THE CALCIUM-ANTAGONIST NISOLDIPINE IMPROVES THE FUNCTIONAL RECOVERY OF REPERFUSED MYOCARDIUM ONLY WHEN GIVEN BEFORE ISCHEMIA

It is unclear whether the protective effects of calcium antagonists on reperfused myocardium are secondary to increased blood flow during ischemia (anti-ischemic action) or reperfusion (Gregg phenomenon), or are mediated through altered calcium kinetics in ischemic or reperfused myocardium. To study the effect of the calcium antagonist nisoldipine on the functional recovery of stunned myocardium, 32 enflurane-anesthetized dogs were subjected to 15 min of occlusion of the left circumflex coronary artery and subsequent 4 h of reperfusion. Eight dogs served as placebo controls (group I), and eight dogs received nisoldipine (5-mu-g/kg i.v.) before occlusion (group II), eight dogs at 10 min of occlusion (group III), and eight dogs at 4 min of reperfusion (group IV). The mean aortic pressure was kept constant with an intra-aortic balloon, and the heart rate did not change. In group I, posterior systolic wall thickening (WT, sonomicrometry) decreased from 18.3 +/- 2.4% (mean +/- SD) during control conditions to -3.0 +/- 2.0% at 13 min of occlusion. At 10 min of reperfusion, WT was 1.7 +/- 3.9% and did not recover further (-1.2 +/- 3.7% at 4 h of reperfusion). Posterior transmural blood flow (BF, colored microspheres) decreased from 1.42 +/- 0.43 ml/min/g during control conditions to 0.26 +/- 0.08 ml/min/g at 13 min of occlusion. BF was 2.07 +/- 0.93 ml/min/g at 10 min and 0.95 +/- 0.31 ml/min/g at 4 h of reperfusion. In groups III and IV, the WT and BF were not different from those in group I throughout the experimental protocol. In group II, however, the WT, although similar to the WT of group I before and during ischemia, recovered from 2.7 +/- 4.3% at 10 min to 11.8 +/- 6.0% at 4 h of reperfusion (p < 0.05 vs. groups I, III, and IV). The BF in group 11 decreased from 2.52 +/- 0.66 ml/min/g after administration of nisoldipine to 0.22 +/- 0.14 ml/min g at 13 min of occlusion. The BF was 1.31 +/- 0.51 ml/min/g at 10 min and 1.33 +/- 0.43 ml/min/g at 4 h of reperfusion. Nisoldipine exerts no beneficial effect when given immediately before or after the onset of reperfusion. The improved functional recovery of reperfused myocardium in dogs pretreated with nisoldipine cannot be attributed to an increased regional myocardial blood flow during ischemia or reperfusion. The better myocardial recovery, therefore, appears to be related to an attenuated myocardial calcium overload during the first few minutes of ischemia.