We, and others, have demonstrated dietary content of long chain polyunsaturated fattly acids (PUFA) affects their incorporation into cell membrane lipid rafts. PUFA have a dramatic impact on cell ion homeostasis and redox chemistry. Omega 3 PUFA, the good variety of PUFAs, type typified by Docosohexanoic acid, protect from lethal post-ischemic arrythmias, whilst the Omega 6, bad variety of PUFA, promote theses arrythmias. With advancing age in rodents, membrane Omega 3 decrease and Omega 6 increase. Old rats are extremely vulnerable to post ischemic ventricular fibrillation. The age-associated change in membrane PUFA profile is completely reversed by diets rich in Omega 3 PUFA, as is the vulnerability to ventricular fibrillation. Accumulating epidemiological evidence indicates that dietary PUFA (from fish) confer secondary protection from death due to cardiovascular events related to Alzheimers CV disease. In these studies, it was noted that those individuals who consumed diets high in Omega 3 PUFA also had a reduction in resting heart rate. Numerous other recent epidemiological studies have demonstrated a beneficial effect to a lower (but normal) heart rate with respect to morbid outcomes with CV disease. The Pharma industry has begun to capitalize upon these discoveries by initiating clinical outcome studies to reduce heart rate using bradycardic drug as the active arm. Results to date demonstrate that there is a moderate, but significant reduction in baseline and intrinsic (elimination of sympathetic and residual nerve control) heart rate following 40-60 day diet of Omega 3 PUFA compared to a diet of Omega 6 PUFA. Analysis of data is ongoing for studies employed to identify mechanistic causes for altered beating rates in isolated sinoatrial nodal cells between the two dietary groups: 1) patch clamp protocols to evaluate their beating rate and also possible changes in some other electrophysiological parameters, 2) skinned cell methodologies to compare local calcium release (LCR) and sarcoplasmic reticulum (SR) load, and 3) cytosolic Ca2+ transients. The large amount of cardiac tissue collected is being analyzed for fatty acid content and incorporation. Gas chromatography of fatty acid methyl ester extracted from the ventricle, sinoatrial node, atria and aorta revealed overall increases in membrane n-3 PUFA in fish oil diet versus control diet. Mole to mole (Omega-3/Omega-6) ratios of the two most biologically active Omega-3 PUFAs DHA and EPA were found in ranges of all fish oil tissues from 3:1 to 31:1. Specifically, the affinity for n-3 EPA was found to be the highest in the sinoatrial node at 31:1 followed by the atria 29:1, aorta 27:1 and ventricle 3:1. The aorta showed the highest affinity for DHA at 21:1 followed by the ventricle 13:1, atria 15:1 and the sinoatrial node 8:1. Total Omega-3 fatty acids comprised 15% of total lipids in fish oil diets 2% in control diets. Also, there was an increase in incorporation of Omega-3 PUFA proportionate to the number of days on the fish oil diet. These data indicate an important cardiovascular tissue specific incorporation of dietary PUFA .