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 micrograms/kg bolus plus 40 micrograms/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 mumol/g dry wt., p < 0.05). The difference in TF between the rabbit with and without
verapamil treatment could not be explained by afterload reduction. When
verapamil (100 micrograms/kg bolus plus 20 micrograms/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 pretreatment, not by post-ischemic treatment with
verapamil.