Treatment with l-cis diltiazem before reperfusion reduces infarct size in the ischemic rabbit heart in vivo.
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 microg/kg and 15 microg/kg per minute for 25 min, i.v.; 575 microg/kg total) showed slightly depressed hemodynamic parameters, while l-cis diltiazem (1150 microg/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 microg/kg) or diltiazem (575 microg/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.
Nishida
M
M
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Sakamoto
K
K
Urushidani
T
T
Nagao
T
T
D000758:Anesthesia; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007536:Isomerism; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D017202:Myocardial Ischemia / Q000473:pathology*; D011817:Rabbits; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors
D002317:Cardiovascular Agents; D004110:Diltiazem