The hypothesis underlying the present proposal is that physiologic hypertrophy of the myocardium protects against and possibly reverses the myocardial deterioration associated with pathologic hypertrophy. To explore this hypothesis, several experimental models of hypertrophy will be characterized in the rat. These will include systolic overload (secondary to abdominal or ascending aortic banding), diastolic overload (secondary to arterio-venous fistula formation), chronic beta-adrenergic stimulation (using chronic sub-cutaneous dobutamine infusion), and physical training. The resultant hypertrophy will be characterized physiologically, using an isolated working heart preparation, and biochemically as regards myosin isozyme content and ATPase activity and as to adrenergic receptor number and affinity. It will then be possible to superimpose physiologic stimuli on pathologically loaded hearts to investigate the mechanical and biochemical characteristics of the resultant hypertrophy. Since ventricular function is a prime determinant of prognosis in a wide variety of clinical conditions, a basic understanding of the mechanisms by which the heart responds to pathologic overload states and an approach to preventing and perhaps reversing the associated ventricular dysfunction is of great importance.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001552-03
Application #
3081936
Study Section
Research Manpower Review Committee (MR)
Project Start
1985-07-01
Project End
1990-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Montefiore Medical Center (Bronx, NY)
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10467
Buttrick, P; Perla, C; Malhotra, A et al. (1991) Effects of chronic dobutamine on cardiac mechanics and biochemistry after myocardial infarction in rats. Am J Physiol 260:H473-9
Rosen, S; Lahorra, M; Cohen, M V et al. (1991) Ventricular fibrillation threshold is influenced by left ventricular stretch and mass in the absence of ischaemia. Cardiovasc Res 25:458-62
Kitsis, R N; Buttrick, P M; McNally, E M et al. (1991) Hormonal modulation of a gene injected into rat heart in vivo. Proc Natl Acad Sci U S A 88:4138-42
Malhotra, A; Buttrick, P; Scheuer, J (1990) Effects of sex hormones on development of physiological and pathological cardiac hypertrophy in male and female rats. Am J Physiol 259:H866-71
McNally, E M; Buttrick, P M; Leinwand, L A (1989) Ventricular myosin light chain 1 is developmentally regulated and does not change in hypertension. Nucleic Acids Res 17:2753-67
Buttrick, P; Malhotra, A; Factor, S et al. (1988) Effects of chronic dobutamine administration on hearts of normal and hypertensive rats. Circ Res 63:173-81
Buttrick, P M; Malhotra, A; Scheuer, J (1988) Effects of systolic overload and swim training on cardiac mechanics and biochemistry in rats. J Appl Physiol 64:1466-71
Geenen, D; Buttrick, P; Scheuer, J (1988) Cardiovascular and hormonal responses to swimming and running in the rat. J Appl Physiol 65:116-23
Schaible, T; Malhotra, A; Ciambrone, G et al. (1987) Combined effects of hypertension and chronic running program on rat heart. J Appl Physiol 63:322-7
Buttrick, P M; Schaible, T F; Malhotra, A et al. (1987) Effects of pregnancy on cardiac function and myosin enzymology in the rat. Am J Physiol 252:H846-50

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