Heart failure is a syndrome in which abnormalities in cardiac function, disturbances in myocardial bioenergetics, abnormalities in neural and humoral circulatory control and disturbances in the peripheral vascular tone all contribute to the clinical symptomatology and to the progression of the disorder. This program project explores each of the abnormalities in various experimental models as well as in patients with heart failure to help define mechanisms that contribute to the physiologic abnormality characteristic of the process. Advanced technologies are key to many of the experimental protocols. The use of ultrasonic crystals to quantitate ventricular function in the dog is critical to two of the projects, the use of NMR spectroscopy to assess myocardial energetics is a key component of three of the projects, measurements of circulating hormones activated in heart failure are utilized in three projects, microsphere blood flow in the myocardium is a key hemodynamic variable in two of the projects, and measurements of norepinephrine kinetics, forearm blood flow and forearm arterial compliance are key features of the clinical proposal. These studies lean heavy on pharmacological intervention in order to explore mechanisms by directly stimulating or interfering with known pharmacologic receptors. Interaction among the investigators includes the sharing of technology, sharing of experimental models, and the rapid incorporation of advances from one project into experimental design of other projects. The long-term goal of these studies is to gain insight into the interactive nature of all of these pathophysiologic events that appear to be contributory to the syndrome of heart failure with the hope that an understanding of mechanism will lead to improvements in diagnostic acumen and therapeutic success.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL032427-09
Application #
2217020
Study Section
Special Emphasis Panel (SRC (JA))
Project Start
1989-09-30
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
9
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Bank, A J; Lee, P C; Kubo, S H (2000) Endothelial dysfunction in patients with heart failure: relationship to disease severity. J Card Fail 6:29-36
Traverse, J H; Melchert, P; Pierpont, G L et al. (1999) Regulation of myocardial blood flow by oxygen consumption is maintained in the failing heart during exercise. Circ Res 84:401-8
Goldsmith, S R (1999) Angiotensin II and sympathoactivation in heart failure. J Card Fail 5:139-45
Ishibashi, Y; Duncker, D J; Zhang, J et al. (1998) ATP-sensitive K+ channels, adenosine, and nitric oxide-mediated mechanisms account for coronary vasodilation during exercise. Circ Res 82:346-59
Traverse, J H; Kinn, J W; Klassen, C et al. (1998) Nitric oxide inhibition impairs blood flow during exercise in hearts with a collateral-dependent myocardial region. J Am Coll Cardiol 31:67-74
Bank, A J; Shammas, R A; Mullen, K et al. (1998) Effects of short-term forearm exercise training on resistance vessel endothelial function in normal subjects and patients with heart failure. J Card Fail 4:193-201
Bank, A J; Kaiser, D R (1998) Smooth muscle relaxation: effects on arterial compliance, distensibility, elastic modulus, and pulse wave velocity. Hypertension 32:356-9
Goldsmith, S R; Garr, M; McLaurin, M (1998) Regulation of regional norepinephrine spillover in heart failure: the effect of angiotensin II and beta-adrenergic agonists in the forearm circulation. J Card Fail 4:305-10
Wei, H; Merkle, H; Xu, Y et al. (1997) Detection of 13C-labeled metabolites in the in vivo canine heart by B1 insensitive heteronuclear coherent polarization transfer and comparison of signal enhancement with NOE. Magn Reson Med 37:327-30

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