Prevention of ischemia-induced cardiac sudden death by n-3 polyunsaturated fatty acids in dogs.
The objective of this study was to obtain functional information associated with the prevention by n-3 polyunsaturated fatty acids (PUFA) of ischemia-induced fatal cardiac ventricular arrhythmias in the intact, conscious, exercising dog. Thirteen dogs susceptible to ischemia-induced ventricular fibrillation were prepared surgically by ligation of their anterior descending left coronary artery and placement of an inflatable cuff around their left circumflex artery. After 4 wk of recovery, exercise-plus-ischemia tests were performed without and then with an intravenous infusion of an emulsion of free n-3 PUFA just prior to occluding the left circumflex artery while the animals were running on a treadmill. One week later the exercise-plus-ischemia test was repeated but with a control infusion replacing the emulsion of n-3 PUFA. The infusion of the free n-3 PUFA in quantities of 1.0 to 10 g prevented ventricular fibrillation in 10 of the 13 dogs tested (P < 0.005), apparently without esterification of the PUFA into membrane phospholipids. The antiarrhythmic effect of the n-3 PUFA was associated with slowing of the heart rate, shortening of the QT-interval (electrical action potential duration), reduction of left ventricular systolic pressure, and prolongation of the electrocardiographic atrial-ventricular conduction time (P-R interval). These effects are comparable with those we have reported in studies with cultured neonatal rat cardiac myocytes.
Billman
G E
GE
Department of Physiology, Ohio State University, Columbus 45210, USA.
Kang
J X
JX
Leaf
A
A
D000818:Animals; D003250:Constriction; D003331:Coronary Vessels; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004285:Dogs; D004562:Electrocardiography; D004655:Emulsions; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000627:therapeutic use*; D005395:Fish Oils / Q000008:administration & dosage / Q000627:therapeutic use; D006329:Heart Conduction System / Q000503:physiopathology; D006339:Heart Rate; D017202:Myocardial Ischemia / Q000150:complications*; D005082:Physical Exertion; D011312:Pressure; D051381:Rats; D014693:Ventricular Fibrillation / Q000517:prevention & control; D016277:Ventricular Function, Left
D004655:Emulsions; D015525:Fatty Acids, Omega-3; D005395:Fish Oils