Recruitment of perfusion through coronary collateral artery channels is the primary natural defense mechanism available for salvage of myocardium jeopardized by stenosis or obstruction of the native arterial perfusion pathway. Given the incidence of obstructive coronary artery disease, studies oriented toward causal mechanisms involving in the recruitment of collateral channels, the factors that determine the extent and rate of development of collateral channels, the conditions under which pre-existing coronary channels regress and the neural or pharmacological sensitivity of collateral channels are extremely important. Progress in these important areas of research has been seriously limited by the nature of the previously available methodologies used in animal experiments devoted to studies of coronary collaterals. We have developed a methodology for study of coronary collaterals in animals that overcomes the difficulties inherent in the prior approaches. We have found that repeated episodes of brief, reversible, regional myocardial ischemia is an adequate stimulus for recruitment of collateral perfusion sufficient for the metabolic requirements at rest in the dog. Briefly stated, the procedure involves two minute, total occlusion of the left circumflex artery repeated 10 to 15 times daily in the conscious dog instrumented for measurement of circumflex coronary artery flow and regional myocardial function. This model allows detailed study of the progression and regression of collateral perfusion and the factors that modify collateral perfusion. We propose the further development and refinement of this model and use of the model in studies devoted specifically toward understanding of basic mechanisms involved in collateral genesis, collateral dynamics, and collateral physiology and pharmacology. Successful completion of these studies should provide firm experimental and theoretical bases for development of effective regimens of therapy, particularly in the important area of preinfarction, stenotic coronary artery disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL032800-06
Application #
3344276
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1984-08-01
Project End
1993-11-30
Budget Start
1991-12-17
Budget End
1993-11-30
Support Year
6
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Type
Other Domestic Higher Education
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Fujita, M; Yamanishi, K; Araie, E et al. (1994) Determinants of collateral development in a canine model with repeated coronary occlusion. Heart Vessels 9:292-9
Fujita, M; Mikuniya, A; McKown, D P et al. (1991) Effects of nitroglycerin and diltiazem on well-developed coronary collateral circulation in conscious dogs. Angiology 42:628-38
Fujita, M; McKown, D P; McKown, M D et al. (1991) Bidirectional function of coronary collateral channels in conscious dogs. Cardiovasc Res 25:58-67
Sarazan, R D; Krause, G F; Franklin, D et al. (1991) Effects of coronary occlusion duration on reactive hyperemia in conscious dogs and ponies. Am J Physiol 261:H768-73
Fujita, M; Sasayama, S; Ohno, A et al. (1990) Importance of myocardial ischemia for coronary collateral development in conscious dogs. Int J Cardiol 27:179-86
Fujita, M; McKown, D P; McKown, M D et al. (1990) Coronary collateral regression in conscious dogs. Angiology 41:621-30
Fujita, M; Mikuniya, A; McKown, D P et al. (1990) Effects of dipyridamole on collateral flow and regional myocardial function in conscious dogs with newly developed collaterals. Basic Res Cardiol 85:142-52
Caldwell, W M; McKown, D P; Bleck, J A et al. (1989) An automatic syringe for coronary occlusion in long-term collateralization studies. Am J Physiol 256:H1707-10
Yonezawa, Y; Caldwell, W M; Schadt, J C et al. (1989) A miniaturized ultrasonic flowmeter and telemetry transmitter for chronic animal blood flow measurements. Biomed Sci Instrum 25:107-11
Fujita, M; Mikuniya, A; McKown, D P et al. (1989) Changes in regional myocardial cross-sectional area during brief coronary occlusion and reperfusion in conscious dogs. Int J Cardiol 22:21-8

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