Animal models of coronary spasm and the pathophysiological events in regional vascular hypercontraction

An animal model of coronary spasm was designed 1) to reproduce coronary spasm similar to that seen in patients with variant angina, 2) to determine whether hypercontraction of the vascular smooth muscle occurs at the site of the spasm, 3) to document the relationship between functional and structural changes of the vascular wall and 4) to characterize the pathophysiological features of coronary spasm. After balloon de-endothelialization and feeding of a high cholesterol diet in mongrel dogs and Göttingen miniature pigs, there was evidence of vascular hypercontraction associated with arteriosclerotic changes. Coronary spasm of more than 75% narrowing of the artery was provoked with ischemic signs in miniature swine. These events could be repeatedly provoked by an intracoronary injection of histamine following pretreatment with cimetidine. The site of hypercontraction corresponded well with the site of the de-endothelialization, an area where the basal vascular tone was increased and was related to histamine activity. Thus, the present animal model will shed light on mechanism involved in vasoactive angina pectoris and aid in clarifying the pathophysiology of vascular smooth muscle.