PERFUSION AND METABOLISM IN COLLATERALIZED MYOCARDIUM

研究将检查心肌适应的机制

Studies will examine mechanisms by which the myocardium adapts to limited coronary arterial inflow and will determine whether 31 P NMR spectroscopy can detect a unique pattern of high energy phosphate content at rest or during stress in regions of viable but dysfunctional myocardium. A collateral-dependent myocardial region will be produced in dogs using intermittent 2 minute coronary artery occlusions followed by permanent occlusion. Animals will be studied when collateralization has increased distal coronary pressure to 60-70 mmHg, but contractile function monitored with ultrasonic crystals in hypokinetic and blood flow measured with microspheres is mildly reduced. Myocardial phosphocreatine (PCr), ATP and inorganic phosphate (Pi) will be measured in 3 transmural left ventricular layers using 31 P NMR spectroscopy. An initial study will characterize the ATP and PCr content in the collateral-dependent region during basal conditions, and examine the response to dobutamine. If contractile function fails to improve or deteriorates during a dobutamine, 31 P NMR spectroscopy will demonstrate whether this abnormal response is the result of ischemia (depletion of PCr and accumulation of Pi) or because the dysfunctional region is partially protected from responding to the inotropic stimulus. A second study will determine whether exercise causes stunning with ATP loss in the collateral-dependent region; results will be compared with animals in which a similar reduction of coronary pressure produced by an acutely applied stenosis is known to result in exercise induced stunning. A subsequent study will use 13C NMR to examine uptake of 13C-labeled glucose and the relative rates of glucose utilization for glycolosis, glucose oxidation and glycogen synthesis in collateral-dependent and normal myocardium. Preliminary studies have demonstrated phosphomonoester accumulation in collateral dependent myocardium; high resolution 31 P NMR spectroscopy will be used to identify these phosphorylated glycolytic intermediates and to find the rate limiting steps for glycolytic flux in the collateralized region. A final study will determine whether endogenous NO production is decreased in collateral-dependent myocardium, and whether supplying NO improves the energy demand/supply relationship as indicated by an increase in the PCr/ATP ratio.