Research under this grant has shown that chronic surgical sympathectomy of the canine ventricles affords a protective effect during coronary artery occlusion and that this effect is due to improved collateral perfusion and reduced blood flow requirement. These findings are extremely important to the understanding and treatment of coronary artery disease and are directly applicable to the transplanted heart patient. These findings have been challenged by studies using other sympathectomy procedures (e.g. chemical) and other animal species (e.g. rabbit). Therefore, this renewal is focused both on advancement of our understanding of chronic sympathectomy and exploration of the physiological bases for reported differences. Four new studies are proposed: Study 10 will use conscious dogs and will examine whether chronic chemical sympathectomy [by topical application of phenol] exerts the same influence on the coronary collateral circulation as does surgical sympathectomy. Through a consortial arrangement with an independent laboratory, these experiments conducted """"""""blind"""""""". Study 11 will examine whether the surgical sympathectomy-induced collateral effects in the dog heart can be demonstrated in the pig heart, which like the human has a smaller native collateral bed. An improved collateral circulation in the pig heart after chronic sympathectomy would suggest an actual collateral development rather than a wider opening of existing channels. These experiments will also be conducted blind. Study 12 will systematically examine the influences of changes in heart rate and diastolic pressure on collateral blood flow during coronary occlusion. Evidence indicates that absence of a protective effect in the chronic, totally denervated heart of the conscious dog may be due to lack of reflex tachycardia, such as seen with only ventricular sympathectomy, such that diastolic pressure rises and opposes collateral perfusion. Study 13 will examine an apparent cardiocoronary reflex causing coronary constriction during myocardial ischemia. What are the roles of a local ischemia-induced release of norepinephrine or of a neural reflex affecting ischemic and nonischemic muscle? This study will also examine whether chronic ventricular sympathectomy alters this reflex in conscious dogs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029232-07
Application #
3340353
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1982-01-01
Project End
1994-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
7
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of North Texas
Department
Type
Schools of Osteopathy
DUNS #
110091808
City
Fort Worth
State
TX
Country
United States
Zip Code
76107
Barron, B A; Laughlin, M H; Gwirtz, P A (1997) Exercise effect on canine and miniswine cardiac catecholamines and enkephalins. Med Sci Sports Exerc 29:1338-43
Dodd-o, J M; Gwirtz, P A (1996) Coronary alpha 1-adrenergic constrictor tone varies with intensity of exercise. Med Sci Sports Exerc 28:62-71
Kim, S J; Kline, G; Gwirtz, P A (1996) Limitation of cardiac output by a coronary alpha 1-constrictor tone during exercise in dogs. Am J Physiol 271:H1125-31
Gwirtz, P A (1995) Coronary alpha 1-constrictor tone during renovascular hypertension. Circulation 92:1576-81
Barron, B A; Jones, C E; Caffrey, J L (1995) Pericardial repair depresses canine cardiac catecholamines and met-enkephalin. Regul Pept 59:313-20
Tsuchida, A; Liu, Y; Liu, G S et al. (1994) alpha 1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase C. Circ Res 75:576-85
Quist, E E; Lee, S C; Vasan, R et al. (1994) Chronic sympathectomy of canine cardiac ventricles affects Gs-adenylyl cyclase coupling and muscarinic receptor density. J Cardiovasc Pharmacol 23:936-43
Brandt, M A; Jones, C E; Gwirtz, P A (1993) Augmented coronary blood flow response to intracoronary norepinephrine after ventricular sympathectomy. Coron Artery Dis 4:101-7
Thornton, J D; Daly, J F; Cohen, M V et al. (1993) Catecholamines can induce adenosine receptor-mediated protection of the myocardium but do not participate in ischemic preconditioning in the rabbit. Circ Res 73:649-55
Gwirtz, P A; Dodd-O, J M; Downey, H F et al. (1992) Effects of a coronary alpha 1-constriction on transmural left ventricular flow and contractile function. Am J Physiol 262:H965-72

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