IMPROVEMENT OF LONG-TERM PRESERVATION OF ISOLATED ARRESTED RAT-HEART - BENEFICIAL EFFECT OF THE ANTIISCHEMIC AGENT TRIMETAZIDINE

Rat hearts, arrested in situ after intracaval injection of a simple mineral cardioplegic solution (St. Thomas), were preserved for 15 h at 4-degrees-C either by simple immersion in the cardioplegic solution or low-flow perfusion by the same liquid (0.3 ml/min). Trimetazidine (TMZ) was added to the cardioplegic solution at a concentration of 10(-6)M in two additional groups corresponding to both preservation conditions. The biochemically determined ventricular ATP content was increased in immersed hearts by TMZ (+ 78%). The [ATP]/[Pi] ratio, as calculated from P-31 nuclear magnetic resonance (NMR) spectroscopy, was significantly increased in both preservation conditions by TMZ: 0.08 +/- 0.03 versus 0.04 +/- 0.01 in immersed hearts and 0.53 +/- 0.13 versus 0.26 +/- 0.16 in perfused hearts (mean +/- SD). Intracellular pH was increased when TMZ was administered in perfused hearts (7.02 +/- 0.14 vs. 6.67 +/- 0.14, mean +/- SD). Functional recovery, estimated by the pressure developed by the left ventricle (intraventricular isovolumic balloon) when hearts were reperfused with a physiologic solution, was improved by TMZ in both preservation conditions: + 137% in immersed hearts and + 54% in perfused hearts. These results demonstrate that both the bioenergetic status of the myocardial cell and the functional capabilities of isolated, arrested, stored rat heart can be significantly improved by addition of the antiischemic drug TMZ to the preservation solution.