Chapter 3
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on May 26, 2018 | https://pubs.acs.org Publication Date: March 27, 2001 | doi: 10.1021/bk-2001-0788.ch003
Electrophysiologic and Functional Effects of Polyunsaturated Fatty Acids on Excitable Tissues: Heart and Brain 1
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A. Leaf , J. X. Kang , Y-F. Xiao , G. E. Billman , and R. A. Voskuyl 1
Department of Medicine, Massachusetts General Hospital East and Harvard Medical School, 149 Thirteenth Street-1494001, Charlestown, MA 02129-6020 Cardiology Research, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215 Department of Physiology, The Ohio State University, Columbus, OH 45210 Department of Physiology, Leiden University Medical Center and the Stichting Epilepsie Instellingen Nederland, P.O. Box 21, 2100 AA Heemstede, The Netherlands 2
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The n-3 polyunsaturated fatty acids (PUFAs) have been shown to be antiarrhythmic in animals and probably in humans. The PUFAs stabilize the electrical activity of isolated cardiac myocytes by inhibiting sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the relative refractory period is markedly prolonged. Inhibition of voltage dependent sodium currents which initiate action potentials in excitable tissues, and of the L-type calcium currents, which initiate release of sarcoplasmic calcium stores, that increase cytosolic free calcium concentrations and activate the contractile proteins in myocytes, appear at present to be the probable major antiarrhytmic mechanism of the PUFAs.
Following earlier suggestions (J, 2) that unsaturated fatty acids may have antiarrhytmic effects, McLennan et al. (5, 4) reported, that feeding rats a diet in which the fat content was largely saturated or monounsaturated resulted in a high incidence of irreversible ventricular fibrillation when their coronary arteries were subsequently experimentally heated. When vegetable oils were the major source of the dietary fat, there was a reduction in artliythmic mortality by some 70%.
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© 2001 American Chemical Society Shahidi and Finley; Omega-3 Fatty Acids ACS Symposium Series; American Chemical Society: Washington, DC, 2001.
29 With tuna fish oil, however, McLennan (4) reported irreversible ventricular arrhythmias to be completely prevented with or without reflow to the ischemic myocardium. The essential findings were confirmed in marmosets (5). These striking observations led us to pursue the possible mechanism(s) for such an antiarrhythmic action of the fish oil.
Downloaded by UNIV OF CALIFORNIA SANTA BARBARA on May 26, 2018 | https://pubs.acs.org Publication Date: March 27, 2001 | doi: 10.1021/bk-2001-0788.ch003
Beneficial Effects of Polyunsaturated Fatty Acids To confirm previous findings, we first studied a canine model of sudden cardiac death. A surgically induced myocardial infarction was produced by ligating the left main coronaiy arteiy and an inflatable cuff was placed around the left circumflex arteiy of dogs as experimental animals. The dogs were allowed about a month to recover froi-n the surgery and their myocardial infarction during which they were trained to run on a treadmill. The animals were then screened for susceptibility to fatal ventricular arrhythmias (VF) when their left circumflex arteiy was occluded while they were running on a treadmill. Some 60% of animals were found susceptible and these were the dogs studied. Once an animal is "susceptible" it remains susceptible on further exercise-ischemia trials. In 10 of the 13 such dogs intravenous infusion of an emulsion of a concentrate of the fish oil free fatty acids (PUFAs) just prior to the exercise-ischemia test prevented the fatal VF (p
