EFFECT OF SUBSTRATE MANIPULATION ON REDUCING ISCHEMIA-REPERFUSION INJURY IN ISOLATED-PERFUSED RAT HEARTS

The objective of this investigation was to assess the effect of substr ate manipulation on reducing ischemia/reperfusion injury (IRI). Isolat ed rat hearts were perfused with modified Krebs-Henseleit buffer conta ining either (in mM): glucose 11 (G1), glucose 22 (G2), or glucose 11 with either xylitol 11 (GX), mannitol 11 (GM), L-leucine 1 (GL), or L- glutamic acid 2 (GGA), respectively. Hearts were subjected to 10 min o f global no-flow ischemia, followed by 20 min of reperfusion. Mean tis sue perfusion, oxygen consumption, and peak left ventricular pressure (PLVP) were determined at baseline, in the first minute of regular hea rt rhythm following ischemia, and after 20 minutes of reperfusion. Rep erfusion arrhythmia (in sec) was significantly (all p < 0.05) shorter in GGA (115 +/- 33) vs G1 (315 +/- 29) and G2 (273 +/- 33), and also i n GL (161 +/- 26) vs G1. Dry/wet heart weight ratios were also greater in GGA (0.20), when compared with G2 (0.16), GX (0.17), GM (0.17), GM (0.17), and GL (0.17) (all p < 0.02), suggesting less cellular/inters titial edema. Percent recovery in PLVP was improved (p < 0.03) in GL ( 81 +/- 2) and GGA (81 +/- 2) vs. G2 (71 +/- 3), without significant al terations in oxygen consumption. Thus, cardiac IRI can be diminished b y substrate manipulation, especially by augmentation of glutamate and leucine, most likely due to an improved anaerobic energy generation an d utilization.