ATTENUATION OF REPERFUSION INJURY BY THE ANTIOXIDANT N-PROPYL GALLATE

We studied the effects of n-propyl gallate (n-PG) on Langendorff preparations of isolated rat hearts. Perfusion of the hearts with Krebs-Henseleit (KH) solution containing 20 mu M n-PG did not cause a statistically significant change in either left ventricular systolic pressure (LVSP), end-diastolic pressure (LVEDP), developed pressure (LVDP), or heart rate (HR), indicating that n-PG has little acute myocardial toxicity. The effects of n-PG on the reperfused and ischemic myocardium were tested in hearts subjected to 15-min global normothermic ischemia followed by 15-min reperfusion. Reperfusion of the ischemic hearts with KH buffer resulted in the recovery of the LVDP to 66 +/- 7% (mean +/- SEM, n = 11) and the recovery of the rate-pressure product (RPP) to 65 +/- 7% of their preischemic values. The LVEDP of the reperfused hearts was 30 +/- 5 mm Hg as compared with the preischemic LVEDP of 5.2 +/- 0.9 mm Hg. The difference between the coronary flow rate of the preischemic hearts (15.4 +/- 0.8 ml/min) and the reperfused hearts (13.9 +/- 0.9 ml/min) was not statistically significant (p > 0.05). Addition of n-PG, at the time of reperfusion, resulted in markedly better recovery of function. Hearts reperfused with KH buffer containing 20 mu M n-PG had LVEDP of 6.2 +/- 0.4 mm Hg, and both LVDP and RPP recovered to 92 +/- 4% of the preischemic control. Reperfusion with n-PG did not alter the coronary flow rate, but decreased the release of lactate dehydrogenase (LDH) in reperfused hearts (0.71 +/- 0.5 vs. 1.7 +/- 0.6 U/mg wet weight, p < 0.05). When n-PG was added to the perfusate before ischemia, the severity of the ischemic contracture was not affected. The postischemic recovery of the hearts in which n-PG was added before ischemia and maintained in the perfusate throughout the experiment was comparable to that of the group in which n-PG was added only at the time of reperfusion. These data suggest that the antioxidant n-PG effectively attenuates myocardial reperfusion injury.