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 micrograms/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 less than 0.05 vs. groups I, III, and IV). The BF in group II 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.