Many coronary stenoses are dynamic and are capable of changes in caliber. In the presence of a severe compliant coronary stenosis, even small changes in the area of the stenosis due to physiologic processes or to drugs may importantly affect blood flow through the stenotic artery. In order to understand the factors which affect blood flow through stenotic coronary arteries the mechanisms which control the diameter of normal epicardial coronary arteries must be understood. In this project, these mechanisms will be studied using awake chronically instrumented dogs in which coronary arterial diameter will be measured with sonomicrometry. Little information is presently available concerning control of coronary arterial diameter during exercise. In the proposed project drugs which block specific receptors will be used to study the effects of the sympathetic nervous system on epicardial coronary arterial diameter during exercise. The effects of adenosine and prostaglandins on coronary arterial diameter during exercise will also be studied. Hypertension and hypercholesterolemia affect the vasomotion of arteries. In the proposed project, vasomotion of epicardial coronary arteries at rest and during exercise will be evaluated in dogs with hypertension-induced hypertrophy and in dogs with hypercholesterolemia. In addition, the effects of vasoactive drugs on the hemodynamics of compliant coronary stenoses will be studied in chronically instrumented dogs. This project is planned to contribute to an understanding of the factors controlling the diameter of epicardial coronary arteries and compliant coronary stenoses. These experiments may lead to improved understanding of the pathophysiology of the development of myocardial ischemia and to more rational therapy for ischemic heart disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL031510-04A1
Application #
3342677
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Canty Jr, J M; Schwartz, J S (1994) Nitric oxide mediates flow-dependent epicardial coronary vasodilation to changes in pulse frequency but not mean flow in conscious dogs. Circulation 89:375-84
Baran, K W; Bache, R J; Dai, X Z et al. (1992) Effect of alpha-adrenergic blockade with prazosin on large coronary diameter during exercise. Circulation 85:1139-45
Schwartz, J S; Baran, K W; Bache, R J (1990) Effect of stenosis on exercise-induced dilation of large coronary arteries. Am Heart J 119:520-4
Schwartz, J S; Bache, R J (1988) Effect of ouabain on large coronary artery diameter. J Cardiovasc Pharmacol 11:608-13
Schwartz, J S; Bache, R J (1988) Combined effects of calcium antagonists and nitroglycerin on large coronary artery diameter. Am Heart J 115:964-9
Bache, R J; Dai, X Z; Schwartz, J S et al. (1988) Role of adenosine in coronary vasodilation during exercise. Circ Res 62:846-53
Schwartz, J S (1987) Effect of nitroprusside-induced fall in systemic pressure on coronary stenoses. Int J Cardiol 14:15-24
Schwartz, J S; Bache, R J (1987) Effect of anesthesia on reactivity of large coronary arteries in the dog. J Cardiovasc Pharmacol 9:87-90
Schwartz, J S; Bache, R J (1985) Effect of arteriolar dilation on coronary artery diameter distal to coronary stenoses. Am J Physiol 249:H981-8