This project will examine the effects of acute myocardial ischemia, produced by ligation of either the right or left coronary arteries and subsequent reperfusion on the activity and reflex properties of cardiopulmonary vagal and sympathetic afferents in rats. Production of free oxygen radicals in ischemia and reperfusion may play an important role in the mechanism of these effects. While studies have made progress in understanding the role of free-radical oxidation in ischemia/reperfusion damage of the heart and in the onset of arrhythmias, there have been no studies, to date, to examine the effect of free-radical oxidation on cardiac sensory receptors. Furthermore, there have been no studies to date to assess the effect of right ventricular ischemia and reperfusion on the afferent and reflex properties of cardiac afferent fibers. The investigators will measure impulse activity form single, afferent fibers in the vagus and thoracic sympathetic trunk that arise form mechano-and chemosensitive endings in the heart (afferent studies) and from efferent fibers in a branch of the renal sympathetic nerve (RSN, reflex studies). The investigators will determine whether free-radical oxidation (by topical administration of chemical activators of free-radical formation (xanthine/xanthine oxidase, hydroperoxides)) activate vagal and sympathetic afferents and RSN reflexes from the heart and other vascular regions; and to determine whether the effects can be reversed by enzymatic and nonenzymatic antioxidants (superoxide dismutase (SOD), catalase, deferoxamine, allopurinol, dimethylthiourea). The investigators will also determine whether free-radical oxidation contributes to the activation of cardiac afferents and RSN reflexes in response to acute right or left main coronary occlusion and subsequent reperfusion. The investigators will limit free-radical formation during ischemia and reperfusion by systemic administration of enzymatic and nonenzymatic antioxidants as described above. Possible interactions of free radicals with cyclooxygenase production of prostaglandins and their effects on cardiac afferents and RSN reflexes also will be investigated. An elucidation of the effects of free radicals on cardiac afferents and RSN reflexes will provide further insights into the role of oxygen free radicals in regulatory disturbances during ischemia and reperfusion of both the right and left ventricles.
