Biomedical Sciences ETDs

Publication Date

5-3-1977

Abstract

Recent work has demonstrated that vagus nerve stimulation increases the ventricular fibrillation threshold (VFT) of the ischemic canine ventricle. This project was undertaken to show a direct, vagally-mediated, electrical effect giving a mechanism for the increase in VFT. Barbitu­rate-anesthetized adult mongrel dogs were prepared using a left thoracotomy in the 5th interspace. The heart was suspended in a pericardial cradle and a distal branch of the left anterior descending coronary artery (LAD) was dissected free with a removeable silk or dacron ligature placed around it. Bipolar surface electrodes were sutured to the surface of the left ventricle within and without the regions of intended ischemia. The heart was paced from the left ventricle at approximately 180/minute. The LAD was occluded for periods of 3½ minutes with and without supramaximal right vagus nerve stimulation (RVS). Periods of ischemia without RVS caused a depression of both surface electrogram amplitude (EA) and upstroke dV/dt (U-dV/dt). RVS in conjunction with ischemia produced no significant difference in EA or U-dV/dt. However, in the presence of beta-adrenergic blockade with practolol, RVS during ischemia significantly increased both EA and U-dV/dt over ischemia without RVS. Following the administration of the cholinergic blocker, atropine, the RVS­effect was reduced, but not abolished. Practolol itself produced no stabilizing influence; however, atropine did seem to give a slight stabilizing effect. This may be why atropine yielded only a partial blockade of the RVS-effect. In order to identify the source of the sympathetic antagonism of the RVS-effect, 6-OHDA was administered to deplete the postganglionic sympathetic nerve terminals of norepinephrine. Now, no RVS-mediated stabilization was seen. It was therefore concluded that a high blood level of circulating catecholamines was the source of sympathetic antagonism of the RVS-effect. To see whether the RVS-effect might be mediated via a direct membrane phenomenon, lidocaine (a well known potassium ion conductance blocker) and practolol were administered with and without RVS. The RVS-effect was now blocked. These results suggest that a post-ischemic RVS-mediated stabilization of the canine left ventricle does exist and is unmasked only in the absence of sympathetic neural activity. This RVS stabilizing effect appears to be only partially mediated via the muscarinic cholinergic receptor. The other mechanism appears to be a direct membrane phenomenon, possibly initiated by an acetylcholine-induced increase in potassium ion conductance. Two clinical correlations may by presented. The use of atropine, prophylactically, in the patient presenting with ischemic heart disease should be reconsidered. Secondly, since the presence of sympathetic neural activity may actually be detrimental to the electrical stability of the ischemic heart, a better choice of a pharmacologic agent might be the sympathetic blocker, practolol.

Document Type

Dissertation

Language

English

Degree Name

Biomedical Sciences

Level of Degree

Doctoral

Department Name

Biomedical Sciences Graduate Program

First Committee Member (Chair)

Donald Victor Priola

Second Committee Member

Gerald K. Weiss

Third Committee Member

William Glenn Dail, Jr.

Fourth Committee Member

Paul Terry Cochran

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