title: Clentiazem given at reperfusion improves subendocardial reflow and reduces myocardial infarct size in the dog.
abstract: The postischemic cardioprotection by calcium antagonists and the interplay between neutrophils and regional myocardial blood flow were investigated further, using clentiazem, a new potent calcium channel blocker derived from diltiazem. A 90-min occlusion of the interventricular coronary artery was followed by 6 hr of reperfusion in anesthetized dogs. One group was given clentiazem: 100 micrograms/kg at 5 min before reperfusion followed by a perfusion of 1 microgram/kg/min until sacrifice; controls received saline. Infarct size (% of area at risk) estimated with triphenyltetrazolium staining and by histology was reduced by nearly 50% (P < .05) in treated (16.6 +/- 3.0%), as compared to control (31.6 +/- 6.3%) dogs. Regional and collateral myocardial flows estimated with radioactive microspheres were similar between groups before and during occlusion. However, after an initial recovery to preocclusion values at 30-min reperfusion in both groups, flow declined to 50% normal (P < .05) in control animals after 3 and 6 hr in midwall and subendocardium, but the change was remarkably attenuated (P < .05) in subendocardium of clentiazem-treated dogs. Also, neutrophil accumulation at the epicardial side of the infarct, at the edge of salvaged myocardium, and estimated by tissue myeloperoxidase measurement, was reduced by 50% in treated dogs (clentiazem: 17.2 +/- 2.8; controls: 32.3 +/- 2.7 x 10(6) neutrophils/g). We conclude that administration of clentiazem at reperfusion reduces infarct size by interfering with both neutrophil accumulation and development of subendocardial no reflow in reperfused myocardium.
authors.affiliation: Laboratory of Experimental Pathology, Montreal Heart Institute, University of Montreal, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Rousseau
authors.forename: P
authors.initials: P
authors.lastname: Provost
authors.forename: D
authors.initials: D
authors.lastname: Tran
authors.forename: G
authors.initials: G
authors.lastname: Caillé
authors.forename: J G
authors.initials: JG
authors.lastname: Latour
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003097:Collateral Circulation / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007958:Leukocyte Count; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects
chemical_list: D002121:Calcium Channel Blockers; C056595:clentiazem; D004110:Diltiazem