Nitric Oxide Contributes to Right Coronary Vasodilation During Systemic Hypoxia

Martinez, Rodolfo Randy. Nitric Oxide Contributes to Right Coronary Vasodilation During Systemic Hypoxia. Master of Science (Biomedical Sciences), August, 2003, 85 pp., 1 table, 5 figures, references, 121 titles. Background: Hypoxia increases right ventricular (RV) work, as arterial O2 is reduced. Mechanisms responsible for RV O2 supply/demand balance during hypoxia have not been delineated. To address this problem, right coronary blood flow (RCF) was directly measured, for the first time, in conscious, instrumented dogs exposed to acute hypoxia. Since we have found that nitric oxide (NO) contributes to RV O2 supply/demand balance during acute pulmonary hypertension, we investigated the role of NO in hypoxia-induced coronary hyperemia. Methods: Nine mongrel dogs were chronically instrumented. Briefly, catheters were placed in the RV for measuring pressure, in the ascending aorta for measuring arterial pressure and for sampling arterial blood and in a right coronary vein in order to obtain right coronary venous blood. A flow transducer was placed around the right coronary artery. After recovery from surgery, the dogs were exposed to normobaric hypoxia in a Plexiglas chamber ventilated with N2. O2 in the chamber was monitored, and blood samples and hemodynamic data were collected as chamber O2 was reduced progressively to 8-10%. Following control measurements, the chamber was opened and the dog allowed to recover. LNA was then administered (35mg/kg, via RV catheter) to inhibit nitric oxide production, and the hypoxic protocol was repeated. Results: RCF increased exponentially as PaO2 decreased. To normalize changes in arterial pressure, RC conductance was computed from the ration of RCF and arterial pressure. LNA blunted the hypoxia-induced increase in conductance. RV O2 extraction remained constant as PaO2 was decreased but extraction increased when after LNA. Hypoxia increased RV myocardial oxygen consumption (MVO2), but LNA decreased RV MVO2 any respective PaO2. Analysis of RC conductance as a function of RV MVO2 confirmed that LNA depressed the slope of the conductance/MVO2 relationship (P-0.03). Conclusion: Increases in RV MVO2 during hypoxia are met by increasing right coronary blood flow. In the absence of NO, myocardial supply/demand balance during hypoxia was maintained by increasing flow and extraction. Nitric oxide contributes to RC vasodilation and thus helps to maintain RV oxygen supply/demand balance during systemic hypoxia.