Coronary artery disease can cause angina, infarction and sudden death and transient ischemia underlies these symptoms and may herald the onset of ventricular damage. Holter monitoring of ischemic ST segment depression in carefully characterized patients has shown recently that transient ischemic activity is not represented by pain, it is much more frequent than symptoms would suggest and occurs mostly with no appreciable increase in heart rate, suggesting that the traditional trigger mechanisms such as exercise do not operate frequently in everyday life. This study has 3 short-term aims: 1) we plan to study transient ischemia out of hospital in characterized patients with angina and obstructive coronary disease to quantify the relative importance of extrinsic provocative factors (eg; mental arousal, exercise, cold) as against intrinsic triggers of myocardial ischemia, i.e., events unrelated to any external circumstances. 2) Having characterized the relevant trigger mechanism in each patient, we plan to use quantitative angiography and monitoring of hemodynamics to describe the effects of these trigger mechanisms on the stenosed vessels responsible for ischemia and describe the sequence of events leading to the ischemic response. 3) In similarly characterized patients, we plan to test certain specific cellular mechanisms in the atherosclerotic coronary lesions, that will, for example, assess the loss of endothelial dependent vasomotion and look for the abnormal increase in sensitivity to certain physiological vasoconstrictor agents as possible causes of myocardial ischemia. In looking for the causes of transient ischemia, the long-term aims consist firstly of determining the relative importance of internal and external trigger mechanisms to identify if external mechanisms need to be manipulated to benefit transient ischemia. In addition and more importantly, we seek to understand the relationship between the cellular activiy of atherosclerotic coronary lesions and the functional disturbances of vasomotion that lead to ischemia. This research seeks pathophysiological mechanisms in intact patients with a disease that cannot be reproduced in an animal laboratory. On the other hand, we plan to use concepts arising from the basic laboratory (eg; endothelial dependent vasomotion) in order to test in man the relationship between atherosclerotic lesion activity and functional consequences causing clinical ischemia.
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