The goal of this project is to determine the sequence of morphologic and ultrastructural changes occurring in the myocardium and blood vessels of hearts subjected to chronic work overload which results in cardiac hypertrophy. These observations will be made during the development of hypertrophy and during regression of hypertrophy; i.e., after removal of the chronic work overload. By correlating these structural changes with regional myocardial function as determined by sonomicrometry in the different stages of hypertrophy, we will define the factors that characterize early irreversibility of cardiac hypertrophy. The interaction of the type of workload inducing hypertrophy and coronary perfusion pressure will be examined to see what changes occur in these different settings. Morphometric analysis of blood vessels will be conducted at the capillary and arteriolar levels. Changes at the capillary level might increase diffusion distance and affect oxygen transport to the myocardial cell while changes at the arteriolar level may alter myocardial blood flow distribution. Specifically, we will: A) Study different models of hypertrophy including pressure overload hypertrophy with normal or elevated coronary perfusion pressure, volume overload hypertrophy and hypertrophy induced by renal hypertension or exercise or thyroxine administration; B) Quantitate ultrastructural changes in myocardial cells of these different models. These changes will be studied during the development of hypertrophy and after the removal of the overload; i.e., during regression; C) Quantitate changes of cell size, capillary density and arteriolar dimensions in these different models during the development of hypertrophy and during regression; D) Determine regional myocardial function to correlate with morphologic changes of the collagen stress resistant network in the different stages of hypertrophy and during regression. These observations will provide a better understanding of the interaction of factors inducing an irreversible state of hypertrophy or leading to limited or complete reversal when chronic work overload is removed.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL020190-12
Application #
3485675
Study Section
Cardiovascular Study Section (CVA)
Project Start
1976-12-01
Project End
1990-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Carroll, S M; Nimmo, L E; Knoepfler, P S et al. (1995) Gene expression in a swine model of right ventricular hypertrophy: intercellular adhesion molecule, vascular endothelial growth factor and plasminogen activators are upregulated during pressure overload. J Mol Cell Cardiol 27:1427-41
Neal, T F; Holland, H K; Baum, C M et al. (1995) CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1. Blood 86:1749-56
White, F C; Carroll, S M; Kamps, M P (1995) VEGF mRNA is reversibly stabilized by hypoxia and persistently stabilized in VEGF-overexpressing human tumor cell lines. Growth Factors 12:289-301
McKirnan, M D; Bloor, C M (1994) Clinical significance of coronary vascular adaptations to exercise training. Med Sci Sports Exerc 26:1262-8
Kassab, G S; Imoto, K; White, F C et al. (1993) Coronary arterial tree remodeling in right ventricular hypertrophy. Am J Physiol 265:H366-75
White, F C; Bloor, C M (1992) Coronary vascular remodeling and coronary resistance during chronic ischemia. Am J Cardiovasc Pathol 4:193-202
White, F C; Nakatani, Y; Nimmo, L et al. (1992) Compensatory angiogenesis during progressive right ventricular hypertrophy. Am J Cardiovasc Pathol 4:51-68
White, F C; Witzel, G; Breisch, E A et al. (1988) Regional capillary and myocyte distribution in normal and exercise trained male and female rat hearts. Am J Cardiovasc Pathol 2:247-53
Hammond, H K; White, F C; Brunton, L L et al. (1987) Association of decreased myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise. Circ Res 60:720-6
Hammond, H K; White, F C; Buxton, I L et al. (1987) Increased myocardial beta-receptors and adrenergic responses in hyperthyroid pigs. Am J Physiol 252:H283-90

Showing the most recent 10 out of 12 publications