DIETARY FATTY ACID MODULATION OF MYOCARDIAL FUNCTION AND INFLUENCES ON AGING

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This laboratory has shown that cardiac myocyte contraction time, its action potential and cytosolic Ca++ transient are extended with increasing age in rats. In addition, with increased age the threshold for Ca2+ overload of ra cardiac cells is reduced. Age-related changes in cardiac function and increased vulnerability to arrhythmogenic stimuli may be associated with alterations to membrane composition which may be intervened by dietary lipi modification of myocardial cell membranes. In this project we demonstrated following 8 weeks feeding of a basic reference diet to Wistar rats the proportion of ventricular membrane arachidonic acid (AA; n-6 polyunsaturate fatty acid, PUFA) increased and docosahexaenoic acid (DHA; n-3 PUFA) decreased in 24mo rats compared to 6mo rats. Treatment with a diet rich in saturated fat (SAT) distinctly augmented this age effect whereas FO prevented the age-related decrease in the n-3/n-6 PUFA ratio. An experimental protocol was employed which stresses cell membrane ion homeostasis related to membrane function. When stimulated at 2 Hz contraction amplitudes decreased in all groups, while SAT myocytes had the smallest contraction amplitude, FO myocytes were relatively resistant to this effect. When 0.5 or 2Hz stimulation was ceased no difference in the number of "spontaneous" cell contractions or "waves" (indicative of intracellular Ca2+ rising above the threshold for Ca2+ induced Ca2+ release and causing a spontaneous Ca2+ release from SR and thus potentially spontaneous contractions). However, the time to the first spontaneous wave was significantly longer for FO myocytes. Isoproterenol or BAYK8644 increased the number of waves and decreased the time to their onset. SAT diet markedly augmented this but FO diet provided protection by attenuating the severity of these effects. Thus results indicate that SAT diet exacerbates, and FO diet provides resistance against, age associated cardia cell Ca2+ tolerance and arrythmogenic triggers. These effects may be due to changes in cell membrane lipid composition.