CP-060S, a novel cardioprotective drug, limits myocardial infarct size in anesthetized dogs.
The myocardial infarct size (IS)-limiting effect of CP-060S, a novel cardioprotective drug that prevents Na+-, Ca2+-overload and has Ca2+ channel-blocking activity, was compared with that of diltiazem, a pure Ca2+ antagonist, to determine whether the prevention of Na+-, Ca2+-overload contributes to this IS-limiting effect. Dogs were subjected to 90 min of left circumflex coronary artery (LCx) occlusion followed by 5 h of reperfusion. Either CP-060S (300 microg/kg) or diltiazem (600 microg/kg) was administered intravenously 20 min before the occlusion. CP-060S significantly limited IS compared with that of vehicle (percentage of the area at risk: vehicle, 50.64 +/- 6.08%; CP-060S, 21.13 +/- 3.75%; p < 0.01 vs. vehicle). Although diltiazem exerted a significant decrease in rate-pressure product (RPP; an index of myocardial oxygen consumption) during occlusion equal to that of CP-060S, diltiazem did not significantly reduce IS (33.90 +/- 4.30%). Regional myocardial blood flow (RBF) was not significantly different between any of the groups. Therefore the IS-limiting effect of CP-060S cannot be explained in terms of changes in RPP or RBF. Thus the IS limitation induced by CP-060S is probably the consequence of a direct cardioprotective effect on myocytes. The prevention of Na+-, Ca2+-overload may be the primary reason for this IS-limiting effect.
Suzuki
Y
Y
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Tamura
K
K
Akima
M
M
Adachi
Y
Y
Fukazawa
M
M
Kato
T
T
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009336:Necrosis; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use*; D053778:Thiazolidines
C104781:CP 060S; D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D013844:Thiazoles; D053778:Thiazolidines