Date of Award

1-9-2000

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

H. Fred Downey

Second Advisor

Patricia A. Gwirtz

Third Advisor

James L. Caffrey

Abstract

Setty, Srinath Varadaraj. Effects of Nitric Oxide on Right Ventricular Metabolism and Coronary Blood Flow Doctor of Philosophy (Biomedical Sciences), January, 9, 2001, 123 pp, 3 tables, 16 figures, references, 211 titles. Nitric oxide (NO) formed from L-arginine and released from vascular endothelium causes relaxation of vascular smooth muscle via a cGMP mechanism. However, the of NO as a regulator of coronary blood flow control is unclear. NO has been shown also to reduce oxygen consumption in various in-vitro preparations, but its effect on myocardial oxygen consumption (MVO2) in the left ventricle of the working heart is controversial. The effect of NO on MVO2 in the right ventricle (RV) is unknown. This investigation delineated the effects of NO on RV MVO2 during controlled systemic and coronary hemodynamic conditions. In open chest dogs, NO synthesis was blocked by intracoronary infusion of NO synthesis with Nω-nitro-L-arginine methyl ester (L-NAME, 150 μg/min). To avoid effects of NO synthesis blockade on right coronary blood flow (RCBF), which might have altered RV MVO2, experiments were conducted during adenosine-induced maximal right coronary vasodilation (n=12). RCBF, RV MVO2, and other variables were measured at baseline and at elevated right coronary perfusion pressures (RCP). Under these conditions, L-NAME significantly increased RV MVO2 at baseline and at elevated RCP (P<0.05 vs. untreated control condition). These results indicate that NO acts to retard RV oxidative metabolism. We further characterized the role of NO on RV MVO2 during increases in RV workload, estimated as a product of heart rate X RV peak systolic pressure X RV dP/dt. RV workload, RCBF, and RV MVO2 were increased by intracoronary norepinephrine infusions at baseline RCP (n=5). L-NAME significantly reduced RCBF (P<0.05 vs. untreated control condition), and RV MVO2 was significantly higher at any measured RV workload during L-NAME (P<0.05 vs. untreated control condition). These findings indicate that NO is an important component of RCBF control and that NO blunts norepinephrine-induced increase in RV MVO2. If NO reduced RV MVO2 it may be cardioprotective during moderate right coronary hypoperfusion. Thus, we sought to determine if in fact the RV MVO2 was reduced by NO during moderate right coronary hypoperfusion (n=9). RCP was reduced to 60 (n=5) and 40 mmHg (n=4), and RCBF and RV MVO2 fell as RCP was reduced. L-NAME significantly increased RV MVO2 at RCP of 60 and 40 mmHg (P<0.05 vs. untreated control condition), although RV workload was not altered. Since NO reduced RV MVO2 without compromising RV mechanical performance, RV oxygen utilization efficiency was enhanced. Taken together, these findings demonstrate that NO has a significant dampening effect on RV MVO2.

Comments

Setty, Srinath Varadaraj. Effects of Nitric Oxide on Right Ventricular Metabolism and Coronary Blood Flow Doctor of Philosophy (Biomedical Sciences), January, 9, 2001, 123 pp, 3 tables, 16 figures, references, 211 titles. W 4 S495E 2000

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