Vasospasm in Ischemic Heart Disease—A Hypothesis

VASOSPASM IN ISCHEMIC HEART DISEASE-A HYPOTHESIS H. RICHARD HELLSTROM, M.D.* I. Introduction Ischemic or arteriosclerotic heart disease includes the closely related disorders myocardial infarction and angina pectoris, which generally are associated with prominent coronary arterial sclerosis. The high and increasing number of deaths due to ischemic heart disease, 500,000 yearly in the United States alone [1], suggests that there might be an incorrect assessment of the cause of this disorder. In keeping with this, Ancel Keys [2] recently asserted that in preventing coronary artery disease nothing has been "altered in the slightest" by a quarter-century of intensive work. This lack of progress has stimulated renewed scrutiny of ischemic heart disease, especially myocardial infarction; and there is current awareness that the standard pathogenetic mechanism of infarction is unsatisfactory [3-13]. Several alternate mechanisms have been proposed [14-21], but the possibility that vasospasm—that is, pathologic vascular constriction—may play a significant role is mentioned only occasionally [3, 8, 11, 19, 22], probably because the evidence for coronary arterial vasospasm has been scant. After experimental coronary arterial obstruction, reflex coronary arterial spasm has been reported [23]; but this finding is controversial and has been denied [24, 25]. In individuals with angina, spasm has been demonstrated in epicardial arteries by angiograms [26], but this spasm may be due to the catheter tip [16, 27]. In a recent experiment in dogs [28] designed to study coronary arterial thrombosis, I found evidence for pathologic vasospasm of coronary arteries. This observation led to renewed scrutiny of the possibility that vasospasm might be involved in the pathogenesis of * Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and the Veterans Administration Hospital, University Drive C, Pittsburgh , Pennsylvania 15240. Address reprint requests to the latter. Perspectives in Biology and Medicine · Spring1973 | 427 ischemie heart disease. A number of features of this disorder are not easily explained by the standard concepts but appear to be consistent with vasospasm. The experimental study [28] and these unusual clinical features of ischemic heart disease have provided the basis for a proposal in which coronary arterial vasospasm plays a significant role in the pathogenesis of myocardial infarction, angina pectoris, and, also, coronary arterial thrombosis. The experimental study and the hypothesis are discussed in Sections V and VI. //. Ischemic Heart Disease—a Selective History A. ANGINA PECTORIS—SPASM AND/OR CORONARY ARTERIAL SCLEROSIS Heberden [29], in 1768, in the original description of angina, considered the origin of the pain to be spastic or spasmodic but did not identify the involved organ system. Shortly thereafter, in 1772, E. Jenner (quoted in [30, p. 262]) demonstrated coronary arterial "ossification" in angina. In the nineteenth century, spasm was revived in the form of "heart spasm" [31] until advances in physiology discredited spasm of the myocardium itself [32]. By the turn of this century, spasm of coronary arteries was considered likely; and in 1910, Osier [33], in his Lumleian lecture, advocated this position. He also accepted the "Jennerian view of the close connexion of lesions of the coronary arteries with the disease" and suggested that spasm was more likely with focal atherosclerotic lesions. Osier's concept expresses the apparent contradiction between spasm and the immobility of sclerotic coronary arteries [34]. The modern era can be dated to 1940, when Blumgart, Schlesinger, and Davis [35] reaffirmed the importance of mechanical coronary arterial obstruction in angina. The quantitative relationship between effort and chest pain in the usual patient, and the common finding of severe coronary arterial disease at necropsy, provided confirmation of the importance of chronic sclerotic vascular obstruction. In 1951, Pickering [36] said that extensive involvement of spasm in angina was an "extravagant and improbable hypothesis." The possibility of spasm occurring in angina has also been considered less likely because of the recent assertion that nitroglycerine does not cause coronary arterial vasodilation but has a noncardiac action [37]. Today, there is a cautionary attitude toward spasm in angina [16]. Although many have deemphasized [38] or abandoned [39] coronary arterial vasospasm in this disorder, there is some recent interest in spasm, especially in unusual examples of angina [40]. 428 I H. Richard Hellstrom · Vasospasm in Ischemic Heart Disease B. MYOCARDIAL INFARCTION 1. Coronary...