Why should we study the coronary microcirculation?

THE QUESTION we are posing to the readers is why should we study the microcirculation of the heart. First, let us define who are “we.” In this issue of the American Journal of Physiology: Heart and Circulatory Physiology, a collection of papers are included as part of a Special Call on “Emerging Concepts in the Control of the Coronary Microcirculation.” It is obvious why the coronary microcirculation should be studied from a basic perspective; even the most seminal reactions, autoregulation and metabolic dilation, are incompletely understood. Our editorial will not highlight basic problems but rather discuss the clinical importance of the coronary microcirculation. Our opinion is that the “we” who should study the coronary microcirculation are both basic scientists and clinicians, so that a much clearer understanding of the role of coronary microvessels in the etiology of ischemic heart disease may be elucidated. Most cardiologists believe that coronary artery disease is only a disease of large vessels, and there is little microvascular involvement in this pathology. We believe otherwise! In our opinion, abnormal coronary microvascular reactions to many stimuli contribute and possibly cause cardiac pathologies. To put our view in perspective, a case history from our institute provides a useful example (2). Several years ago we were treating a patient with angina pectoris who had rapidly decreasing tolerance to exercise. Coronary angiography documented a single subocclusive stenosis of the left anterior descending coronary artery, which was characterized by a complex morphology. Because of the presence of ischemia, the lesion was thought to be significant, and an angioplasty procedure was performed. Two minutes following successful dilation of the lesion, the patient complained of chest pain while the electrocardiogram monitoring the patient showed S-T segment elevation on the anterior leads. Another angiogram was immediately performed and showed a patent, nonstenotic left coronary artery characterized by a slow antegrade flow of the contrast medium. Measurement of coronary pressure by the balloon catheter did not show significant pressure gradients along the coronary artery, indicating that the resistance to flow was located distally to the epicardial vessel, i.e., in the coronary microcirculation. Despite intracoronary administration of nitrates, the transmural anterior ischemia persisted. The patient underwent emergency bypass grafting; however, at discharge, an anterior infarction was diagnosed with a severe impairment in left ventricular function that required cardiac transplantation in the follow-up. This case history and numerous others (28) with remarkable similarity have been published in the literature. These histories have promulgated the hypothesis that, at least in some patients, the basis for myocardial ischemia could be also due to abnormalities in the control of coronary resistance vessels rather than the more generally accepted view that the disease is exclusive to stenotic, epicardial coronary arteries (13). Difficulty in the clinical evaluation of coronary microvascular function has prevented a complete identification of the role of the coronary microcirculation as a cause of ischemic heart disease. In fact, in patients in whom coronary microvascular dysfunction was initially advocated, these uncertainties led to the naming of this condition syndrome X. The difficulty of diagnosing syndrome X has led to an alternative view; namely, that it does not exist! This opposing view to syndrome X and a culprit role for the coronary microcirculation credits many of the pathophysiological manifestations to alterations in the myocardium and even psychosomatic disorders. The goal of this review is to cite cogent literature that supports the hypothesis that coronary microvascular dysfunction can produce pathological manifestations in patients with coronary artery disease. Clearly, the potential for the coronary microcirculation to produce cardiac abnormalities exists. For example, intracoronary infusion of the potent constrictor endothelin-1 in a normal experimental animal without coronary disease can produce such severe constriction that ischemia ensues, followed by myocardial dysfunction and often fibrillation (W. Chilian, personal communi-