When cardiac oxygen metabolism increases, as during exercise, there is a simultaneous increase in coronary blood flow that supplies more oxygen to the heart. How the match between oxygen supply and demand occurs is the fundamental question in coronary physiology. In humans with coronary artery disease, the oxygen supply is inadequate, and the resulting myocardial ischemia causes anginal chest pain. It is postulated that adenosine and/or K+ATP channels (which interact with adenosine) are involved in the feedback control of coronary blood flow that normally maintains an adequate oxygen supply to the heart. The key element in testing the adenosine hypothesis is an estimation of interstitial adenosine concentration, which cannot be directly measured. A mathematical model will be used to calculate the interstitial adenosine concentration from coronary blood flow and the venous plasma adenosine concentration. The role of adenosine will be tested with a selective adenosine receptor blocking agent, 8-phenyltheophylline, and the role of K+ATP channels with the selective channel blocking agent glibenclamide. The use of these blocking agent in combination with adenosine concentration measurements will critically test the role of adenosine and/or K+ATP channels in controlling coronary blood flow during catecholamine stimulation of the heart, cardiac pacing and exercise. The significance of this research is that the basic mechanism of coronary control will be studied. An understanding of normal physiological control is important in itself but is also relevant to pathological states.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL049822-05
Application #
2028863
Study Section
Special Emphasis Panel (ZRG4-CVB (03))
Project Start
1993-05-25
Project End
2002-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B (2016) Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy. Am J Physiol Heart Circ Physiol 310:H351-64
Farias 3rd, Martin; Gorman, Mark W; Savage, Margaret V et al. (2005) Plasma ATP during exercise: possible role in regulation of coronary blood flow. Am J Physiol Heart Circ Physiol 288:H1586-90
Gorman, Mark W; Farias 3rd, Martin; Richmond, Keith N et al. (2005) Role of endothelin in alpha-adrenoceptor coronary vasoconstriction. Am J Physiol Heart Circ Physiol 288:H1937-42
Tune, Johnathan D; Gorman, Mark W; Feigl, Eric O (2004) Matching coronary blood flow to myocardial oxygen consumption. J Appl Physiol 97:404-15
Gorman, Mark W; Ogimoto, Kayoko; Savage, Margaret V et al. (2003) Nucleotide coronary vasodilation in guinea pig hearts. Am J Physiol Heart Circ Physiol 285:H1040-7
Gorman, Mark W; Marble, David R; Ogimoto, Kayoko et al. (2003) Measurement of adenine nucleotides in plasma. Luminescence 18:173-81
Tune, J D; Richmond, K N; Gorman, M W et al. (2001) K(ATP)(+) channels, nitric oxide, and adenosine are not required for local metabolic coronary vasodilation. Am J Physiol Heart Circ Physiol 280:H868-75
Tune, J D; Richmond, K N; Gorman, M W et al. (2000) Role of nitric oxide and adenosine in control of coronary blood flow in exercising dogs. Circulation 101:2942-8
Richmond, K N; Tune, J D; Gorman, M W et al. (2000) Role of K(ATP)(+) channels and adenosine in the control of coronary blood flow during exercise. J Appl Physiol 89:529-36
Tune, J D; Richmond, K N; Gorman, M W et al. (2000) Adenosine is not responsible for local metabolic control of coronary blood flow in dogs during exercise. Am J Physiol Heart Circ Physiol 278:H74-84

Showing the most recent 10 out of 18 publications