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Prevention of ischemia-induced cardiac Sudden death by n−3 polyunsaturated fatty acids in dogs

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Lipids

Abstract

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 suceptible 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.

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Abbreviations

DHA:

cis-5,8, 11, 14, 17, 20-docosahexaenoic acid (22:6n−3)

ECG:

electrocardiogram

EPA:

cis-5,8,11,14,17-eicosapentaenoic acid (20:5n−3)

NEFA:

nonesterified fatty acids [fraction of plasma lipids which includes the free fatty acids of which over 99.9% are bound to albumin and other plasma proteins plus a very small fraction of monometric free or aggregated clusters of fatty acids (lamellar or micellar aggregates) in plasma water]

P-R interval:

duration of conduction time from the start of the auricular P-wave to start of the ventricular R-wave conventionally measured from the ECG

PUFA:

polyunsaturated fatty acids (denotes the n−3 class of essential long-chain PUFA but more generally applied to both the n−3 and n−6 classes)

QT interval:

an electrocardiographic interval from the start of the Q-wave to the start of the T-wave of the ECG (equivalent to the duration of the action potential observed in individual cardiac myocytes as an abrupt rise and fall in the transmembrane potential when their resting or diastolic membrane potential is depolarized and measured with an intracellular electrode and an external reference electrode; the electrical signal that initiates contractions of the heart muscle

TLC:

thin-layer chromatography

VF:

ventricular fibrillation, a fatal cardiac arrhythmia when sustained, characterized by grossly irregular, rapid, and chaotic beating

VT:

ventricular flutter, a very rapid but regular beating rate which is also fatal is sustained

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Author information

Authors and Affiliations

  1. Department of Physiology, The Ohio State University, 45210, Columbus, Ohio

    George E. Billman

  2. Department of Medicine, Massachusetts General Hospital, 02114, Boston, Massachusetts

    Jing X. Kang & Alexander Leaf

  3. Harvard Medical School, 02115, Boston, Massachusetts

    Jing X. Kang & Alexander Leaf

Authors
  1. George E. Billman
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  2. Jing X. Kang
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  3. Alexander Leaf
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Corresponding author

Correspondence to Alexander Leaf.

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Billman, G.E., Kang, J.X. & Leaf, A. Prevention of ischemia-induced cardiac Sudden death by n−3 polyunsaturated fatty acids in dogs. Lipids 32, 1161–1168 (1997). https://doi.org/10.1007/s11745-997-0149-2

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  • DOI: https://doi.org/10.1007/s11745-997-0149-2

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