Moderate Hypothermia Diminishes Death of Cardiomyocytes following Ischemia

Introduction: Therapeutic hypothermia (TH) is an established protective strategy in patients suffering from cardiac arrest involving global cardiac ischemia. Although the neuroprotective properties of TH have been investigated, the effects of hypothermia on heart muscle tissue are not fully understood. The authors investigated the effects of moderate hypothermia (33.5 °C) during cardiac ischemia and reperfusion in cardiomyocytes.

Methods: The authors used cultured HL-1 cells, which are spontaneously contracting cardiomyocytes derived from mice. Cardiac ischemia was simulated by glucose and serum deprivation with hypoxia. Cooling to 33.5 °C was started during ischemia and continued for 24 hours. Cell death was determined by lactate dehydrogenase (LDH) and cardiac troponin T (cTNT) release to cell culture supernatant. ATP content was evaluated by CellTiter-Glo Assay. RNA expression of iNOS was analyzed by qRT-PCR.

Results: Reperfusion after ischemia resulted in an increase in cell death as seen in significantly higher LDH and cTNT releases compared with normoxic controls. The authors observed a decrease in ATP content and increase in iNOS gene induction compared with controls kept at normoxia. Cooling to 33.5 °C attenuated cell injury as observed in significantly decreased LDH and cTNT releases in hypothermic groups compared with normothermic groups. Hypothermia preserved ATP contents at 75.5% compared with only 35.5% in cells kept at normothermia. Furthermore, iNOS gene expression was significantly down-regulated by hypothermia in the ischemia/reperfusion group.

Conclusions: Cooling heart muscle tissue is a promising intervention to protect the heart from tissue loss due to reperfusion injury following cardiac ischemia. The prevention of ischemic ATP diminishment and iNOS up-regulation by hypothermia may convey this protective effect and contribute to minimizing myocardial cell death after ischemia.