Motohiro Nishida, Kenji Sakamoto, Tetsuro Urushidani and Taku Nagao (*)
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical
Sciences, University of Tokyo, Tokyo 113 - 0033, Japan
(*) To whom correspondence should be addressed.
Abstract: l-cis Diltiazem, an optical isomer of diltiazem,
protects against myocardial dysfunction in vitro, whereas its Ca2+
channel blocking activity is about 100 times less potent than that of diltiazem.
However, there is no evidence that l-cis diltiazem actually protects
against ischemia/reperfusion injury 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 min. Treatment with diltiazem before and
during ischemia (bolus 200 ƒÊg/kg and 15 ƒÊg/kg per minute for 25 min, i.v.;
575 ƒÊg/kg total) showed slightly depressed hemodynamic parameters, while
l-cis diltiazem (1150 ƒÊg/kg) had no effect. Treatment with l-cis
diltiazem produced a high recovery of the thickening fraction and limited
the infarct size in a dose-dependent manner. Furthermore, the treatment
with l-cis diltiazem (1150 ƒÊg/kg) or diltiazem (575 ƒÊg/kg) 5 min
before reperfusion also limited the infarct size, but not after reperfusion.
These results suggest that l-cis diltiazem affects some events in
the onset of reperfusion, independently of Ca2+-channel-blocking
action. Our observations are the first to show that l-cis diltiazem
demonstrated its cardioprotective action in the ischemic rabbit heart in
vivo.
Keywords: l-cis Diltiazem, Ischemia (rabbit), Infarct size