Coronary blood flow (CBF) is closely coupled to myocardial oxygen requirements (MV02). However, the mechanisms which link the regulation of CBF to changes in myocardial energy metabolism remain unknown. The purpose of the proposed work is to investigate the mechanism of CBF regulation by examining the relationship between instantaneous CBF and intracellular myocardial energy state (assessed by 31P NMR spectroscopy) in the transient phases of both functional and reactive myocardial hyperemia. The following specific hypotheses will be tested: 1. The level of myocardial high energy phosphates is tightly controlled despite changes in MVO2 by means of a rapid and precise regulation of CBF, and hence oxygen delivery. 2. Myocardial reactive hyperemia (RH), with its prolonged duration and gross overpayment of blood flow debt, is related to a temporary dissociation of instantaneous CBF from myocardial energy state Open-chest, anesthetized pigs with instrumentation including an extramural Doppler coronary flow probe will be studied in a 1- meter, 2 Tesla magnetic resonance spectrometer. Hemodynamic data, including phasic CBF, and 31P NMR spectra will be obtained while the experimental system is perturbed by a step augmentation of MV02 (by paired ventricular pacing and/or aortic constriction) or a step decrease in myocardial oxygen delivery (brief coronary occlusion). The first hypothesis predicts that a step increase in MV02 will be followed by a brief decline in high energy phosphate levels, compensatory coronary vasodilation with increased 02 delivery, and a rapid restoration of high energy phosphates to control levels. The second hypothesis predicts that myocardial high energy phosphates, partially depleted during coronary occlusion, are restored to normal upon release of the occlusion sooner than RH flow returns to its baseline. This would indicate that RH flows is in excess of that required to restore myocardial metabolic conditions. These studies will provide insight into the normal metabolic regulation of CBF, and the mechanisms of functional and reactive myocardial hyperemia. Subsequent studies will examine the potential abnormalities of such regulation in experimental models of coronary artery disease, left ventricular pressure or volume overload, or in the clinical syndrome of """"""""impaired coronary vasodilator reserve"""""""". This work may also lead to a better understanding of the myocardial metabolic consequences of brief coronary occlusion during angioplasty.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL002155-04
Application #
3087554
Study Section
Special Emphasis Panel (SRC (VO))
Project Start
1988-09-01
Project End
1993-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Schwartz, G G; Greyson, C; Wisneski, J A et al. (1994) Inhibition of fatty acid metabolism alters myocardial high-energy phosphates in vivo. Am J Physiol 267:H224-31
Schaefer, S; Schwartz, G G; Steinman, S et al. (1994) Effects of regional myocardial lidocaine infusion on high energy phosphates. J Mol Cell Cardiol 26:1601-11
Massie, B M; Schwartz, G G; Garcia, J et al. (1994) Myocardial metabolism during increased work states in the porcine left ventricle in vivo. Circ Res 74:64-73
Schwartz, G G; Greyson, C R; Wisneski, J A et al. (1994) Relation among regional O2 consumption, high-energy phosphates, and substrate uptake in porcine right ventricle. Am J Physiol 266:H521-30
Schwartz, G G; Schaefer, S; Trocha, S D et al. (1992) Effect of supranormal coronary blood flow on energy metabolism and systolic function of porcine left ventricle. Cardiovasc Res 26:1001-6
Schwartz, G G; Steinman, S K; Weiner, M W et al. (1992) In vivo 31P-NMR spectroscopy of right ventricle in pigs. Am J Physiol 262:H1950-4
Schaefer, S; Schwartz, G G; Wisneski, J A et al. (1992) Response of high-energy phosphates and lactate release during prolonged regional ischemia in vivo. Circulation 85:342-9
Schwartz, G G; Steinman, S; Garcia, J et al. (1992) Energetics of acute pressure overload of the porcine right ventricle. In vivo 31P nuclear magnetic resonance. J Clin Invest 89:909-18
Schaefer, S; Schwartz, G G; Steinman, S K et al. (1992) Metabolic response of the human heart to inotropic stimulation: in vivo phosphorus-31 studies of normal and cardiomyopathic myocardium. Magn Reson Med 25:260-72
Schwartz, G G; Schaefer, S; Trocha, S D et al. (1991) Metabolic and functional consequences of blunted myocardial reactive hyperemia. Am J Physiol 261:H892-900

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