Comparative anti-ischemic effects of dihydropyridine calcium antagonists in isolated perfused rat hearts: relationship of cardiodepression and cardioprotection.
A comparison was made of the anti-ischemic effects of dihydropyridine calcium antagonists in isolated globally ischemic rat hearts. Pretreatment with amlodipine, nifedipine, nitredipine, or nisoldipine reduced reperfusion enzyme (lactate dehydrogenase) release and contracture after 25 min of global ischemia and 30 min of reperfusion. Increasing concentrations of all compounds resulted in proportionally smaller reductions in the severity of ischemia, with larger decreases in nonischemic tissue contractility occurring. Reperfusion function was significantly improved at 30 min with nifedipine only; however, at 60 min reperfusion function was significantly improved for all except nisoldipine. Washout data from nonischemic hearts (rate of disappearance of cardiodepressant effects) showed that the dihydropyridines washed out in the following order (fastest to slowest): nifedipine greater than nitrendipine greater than nisoldipine greater than amlodipine. Thus, these dihydropyridines are anti-ischemic, though at higher concentrations cardiodepressant effects increase disproportionately. Differences in washout also effect the ability of these compounds to improve reperfusion function.
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, N.J.
Dzwonczyk
S
S
Sleph
P G
PG
D000818:Animals; D000889:Anti-Arrhythmia Agents; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003327:Coronary Disease / Q000503:physiopathology*; D003864:Depression, Chemical; D004095:Dihydropyridines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D015425:Myocardial Reperfusion; D051381:Rats; D011919:Rats, Inbred Strains
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007770:L-Lactate Dehydrogenase