Effects of the anesthetics isoflurane, halothane, enflurane, and nitrous oxide upon epicardial coronary dimensions and coronary arteriolar tone will be studied in dogs and humans. The coronary vasculature consists of proximal epicardial coronary arteries that conduct blood from the aorta to myocardium and smaller distal intramyocardial arteries and arterioles that regulate flow. Coronary artery disease affects only the proximal epicardial vessels, not the arterioles. Atherosclerotic lesions are responsible for blood flow restriction. Epicardial lesions are not static and fixed but are-capable of considerable constriction and dilatation, depending upon underlying coronary vascular tone. Episodic changes in coronary tone occur in both variant and typical coronary disease. Endothelial damage may be responsible for increased sensitivity to endogenous vasconstrictor substances. Drugs that reduce elevated epicardial tone are therapeutic in both conditions while drugs that increase large vessel tone may further impair blood supply to the heart. Volatile anesthetics have definite effects on peripheral vasculature tone. Preliminary evidence suggests they also may dilate or attenuate constriction of epicardial coronary arteries. Nitrous oxide increases pulmonary and systemic vascular resistance. Preliminary data suggests it may also constrict epicardial coronary arteries. Little is currently known concerning the effects of anesthetics on epicardial coronary arteries. Effects on resistance arterioles have been reported but results are controversial. In intact dogs, anesthetic actions will be determined by measuring epicardial artery crosssectional dimensions using high resolution computer assisted coronary angiography. Effects on arteriolar vessels will be assessed by measuring coronary blood flow using both 133Xenon washout and coronary sinus thermodilution. In order to mimic coronary artery disease, in some experiments vascular endothelium will be removed and in others vasoconstrictors associated with vasospasm in man will be administered. Using isolated canine epicardial coronary rings, the ability of anesthetics to inhibit vasoconstriction will be tested. In patients undergoing coronary angiography, effects of nitrous oxide on coronary dimensions and myocardial blood flow will be determined. An understanding of the relationship anesthetic drugs have to coronary vasomotion is likely to help in the anesthetic management of patients with coronary artery disease undergoing both cardiac and non-cardiac surgery.
