Myocardial ischemia remains a serious problem for anesthetized patients with coronary artery disease. Despite advances made in control of systemic hemodynamics during anesthesia and surgery, a sizeable fraction of patients (30-40%) manifest ischemia with attendant problems of infarction, arrhythmias and congestive heart failure. Likely causes of this non- hemodynamic ischemia include coronary thrombosis, and """"""""coronary steal"""""""", the diversion of blood away from an ischemic zone of myocardium by pharmacologic vasodilation. There is accumulating evidence that halothane and isoflurane, the major inhalation anesthetics in use today, differ in their effects on coronary vessels and platelets and thus differ in their tendency to cause or worsen ischemia due to thrombus formation or steal. The proposed human study will compare isoflurane with halothane in patients with coronary artery disease undergoing vascular surgery. The use of a cross-over design in which each patient receives both agents will increase the sensitivity of the comparison. Since intraoperative ischemia can result from multiple mechanisms, independent measures of each subject's proclivity to coronary steal and the stability of the coronary lesions will be used to stratify the population. In parallel laboratory experiments, both halothane and isoflurane will be administered to dogs with a coronary stenosis. Measurements of transmural perfusion (microspheres), myocardial metabolism (oxygen consumption and lactate extraction) and myocardial function (sonomicrometry) will test transmural steal and resulting myocardial ischemia. Other experiments will explore the interaction between stenosis severity and anesthetic concentration in producing transmural steal, whether or nor transmural steal can be antagonized with a coronary constricting agent such as phenylephrine, and the relative significance of hypotension as compared to a steal phenomenon in determining the degree of ischemia that results from administration of isoflurane. The clinical study will determine which of these anesthetics is preferred in specific subsets of patients with coronary artery disease. The laboratory studies will provide insight into the underlying mechanisms. The project will improve clinical care of this high-risk population by providing basic science and clinical information.
| Mignella, R; Buffington, C W (1995) Inhaled anesthetics alter the determinants of coronary collateral blood flow in the dog. Anesthesiology 83:799-808 |
| Buffington, C W; Watanabe, S (1995) Vessel tone affects transmural distribution of coronary flow during hypoperfusion. Am J Physiol 268:H1284-92 |
| Buffington, C W; Rothfield, K P (1995) Effects of intracoronary calcium chloride on the postischemic heart in pigs. Ann Thorac Surg 59:1448-55 |
| Buffington, C W; Strum, D P; Watanabe, S (1994) Regional oxygen consumption persists in dyskinetic canine myocardium. J Cardiovasc Pharmacol 24:37-44 |
