Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Zuo Hui Shao, Wei Tien Chang, Chai Chan Kim, Kim R. Wojcik, Chin Wang Hsu, Chang Qing Li, Juan Li, Travis Anderson, Yimin Qin, Lance B. Becker, Kimm J. Hamann, Terry L. Vanden Hoeke

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28 引文 斯高帕斯(Scopus)


Optimal timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 ± 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 ± 0.6% death, P < 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 ± 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 ± 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N ω-nitro-L-arginine methyl ester (200 ±M) reversed these changes and abrogated hypothermia protection. In addition, the PKCε inhibitor myr-PKCε v1-2 (5 μM) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase Cε; nitric oxide synthase.

頁(從 - 到)H1995-H2003
期刊American Journal of Physiology - Heart and Circulatory Physiology
出版狀態已發佈 - 4月 2007

ASJC Scopus subject areas

  • 生理學
  • 心臟病學與心血管醫學
  • 生理學(醫學)


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