ArticleAmerican journal of physiology. Heart and circulatory physiology2010
Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants.
Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Intra-arrest hypothermia during cardiac arrest: a systematic review.Critical care (London, England) · 2012Pooled it
- Heat stress enhances mTOR signaling after resistance exercise in human skeletal muscle.The journal of physiological sciences : JPS · 2011Trial
- Hemodynamics in infants with hypoxemic ischemic encephalopathy: pathophysiology and beyond.Journal of perinatology : official journal of the California Perinatal Association · 2026Review
- From the Bench to the Bedside and Back: Contemporary Applications of Basic Science to Innovations in Heart Transplantation.The Canadian journal of cardiology · 2026Review
- Cardiomyocytes in Hypoxia: Cellular Responses and Implications for Cell-Based Cardiac Regenerative Therapies.Bioengineering (Basel, Switzerland) · 2025Review
- Hypothermia for Cardioprotection in Acute Coronary Syndrome Patients: From Bench to Bedside.Journal of clinical medicine · 2024Review
- Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity.Journal of the American Heart Association · 2024Article
- Autophagy Behavior under Local Hypothermia in Myocardiocytes Injury.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- A cell-penetrating PHLPP peptide improves cardiac arrest survival in murine and swine models.The Journal of clinical investigation · 2023Article
- Intra-ischemic hypothermia cardioprotection involves modulation of PTEN/Akt/ERK signaling and fatty acid oxidation.Physiological reports · 2023Article
- Nicotinamide restores tissue NAD+ and improves survival in rodent models of cardiac arrest.PloS one · 2023Article
- Hypothermia Alleviates Reductive Stress, a Root Cause of Ischemia Reperfusion Injury.International journal of molecular sciences · 2022Article
- Hypothermia for Cardioprotection in Patients with St-Elevation Myocardial Infarction: Do Not Give It the Cold Shoulder Yet!Journal of clinical medicine · 2022Review
- Effects of Different Hypothermia on the Results of Cardiopulmonary Resuscitation in a Cardiac Arrest Rat Model.Disease markers · 2022Article
- TAT delivery of a PTEN peptide inhibitor has direct cardioprotective effects and improves outcomes in rodent models of cardiac arrest.American journal of physiology. Heart and circulatory physiology · 2021Article
- Effects of Therapeutic Hypothermia on Normal and Ischemic Heart.Frontiers in cardiovascular medicine · 2021Review
- Moderate Hypothermia Modifies Coronary Hemodynamics and Endothelium-Dependent Vasodilation in a Porcine Model of Temperature Management.Journal of the American Heart Association · 2020Article
- Protection against cardiac ischemia-reperfusion injury by hypothermia and by inhibition of succinate accumulation and oxidation is additive.Basic research in cardiology · 2019Article
- Successful Re-Initiation of Therapeutic Hypothermia as Adjunctive Salvage Therapy in a Case of Refractory Cardiogenic Shock Due to Acute Myocardial Infarction.The American journal of case reports · 2019Article
- Akt1-mediated CPR cooling protection targets regulators of metabolism, inflammation and contractile function in mouse cardiac arrest.PloS one · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Therapeutic hypothermia (TH) is a promising cardioprotective treatment for cardiac arrest and acute myocardial infarction, but its cytoprotective mechanisms remain unknown. In this study, we developed a murine cardiomyocyte model of ischemia-reperfusion injury to better determine the mechanisms of TH cardioprotection. We hypothesized that TH manipulates Akt, a survival kinase that mediates mitochondrial protection by modulating reactive oxygen species (ROS) and nitric oxide (NO) generation. Cardiomyocytes, isolated from 1- to 2-day-old C57BL6/J mice, were exposed to 90 min simulated ischemia and 3 h reperfusion. For TH, cells were cooled to 32 degrees C during the last 20 min of ischemia and the first hour of reperfusion. Cell viability was evaluated by propidium iodide and lactate dehydrogenase release. ROS production was measured by 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate and mitochondrial membrane potential (DeltaPsim) by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazoly-carbocyanine iodide (JC-1). Phospho (p)-Akt (Thr308), p-Akt (Ser473), and phosphorylated heat shock protein 27 (p-HSP27) (Ser82) were analyzed by Western blot analysis. TH attenuated reperfusion ROS generation, increased NO, maintained DeltaPsim, and decreased cell death [19.3 + or - 3.3% (n = 11) vs. 44.7 + or - 2.7% (n = 10), P < 0.001]. TH also increased p-Akt during ischemia before reperfusion. TH protection and attenuation of ROS were blocked by the inhibition of Akt and NO synthase but not by a cGMP inhibitor. HSP27, a regulator of Akt, also exhibited increased phosphorylation (Ser82) during ischemia with TH. We conclude that TH cardioprotection is mediated by enhanced Akt/HSP27 phosphorylation and enhanced NO generation, resulting in the attenuation of ROS generation and the maintenance of DeltaPsim following ischemia-reperfusion.
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Registered trials
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