Mild hypothermia after cardiac arrest in dogs does not affect postarrest multifocal cerebral hypoperfusion.

Abstract

Background and Purpose: Although mild resuscitative hypothermia (34°C) immediately after cardiac arrest improves neurological outcome in dogs, its effects on cerebral blood flow and metabolism are unknown.Methods: We used stable xenon-enhanced computed tomography to study local, regional, and global cerebral blood flow patterns up to 4 hours after cardiac arrest in dogs. We compared a normothermic (37.50C) control group (group I, n=5) with a postarrest mild hypothermic group (group II, n=5). After ventricular fibrillation of 12.5 minutes and reperfusion with brief cardiopulmonary bypass, the ventilation, normotension, normoxia, and mild hypocapnia were controlled to 4 hours after cardiac arrest. Group II received (minimal) head cooling during cardiac arrest, followed by systemic bypass cooling (to 34°C) during the first hour of reperfusion after cardiac arrest.Results: The postarrest homogeneous transient hyperemia was followed by global hypoperfusion from 1 to 4 hours after arrest, with increased "no-flow" and "trickle-flow" voxels (compared with baseline), without group differences. At 1 to 4 hours, mean global cerebral blood flow in computed tomographic slices was 55% of baseline in group I and 64% in group II (NS) and CMRO2 after cardiac arrest and cardiopulmonary resuscitation (CPR) remains to be studied. From 1986 through 1990 we explored global, regional, and local CBF and CMRO2 patterns before and after cardiac arrest, using established dog models21'22 and stable xenon-enhanced computed tomography (Xe-CT).23-25 First, we established the CBF method under normothermia throughout in a model of external CPR and then reconfirmed the sequence of hyperemia-hypoperfusion after cardiac arrest.8 Second, we documented the reproducible heterogeneity of delayed postarrest hypoperfusion after reperfusion with open-chest CPR or cardiopulmonary bypass (CPB).9 Third, we found that hypertensive reperfusion plus hemodilution normalized global, regional, and local CBF after cardiac arrest10; hemodilution, however, by reducing arterial 02 content, did not improve cerebral 02 delivery. Fourth, we found the aminosteroid U74006F to have no effect on CBF and CMRO2 after cardiac arrest. '1 In the present (fifth) study,26 using the same model and methods, we compared global, regional, and local CBF patterns in a previously reported normothermic control group (group I, n=5)9 with those in a mild hypothermic group (group II, n=5). We also compared global CMRO2 in group I (n=3) with that in group II (n=5). In previous studies5,6,9 we found that global CMRO2 reached or exceeded normal values during hypoperfusion between 2 hours and 10 hours after cardiac arrest, ie, was mismatched with oxygen delivery. We hypothesize that mild hypothermia might alter CBF and CMRO2 patterns after cardiac arrest in a way that could explain (at least in part) its mitigating effect on brain damage.3 Materials and MethodsThis project was approved by the Animal Use Committee of the University of Pittsburgh. We used 11 healthy, custom-bred male coon hounds...

Combination Drug Therapy and Mild Hypothermia

“…9,32 In accordance with our results, Baldwin et al 33 and Oku et al 34 found that transient hypothermia is associated with a more pronounced postischemic hyperemia but does not alter delayed hypoperfusion after global ischemia in dogs. Other authors failed to demonstrate any influence of brain temperature on CBF in rats subjected to global 35 or focal 36 ischemia.…”

Combination Drug Therapy and Mild Hypothermia

“…9,32 In accordance with our results, Baldwin et al 33 and Oku et al 34 found that transient hypothermia is associated with a more pronounced postischemic hyperemia but does not alter delayed hypoperfusion after global ischemia in dogs. Other authors failed to demonstrate any influence of brain temperature on CBF in rats subjected to global 35 or focal 36 ischemia.…”

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model

“…It should be pointed out that cerebral cortical hypoperfusion in the IT‐saline group was not as pronounced as expected. In ventricular fibrillation cardiac arrest models with untreated cardiac arrest duration similar to that in our study, 10 , 25 , 56 , 57 cerebral blood flow was reduced to 50% to 60% of the baseline values in the early postresuscitation period. However, in the IT‐saline group of our study, only a subtle reduction in cerebral cortical microcirculation was observed during the 5‐hour observation period.…”

Derangements of post-ischemic cerebral blood flow by protein kinase C delta

“…This assertion is further confirmed by our results in which administration of δV1-1 at 24 hrs after ACA was able to reverse hypoperfusion even at that late stage of reperfusion. In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings.…”

“…In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings. In fact, the significance of elucidating the mechanism of how δPKC affects CBF after cardiac arrest is further emphasized by the fact that Phase II clinical trials are underway to test the safety and efficacy of the δPKC inhibitor peptide (KAI-9803; Kai Pharmaceuticals, San Francisco, CA) in acute myocardial infarction (Bates et al, 2008).…”

Combination Drug Therapy and Mild Hypothermia

“…9,32 In accordance with our results, Baldwin et al 33 and Oku et al 34 found that transient hypothermia is associated with a more pronounced postischemic hyperemia but does not alter delayed hypoperfusion after global ischemia in dogs. Other authors failed to demonstrate any influence of brain temperature on CBF in rats subjected to global 35 or focal 36 ischemia.…”

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model

“…It should be pointed out that cerebral cortical hypoperfusion in the IT‐saline group was not as pronounced as expected. In ventricular fibrillation cardiac arrest models with untreated cardiac arrest duration similar to that in our study, 10 , 25 , 56 , 57 cerebral blood flow was reduced to 50% to 60% of the baseline values in the early postresuscitation period. However, in the IT‐saline group of our study, only a subtle reduction in cerebral cortical microcirculation was observed during the 5‐hour observation period.…”

Derangements of post-ischemic cerebral blood flow by protein kinase C delta

“…This assertion is further confirmed by our results in which administration of δV1-1 at 24 hrs after ACA was able to reverse hypoperfusion even at that late stage of reperfusion. In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings.…”

“…In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings. In fact, the significance of elucidating the mechanism of how δPKC affects CBF after cardiac arrest is further emphasized by the fact that Phase II clinical trials are underway to test the safety and efficacy of the δPKC inhibitor peptide (KAI-9803; Kai Pharmaceuticals, San Francisco, CA) in acute myocardial infarction (Bates et al, 2008).…”

Combination Drug Therapy and Mild Hypothermia

“…9,32 In accordance with our results, Baldwin et al 33 and Oku et al 34 found that transient hypothermia is associated with a more pronounced postischemic hyperemia but does not alter delayed hypoperfusion after global ischemia in dogs. Other authors failed to demonstrate any influence of brain temperature on CBF in rats subjected to global 35 or focal 36 ischemia.…”

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model

“…It should be pointed out that cerebral cortical hypoperfusion in the IT‐saline group was not as pronounced as expected. In ventricular fibrillation cardiac arrest models with untreated cardiac arrest duration similar to that in our study, 10 , 25 , 56 , 57 cerebral blood flow was reduced to 50% to 60% of the baseline values in the early postresuscitation period. However, in the IT‐saline group of our study, only a subtle reduction in cerebral cortical microcirculation was observed during the 5‐hour observation period.…”

Derangements of post-ischemic cerebral blood flow by protein kinase C delta

“…This assertion is further confirmed by our results in which administration of δV1-1 at 24 hrs after ACA was able to reverse hypoperfusion even at that late stage of reperfusion. In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings.…”

“…In humans, hypoperfusion 24 hrs after cardiac arrest and restoration of spontaneous circulation (ROSC) is associated with poor prognosis and rate of recovery (Roine et al, 1991; Oku et al, 1993). The lack of successful treatment modalities (Oku et al, 1993) adds further clinical relevance to our findings. In fact, the significance of elucidating the mechanism of how δPKC affects CBF after cardiac arrest is further emphasized by the fact that Phase II clinical trials are underway to test the safety and efficacy of the δPKC inhibitor peptide (KAI-9803; Kai Pharmaceuticals, San Francisco, CA) in acute myocardial infarction (Bates et al, 2008).…”