Prolonged Ventricular Fibrillation Cardiac Arrest Research Articles

Neuroprotection with hypothermic reperfusion and extracorporeal cardiopulmonary resuscitation - A randomized controlled animal trial of prolonged ventricular fibrillation cardiac arrest in rats.

Extracorporeal cardiopulmonary resuscitation (ECPR) facilitates resuscitation with immediate and precise temperature control. This study aimed to determine the optimal reperfusion temperature to minimize neurological damage after ventricular fibrillation cardiac arrest (VFCA). Twenty-four rats were randomized (n = 8 per group) to normothermia (NT = 37°C), mild hypothermia (MH = 33°C) or moderate hypothermia (MOD = 27°C). The rats were subjected to 10 minutes of VFCA, before 15 minutes of ECPR at their respective target temperature. After ECPR weaning, rats in the MOD group were rapidly rewarmed to 33°C, and temperature maintained at 33°C (MH/MOD) or 37°C (NT) for 12 hours before slow rewarming to normothermia (MH/MOD). The primary outcome was 30-day survival with overall performance category (OPC) 1 or 2 (1 = normal, 2 = slight disability, 3 = severe disability, 4 = comatose, 5 = dead). Secondary outcomes included awakening rate (OPC ≤ 3) and neurological deficit score (NDS, from 0 = normal to 100 = brain dead). The survival rate did not differ between reperfusion temperatures (NT = 25%, MH = 63%, MOD = 38%, p = 0.301). MH had the lowest NDS (NT = 4[IQR 3-4], MH = 2[1-2], MOD = 5[3-5], p = 0.044) and highest awakening rate (NT = 25%, MH = 88%, MOD = 75%, p = 0.024). In conclusion, ECPR with 33°C reperfusion did not statistically significantly improve survival after VFCA when compared with 37°C or 27°C reperfusion but was neuroprotective as measured by awakening rate and neurological function.

Abstract 372: Regional Cerebral Saturation in a Swine Model of Goal-directed Resuscitation of Prolonged Ventricular Fibrillation Cardiac Arrest

Introduction: The characteristics and limitations of near-infrared spectroscopy (NIRS) measurement of regional cerebral saturation (rSO2) for reflecting key moment-to-moment physiological changes needed to guide cardiopulmonary resuscitation (CPR) have yet to be fully determined. Objective: Examine the impact of NIRS sensor placement and resuscitation process variation on rSO2 measurements during prolonged cardiac arrest. Methods: Thirty mixed-breed domestic pigs (mean weight: 25.0kg+/-2.0) were sedated (ketamine / xylazine), anesthetized (fentanyl), paralyzed (vecuronium) and mechanically ventilated. Micromanometer pressure transducers were placed in the aorta and right atrium via femoral cutdown to measure central pressures, including mean arterial pressure (MAP) and coronary perfusion pressure (CPP). Two NIRS sensors were placed on the cranium: one on the skin surface and one on the bare skull. Ventricular fibrillation was induced electrically and untreated for 8 minutes followed by CPR. Initial BLS phase: 4 minutes of CPR at 100 compressions per minute (CPM) and 2 inches depth with manual ventilations (30:2). Randomized ALS phase: CPR with a pressor-titrated (Group A) or a compression rate/depth-titrated (Group B) strategy targeting 25mmHg CPP. Group A animals received pressor doses q1min and fixed rate/depth CPR. Group B animals received increasing rates and depth of CPR with epinephrine q3min. Defibrillation was attempted at 6min CPR q2min. rSO2 was compared between skin and skull across phases of resuscitation with t-tests and generalized estimating equations (GEE). Results: Mean skin and skull rSO2 differed marginally overall (63.8 vs 62.0, p < 0.001), at baseline (69.9 vs 64.9, p < 0.001), during BLS CPR (56.9 vs 48.7, p < 0.001), during ALS CPR (59.5 vs 51.0, p < 0.001), and following ROSC (70.0 vs 60.5, p<0.001). rSO2 measured on either skull or skin both varied throughout phases of the experiment but not between CPR groups. In GEE models, rSO2 measured on skin or skull was not associated with MAP at baseline, but was directly associated during BLS (coef 0.13; p<0.001) & ALS CPR (coef 0.09; p<0.001), and after ROSC (coef 0.02; p=0.017). Conclusion: rSO2 measures differ between skin and skull though both correlate with MAP.

Extracorporeal Life Support Increases Survival After Prolonged Ventricular Fibrillation Cardiac Arrest in the Rat.

ABSTRACTBackground:Extracorporeal life support (ECLS) for cardiopulmonary resuscitation (CPR) may increase end organ perfusion and thus survival when conventional CPR fails. The aim was to investigate, if after ventricular fibrillation cardiac arrest in rodents ECLS improves outcome compared with conventional CPR.Methods:In 24 adult male Sprague–Dawley rats (460–510 g) resuscitation was started after 10 min of no-flow with ECLS (consisting of an open reservoir, roller pump, and membrane oxygenator, connected to cannulas in the jugular vein and femoral artery, n = 8) or CPR (mechanical chest compressions plus ventilations, n = 8) and compared with a sham group (n = 8). After return of spontaneous circulation (ROSC), all rats were maintained at 33°C for 12 h. Survival to 14 days, neurologic deficit scores and overall performance categories were assessed.Results:ECLS leads to sustained ROSC in 8 of 8 (100%) and neurological intact survival to 14 days in 7 of 8 rats (88%), compared with 5 of 8 (63%) and 1 of 8 CPR rats. The median survival time was 14 days (IQR: 14–14) in the ECLS and 1 day (IQR: 0 to 5) for the CPR group (P = 0.004).Conclusion:In a rat model of prolonged ventricular fibrillation cardiac arrest, ECLS with mild hypothermia produces 100% resuscitability and 88% long-term survival, significantly better than conventional CPR.

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs

BackgroundOut-of-hospital cardiac arrest (CA) is a prevalent medical crisis resulting in severe injury to the heart and brain and an overall survival of less than 10%. Mitochondrial dysfunction is predicted to be a key determinant of poor outcomes following prolonged CA. However, the onset and severity of mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) is not fully understood. Ischemic postconditioning (IPC), controlled pauses during the initiation of CPR, has been shown to improve cardiac function and neurologically favorable outcomes after 15min of CA. We tested the hypothesis that mitochondrial dysfunction develops during prolonged CA and can be rescued with IPC during CPR (IPC-CPR). MethodsA total of 63 swine were randomized to no ischemia (Naïve), 19min of ventricular fibrillation (VF) CA without CPR (Untreated VF), or 15min of CA with 4min of reperfusion with either standard CPR (S-CPR) or IPC-CPR. Mitochondria were isolated from the heart and brain to quantify respiration, rate of ATP synthesis, and calcium retention capacity (CRC). Reactive oxygen species (ROS) production was quantified from fresh frozen heart and brain tissue. ResultsCompared to Naïve, Untreated VF induced cardiac and brain ROS overproduction concurrent with decreased mitochondrial respiratory coupling and CRC, as well as decreased cardiac ATP synthesis. Compared to Untreated VF, S-CPR attenuated brain ROS overproduction but had no other effect on mitochondrial function in the heart or brain. Compared to Untreated VF, IPC-CPR improved cardiac mitochondrial respiratory coupling and rate of ATP synthesis, and decreased ROS overproduction in the heart and brain. ConclusionsFifteen minutes of VF CA results in diminished mitochondrial respiration, ATP synthesis, CRC, and increased ROS production in the heart and brain. IPC-CPR attenuates cardiac mitochondrial dysfunction caused by prolonged VF CA after only 4min of reperfusion, suggesting that IPC-CPR is an effective intervention to reduce cardiac injury. However, reperfusion with both CPR methods had limited effect on mitochondrial function in the brain, emphasizing an important physiological divergence in post-arrest recovery between those two vital organs.

Extracorporeal live support increases survival after prolonged ventricular fibrillation cardiac arrest in the rat as compared to conventional cardiopulmonary resuscitation

Extracorporeal live support increases survival after prolonged ventricular fibrillation cardiac arrest in the rat as compared to conventional cardiopulmonary resuscitation

Extracorporeal live support improves cerebral perfusion pressure during and haemodynamic stability following resuscitation from prolonged ventricular fibrillation cardiac arrest in the rat

s / Resuscitation 96S (2015) 5–42 9 Conclusion: ECPR avoids hypercarbia and improves perfusion pressures during resuscitation as compared to CPR. After ROSC, haemodynamic stability is improved in a prolonged VFCA rat model. http://dx.doi.org/10.1016/j.resuscitation.2015.09.020

Potassium induced cardiac standstill during conventional cardiopulmonary resuscitation in a pig model of prolonged ventricular fibrillation cardiac arrest: A feasibility study

Aim of the studyPotassium-based cardioplegia has been the gold standard for cardioprotection during cardiac surgery. We sought to evaluate the feasibility and the effects of potassium-induced cardiac standstill during conventional cardiopulmonary resuscitation (CPR) in a pig model of prolonged ventricular fibrillation (VF). MethodsVF was induced in 20 pigs, and circulatory arrest was maintained for 14min. Animals were then resuscitated by standard CPR. Coincident with the start of CPR, 20ml of saline (control group) or 0.9mequiv.kg−1 of potassium chloride diluted to 20ml (potassium group) was administered into right atrium. ResultsAdministration of potassium resulted in asystole lasting for 1.0min (0.2) in the potassium group animals. VF reappeared in all but one animal, in which wide QRS complex bradycardia followed. Restoration of spontaneous circulation (ROSC) was attained in two animals (20%) in the control group and in seven animals (70%) in the potassium group (p=0.070). Resuscitated animals in the potassium group required fewer countershocks (3, 4 vs. 2 (1–2)), smaller doses of adrenaline (1.84, 1.84 vs. 0.94 (0.90–1.00)mg), and shorter duration of CPR (8, 10 vs. 4.0 (4.0–4.0)min) than did the control group. Potassium concentrations normalised rapidly after ROSC in both groups, and the potassium concentrations at 5min (5.5, 6.6 vs. 6.8 (6.5–7.8)mequiv.l−1) and 4h (4.9, 5.4 vs. 5.9 (5.1–6.4)mequiv.l−1) after ROSC were similar in the both groups. ConclusionIn a pig model of untreated VF cardiac arrest for 14min, resuscitation with potassium-induced cardiac standstill during conventional CPR was found to be feasible.

Cold aortic flush and chest compressions enable good neurologic outcome after 15 mins of ventricular fibrillation in cardiac arrest in pigs*

The induction of deep cerebral hypothermia via ice-cold saline aortic flush during prolonged ventricular fibrillation cardiac arrest, followed by hypothermic stasis and delayed resuscitation (emergency preservation and resuscitation), improved neurologic outcome after cardiac arrest in pigs, as compared to conventional resuscitation. We hypothesized that emergency preservation and resuscitation with chest compressions would further improve outcome in the same model. Prospective experimental study. University research laboratory. : Twenty-four female, large, white breed pigs (27-37 kg). Fifteen minutes of ventricular fibrillation cardiac arrest were followed by 20 mins of resuscitation with chest compressions (control, n = 8), deep cerebral hypothermia via 200 mL/kg 4 degrees C saline aortic flush and hypothermic stasis (emergency preservation and resuscitation, n = 8), and emergency preservation and resuscitation combined with chest compressions (emergency preservation and resuscitation plus chest compressions, n = 8). At 35 mins after cardiac arrest, cardiopulmonary bypass was initiated, followed by defibrillation. Mild hypothermia was continued for 20 hrs. Pigs were evaluated after 9 days using a neurologic deficit (neurologic deficit score: 100% = brain dead; 0%-10% = normal) and an overall performance category score (overall performance category score: 1 = normal; 2 = slightly handicapped; 3 = severely handicapped; 4 = comatose; 5 = dead/brain dead). Brain temperature decreased from 38.5 degrees C to 15.3 degrees C +/- 3.3 degrees C in the emergency preservation and resuscitation group, and to 11.3 degrees C +/- 1.2 degrees C in the emergency preservation and resuscitation plus chest compressions group. In the control group, restoration of spontaneous circulation was achieved in four out of eight pigs, and one survived to 9 days. In the emergency preservation and resuscitation group, restoration of spontaneous circulation was achieved in seven out of eight pigs and five survived; in the emergency preservation and resuscitation plus chest compressions group, all had restoration of spontaneous circulation and seven survived (restoration of spontaneous circulation, p = .08). Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2-5) and neurologic deficit score was 45% (36; 50) and in the emergency preservation and resuscitation plus chest compressions group, overall performance category score was 2 (1-3) and neurologic deficit score was 13% (5; 21) (overall performance category score, p = .04; neurologic deficit score emergency preservation and resuscitation vs. emergency preservation and resuscitation plus chest compressions, p = .003). Emergency preservation and resuscitation by deep cerebral hypothermia combined with chest compressions during prolonged cardiac arrest in pigs are feasible and improve neurologic outcome.

Invited Commentary

Invited Commentary

Myocardial cytokine IL-8 and nitric oxide synthase activity during and after resuscitation: Preliminary observations in regards to post-resuscitation myocardial dysfunction

Increases in serum cytokines have been reported after successful resuscitation from prolonged ventricular fibrillation (VF). Pro-inflammatory cytokines can stimulate inducible nitric oxide synthase (iNOS) to produce excessive levels of nitric oxide (NO). High levels of both myocardial inflammatory cytokines and nitric oxide levels can depress myocardial contractile function. We hypothesized that myocardial pro-inflammatory cytokines and iNOS activity would increase following successful resuscitation from prolonged ventricular fibrillation cardiac arrest, and that such increases would parallel the development of post-resuscitation myocardial dysfunction. Ventricular fibrillation cardiac arrest was induced in seven domestic swine (25+/-5 kg). After 10 min of untreated VF, the animals were defibrillated and resuscitated. Left ventricular (LV) systolic and diastolic function measurements, serum samples (arterial and coronary sinus) for IL-8 cytokine quantification, and LV myocardial biopsies were collected before, during, and after resuscitation. Quantification of myocardial endothelial (eNOS) and inducible (iNOS) nitric oxide synthase protein levels were determined using immunoblot analyses and protein localization was examined using immunohistochemistry. Post-resuscitation LV systolic and diastolic functions were depressed while increases in both coronary sinus IL-8 levels and myocardial iNOS activity were found. Compared to pre-arrest baseline, levels of iNOS protein increased during VF (p < or = 0.05) and continued to increase throughout the post-resuscitation study period of 6 h (p < or = 0.05). Myocardial inflammatory cytokines and iNOS activity increase during and after prolonged cardiac arrest and successful resuscitation. These increases correspond to the well described decrease in LV function post-resuscitation.

One-Shock Versus Three-Shock Defibrillation Protocol Significantly Improves Outcome in a Porcine Model of Prolonged Ventricular Fibrillation Cardiac Arrest

The success of resuscitation with a 1-shock versus the conventional 3-shock defibrillation protocol was investigated subject to the range of treatment variation imposed by automated external defibrillators (AEDs). Ventricular fibrillation was induced in 44 domestic pigs. After 7 minutes of untreated VF, animals were randomized among 4 groups representing all combinations of the 1- versus 3-shock protocol and 2 different AED regimens (AED1, AED2). Because few AEDs support a 1-shock protocol, manual defibrillators were used to replicate the AED treatment regimen: electrical waveform, dose sequence, and cardiopulmonary resuscitation (CPR) interruption intervals. Initial shock(s) were delivered, followed by 60 seconds of CPR, and the treatment was repeated until resuscitation was successful or for 15 minutes. The 1-shock protocol was associated with improved outcome, reducing CPR interruptions from 45% to 34% of total resuscitation time (P=0.019) and increasing survival from 64% to 100% (P=0.004). Survival was 91% for AED1 versus 36% for AED2 (P=0.024) with a 3-shock protocol but was increased to 100% for both by adoption of a 1-shock protocol. Improvements in postresuscitation left ventricular ejection fraction and stroke volume were observed with AED1 compared with AED2 (difference of means, 15% and 28% of baseline respectively, P<0.001) regardless of defibrillation protocol. Adoption of a 1-shock versus a 3-shock resuscitation protocol improved survival and minimized outcome differences imposed by variations in AED design and implementation. When a conventional 3-shock defibrillation protocol was used, however, the choice of AED had a significant impact on resuscitation outcome.

Ventricular Fibrillation Median Frequency May Not Be Useful for Monitoring During Cardiac Arrest Treated with Endothelin-1 or Epinephrine

In this study, we evaluated whether median fibrillation frequency (MF) and mean fibrillation amplitude (AMP) reflect coronary perfusion pressure (CoPP) and predict successful defibrillation. MF, AMP, and CoPP were measured during prolonged ventricular fibrillation (VF) cardiac arrest and resuscitation in pigs. After 5 min of VF, cardiopulmonary resuscitation was started. At 10 min, the pigs received randomly a single dose of endothelin-1 50 mug (n = 7), 100 mug (n = 7), or 200 mug (n = 5), or repeated doses of epinephrine 0.04 mg/kg (n = 6), or saline (n = 6) every 3 min. At 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation (ROSC). In a nonparametric spectral analysis of the individual MF versus CoPP and AMP versus CoPP curves, we found no link between the different curves in different animals or therapies. No difference was found in MF in pigs with ROSC (n = 8) compared with animals not achieving ROSC (n = 23) immediately before defibrillation (P = 0.85). Our data suggest that, in prolonged VF cardiac arrest, MF and AMP might not be useful tools to reflect myocardial perfusion.

Endothelin-1 elevates regional cerebral perfusion during prolonged ventricular fibrillation cardiac arrest in pigs

Since adrenaline (epinephrine) also has negative effects during and after cardiopulmonary resuscitation (CPR) a non-adrenergic vasoconstrictor like endothelin might be an alternative to increase vital organ blood flow. We studied the effect of different doses of endothelin-1 compared with adrenaline on the ability to resuscitate, cerebral and myocardial blood flow (MBF) in a closed chest cardiac arrest pig model. After 5 min of ventricular fibrillation, CPR with a ventilator and a mechanical compression device was started. At 10 min, 31 pigs were randomized to receive a single dose of endothelin-1 50, 100 or 200 μg or repeated doses of adrenaline 0.04 mg kg −1 or saline every 3 min. After 25 min, the pigs were defibrillated to achieve restoration of spontaneous circulation. Blood flow was measured with the fluorescent microsphere method. In animals receiving endothelin-1 50, 100 and 200 μg the cerebral blood flow (CBF) increased from median 28 (25th; 75th quartile: 16; 40), 32 (15; 48) and 17 (4; 65) to 36 (31; 54), 47 (39; 57) and 63 (35; 83) ml min −1 per 100 g, respectively, 6 min after drug administration ( P<0.05 endothelin-1 50 μg vs. Control, P<0.01 endothelin-1 100 and 200 μg vs. Control). At the same time CBF decreased in the control and adrenaline group from 36 (21; 41) and 39 (15; 50) to 12 (2; 25) and 24 (15; 26) ml min −1 per 100 g, respectively, ( P<0.05 adrenaline vs. endothelin-1 200 μg). There was no difference in MBF between the treatment groups despite a higher coronary perfusion pressure (CoPP) in the endothelin-1 groups. Restoration of spontaneous circulation could be only achieved in the endothelin-1 50 μg (3 of 7; 43%) and 100 μg (5 of 7; 71%) group. This study suggests that endothelin-1 enhances CBF during CPR better than adrenaline and increases resuscitation success.

Minimally invasive direct cardiac massage versus closed-chest cardiopulmonary resuscitation in a porcine model of prolonged ventricular fibrillation cardiac arrest

Open chest cardiac massage has been shown to be superior to closed-chest cardiopulmonary resuscitation for both hemodynamics produced during resuscitation and ultimate resuscitation success. The inexperience of many rescuers with emergency thoracotomy, along with the associated morbidity contributes to the continued reluctance in the use of invasive cardiopulmonary resuscitation techniques. A device has been developed for performing ‘minimally invasive’ direct cardiac massage. This technique was compared to standard closed-chest CPR for resuscitation results in 20 swine during prolonged ventricular fibrillation cardiac arrest. Minimally invasive direct cardiac massage was superior to closed-chest CPR for return of spontaneous circulation (7/10 vs. 2/10; P<0.02) and coronary perfusion pressure at 30 min of CPR (17±9 vs. 6±6 mmHg; P<0.05). No significant injuries altering outcome were found with the invasive device. Throughout most of the time course of the study no significant differences in end-tidal expired carbon dioxide levels were noted. Nor were there any differences in 24-h survival. Improvements in assuring proper placement of the device on the epicardium should make this technique a potent advanced cardiac life support adjunct.

Postresuscitation left ventricular systolic and diastolic dysfunction. Treatment with dobutamine.

Global left ventricular dysfunction after successful resuscitation is well documented and appears to be a major contributing factor in limiting long-term survival after initial recovery from out-of-hospital sudden cardiac death. Treatment of such postresuscitation myocardial dysfunction has not been examined previously. Systolic and diastolic parameters of left ventricular function were measured in 27 swine before and after successful resuscitation from prolonged ventricular fibrillation cardiac arrest. Dobutamine infusions (10 micrograms.kg-1.min-1 in 14 animals or 5 micrograms.kg-1.min-1 in 5 animals) begun 15 minutes after resuscitation were compared with controls receiving no treatment (8 animals). The marked deterioration in systolic and diastolic left ventricular function seen in the control group after resuscitation was ameliorated in the dobutamine-treated animals. Left ventricular ejection fraction fell from a prearrest 58 +/- 3% to 25 +/- 3% at 5 hours after resuscitation in the control group but remained unchanged in the dobutamine (10 micrograms.kg-1.min-1) group (52 +/- 1% prearrest and 55 +/- 3% at 5 hours after resuscitation). Measurement of the constant of isovolumic relaxation of the left ventricle (tau) demonstrated a similar benefit of the dobutamine infusion for overcoming postresuscitation diastolic dysfunction. The tau rose in the controls from 28 +/- 1 milliseconds (ms) prearrest to 41 +/- 3 ms at 5 hours after resuscitation whereas it remained constant in the dobutamine-treated animals (31 +/- 1 ms prearrest and 31 +/- 5 ms at 5 hours after resuscitation). Dobutamine begun within 15 minutes of successful resuscitation can successfully overcome the global systolic and diastolic left ventricular dysfunction resulting from prolonged cardiac arrest and cardiopulmonary resuscitation.

External cardiopulmonary resuscitation preserves brain viability after prolonged cardiac arrest in dogs

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 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 doficit score (0%, best; 100% worst) was lower (better) in group I (15% ± 20%) than in group II (51% ± 6%; P < .001). Final canine coma score (15, best; 3, worst) was higher (better) in group I (13.0 ± 2.8) than in group II (8.0 ± 1.3; P = .002). It was concluded that optimal standard external CPR steps A-B-C can sustain cerebral viability during prolonged VF cardiac arrest, even after no flow of 10 minutes.

Amelioration of brain damage by lidoflazine after prolonged ventricular fibrillation cardiac arrest in dogs.

Calcium entry blockers can ameliorate postischemic cerebral hypoperfusion, protect the myocardium against ischemia, and may protect against early postischemic neurologic deficit. This study documents that a calcium entry blocker, given after cardiac arrest, can ameliorate late postischemic neurologic deficit (ND). Thirty-four dogs received 10 min of ventricular fibrillation, restoration of spontaneous circulation by external cardiopulmonary resuscitation, and standard postarrest intensive care. Eleven of these dogs were given lidoflazine, 1 mg/kg body weight, within 10 min postarrest and again at 8 h and 16 h. Pupillary light reflexes, EEG activity, arterial-cerebrovenous oxygen gradients (O2 demand/supply ratios) and intracranial pressure were the same in both groups. After weaning from controlled ventilation at 24 h, ND scores improved consistently through the 96-h observation period in the lidoflazine-treated dogs. In the control group, ND scores were significantly higher than in the lidoflazine-treated dogs. In the lidoflazine-treated group, 5/11 dogs achieved normal overall performance and none remained comatose, whereas all control dogs had some deficit and 4/11 remained comatose. Delayed neurologic deterioration occurred in 6/11 control and 0/11 lidoflazine-treated dogs. Total mean cerebral histopathologic damage (HD) scores at 96 h were not significantly different between the two groups; however, individual HD scores and maximum cerebro-spinal fluid (brain-specific) creatine-phosphokinase activity--which increases after brain insults--correlated well with 96-h ND scores. In the lidoflazine group, life-threatening dysrhythmias were less frequent and the norepinephrine requirement for blood pressure maintenance was the same as in the control group. Cardiac output remained at prearrest levels in the lidoflazine-treated dogs, but decreased in the control group, particularly during the first 4 h postarrest.