Treatment with l-cis diltiazem before reperfusion reduces infarct size in the ischemic rabbit heart in vivo

l-cis Diltiazem, an optical isomer of diItiazem, protects against myocardia l dysfunction in vitro, whereas its Ca2+ channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidenc e that I-cis diItiazem actually protects against ischemia/reperfusion injur y in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 m in. Treatment with diltiazem before and during ischemia (bolus 200 mu g/kg and 15 mu g/kg per minute for 25 min, i.v.; 575 mu g/kg total) showed sligh tly depressed hemodynamic parameters, while I-cis diltiazem (1150 mu g/kg) had no effect. Treatment with I-cis diItiazem produced a high recovery of t he thickening fraction and limited the infarct size in a dose-dependent man ner. Furthermore, the treatment with l-cis diltiazem (1150 mu g/kg) or dilt iazem (575 mu g/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that l-cis diltiazem affe cts some events in the onset of reperfusion, independently of Ca2+-channel- blocking action. Our observations are the first to show that I-cis diltiaze m demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.