The ultimate objective of the proposed research is to characterize and quantify basic cellular electrophysioloigcal properties of the developing myocardium. It is hoped that an analysis of this information will provide an understanding of the dynamic relationship between the maturation of cardiac cellular processes, and the response of the myocardium to ischemia, hypoxia, and acidosis. A comprehensive study of the changes in cellular membrane currents, ionic fluxes, and excitation-contraction coupling processes that accompany growth appears to be a prerequisite to understanding the differences in electrophysiological and mechanical properties of neonatal and adult hearts. Although there is evidence suggesting that certain intrinsic electrophysiological and mechanical properties of heart muscle may be age-dependent, many difficulties have surrounded efforts to quantitatively analyze these properties. These problems have arisen because of the technical complexity of adapting standard quantitative techniques to the smaller, more fragile neonatal tissue. However, it now appears that newer methods of examining isolated heart mescle may obviate the technical difficulties that have quantitative data and meaningful comparisons of neontal and adult ardiac tissues. The proposed investigation will utilize the voltage clamp technique and preparations to quantitatively elucidate developmental changes in cellular ionic fluxes. Furthermore, a study will be undertaken of the age-related changes in the response of these variables to hypoxia, ischemia, and acidosis. Integration of this data will provide insight into the cellular electrophysiological and mechanical effects of hypoxia and ischemia on the developing myocardium.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035783-03
Application #
3350068
Study Section
(SRC)
Project Start
1985-09-30
Project End
1988-09-29
Budget Start
1987-09-30
Budget End
1988-09-29
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Huynh, T V; Chen, F; Wetzel, G T et al. (1992) Developmental changes in membrane Ca2+ and K+ currents in fetal, neonatal, and adult rabbit ventricular myocytes. Circ Res 70:508-15
Chen, F; Wetzel, G T; Friedman, W F et al. (1991) Single-channel recording of inwardly rectifying potassium currents in developing myocardium. J Mol Cell Cardiol 23:259-67
Wetzel, G T; Chen, F; Klitzner, T S (1991) L- and T-type calcium channels in acutely isolated neonatal and adult cardiac myocytes. Pediatr Res 30:89-94
Wetzel, G T; Chen, F; Friedman, W F et al. (1991) Calcium current measurements in acutely isolated neonatal cardiac myocytes. Pediatr Res 30:83-8
Baum, V C; Klitzner, T S (1991) Excitation-contraction coupling in neonatal myocardium: effects of halothane and isoflurane. Dev Pharmacol Ther 16:99-107
Klitzner, T S (1991) Maturational changes in excitation-contraction coupling in mammalian myocardium. J Am Coll Cardiol 17:218-25
Klitzner, T S; Chen, F H; Raven, R R et al. (1991) Calcium current and tension generation in immature mammalian myocardium: effects of diltiazem. J Mol Cell Cardiol 23:807-15
Chin, T K; Friedman, W F; Klitzner, T S (1990) Developmental changes in cardiac myocyte calcium regulation. Circ Res 67:574-9
Klitzner, T S; Shapir, Y; Ravin, R et al. (1990) The biphasic effect of amrinone on tension development in newborn mammalian myocardium. Pediatr Res 27:144-7
Klitzner, T S; Friedman, W F (1989) Cardiac arrhythmias: the role of pharmacologic intervention. Cardiol Clin 7:299-318

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