Profound Hypothermia Decreases Cardiac Apoptosis Through Akt Survival Pathway

Fahad Shuja, Malek Tabbara, Yongqing Li, Baoling Liu, Muhammad Umar Butt, George C. Velmahos, Marc deMoya, Hasan B. Alam*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background: Hypothermia increases the tolerable ischemia time for myocardium in hemorrhagic shock, but precise mechanisms are not clearly established. Here we studied activation of Akt cell survival pathway in a rodent model of emergency preservation and delayed resuscitation. Study Design: Wistar-Kyoto rats underwent 40% blood volume arterial hemorrhage during 10 minutes and were randomized into 2 groups based on core body temperatures (n = 7/group): hypothermia (15°C) and normothermia (37°C). Hypothermia was induced by infusing cold isotonic solution using cardiopulmonary bypass (CPB) setup. After reaching target body temperature, low-flow state (CPB flow rate of 20 mL/kg/min) was maintained for 60 minutes. Hypothermic rats were rewarmed to baseline temperature; all rats were resuscitated on CPB and monitored for 3 hours. The normothermia group underwent identical CPB management. Sham rats (no hemorrhage, no instrumentation) were used as controls (n = 7). Tissues were harvested at the end of experiment. Results: Induction of hypothermia increased survival rates (100% versus 0% in normothermia group). Western blot analysis of cardiac tissue revealed increased levels of phospho-Akt (active) in hypothermia and sham groups compared with the normothermia group (p < 0.05). Among downstream targets of Akt, phospho-GSK-3β (inactive), phospho-Bad (inactive), β-catenin, and Bcl-2 were considerably elevated in the hypothermia group compared with the normothermia group. Hypothermia also showed decreased activity of caspase-3 protein compared with normothermia (p < 0.05), suggesting decreased apoptosis. Conclusions: Profound hypothermia increases survival in a rodent model of hemorrhagic shock and prolonged low-flow state. Hypothermia preserves Akt signaling pathway in cardiomyocytes with a concurrent decrease in cardiac apoptosis.

Original languageEnglish (US)
Pages (from-to)89-99
Number of pages11
JournalJournal of the American College of Surgeons
Volume209
Issue number1
DOIs
StatePublished - Jul 2009
Externally publishedYes

ASJC Scopus subject areas

  • Surgery

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