Effect of calcium channel blocking agents on infarct size after ischaemia-reperfusion in anaesthetised pigs: relationship between cardioprotection and cardiodepression.
We compared the abilities of verapamil and nicardipine to protect the porcine myocardium from the consequences of ischaemia-reperfusion in vivo. Infusion of verapamil (50 micrograms/kg) into the left anterior descending coronary artery LAD (i.c.a.), in 15 min immediately before ligation depressed regional contractile function, reduced infarct size by 80%, and enabled contractile function to recover partially during reperfusion. Verapamil (10 micrograms/kg i.c.a.) did not depress contractile function before ligation or permit its recovery during reperfusion, despite reducing infarct size by 80%. Lower doses of verapamil were not cardioprotective. Nicardipine (10 and 30 micrograms/kg i.c.a.) depressed contractile function before ligation but did not permit its recovery during reperfusion. Nicardipine did not reduce infarct size development. Thus, drug-induced negative inotropic activity (which presumably reflects myocardial calcium channel blockade) and cardioprotection are not linked. Verapamil can markedly reduce infarct size development at a dose that exerts no detectable negative inotropic activity. This cardioprotective effect of verapamil was greatly reduced by intravenous (i.v) pretreatment with aspirin (30 mg/kg), which alone did not alter infarct size development. Thus, the cardioprotective effect of verapamil (10 micrograms/kg i.c.a.) appears to be mediated by a cyclooxygenase product, possibly prostacyclin.
Sullivan
A T
AT
Department of Peripheral Pharmacology, Glaxo Group Research, Hertfordshire, England.
Baker
D J
DJ
Drew
G M
GM
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology; D003864:Depression, Chemical; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D008297:Male; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009529:Nicardipine / Q000627:therapeutic use; D013552:Swine; D013997:Time Factors; D014700:Verapamil / Q000627:therapeutic use*
D014700:Verapamil; D009529:Nicardipine; D001241:Aspirin