The working heart may experience transient insult in coronary vasospasm; or from increased blood carbon monoxide levels induced by smoking or inhalation of polluted atmospheres. Cardioplegic solutions used during cardiac surgery must preserve viability and promote recovery of the heart tissue. On a basic level the maintenance of heart function in the face of transient insult requires: 1) that the heart cells maintain their st;ructural morphology and viability during the insult and 2) that they are able to maintain or resume the contractile function after the insult. Our interest is in the elucidation of bioenergetic mechanisms which maintain both the viability and the normal work output of heart cells. A preparation of functionally intact cardiac myocytes isolated from the adult rat heart will be studied by a diversity of techniques including: polarographic determination of oxygen consumption at defined steady states of extracellular oxygen pressure, microscopy, destructive chemical analysis and non-invasive analysis by optical and NMR spectroscopy. Clearly defined insults including hypoxia, acidosis, substrate deprivation, and increased work output as well as pharmacological inhibition or stimulation of specific intracellular enzymes will be imposed individually and in consort on suspensions of cardiac myocytes to examine basic bioenergetic failures which result in functional damage, so that protection and healing can be addressed specifically. Steady state CP and ATP levels will be taken as indicators of intracellular energy balance. Functional deficits of the cells will be studied under conditions of insufficient ATP generation.
Specific aims i nclude: a) Studies of the effect of low levels of carbon monoxide and oxygen on intracellular oxygen transport, respiratory oxygen flux phosphate potential and heart cell function. b) Studies of the effect of substrate deprivation or alteration, extracellular and intracellular pH and pCa changes, increased work output, specific inhibitors, and hormones on the ability of heart cells to maintain energy production at a rate sufficient to maintain both their viability and their contractile function.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL019299-17
Application #
3335786
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1979-05-01
Project End
1995-01-31
Budget Start
1993-02-01
Budget End
1994-01-31
Support Year
17
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
White, R L; Wittenberg, B A (2000) Mitochondrial NAD(P)H, ADP, oxidative phosphorylation, and contraction in isolated heart cells. Am J Physiol Heart Circ Physiol 279:H1849-57
White, R L; Wittenberg, B A (1995) Effects of calcium on mitochondrial NAD(P)H in paced rat ventricular myocytes. Biophys J 69:2790-9
Jelicks, L A; Wittenberg, B A (1995) 1H nuclear magnetic resonance studies of sarcoplasmic oxygenation in the red cell-perfused rat heart. Biophys J 68:2129-36
Doeller, J E; Kraus, D W; Shick, J M et al. (1993) Heat flux, oxygen flux, and mitochondrial redox state as a function of oxygen availability and ciliary activity in excised gills of Mytilus edulis. J Exp Zool 265:1-8
Gupta, R K; Wittenberg, B A (1993) 19F nuclear magnetic resonance studies of free calcium in heart cells. Biophys J 65:2547-58
White, R L; Wittenberg, B A (1993) NADH fluorescence of isolated ventricular myocytes: effects of pacing, myoglobin, and oxygen supply. Biophys J 65:196-204
Gupta, R K; Wittenberg, B A (1991) 31P-NMR studies of isolated adult heart cells: effect of myoglobin inactivation. Am J Physiol 261:H1155-63
Doeller, J E; Wittenberg, B A (1991) Myoglobin function and energy metabolism of isolated cardiac myocytes: effect of sodium nitrite. Am J Physiol 261:H53-62
Doeller, J E; Wittenberg, B A (1990) Intracellular calcium and high-energy phosphates in isolated cardiac myocytes. Am J Physiol 259:H1851-9
White, R L; Doeller, J E; Verselis, V K et al. (1990) Gap junctional conductance between pairs of ventricular myocytes is modulated synergistically by H+ and Ca++. J Gen Physiol 95:1061-75

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