Adding ROS Quenchers to Cold K+ Cardioplegia Reduces Superoxide Emission During 2-Hour Global Cold Cardiac Ischemia

We reported that the combination of reactive oxygen species (ROS) quenchers Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), catalase, and glutathione (MCG) given before 2 hours cold ischemia better protected cardiac mitochondria against cold ischemia and warm reperfusion (IR)-induced damage than MnTBAP alone. Here, we hypothesize that high K+ cardioplegia (CP) plus MCG would provide added protection of mitochondrial bioenergetics and cardiac function against IR injury. Using fluorescence spectrophotometry, we monitored redox balance, ie reduced nicotinamide adenine dinucleotide and flavin adenine dinucleotide (NADH/FAD), superoxide (O-2(center dot-)), and mitochondrial Ca2+ (m[Ca2+]) in the left ventricular free wall. Guinea pig isolated hearts were perfused with either Krebs Ringer's (KR) solution, CP, or CP + MCG, before and during 27 degrees C perfusion followed immediately by 2 hours of global ischemia at 27 degrees C. Drugs were washed out with KR at the onset of 2 hours 37 degrees C reperfusion. After 120 minutes warm reperfusion, myocardial infarction was lowest in the CP + MCG group and highest in the KR group. Developed left ventricular pressure recovery was similar in CP and CP + MCG and was better than in the KR group. O-2(center dot-), m[Ca2+], and NADH/FAD were significantly different between the treatment and KR groups. O-2(center dot-) was lower in CP + MCG than in the CP group. This study suggests that CP and ROS quenchers act in parallel to improve mitochondrial function and to provide protection against IR injury at 27 degrees C.