Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+] levels during short-term 17 °C ischemia in intact hearts

Objective: Different cardioprotective strategies such as ischemic or pharmacologic preconditioning lead to attenuated ischemia/reperfusion (I/R) injury with less mechanical dysfunction and reduced infarct size on reperfusion. Improved mitochondrial function during ischemia as well as on reperfusion is a key feature of cardioprotection. The best reversible cardioprotective strategy is hypothermia. We investigated mitochondrial protection before, during, and after hypothermic ischemia by measuring mitochondrial (m)Ca2+, NADH, and reactive oxygen species (ROS) by online spectrophotofluorometry in intact hearts. Methods: A fiberoptic cable was placed against the left ventricle of Langendorff-prepared guinea pig hearts to excite and record transmyocardial fluorescence at the appropriate wavelengths during 37 and 17 degreesC perfusion and during 30 min ischemia at 37 and 17 degreesC before 120 min reperfusion/rewarming. Results: Cold perfusion caused significant reversible increases in m[Ca2+], NADH, and ROS. Hypothermia prevented a further increase in m[Ca2+], excess ROS formation and NADH oxidation/reduction imbalance during ischemia, led to a rapid return to preischemic values on warm reperfusion, and preserved cardiac function and tissue viability on reperfusion. Conclusions: Hypothermic perfusion at 17 degreesC caused moderate and reversible changes in mitochondrial function. However, hypothermia protects during ischemia, as shown by preservation of mitochondrial NADH energy balance and prevention of deleterious increases in m[Ca2+] and ROS formation. The close temporal relations of these factors during cooling and during ischemia suggest a causal link between mCa(2+), mitochondrial energy balance, and ROS production. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.