Mild Cerebral Hypothermia during and after Cardiac Arrest Improves Neurologic Outcome in Dogs

Leonov, Yuval; Sterz, Fritz; Šafář, Peter; Radovsky, Ann; Oku, Ken-ichi; Tisherman, Samuel A.; Stezoski, S. William

doi:10.1038/jcbfm.1990.8

Cited by 346 publications

(129 citation statements)

References 49 publications

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“…12 The few studies that attempted intra-arrest hypothermia have demonstrated encouraging protection patterns. Leonov et al 13 performed external cranial intra-arrest cooling in a canine model of cardiac arrest, with additional cooling provided by cardiac bypass. Cooling in this combined fashion was more protective than normothermia.…”

Section: Discussionmentioning

confidence: 99%

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Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

et al. 2004

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Background-Recent clinical studies have demonstrated that hypothermia to 32°to 34°C provides significant clinical benefit when induced after resuscitation from cardiac arrest. However, cooling during the postresuscitation period was slow, requiring 4 to 8 hours to achieve target temperatures after return of spontaneous circulation (ROSC). Whether more rapid cooling would further improve survival remains unclear. We sought to determine whether cooling during cardiac arrest before ROSC (ie, "intra-arrest" hypothermia) has survival benefit over more delayed post-ROSC cooling, using a murine cardiac arrest model. Methods and Results-A model of potassium-induced cardiac arrest was established in C57BL/6 mice. After 8 minutes of untreated cardiac arrest, resuscitation was attempted with chest compression, ventilation, and intravenous fluid. Mice were randomized to 3 treatment groups (nϭ10 each): an intra-arrest hypothermia group, in which mice were cooled to 30°C just before attempted resuscitation, and then rewarmed after 1 hour; a post-ROSC hypothermia group, in which mice were kept at 37°C for 20 minutes after successful ROSC and then were cooled to 30°C for 1 hour; and a normothermic control group, in which mice were kept at 37°C. The intra-arrest hypothermia group demonstrated better 72-hour survival than delayed hypothermia and normothermia groups (6/10 versus 1/10 and 1/10 survivors, respectively, PϽ0.05), with similar differences seen at 6-hour survival and on neurological scoring. Conclusions-Timing of hypothermia is a crucial determinant of survival in the murine arrest model. Early intra-arrest cooling appears to be significantly better than delayed post-ROSC cooling or normothermic resuscitation. (Circulation.

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Section: Discussionmentioning

confidence: 99%

“…9,[13][14][15] The theoretical advantages to cooling before ROSC may include decreasing reperfusion-related injury. Protective cellular mechanisms consistent with this concept include attenuation of the oxidant burst seen within minutes of normothermic reperfusion or the inhibition of reperfusion-activated apoptotic pathways.…”

Section: Discussionmentioning

confidence: 99%

Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

et al. 2004

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“…The animal model used for these studies has been used extensively by us and others to study global cerebral ischemia and reperfusion [15][16][17][18][19][20]. Adult purebred female beagles weighing 10-15 kg were anesthetized initially with an intravenous injection of veterinary thiopental (8-12 mg/kg).…”

Section: Canine Cardiac Arrest Modelmentioning

confidence: 99%

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

Richards

Rosenthal

Kristián

et al. 2006

Free Radical Biology and Medicine

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The pyruvate dehydrogenase complex (PDHC) is a mitochondrial matrix enzyme that catalyzes the oxidative decarboxylation of pyruvate and represents the sole bridge between anaerobic and aerobic cerebral energy metabolism. Previous studies demonstrating loss of PDHC enzyme activity and immunoreactivity during reperfusion after cerebral ischemia suggest that oxidative modifications are involved. This study tested the hypothesis that hyperoxic reperfusion exacerbates loss of PDHC enzyme activity, possibly due to tyrosine nitration or S-nitrosation. We used a clinically relevant canine ventricular fibrillation cardiac arrest model in which, after resuscitation and ventilation on either 100% O 2 (hyperoxic) or 21-30% O 2 (normoxic), animals were sacrificed at 2 h reperfusion and the brains removed for enzyme activity and immunoreactivity measurements. Animals resuscitated under hyperoxic conditions exhibited decreased PDHC activity and elevated 3-nitrotyrosine immunoreactivity in the hippocampus but not the cortex, compared to nonischemic controls. These measures were unchanged in normoxic animals. In vitro exposure of purified PDHC to peroxynitrite resulted in a dose-dependent loss of activity and increased nitrotyrosine immunoreactivity. These results support the hypothesis that oxidative stress contributes to loss of hippocampal PDHC activity during cerebral ischemia and reperfusion and suggest that PDHC is a target of peroxynitrite. KeywordsMitochondria; Hyperoxia; Nitrotyrosine; Normoxia; Oxidative stress; Global ischemia; Selective vulnerability; Free radicals Global cerebral ischemia and reperfusion cause severe neurochemical alterations, including oxidative modifications to lipids, proteins, and DNA. These and other covalent modifications can impair enzyme activities, including those necessary for energy metabolism. Alterations in these enzyme activities can limit postischemic aerobic metabolism and cellular ATP regeneration, thereby contributing to the pathophysiology of delayed neuronal cell death [1][2][3][4]. One enzyme known to be targeted and inactivated by reactive oxygen species is the pyruvate dehydrogenase complex (PDHC) [5]. Effects of ischemia/reperfusion on the PDHC can be particularly devastating because this enzyme forms the bridge between glycolysis and the Krebs cycle and can be the rate-limiting step in aerobic cerebral energy metabolism. NIH Public Access Author ManuscriptFree Radic Biol Med. Author manuscript; available in PMC 2008 October 21. Published in final edited form as:Free Radic Biol Med. 2006 June 1; 40(11): 1960-1970. doi:10.1016/j.freeradbiomed.2006.01.022. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe PDHC is located exclusively in the mitochondrial matrix and catalyzes the oxidative decarboxylation of pyruvate to form NADH and acetyl coenzyme A-the primary form of carbon that enters the Krebs cycle in the adult brain. Several laboratories have shown that PDHC enzyme activity is lost during cerebral ischemia/reperfusion [6][7][8]. PDHC im...

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“…The use of moderate hypothermia after cardiac arrest was initially reported in the late 1950s and early 1960s [75,76]. There were no further investigations conducted on hypothermia as a resuscitative measure until the 1990s, when laboratory studies demonstrated the benefit of mild hypothermia [77][78][79][80]. These studies led to the preliminary clinical research on mild hypothermia.…”

Section: Therapeutic Hypothermiamentioning

confidence: 99%

Therapeutic heat and cold in cardiac rehabilitation

Habash¹,

Habash²,

El-Hage³

2017

Phys Ther Rehabil

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Background: Heart failure (HF) is an emerging epidemic that affects both sexes and all races. It is a complex clinical disease with symptoms caused from any structural or functional cardiac disorder, resulting in reduced longevity. HF is a weakening process that is difficult to treat and it exists in various conditions in which therapy needs to be customized. HF has reached epidemic scopes, mainly among the elderly, in whom it might be a reason for hospitalization. Common types of therapy for HF cases focus on pharmaceuticals and medical instrumentation. However, new approaches of patient-centered care that are based on complementary management strategies, improving quality of life without causing an economic worry or health side effects, are needed to decrease hospitalizations. Purpose: Epidemiology, public health, risk factors, HF management, and several therapeutic heat and cold modalities have been investigated and discussed. Results: Thermotherapy has a scientific evidence-based effect on the human body and can be used for treatment and rehabilitation of the heart. Conclusion: The progress made in bioheat transfer modelling and energy delivery techniques will have an impact on the development of effective therapeutic modalities that deliver controlled heat and/or cold to the human body.

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Mild Cerebral Hypothermia during and after Cardiac Arrest Improves Neurologic Outcome in Dogs

Cited by 346 publications

References 49 publications

Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

Intra-Arrest Cooling Improves Outcomes in a Murine Cardiac Arrest Model

Postischemic hyperoxia reduces hippocampal pyruvate dehydrogenase activity

Therapeutic heat and cold in cardiac rehabilitation

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