title: Sustained myocardial protection by clentiazem (TA-3090) after a 90-minute coronary occlusion and 72 hours of reperfusion in dogs with collateral flow.
abstract: Reduction of infarct size by calcium channel blockers, given at reperfusion, has been reported with diltiazem and clentiazem after 6 h of reperfusion following a 90-min coronary occlusion in the dog. The aims of the present study were to establish that the postischemic cardioprotection is not simply a delay in cell death, but a sustained or permanent myocardial salvage. Dogs with a 90-min occlusion of the left descending coronary artery underwent reperfusion for 72 h. Five minutes before reperfusion, they received, at random, i.v. saline (controls) or clentiazem (125 micrograms/kg i.v.), followed by infusion of 1 microgram/kg/min, until sacrifice. Transmural collateral flow measured 15 min after occlusion with radioactive microspheres was not statistically different between groups [(means +/- SE) control: 0.123 +/- 0.040; treated: 0.150 +/- 0.042 ml/min/g]. The area at risk (percentage of left ventricle), delimited by Evans blue perfusion was also similar (control: 39.9 +/- 1.5%; treated: 42.4 +/- 1.6%). Infarct size, estimated as percentage of the area at risk by triphenyltetrazolium chloride and histology, was reduced (p < 0.05) in treated dogs (control, 42.4 +/- 4.7%; treated, 26.5 +/- 5.4%) with collateral flow (> 0.02 ml/min/g), but not in those with virtually no (< 0.02 ml/min/g) collateral flow (control, 62.0 +/- 8.9%; treated, 72.7 +/- 6.8%). Therefore clentiazem, at reperfusion after a 90-min ischemia, increases myocardial salvage limiting postischemic injury and providing sustained reduction of infarct size in dogs with collateral blood flow.
authors.affiliation: Laboratory of Experimental Pathology, Montreal Heart Institute, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Rousseau
authors.forename: P
authors.initials: P
authors.lastname: Provost
authors.forename: J G
authors.initials: JG
authors.lastname: Latour
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004110:Diltiazem / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004285:Dogs; D005070:Evans Blue; D005260:Female; D008297:Male; D008863:Microspheres; D009203:Myocardial Infarction / Q000473:pathology; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; C056595:clentiazem; D005070:Evans Blue; D004110:Diltiazem