Dobutamine Increases Mechanical Function and Cytosolic Phosphorylation Potential During Moderate Right Ventricular Hypoperfusion

Abstract

Yi, Kun Don. Dobutamine increases mechanical function and cytosolic phosphorylation potential during moderate right ventricular hypoperfusion Master of Science (Biomedical Sciences), August, 2000, 101 pp, 4 tables, 18 figures, references, 108 titles. This study was conducted to investigate the functional and metabolic effects of regional inotropic stimulation with dobutamine during right ventricular (RV) hypoperfusion. Right coronary perfusion pressure was incrementally lowered to 40 mmHg from 100 mmHg, and two-doses of dobutamine (0.01 and 0.06 μg/kg/min) were continuously infused for 15 min into the right coronary artery in pentobarbital sodium-anesthetized mongrel dogs of either sex. Myocardial energy metabolites, glycolytic intermediates, glycogen, and phosphorylation potential were measured in freeze-clamped RV biopsies. RV hypoperfusion caused a 54% decrease in right coronary blood flow, a decrease in lactate uptake, and an increase in glucose uptake. Systolic segment shortening, isometric force, MVO2, and oxygen utilization efficiency (O2UE: power/MVO2) decreased significantly. Energy reserves were unaffected by the hypoperfusion. Low-dose dobutamine during hypoperfusion improved regional mechanical function without increasing MVO2, and thus, improved O2UE. Remarkably, low-dose dobutamine markedly increased phosphocreatine content and phosphorylation potential. In contrast, high-dose dobutamine produced only transient improvements in function and efficiency and sharp decreases in energy reserves. Analysis of glycolytic intermediates showed a sustained augmentation of glycolysis during low-dose dobutamine, but glycolysis was limited by high-dose dobutamine at the level of glyceraldehyde-3-phosphate dehydrogenase. Dobutamine is capable of improving both contractile function and cellular energetics in underperfused RV myocardium at low but not high dose dobutamine. Therefore, dosage should be carefully selected.