Sustained myocardial protection by clentiazem (TA-3090) after a 90-minute coronary occlusion and 72 hours of reperfusion in dogs with collateral flow.
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.
Rousseau
G
G
Laboratory of Experimental Pathology, Montreal Heart Institute, Quebec, Canada.
Provost
P
P
Latour
J G
JG
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
D000806:Angiotensin-Converting Enzyme Inhibitors; C056595:clentiazem; D005070:Evans Blue; D004110:Diltiazem