Browsing by Subject "myocardial oxygen consumption"
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Item Effects of Nitric Oxide on Right Ventricular Metabolism and Coronary Blood Flow(2000-01-09) Setty, Srinath; H. Fred Downey; Patricia A. Gwirtz; James L. CaffreySetty, 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 [less than] 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 [less than] 0.05 vs. untreated control condition), and RV MVO2 was significantly higher at any measured RV workload during L-NAME (P [less than] 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 [less than] 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.Item Mechanisms of Right Ventricular Oxygen Supply/Demand Balance in the Concious Dog(2000-06-01) Hart, Bradley; H. Fred Downey; Patricia A. Gwirtz; James L. CaffreyHart, Bradley Joe. Mechanisms of Right Ventricular Oxygen Supply/Demand Balance in the Conscious Dog Doctor of Philosophy (Biomedical Sciences), August,2000, 119 pp, 4 tables, 13 figures, references, 79 titles. No data exist in the literature describing the myocardial oxygen supply/demand relationship of the right ventricle in a conscious, anaesthetized animal. A novel technique developed in our laboratory enables us to collect right ventricular (RV) venous blood samples from conscious dogs to determine RV myocardial oxygen consumption (MVO2). RV oxygen supply/demand balance was examined in conscious dogs, chronically instrumented to measure right coronary blood flow (RCBF), segmental shortening (%SS) and RV pressure (RVP) during increases and decreases in RV myocardial oxygen demand. Right ventricular MVO2 and O2 extraction (O2E2) were determined; RCBF, RVP, dP/dt, and %SS were recorded concomitantly. Acute increases in RV MVO2 were accomplished by atrial pacing (200 beats/min), increasing RV afterload by 65%, infusion of isoproterenol (0.1 μg/kg/min, i.v.), and by conducting a submaximal exercise routine (70-75% of maximum VO2). An acute decrease in RV MVO2 was created by propranolol administration (1 mg bolus, i.c.). During acute increases in RV MVO2, the extraction reserve is utilized primarily; flow is not affected in the absence of direct vasodilatory effects of the intervention. A decrease in RV oxygen demand is associated with a further increase in the RV extraction reserve. Since RV O2E increases linearly with increases in RV MVO2, these data show that changes in RV venous O2 tension can occur with little or no change in RCBF. LC resistance is very sensitive to alterations in LC venous pO2; therefore, there appear to be significant differences between the left and right ventricles concerning the matching of oxygen supply with myocardial oxygen demand.Item Nitric Oxide Contributes to Right Coronary Vasodilation During Systemic Hypoxia(2003-08-01) Martinez, Rodolfo B.; Downey, H. Fred; Mallet, Robert T. ; Singh, MeharvanMartinez, 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.