseless electrical activity cardiac arrest. Cardiopulmonary bypass is less effective when used after 15 min of pulseless electrical activity with no survivors following 20 min of arrest.

After prolonged cardiac arrest, under controlled normotension, cardiac output and cerebral blood flow are reduced for several hours. This dog study documents for the first time the postarrest reduction in oxygen (O2) delivery in relation to O2 uptake for brain and entire organism.

In eight dogs we used our model of ventricular fibrillation (VF) cardiac arrest of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled normotension, normoxemia, and mild hypocapnia to 24 h.

Between 4 and 24 h after cardiac arrest, cardiac output decreased by about 25% and the systemic arteriovenous O2 content difference doubled, while the calculated systemic O2 utilization coefficient (O2 UC) increased and the systemic venous PO2 decreased, both not to critical levels. The cerebral arteriovenous O2 content difference however, which was 5.6 +/- 1.7 ml/dl before arrest, increased between 1 and 18 h, to 10.8 +/- 3.2 ml/dl at 4 h. The cerebral O2 UC increased and the cerebral venous PO2 decreased, both to critical levels.

After prolonged cardiac arrest in dogs with previously fit hearts, the reduction of O2 transport to the brain is worse than its reduction to the whole organism. Monitoring these values might help in titrating life-support therapies.

Researchers are interested in improved uniformity of definitions and standards of reporting data for human CPR studies, and international guidelines (Utstein style) have been developed. However, no guidelines exist for animal CPR investigations.

To assess published animal CPR studies for adequacy of reporting and uniformity of methods and definitions regarding such important factors as the interval from the onset of ventricular fibrillation to the start of CPR (the nonintervention interval), ventilation, chest compression, coronary perfusion pressure, and return of spontaneous circulation.

A blinded review of the methodology described in 42 articles concerned with animal CPR research published during the last ten years. An article had to report cardiac arrest and CPR as part of the protocol and return of spontaneous circulation as one of the outcome variables in order to be included in this study. We excluded abstracts, nonresuscitation models, and human CPR studies.

There was wide variation in the experimental methods reported in the studies. The nonintervention interval ranged from 0 to 15 minutes. The majority of studies initiated CPR within three minutes after the onset of ventricular fibrillation. Twenty-two percent of studies reported tidal volume, and 18% reported minute ventilation. Of the 14 studies that used blood pressure or coronary perfusion pressure as a target for titration of chest compression force, 12 used different target blood pressure values. We found 29 different definitions of return of spontaneous circulation. The duration of return of spontaneous circulation ranged from 30 seconds to 60 minutes; however, 52% of studies did not report a duration.

Important differences exist in animal CPR research methodology among laboratories. Failure to define or report minute ventilation, coronary perfusion pressure, and return of spontaneous circulation made it difficult to compare studies. In order to make valid comparisons of studies, blood flow and ventilation should be measured and controlled when they are not experimental variables. Uniform definitions and guidelines for reporting should be developed for laboratory CPR research.

After prolonged cardiac arrest, conventional methods of closed-chest cardiac compression are ineffective. This is primarily because of failure to generate minimal threshold levels of coronary perfusion pressure for cardiac resuscitation. This report introduces a new option for cardiac resuscitation by use of a combination of intermittent ascending aortic balloon occlusion, aortic infusion, and precordial compression to increase the pressure gradient for coronary perfusion.

Twenty anesthetized, mechanically ventilated, normovolemic domestic pigs were investigated. A 10F balloon catheter was advanced from the left femoral artery into the ascending aorta. Ventricular fibrillation was induced with an AC current delivered through an electrode catheter advanced into the right ventricle. Precordial compression was initiated after 7 minutes of untreated ventricular fibrillation. The animals were randomized to one of four groups: (1) balloon occlusion with proximal infusion of oxygenated saline, (2) balloon occlusion alone, (3) proximal aortic infusion together with epinephrine without balloon occlusion, and (4) injection of epinephrine without balloon occlusion or proximal infusion. For balloon occlusion, the balloon was inflated for 30 seconds during each minute of cardiopulmonary resuscitation. In the subsets of animals that received infusions, oxygenated saline (30 mL) was injected into the proximal aorta immediately after balloon occlusion. Epinephrine was used in two subsets: It was injected as a bolus in amounts of 30 micrograms/kg into the right atrium at 30 seconds after start of precordial compression and repeated as required to maintain coronary perfusion pressure within the range of 25 to 30 mm Hg. Defibrillation was attempted at 1 minute after start of precordial compression and at 1-minute intervals thereafter. Resuscitation attempts were continued until there was return of spontaneous circulation or for a total of 30 minutes after start of precordial compression. Coronary perfusion pressure generated by precordial compression was significantly increased after balloon occlusion. Each of 10 animals was successfully resuscitated and survived for 48 hours after balloon occlusion whether or not it was combined with infusion. Three of five animals were resuscitated by a combination of infusion and epinephrine in the absence of aortic occlusion, but none survived for 48 hours (P = .02). Only one epinephrine-treated animal was successfully resuscitated and survived for 48 hours in the absence of balloon occlusion or infusion (P < .05).

Ascending aortic balloon occlusion with or without proximal aortic infusion strikingly increased resuscitability and 48-hour survival after cardiac arrest under conditions when conventional methods failed.

Twenty-seven dogs, divided into three groups, were subjected to a normothermic ventricular fibrillation (VF) cardiac arrest of 15 min and resuscitated by using cardiopulmonary bypass through the femoral veins and artery (F-F bypass). Group I (n = 15): Cardiac beating did not return in any dogs during an initial 3-min conventional cardiopulmonary resuscitation, but it returned 5.2 +/- 3.8 min (mean +/- S.D.) after the successive initiation of the F-F bypass in all dogs, except in one with bypass trouble. Intermittent burst waves appeared on the electroencephalogram and continuous waves returned, 90.0 +/- 24.7 min and 130.7 +/- 28.1 min after the start of resuscitation, respectively. Values of blood glucose, lactate and potassium 5-15 min after the F-F bypass were significantly higher than those before induction of VF, while those of blood pH, base excess, hemoglobin, hematocrit, platelet and serum protein decreased significantly. Group II (n = 7): Both local cerebral (CBF) and myocardial blood flow (MCBF) returned to the pre-arrest level soon after the initiation of the F-F bypass, even though spontaneous cardiac beating was not yet restored. Closed or open chest cardiac massage could not produce as much blood flow as the F-F bypass did. In the early stage of restoration of spontaneous circulation, temporary interruption of the bypass led to a decrease in both local CBF and MCBF. Group III (n = 5): Spontaneous circulation was restored in all five dogs 5.2 +/- 1.1 min after the institution of the F-F bypass, which was continued for 164 +/- 30 min under mild hypothermia. After intensive care for a subsequent 6-36 h, the animals barked, moved their forelegs and could drink water. The mean neurological deficit score (normal: 0, brain death: 500) was 100.6. However, macroscopic examination of the brain in two dogs with prominent recovery revealed atrophy of the central gyrus and microscopic examination revealed injuries of the vulnerable neurons of the brain.

We studied the post-resuscitation syndrome in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We reported previously, in the same dogs, no difference in resuscitability, mortality, or neurologic outcome between the three insult groups. There was no pulmonary dysfunction, but post-arrest cardiovascular failure, of greater severity in the 12.5 min arrest group. This report concerns renal, hematologic, hepatic and bacteriologic changes. Renal function recovered within 1 h after arrest, without permanent dysfunction. Clotting derangements at 1-24 h postarrest reflect transient disseminated intravascular coagulation with hypocoagulability, more severe after longer arrests, which resolved by 24 h after arrest. Hepatic dysfunction was transient but more severe in the animals that did not recover consciousness and correlated with neurologic dysfunction, but not with brain histologic damage. Bacteremia was present in all animals postarrest. We conclude that in the previously healthy organism after cardiac arrest of 7.5-12.5 min no flow, visceral and hematologic changes, although transient, can retard neurologic recovery.

We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched-chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated.

We studied cardiovascular changes and neurologic outcome at 72 h in 42 healthy dogs after normothermic ventricular fibrillation cardiac arrest (no blood flow) of 7.5, 10, or 12.5 min duration, reversed by standard external cardiopulmonary resuscitation (CPR) (< or = 10 min) and followed by controlled ventilation to 20 h and intensive care to 72 h. We found no difference in resuscitability, mortality, neurologic deficit scores, or overall performance categories between the three insult groups. There was no major pulmonary dysfunction. During controlled normotension post-CPR, all dogs presented a transient reduction in cardiac output. In the 12.5-min cardiac arrest group the decrease in cardiac output persisted beyond 12 h post-CPR (P < 0.01) and was associated with more severe arrhythmias (P < 0.05) and worse morphologic myocardial damage (P < 0.01). Both cardiac and neurologic malfunction at 72 h correlated with arrest time. Only cardiac malfunction correlated with CPR time. Neurologic recovery correlated with mild (inadvertent) pre-arrest hypothermia, diastolic arterial pressure during CPR and absence of cardiovascular impairment at 12 h post-CPR. We conclude that prolonged cardiac arrest in previously healthy dogs is followed by persistent cardiovascular derangements that correlate with impaired neurologic recovery.

At present, fewer than 10% of cardiopulmonary resuscitation (CPR) attempts prehospital or in hospitals outside special care units result in survival without brain damage. Minimizing response times and optimizing CPR performance would improve results. A breakthrough, however, can be expected to occur only when cerebral resuscitation research has achieved consistent conscious survival after normothermic cardiac arrest (no flow) times of not only five minutes but up to ten minutes. Most cerebral neurons and cardiac myocytes tolerate normothermic ischemic anoxia of up to 20 minutes. Particularly vulnerable neurons die, in part, because of the complex secondary post-reflow derangements in vital organs (the postresuscitation syndrome) which can be mitigated. Brain-orientation of CPR led to the cardiopulmonary-cerebral resuscitation (CPCR) system of basic, advanced, and prolonged life support. In large animal models with cardiac arrest of 10 to 15 minutes, external CPR, life support of at least three days, and outcome evaluation, the numbers of conscious survivors (although not with normal brain histology) have been increased with more effective reperfusion by open-chest CPR or emergency cardiopulmonary bypass, an early hypertensive bout, early post-arrest calcium entry blocker therapy, or mild cerebral hypothermia (34 C) immediately following cardiac arrest. More than ten drug treatments evaluated have not reproducibly mitigated brain damage in such animal models. Controlled clinical trials of novel CPCR treatments reveal feasibility and side effects but, in the absence of a breakthrough effect, may not discriminate between a treatment's ability to mitigate brain damage in selected cases and the absence of any treatment effect. More intensified, coordinated, multicenter cerebral resuscitation research is justified.

From November 1987 to February 1992, extracorporeal life support (ECLS) was used for four patients undergoing prolonged external cardiac massage following cardiac arrest. Their underlying diseases consisted of acute pulmonary embolism, pulmonary arterial thrombosis due to protein C deficiency, acute inferior left ventricular infarction accompanied by right ventricular infarction and thoracic contusion. After the initiation of ECLS, hemodynamic variables and metabolic acidosis improved in all of the cases. The case of pulmonary embolism and the case of acute myocardial infarction were successfully weaned from ECLS without complications. They were later discharged ambulatory from the hospital. The patient with pulmonary arterial thrombosis, who was comatose, became alert after the initiation of ECLS. However the patient finally died due to diffuse and massive pulmonary arterial thrombosis, which was probably related to protein C deficiency. The patient with thoracic contusion was also comatose before ECLS. He did not recover from the coma and died soon after the disconnection of ECLS. The latter two cases were suspected to have had irreversible organ failures not responsive to mechanical support of both circulation and respiration. We conclude that ECLS is a very useful method for patients requiring prolonged cardiac massage following cardiac arrest.

Mild cerebral hypothermia (34 degrees C) induced immediately after cardiac arrest improves outcome. Deep postarrest hypothermia (15 degrees C) has not been studied.

We used our dog model of normothermic ventricular fibrillation (no blood flow) of 12.5 minutes, reperfusion by brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 72 hours. Head surface cooling and bypass cooling were performed from start of reperfusion to 1 hour. Five groups of six dogs each were compared: group I, normothermic controls; group II, deep hypothermia (15 degrees C); group III, moderate hypothermia (30 degrees C); group IV, mild hypothermia (34 degrees C); and group V, mild hypothermia with head surface cooling begun during no flow.

In control group I, five dogs remained comatose (overall performance category [OPC] 4) and one severely disabled (OPC 3). In group II, four dogs achieved OPC 4 and two dogs OPC 3 (NS versus group I). Compared with group I, OPCs were better in group III (p less than 0.05), group IV (p less than 0.05), and group V (p less than 0.05). Neurological deficit scores were also better in groups III, IV, and V than in groups I or II (p less than 0.05). Total brain histological damage scores were better in group III (p = 0.02), group IV (p = 0.06), and group V (p less than 0.05) than in group I. In group II, OPC and neurological deficit scores were the same and histological damage scores numerically worse than in group I and all were worse than in groups III, IV, and V (p less than 0.05). Cardiovascular complications and myocardial morphological damage in groups II and III were worse than in groups I, IV, and V (p less than 0.05).

Mild or moderate cerebral hypothermia induced immediately after cardiac arrest improves cerebral outcome, more likely when initiated during arrest, whereas deep postarrest hypothermia can worsen cerebral and cardiac outcome.

To determine the effects of cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, and standard-dose epinephrine on perfusion pressures, myocardial blood flow, and resuscitation from post-countershock electromechanical dissociation.

Prospective, controlled laboratory investigation using a canine cardiac arrest model randomized to receive one of three resuscitation therapies.

After the production of post-countershock electromechanical dissociation, 25 animals received ten minutes of basic CPR and were randomized to receive cardiopulmonary bypass with standard-dose epinephrine, high-dose epinephrine, or standard-dose epinephrine.

Myocardial blood flow was measured using a colored microsphere technique at baseline, during basic CPR, and after intervention. Immediate and two-hour resuscitation rates were determined for each group. Return of spontaneous circulation was achieved in eight of eight cardiopulmonary bypass with standard-dose epinephrine compared with four of eight high-dose epinephrine and three of eight standard-dose epinephrine animals (P less than .04). One animal was resuscitated with CPR alone and was excluded. Survival to two hours was achieved in five of eight cardiopulmonary bypass with standard-dose epinephrine, four of eight high-dose epinephrine, and three of eight standard-dose epinephrine animals (NS). Coronary perfusion pressure increased significantly in the cardiopulmonary bypass with standard-dose epinephrine group when compared with the other groups (cardiopulmonary bypass with standard-dose epinephrine, 76 +/- 45 mm Hg; high-dose epinephrine, 24 +/- 12 mm Hg; standard-dose epinephrine, 3 +/- 14 mm Hg; P less than .005). Myocardial blood flow was higher in cardiopulmonary bypass with standard-dose epinephrine and high-dose epinephrine animals compared with standard-dose epinephrine animals but did not reach statistical significance. Cardiac output increased during cardiopulmonary bypass with standard-dose epinephrine (P = .001) and standard-dose epinephrine (NS) compared with basic CPR but decreased after epinephrine administration in the high-dose epinephrine group (NS).

Resuscitation from electromechanical dissociation was improved with cardiopulmonary bypass and epinephrine compared with high-dose epinephrine or standard-dose epinephrine alone. However, there was no difference in survival between groups. Cardiopulmonary bypass with standard-dose epinephrine resulted in higher cardiac output, coronary perfusion pressure, and a trend toward higher myocardial blood flow. A short period of cardiopulmonary bypass with epinephrine after prolonged post-countershock electromechanical dissociation cardiac arrest can re-establish sufficient circulation to effect successful early resuscitation.

Standard external cardiopulmonary resuscitation (CPR) steps A-B-C produce a low blood flow that may or may not preserve brain viability during prolonged cardiac arrest. A dog model was used with ventricular fibrillation (VF) of 20 minutes, reperfusion with brief cardiopulmonary bypass, controlled ventilation to 20 hours, and intensive care to 96 hours. A retrospective comparison was made of the results of one series, now called "group I" (n = 10)--which received CPR basic life support interposed from VF 10 to 15 minutes, and CPR advanced life support with epinephrine (without defibrillation) from VF 15 to 20 minutes--to the results of another series, now "control group II" (n = 10)--which received VF no flow (no CPR) for 20 minutes. All 20 dogs within protocol were resuscitated. All 10 of group I and 7 of 10 of group II survived to 96 hours. Pupillary light reflex returned after the start of cardiopulmonary bypass at 7.7 +/- 3.7 minutes in CPR group I, versus 16.3 +/- 7.4 minutes in control group II (P = .032). At 96 hours postarrest, final overall performance categories (1, normal; 5, brain death) were better in group I. Six of 10 dogs achieved normality (overall performance category 1) in group I, as compared with none of 10 in group II (P = .004). Final neurologic deficit score (0%, best; 100% worst) was lower (better) in group I (15% +/- 20%) than in group II (51% +/- 6%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

After cardiac arrest, open-chest CPR (OCCPR) and cardiopulmonary bypass (CPB) have demonstrated higher resuscitation rates when compared individually with standard external CPR (SECPR). We compared all three techniques in a canine myocardial infarct ventricular fibrillation model.

Twenty-six mongrel dogs were block-randomized to receive SECPR and advanced life support (nine), CPB (nine), or OCCPR (eight).

All dogs received left anterior descending coronary artery occlusion followed by four minutes of ventricular fibrillation without CPR and eight minutes of Thumper CPR. At 12 minutes, dogs received one of three resuscitation techniques. After resuscitation, all animals received four hours of intensive care. Animals that were resuscitated had histochemical determination of ischemic and necrotic myocardial areas.

Intravascular pressures were measured and coronary perfusion pressure was calculated during baseline, cardiac arrest, resuscitation, and postresuscitation periods. Percent necrotic myocardium, percent ischemic myocardium, and necrotic-to-ischemic ratios were determined for resuscitated animals. Epinephrine dosage and number of countershocks were determined for each group.

Nine of nine CPB and six of nine OCCPR, compared with two of eight SECPR animals, were resuscitated (P less than .01). Three of nine CPB and OCCPR and two of eight SECPR dogs survived to four hours (P = NS). Coronary perfusion pressure two minutes after institution of technique was significantly higher with CPB (75 +/- 37 mm Hg) and OCCPR (56 +/- 31 mm Hg) than in SECPR animals (16 +/- 16 mm Hg, P less than .04). Epinephrine required for resuscitation was significantly less with CPB (0.10 +/- 0.02 mg/kg) than for SECPR (0.28 +/- 0.11 mg/kg, P less than .002). The ratio of necrotic to ischemic myocardium at four hours was significantly lower with CPB (0.15 +/- 0.31) and OCCPR (0.39 +/- 0.25) than for SECPR (1.16 +/- 0.31, P less than .02).

OCCPR and CPB produce higher coronary perfusion pressures and improved resuscitation rates from ventricular fibrillation when compared with SECPR in this canine myocardial infarct cardiac arrest model. CPB and OCCPR yielded similar resuscitation results, although less epinephrine was required with CPB.

Resuscitability and outcome after prolonged cardiac arrest were compared in dogs with standard external cardiopulmonary resuscitation (CPR) vs. closed-chest emergency cardiopulmonary bypass (CPB). Ventricular fibrillation (VF) was with no blood flow from VF 0 min to VF 10 min. Subsequent CPR basic life support (BLS) was from 10 min to VF 15 min. Then, group I (n = 13) received CPR advanced life support (ALS) from VF 15 min until restoration of spontaneous circulation to occur not later than VF 40 min. Group II (n = 14) received CPR-ALS from VF 15 min to VF 20 min without defibrillation, and then total CPB to defibrillation attempts started at VF 20 min, followed by assisted CPB to 2 h. Total ischemia time (no-flow time plus CPR time of MAP less than 50 mmHg) was unexpectedly shorter in group I (14.3 +/- 2.5 min) than in group II (18.6 +/- 2.3 min) (P less than 0.01). During CPR-BLS, coronary perfusion pressures were 25 +/- 9 mmHg in group I and 18 +/- 8 mmHg in group II (NS). Epinephrine during CPR-ALS, before countershock, raised coronary perfusion pressure to 40 +/- 10 mmHg in group I and 27 +/- 10 mmHg in group II (NS). In group II, coronary perfusion pressure increased during total CPB to 58 +/- 16 mmHg (P less than 0.01 vs. group I). Spontaneous normotension was restored in 11/13 dogs of group I and all 14 dogs of group II (NS). Ten dogs in each group followed protocol and survived to 96 h. Five of ten in group I and six of ten in group II were neurologically normal (NS). We conclude that: (1) Reperfusion with CPB yields higher coronary perfusion pressures than reperfusion with CPR-ALS; and (2) even after no blood flow for 10 min, optimized CPR can result in cardiovascular resuscitability and neurologic recovery, similar to those achieved by CPB.

Moderate hypothermia (30 degrees C) induced before circulatory arrest is known to improve neurologic outcome. We explored, for the first time in a reproducible dog outcome model, moderate hypothermia induced during reperfusion after cardiac arrest (resuscitation). In three groups of six dogs each (N = 18), normothermic ventricular fibrillation cardiac arrest (no blood flow) of 17 minutes was reversed by cardiopulmonary bypass--normothermic in control group I (37.5 degrees C) and hypothermic to 3 hours in groups II (32 degrees C) and III (28 degrees C). Defibrillation was achieved in less than or equal to 5 minutes and partial bypass was continued to 4 hours, controlled ventilation to 20 hours, and intensive care to 96 hours. All 18 dogs survived. Electroencephalographic activity returned significantly earlier in groups II and III. Mean +/- SD best neurologic deficit between 48 and 96 hours was 44 +/- 8% in group I, 38 +/- 12% in group II, and 35 +/- 7% in group III (differences not significant). Best overall performance category 2 (good outcome) between 48 and 96 hours was achieved in none of the six dogs in group I and in four of the 12 dogs in the combined hypothermic groups II and III (difference not significant). Mean +/- SD brain total histologic damage score was 130 +/- 22 in group I, 93 +/- 28 in group II (p = 0.05), and 80 +/- 26 in group III (p = 0.03). Gross myocardial damage was greater in groups II and III than in group I--numerically higher overall and significantly higher in group III for the right ventricle alone (p = 0.02). Moderate hypothermia after prolonged cardiac arrest may or may not improve cerebral outcome slightly and can worsen myocardial damage.

Does cardiopulmonary bypass (CPB) improve resuscitation rates and limit infarct size after cardiac arrest and acute myocardial infarction?

Controlled randomized trial with all animals undergoing left anterior descending coronary artery occlusion and subsequent ventricular fibrillation and resuscitation. All animals were supported for four hours after resuscitation in an intensive care setting.

Group 1 (eight) was resuscitated with standard external CPR and advanced life support. Group 2 (eight) was resuscitated with CPB.

Group hemodynamic, resuscitation variables, number resuscitated, and number of four-hour survivors were compared. Ischemic and necrotic myocardial weights were determined with histochemical staining techniques in four-hour survivors. Infarct size was measured as the ratio of necrotic weight to ischemic weight. Significantly fewer dogs were resuscitated in group 1 (four of eight) than in group 2 (eight of eight) (P less than .05). Group 2 survivors required significantly less epinephrine and lidocaine than group 1 survivors (P less than .05) and higher aortic diastolic and coronary perfusion pressures after CPB (P less than .001). The ratio of myocardial necrotic weight to ischemic weight at four hours was 0.82 +/- 0.25 in group 1 and 0.22 +/- 0.25 in group 2 (P less than .05). However, collateral blood flow was not measured in this study.

This pilot study further substantiates the improvement in resuscitation rates obtainable with CPB. CPB may also limit infarct size during the postresuscitation period and requires further study.

Cardiopulmonary bypass (CPB) reperfusion has demonstrated improved resuscitation rates in ventricular fibrillation cardiac arrest models. To investigate the effectiveness of CPB reperfusion in an ischemic cardiac arrest setting, simulating the clinical scenario of myocardial ischemia preceding sudden cardiac death, we developed a canine model of acute myocardial infarction followed by ventricular fibrillation. Sixteen dogs were randomly assigned to two groups. Group 1 (eight) had ventricular fibrillation induced without left anterior descending coronary artery occlusion. Group 2 (eight) had a thrombogenic copper coil placed in the left anterior descending artery and showed ECG evidence of acute myocardial infarction before induction of ventricular fibrillation. CPR commenced after eight minutes of ventricular fibrillation. Epinephrine 0.05 mg/kg and NaHCO3 1.0 mEq/kg were administered at ten minutes. CPB was begun at 12 minutes and continued for one hour. Myocardial ischemic and necrotic areas were determined in four-hour survivors by dual histochemical staining. All animals were resuscitated; all eight group 1 and six of eight group 2 animals survived to four hours. With the onset of CPB, coronary perfusion pressures increased significantly by 68.6 +/- 31.8 (SD) mm Hg in group 1 and 56.2 +/- 34.6 mm Hg in group 2 over those obtained with CPR (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of cerebral energy metabolism is used to indicate CNS viability after ischemia. This study utilized 31P nuclear magnetic resonance (NMR) spectroscopy to measure cerebral energy state and intracellular pH in dogs subjected to 8, 12, or 16 min of cardiac arrest and reperfusion using cardiopulmonary bypass. Spectra were obtained throughout ischemia and initial reperfusion and repeated at 30 and 144 h post ischemia. Neurologic deficit scoring was performed at 12 and 24 h post insult and then daily. High-energy phosphates were depleted by the end of all ischemic intervals. Recovery occurred within 60 min of reperfusion and persisted with no differences in the rate of return between groups (p greater than 0.05). Brain pH (pHb) decreased by the end of ischemia in all groups (p less than 0.0001). Neither the pHb nadir nor its recovery differed between groups (p greater than 0.05). Although longterm neurologic outcome differed between groups, the spectra were similar. Assessment of cerebral energy state using 31P NMR spectroscopy does not appear to be a sensitive indicator of neurologic outcome after global ischemia in dogs. Return of high-energy phosphates may be a necessary but not sufficient condition for cerebral recovery after ischemia. The return of high-energy phosphates after a 16-min cardiac arrest, however, indicates a potential for neurological recovery.

After cardiac arrest (no flow) of more than approximately 5 minutes' duration, standard external cardiopulmonary resuscitation (CPR) basic, advanced, and prolonged life support (BLS, ALS, PLS) do not reliably produce cerebral and coronary perfusion pressures to maintain viability and achieve stable spontaneous normotension; nor do they provide prolonged control over pressure, flow, composition, and temperature of blood. Since these capabilities are often needed to achieve conscious survival, emergency closed-chest cardiopulmonary bypass (CPB) by veno-arterial pumping via oxygenator is presented in this review as a potential addition to ALS-PLS for selected cases. In six dog studies by the Pittsburgh group (n = 221; 1982 through 1988), all 179 dogs that received CPB after prolonged cardiac arrest (no flow) or after CPR (low flow) states had restoration of stable spontaneous circulation. The use of CPB enhanced survival and neurological recovery over those achieved with CPR-ALS attempts only. With CPB and standard intensive care, it was possible to reverse normothermic ventricular fibrillation (VF) cardiac arrest (no flow) of up to 15 minutes and to achieve survival without neurologic deficit; VF of 20 minutes to achieve survival but with neurologic deficit; and VF of 30 minutes to achieve transient restoration of spontaneous circulation followed by secondary cardiac death. CPB could restore stable spontaneous circulation after ice water submersion of up to 90 minutes. Other groups' laboratory and clinical results agree with these findings in general. Clinical feasibility trials are needed to work out logistic problems and to meet clinical challenges. Future possibilities for emergency CPB require further research and development.

We previously found mild hypothermia (34-36 degrees C), induced before cardiac arrest, to improve neurologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling during arrest, continued with systemic cooling (34 degrees C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37.5 degrees C was reversed with cardiopulmonary bypass and defibrillation in less than or equal to 5 min, and followed by controlled ventilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normothermic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hypertension and hemodilution. Control Group B-I (n = 12) was maintained normothermic (6 of 12 were not hemodiluted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories (OPCs) achieved between 24 and 96 h postarrest were in Group A-I: OPC 1 (normal) in 0 of 12 dogs, OPC 2 (moderate disability) in 2, OPC 3 (severe disability) in 7, and OPC 4 (coma) in 3 dogs. In Group A-II, OPC 1 was achieved in 5 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.001), OPC 3 in 1, and OPC 4 in 0 dogs. In Group B-I, OPC 1 was achieved in 0 of 12 dogs, OPC 2 in 6, OPC 3 in 5, and OPC 4 in 1 dog. In Group B-II, OPC 1 was achieved in 6 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.05), and OPC 3 or 4 in 0 dogs. Mean neurologic deficit and brain histopathologic damage scores showed similar significant group differences. Morphologic myocardial damage scores were the same in all four groups. We conclude that mild brain cooling during and after insult improves neurologic outcome after cardiac arrest.

Standard external cardiopulmonary resuscitation (SECPR) produces high cerebral venous and intracranial pressure peaks, low cerebral perfusion pressure, and low cerebral blood flow (CBF). Cerebral viability seems to require 20% of normal CBF, which SECPR cannot reliably generate. We tested the hypothesis that SECPR can produce adequate CBF if started immediately, but not if started after a long period of cardiac arrest (no flow, stasis). Cardiac arrest times of 1, 3, 5, 7 and 9 min were studied in rabbits. We measured unifocal cortical CBF with H2 clearance curves after saturation with H2 10%, O2 50% and N2O 40% by intermittent positive-pressure ventilation (IPPV). Measurements were made during spontaneous circulation (control condition), and then after resaturation immediately before induction of asystole by KCl i.v., and H2 clearance starting at end of arrest time during SECPR-basic life support with IPPV 100% and manual chest compressions (120/min) during asystole. Control cortical CBF was 30-40 ml/100 g brain per min. During asystole and SECPR, CBF greater than 20% normal was achieved only after no-flow of 1 min. After longer arrest (no-flow) times, CBF was less than 20% normal. Values were near zero after 7 and 9 min of cardiac arrest. Decrease in mean arterial pressures (MAP) produced by SECPR during asystole paralleled CBF values. Thus, the longer the preceding period of stasis, the lower the MAP and CBF generated by SECPR without epinephrine. This effect may be the result of anoxia-induced vasoparalysis and stasis-induced increased blood viscosity.

We studied a clinically realistic field-to-hospital scenario in dogs with four-minute ventricular fibrillation (VF) cardiac arrest followed by 30-minute standard external CPR basic life support (BLS). At the end of this 34-minute insult, cardiopulmonary bypass (CPB) was used for early defibrillation and assisted circulation for one hour (n = 10). Recovery was compared with that of control dogs (n = 10) in which standard CPR with advanced life support (ALS) for another 30 minutes was used for restoration of spontaneous circulation (ROSC). Both groups had hemodilution and heparinization; controlled blood pressure, blood gases, ventilation, and other parameters for 20 hours; and intensive care to 72 hours. During CPR-BLS of 30 minutes in both groups signs of cerebral viability returned. CPB achieved ROSC more successfully (ten of ten vs five of ten CPR-ALS controls) (P less than .02); and more rapidly, with less defibrillation energy (first countershock in eight of ten) and with less epinephrine (P less than .01). CPB improved 72-hour survival (seven of ten vs three of ten controls) (P less than .05). Between two and 24 hours, of those with ROSC, cardiac complications killed three of ten CPB dogs (after weaning), and two of five CPR-ALS dogs (NS). All seven CPB survivors to 72 hours were neurologically normal; of the three CPR-ALS survivors, one remained with severe neurologic deficit and two were neurologically normal (seven of ten CPB vs two of ten controls, P = .025). Starting CPR-BLS within four minutes of arrest can maintain cerebral viability.(ABSTRACT TRUNCATED AT 250 WORDS)