Myocardial energy metabolism and electrophysiological parameters in the hypertrophied heart: Interrelation with intracellular calcium cycling

59 MYOCARDIAL ENERGY METABOLISM AND ELECTROPHYSIOLOGICAL PARAMETERS IN THE HYPERTROPHIED HEART : INTERRELATION WITH INTRACELLULAR CALCIUM CYCLING. C.Thollon, J.Aussedat, P. Kreher. Laboratoire de Physiologie animale BP 68, 38402 ST MARTIN d'HERES Cedex, France It has been reported that the duration of action potential increases in the hypertrophied myocardium when compared to control values. We have investigated the relationship between electrophysiological changes and metabolic alterations. Cardiac hypertrophy was induced in rats by experimental abdominal aortic stenosis. Measurements of electrophysiological and metabolic parameters were performed in the 3rd, 8th and 15th day after clamping the aorta. During these periods cardiac hypertrophy progressed gradually and myocardial contents of ATP and creatine phosphate were lower than controls hearts while the pyruvate content was higher. Concomitantly 3 days after banding the aorta, the duration of 90% repolarization (APDgD) to the RMP was significantly longer. The, for the 8th and 15th day, this APDgO was the same that for 3 days, but the APD50 was lengthened consistently. By changing the extracellular fluid composition (more calcium, or hypoxia) the mechanism for prolonged action potential was investigated. Our findings suggest that there are longitudinal changes in the myocardial energy metabolism and in the action potential repolarization phases with development of cardiac hypertrophy, probably related to a modification of intracellular calcium cycling.

CARDIAC CONTRACTILE PROTEIN SYNTHESIS: DOES THE PATTERN CHANGE IN STRESS? Schreiber, S.S., Evans, C.D., Oratz, M., Rothschild, M.A. Dept. Nuclear Med., VA Hospital & Dept. Medicine, New York University School of Medicine, NY. The functioning sarcomere appears microscopically unchanged with stresses, such as pressure overload, but does this mean that there are parallel changes in synthesis of We have studied such synthesis in vitro in the guinea pig in contractile proteins? response to pressure stress, with aging, and after prolonged ethanol ingestion and Even under control have found the synthetic alterations which occur are not uniform. contractile proteins have different relative synthetic rates (TM >HC >A > conditions, LCl >LC2) and molar synthesis does not necessarily follow the molar proportions indiWith increased afterload in the young, cating that turnover rates are not the same. With aging, there is initial increase in relative synthesis of HC (compared to LC's). and with application of afterload stress, there is the relative synthesis of HC falls, This difference between young and adult may be no increase in relative HC synthesis. On the other hand, with pressure stress related to the difference in myosin ATPase. 1n contrast, when in the adult there is an increase in relative synthesis of actin. the young animal is exposed to ethanol ingestion during growth, there is a fall in tocal protein synthesis with no fall in synthetic rate of contractile proteins except Thus, despite the necessity to maintain the integrity of the sarfor that of actin. subtle changes in contractile protein synthesis comere structure following stresses, may occur and may also reflect in later functional changes.

USE OF MOLECULAR HYBRIDIZATION J.Z;ihringer, N.Pritzl, G.St&, Klinikum GroRhadern, University

TO QUANTITATE CARDIAC :XXiA IN HEART MUSCLE E.Kreuzer. Med.Klinik I and Dept. of Heart 8ooo Miinchen 70, W.-Germany. of Munich,

BIOPSIES. Surgery,

In a variety of cardiac diseases (heart hypertrophy or atrophy, cardioml-opathy, virus-myocarditis) changes in cardiac gene expression might play a role in the pathogenetic process. To investigate such changes we developed a technique which allows to determine the cardiac mRNA content in small right or left heart biopsies. First, the average sequence length of cardiac mRNA (2050 nucl.) and of its Poly(A)Second, from these values and by hybridizing cDNA or tjact (88 nucl.) were determined. ( H)Poly(U) to mFzNA the mRNA content of rat hearts was determined with cardiac biopsies as working material (57 biopsies from 15 hearts, biopsy weight 2.20+0.87 mg, mRNA-content 72713 ug/g heart). Third, the method was then employed to study changes in cardiac gene expression in heart hypertrophy and atrophy (20430% change in cardiac mRNA conin preliminary experiments we applied the hybriditents in these conditions). Fourth, zation technique to determine the cardiac mFd4A contents in biopsies taken from human papillary muscle, the latter being obtained at open heart surgery for mitral valve replacement. Conclusion : The hybridization method described appears to allow an assessment of chanoes in cardiac acne exoression in cardiac biopsies, in heart hypertrophy and atro-