Limitations in the completeness of autoregulatory flow adjustments may play an important role in the pathophysiology of ischemic heart disease. Preliminary studies by the applicant indicate that vasodilator reserve is not always exhausted, either regionally or globally, when coronary pressure is reduced below the autoregulatory range at constant metabolic demand. These surprising observations seem consonant, in retrospect, with the limited related data available in the literature. The present application is intended to define mechanisms which limit autoregulatory flow responses by addressing the following points: (1) Do reductions in regional blood flow at controlled coronary pressures between 30 and 70 mm Hg represent a limitation of the autoregulatory response to reductions in perfusion pressure which occurs despite residual local vasodilator reserve? (2) What are the interactions among regional myocardial flow, function and metabolic demand over a wide range of perfusion pressures? Is there an intrinsic mechanism which adjusts regional metabolism (through decreases in myocardial function) to match a limited coronary flow and help maintain a supply-demand balance which minimizes myocardial ischemia? (3) How complete are autoregulatory flow adjustments to pressure over a wide range of coronary perfusion pressures? Does the level of myocardial oxygen demand influence the completeness of flow adjustment? What are the maximum constrictor, as well as dilator, limits of intrinsic flow regulation? (4) Do basal levels of adrenergic constrictor tone influence resting coronary flow and/or coronary autoregulatory responses? What is the role of alpha adrenergic tone in limiting autoregulatory responses distal to a coronary stenosis?

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Investigator Award (CIA) (K08)
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State University of New York at Buffalo
Schools of Medicine
United States
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Judd, R M; Redberg, D A; Mates, R E (1991) Diastolic coronary resistance and capacitance are independent of the duration of diastole. Am J Physiol 260:H943-52
Canty Jr, J M; Giglia, J; Kandath, D (1990) Effect of tachycardia on regional function and transmural myocardial perfusion during graded coronary pressure reduction in conscious dogs. Circulation 82:1815-25
Canty Jr, J M; Brooks, A (1990) Phasic volumetric coronary venous outflow patterns in conscious dogs. Am J Physiol 258:H1457-63
Canty Jr, J M (1988) Coronary pressure-function and steady-state pressure-flow relations during autoregulation in the unanesthetized dog. Circ Res 63:821-36
Mates, R E; Klocke, F J; Canty Jr, J M (1988) Coronary capacitance. Prog Cardiovasc Dis 31:1-15
Canty Jr, J M; Klocke, F J; Mates, R E (1987) Characterization of capacitance-free pressure-flow relations during single diastoles in dogs using an RC model with pressure-dependent parameters. Circ Res 60:273-82
Klocke, F J; Ellis, A K; Canty Jr, J M (1987) Interpretation of changes in coronary flow that accompany pharmacologic interventions. Circulation 75:V34-8
Canty Jr, J M; Klocke, F J (1987) Reductions in regional myocardial function at rest in conscious dogs with chronically reduced regional coronary artery pressure. Circ Res 61:II107-16
Klocke, F J; Canty Jr, J M; Arani, D T et al. (1986) Adjustments in regional coronary perfusion accompanying reductions in regional coronary arterial pressure. Can J Cardiol Suppl A:200A-204A
Canty Jr, J M; Klocke, F J (1985) Reduced regional myocardial perfusion in the presence of pharmacologic vasodilator reserve. Circulation 71:370-7

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