© 2004 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Reduced reactive O2 species formation and preserved mitochondrial NADH and [Ca2+] levels during short-term 17 °C ischemia in intact hearts 
aAnesthesiology Research Laboratory, Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
bDepartment of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
cDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Münster, 48129 Münster, Germany
dCardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
eResearch Service, Veterans Affairs Medical Center, Milwaukee, WI 53295, USA
fDepartment of Biomedical Engineering, Marquette University, Milwaukee, WI 53233, USA
* Corresponding author. M4280, 8701 Watertown Plank Road, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Tel.: +1-414-456-5722; fax: +1-414-456-6507. dfstowe{at}mcw.edu
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 °C perfusion and during 30 min ischemia at 37 and 17 °C 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 °C 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 mCa2+, mitochondrial energy balance, and ROS production.
KEYWORDS Calcium; Free radicals; Hypothermia; Ischemia; Mitochondria
Portions of this work have been published in abstract form and presented at the 2002 ASA annual meeting in Orlando, FL, USA, October 12–16, 2002 (Anesthesiology 2002; 97: A608) and at the IARS 77th Congress, New Orleans, LA, USA, March 21–25, 2003 (Anesth Analg 2003; 96 (2S): S18).
Time for primary review 22 days
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