Submitted on May 1, 2006
Accepted on February 5, 2007
ROS scavenging before 27oC ischemia protects hearts and reduces mitochondrial ROS, Ca2+ overload, and changes in redox state
Amadou Camara1, Mohammed Aldakkak1, James S Heisner1, Samhita Shahane Rhodes1, Matthias L. Riess1, Jianzhong An1, Andre Heinen1, and David F Stowe1*
1 Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: dfstowe{at}mcw.edu.
We have shown that cold perfusion of hearts generates reactive oxygen and nitrogen species (ROS/RNS). In this study we determined: 1) if ROS scavenging only during cold perfusion before global ischemia improves mitochondrial and myocardial function, and 2) which ROS lead to compromised cardiac function during ischemia-reperfusion (I/R) injury. Using fluorescence spectrophotometry we monitored redox balance (NADH and FAD), O2·- levels and mitochondrial Ca2+ (m[Ca2+]) at the left ventricular wall in 120 guinea pig isolated hearts divided into control (CON), MnTBAP (SOD2 mimetic), MnTBAP (M)+catalase (C)+glutathione (G) (MCG), C+G (CG), and L-NAME (NOS inhibitor) groups. After initial warm perfusion hearts were treated with drugs before and after 27oC. Drugs were washed out before 2 h 27oC ischemia and 2 h 37oC reperfusion. We found that on reperfusion the MnTBAP group had the worst functional recovery and largest infarction with the highest m[Ca2+], most oxidized redox state, and highest ROS level. The MCG group had the best recovery, the smallest infarction, the lowest ROS level, the lowest m[Ca2+], and the most reduced redox state. CG and L-NAME groups gave results intermediate to those of the MnTBAP and MCG groups. Our results indicate that the scavenging of cold-induced O2·- species to less toxic downstream products additionally protects the heart during and after cold I/R by preserving mitochondrial function. Because MnTBAP treatment showed the worst functional return and poor preservation of mitochondrial bioenergetics, accumulation of H2O2 and/or OH· during cold perfusion may be involved in compromised function during subsequent cold I/R injury.
