Diltiazem and nitrendipine suppress hypoxic contracture in quiescent ventricular myocardium.
Calcium blocking agents may protect the ischaemic heart by reducing ventricular afterload and cardiac contractility, or by augmenting myocardial perfusion. To determine whether protection is mediated in part by mechanisms unrelated to myocardial work and perfusion, we examined effects of diltiazem and nitrendipine on unperfused myocardium subjected to hypoxia. Rabbit right ventricular papillary muscles were mounted in a myograph containing Krebs buffer equilibrated at 37 degrees C with 95% O2-5% CO2. During brief electrical pacing at a frequency of 12 min-1, a preload of 1363 +/- 60 mg produced a maximal isometric force development of 4892 +/- 273 mg (SE; n = 113). After 60 min without pacing, the quiescent muscles were pre-equilibrated randomly for 20 min without drug for control (C = 38), or with 10(-6) diltiazem (n = 38) or 10(-6) mol l-1 nitrendipine (n = 38). Changes in resting force during equilibration did not exceed +/- 12 mg. Subsequent sudden de-oxygenation with 95% N2-5% CO2 evoked in controls an increase in force beginning after 16 +/- 1 min. The onset of hypoxic contracture was significantly (P less than 0.1) delayed in treated muscles and started after 31 +/- 3 min with diltiazem and after 23 +/- 2 min with nifedipine. Peak contracture was significantly (P less than 0.1) inhibited by diltiazem and nitrendipine compared to controls, respectively values averaging 264 +/- 22 mg, 480 +/- 44 mg and 895 +/- 70 mg. Thus, calcium blockers delayed and suppressed hypoxic contracture in quiescent myocardium, demonstrating that the drugs acted directly on cardiac muscle in the absence of rhythmic electrical and mechanical activity.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009568:Nitrendipine; D011817:Rabbits
D001552:Benzazepines; D002121:Calcium Channel Blockers; D009568:Nitrendipine; D004110:Diltiazem; D009543:Nifedipine