The ability of
verapamil to protect severely ischemic myocardium was assessed in dogs using 40 minutes of temporary
coronary occlusion. Reperfusion was established for 4 days after which
infarcts were sized histologically. Untreated dogs developed subendocardial
infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with
verapamil reduced the size of these subendocardial
infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed at risk (identified by postmortem perfusion of the previously occluded and unoccluded arteries with different
dyes). Thus,
verapamil prevented cell death in the severely ischemic subendocardial region for the 40-minute test period. In a second study to establish whether
verapamil could delay cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of
coronary occlusion was used. This period of occlusion caused
infarcts averaging 60 +/- 6% of the ischemic area at risk in untreated dogs. Dogs treated with
verapamil 15 minutes postocclusion and throughout the remaining 165 minutes of the 3-hour test period had no limitation of
infarct size (53 +/- 3% of the area at risk). In this 3-hour study, the effect of variation in collateral blood flow on
infarct size was evaluated by plotting
infarct size versus subepicardial collateral flow.
Verapamil neither improved collateral flow nor altered the relationship between
infarct size and baseline collateral flow. Thus, pretreatment with
verapamil prevented
necrosis of severely ischemic myocytes, when reperfusion was established at 40 minutes, but failed to prevent
necrosis of moderately ischemic myocardium and thus failed to limit
infarct size when the period of
coronary occlusion was prolonged to 3 hours and treatment was started 15 minutes after the onset of
ischemia.