A continuing investigation of right coronary (RC) hemodynamics and right ventricular (RV) metabolic and contractile function is proposed. The investigation will focus on mechanisms which modulate RC blood flow and RV function during perturbations of myocardial 02 supply/demand balance. In the working, in situ canine RV, the investigation will delineate: l) Mechanisms by which changes in RC perfusion pressure alter RV O2 demand; 2) Relative contributions of myocardial PO2 and vasoactive metabolites, especially adenosine, in regulation of RC blood flow; 3) Relative contributions of RC flow and 02 extraction reserves in supplying 02 to RV myocardium when RC arterial 02 content is selectively reduced; 4) Relative potencies of alpha adrenoceptor subtypes in the RC circulation and their respective roles in RC pressure-flow autoregulation, modulation of RC 02 extraction reserve, and possible limitation of RV 02 supply. RV energetics will be evaluated to define subcellular adjustments triggered by states of 02 deficiency and providing for metabolic control of coronary blood flow and for modulation of RV 02 demand. To further investigate pressure-flow autoregulation in the RC circulation, additional experiments will be conducted in a chronically instrumented canine model. With this model in the conscious state, RC blood flow will be measured as RC perfusion pressure is reduced by an adjustable constrictor implanted on the RC artery. Variables to be measured (as appropriate for the respective models): 1) RC blood flow and its transmural distribution (flowmeter and microsphere distribution); 2) RC arterial and venous 02 tension and content; 3) RC arterial and venous lactate concentrations (enzymatic techniques); 4) RC small vessel and total vascular volumes (isotope dilution); 5) right atrial and RV pressures and RV dP/dt; 6) heart rate; 7) systemic and pulmonary arterial pressures; 8) RV regional segment length and isometric force for computing regional segment shortening, work, and systolic stiffness; 9) RV P02 (intramyocardial polarographic electrode and RC venous P02); 10) high energy phosphates in RV biopsy samples (enzymatic techniques); 11) extracellular volume (sucrose distribution space); 12) nucleosides and lactate in RV biopsy samples and in RV myocardial microdialysis samples (HPLC and enzymatic techniques). The investigation is in accordance with long term objectives to define mechanisms which balance myocardial 02 supply/demand under changing conditions of 02 demand and supply, especially in the right ventricle. Results will impact clinical treatment for conditions of altered myocardial 02 supply relative to 02 demand.
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