Failure of experimental atherosclerosis to sensitize coronary arteries to spasm in hypercholesterolemic rabbits

Since hypercholesterolemia sensitizes isolated rabbit coronary arteries to vasoconstrictor stimuli, we assessed the possibility of reproducing occlusive coronary spasm both in vitro and in vivo in atherosclerotic rabbits. In Langendorff-perfused hearts from nine atherosclerotic rabbits (2% cholesterol diet for 18 weeks), despite a threefold increase of cholesterol concentration in the coronary wall compared with nine control rabbits, ergonovine and serotonin did not produce any increase of coronary vascular resistances; the increase produced by pitressin was significantly less in atherosclerotic than in normal hearts (56 +/- 13% vs 138 +/- 28%, p less than 0.05, respectively), whereas that produced by phenylephrine was similar (10.1 +/- 1.8% vs 8.5 +/- 2.4%, p = n.s.). In eight other unanesthetized rabbits we recorded the ECG during ergonovine administration (0.05 mg/kg) and during hypothalamic stimulation before and at regular intervals during the 2% cholesterol diet; rabbits survived for periods ranging from 1 to 22 weeks (mean 9.6 weeks). Only one animal had ST depression during episodes of marked tachycardia; no ischemic ECG changes were ever observed in the other rabbits despite the diffuse subintimal coronary deposition of cholesterol found postmortem. Thus, in atherosclerotic rabbits with chronic marked hypercholesterolemia, coronary arteries do not develop occlusive coronary spasm as observed in patients with variant angina.