EFFECTS OF VERAPAMIL ON MYOCARDIAL STUNNING IN XANTHINE-OXIDASE DEFICIENT HEARTS - PRETREATMENT VS POSTISCHEMIC TREATMENT

The role of free radicals and the protective action of calcium antagonists have been established in myocardial stunning in canine hearts, which contain a considerable level of xanthine oxidase, a free radical producing enzyme. However, myocardial stunning in hearts which lack xanthine oxidase and its modification by calcium antagonists in vivo remain uncharacterized. The present study examined this issue using open-chest anesthetized rabbits. Myocardial stunning was induced by a 10-min coronary occlusion and reperfusion. Regional systolic thickening fraction (TF) was determined using an epicardial Doppler sensor, together with other hemodynamic parameters. In untreated control rabbits, recovery of TF from the 10 min transient ischemia was 43 +/- 3% of the baseline at 30 min after reperfusion. Administration of verapamil (200 mu g/kg bolus plus 40 mu g/kg/min), which was started before the onset of ischemia and continued until 20 min after reperfusion, significantly improved the recovery of TF to 74 +/- 6% (p<0.05). A similar improvement in post-ischemic contractile function (TF = 77 +/- 10%) was observed when verapamil was injected at the same rate, but the infusion was discontinued 1 min after the coronary occlusion. Myocardial ATP depletion after the 10 min ischemia was significantly less in the verapamil-pretreated rabbits compared with untreated controls (10.1 +/- 1.0 vs. 6.2 +/- 0.7 mu mol/g dry wt., p<0.05). The difference in TF between the rabbits with and without verapamil treatment could not be explained by afterload reduction. When verapamil (100 mu g/kg bolus plus 20 mu g/kg/min) was given during the reperfusion period alone, TF recovery was poorer (TF = 22 +/- 8%) than the control value. Thus, it was concluded that verapamil attenuates myocardial stunning in the hearts with trace levels of xanthine oxidase, and that the beneficial effect is achieved only by pre-treatment, not by post-ischemic treatment with verapamil.