Abstract 13042: Mild Hypothermia Through Liquid Ventilation Improves Mitochondrial Respiratory Chain Activity and Maintains Reverse Electron Transport Following Myocardial Ischemia.
Decreasing body temperature to 32°C by liquid ventilation with perfluorocarbons is highly potent at protecting against myocardial infarction in animal models. It is well tolerated hemodynamically and offers possible translation in the resuscitation setting. Perfluorocarbons can indeed use the lung as heat exchangers while maintaining gas exchanges. Although severe hypothermia (<20°C) is known to preserve cardiac ATP content, such a mechanism can not entirely explain the benefit of mild hypothermia (32°C) with liquid ventilation. Accordingly, we investigated whether this could also involve the protection of mitochondria by preserving the mitochondrial respiratory chain. For this purpose, anesthetized rabbits were submitted to 30-min of coronary artery occlusion (CAO) under normothermic conditions (Control group) or with mild hypothermia at 32°C induced by liquid ventilation (MH group). At the end of CAO, mitochondria were isolated from ischemic myocardial areas. In MH, the respiratory control ratio was increased as compared to Control (5.3±0.4 vs 3.3±0.2, respectively; p<0.05), demonstrating the improvement of oxidative phosphorylation. This was due to the significant increases in ATP dependent oxygen consumption (state 3; +52% in MH vs Control) and in respiratory chain activity as shown under fully uncoupled conditions (+83% in MH vs Control). MH also protected the enzymatic activities of individual complexes by inducing a complete recovery for complexes I, II and III (+36%, +53% and +60% in MH vs Control, respectively) and for the reverse electron flow from complex II to complex I. In addition, reduction of temperature to 32°C decreased the production of reactive oxygen species in isolated mitochondria. This was associated with a decrease in oxidative stress as assessed using myocardial malondialdehyde (MDA) as a marker (2.89±0.11 and 3.58±0.25 nmol MDA/mg Pt in MH and Control, respectively; p<0.05). In conclusion, the cardioprotective effect of MH induced by liquid ventilation can be ascribed to a protection of the mitochondrial respiratory chain and in particular to improved interactions between complexes, as shown by the preservation of reverse electron flow. This suggests a protection of respirasomes.
- © 2010 by American Heart Association, Inc.