DIETARY FATTY ACID MODULATION OF MYOCARDIAL FUNCTION AND INFLUENCES ON AGING

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The period of cardiac myocyte contraction, the transmembrane action potential and cytosolic Ca++ transient are extended in old rat cardiac cells compared to those from young adults. The rate of sarcoplasmic reticulum uptake of Ca++ and the level of Ca++ stimulate ATPase activity decreases with senescence and the cardiac response to beta- adrenergic stimulation is reduced with aging. It is proposed that "normal" age-related changes in cardiac function and increased cardiac pathology with age may be associated with alterations to membrane composition which may be intervened by dietary lipid modification of myocardial cell and intracellular membranes.The vulnerability to arrhythmic stimuli increases with age. Short term feeding with n-3 polyunsaturated fatty acid (n-3 PUFA) rich diet in old rats and monkeys significantly reduces the incidence of ventricular arrhythmias whereas saturated fat rich diet (SAT) is pro-arrhythmogenic. SAT diet induces a marked increase in myocardial O2 demand independent of contractile function under control conditions. In contrast O2 demand was very low following n-3 PUFA diet. Coronary vasodilator reserve was greater following n-3 PUFA diet than SAT diet. These differences are not due to any change in basal metabolism or vascular function but rather to intracellular Ca++ homeostasis. The present study (commenced January 1993), investigates the effect of dietary lipid modulation in isolated cardiac myocyte membranes in order to test whether total intracellular Ca++ or Ca++ redistribution between the cytosol and organelles is altered. Cytosolic free calcium fluorescence (indo-1) and twitch amplitude of electrically stimulated isolated cardiac myocytes are currently being measured from n-3 PUFA or saturated fat dietary treated rats (6,12,24 mo). The responsiveness to the stresses of high and low stimulation rates (0.5,2Hz), BAYK8644 (L-type Ca++ channel agonist), isoproterenol (beta-adrenergic receptor agonist) and hypoxia is also to be assessed in these groups. Cell membrane fatty acid profile analysis is currently in progress to confirm the extent of change to cardiac membrane lipid composition.