Cardiovascular Pharmacology: Open Access

Abstract

High Susceptibility of Atherosclerotic Coronary Arteries to the Onset of Vasospasm and Angina Pectoris-like Symptoms due to Coronary Spasm in WHHLMI Rabbits

Tomonari Koike, Tatsuro Ishida, Shiori Tamura, Nobue Kuniyoshi, Ying Yu, Satoshi Yamada, Ken-ichi Hirata and Masashi Shiomi

Objectives: We examined the relationship between atherosclerosis and provocation of coronary spasm as well as influence of coronary spasm on the onset of acute ischemic myocardial disease.
Methods and Results: Coronary spasm was provoked in anesthetized normal Japanese white (JW) rabbits and WHHLMI rabbits, an animal model for coronary atherosclerosis and myocardial infarction, by injecting ergonovine during the infusion of norepinephrine through a marginal ear vein. A decrease in contrast flow in the left circumflex artery was observed on coronary angiograms. Ischemic changes were observed on the electrocardiogram of 29% (2/7) of JW and 79% (27/34) of WHHLMI rabbits. The frequency of coronary spasm was significantly high in rabbits with severe coronary plaques showing diffuse lesions. In addition, the degree of contraction of coronary strips with atherosclerotic plaques was higher than that of normal coronary strips excised from JW rabbits stimulated by a combination of ergonovine and norepinephrine. Left ventricle motility in these vasospasm-positive rabbits, which was evaluated with echocardiograms was decreased by 29% following the ergonovine injection (P<0.001), and every serum ischemic marker examined markedly increased 4 hours after the provocation of vasospasm.
Conclusions: The results of the present study demonstrated that atherosclerotic coronary arteries were positively related to the provocation of vasospasm, and vasospasm in severe atherosclerotic coronary segments evoked angina pectoris and/or non-fatal myocardial infarction.