Effects of dietary omega–3 fatty acids on ventricular function in dogs with healed myocardial infarctions: in vivo and in vitro studies

American Journal of Physiology - Heart and Circulatory Physiology - Tập 298 Số 4 - Trang H1219-H1228 - 2010
George E. Billman1,2, Yoshinori Nishijima3,1, Andriy E. Belevych1,2, Dmitry Terentyev1,2, Ying Xu2, Kaylan M. Haizlip2, Michelle M. Monasky2, Nitisha Hiranandani2, William S. Harris4, Sándor Györke1,2, Cynthia A. Carnes3,1,2, Paul M.L. Janssen1,2
1Davis Heart and Lung Research Institute
2Department of Physiology and Cell Biology
3College of Pharmacy, The Ohio State University, Columbus, Ohio; and
4Sanford Research Institute, University of South Dakota, Sioux Falls, South Dakota

Tóm tắt

Since omega–3 polyunsaturated fatty acids (n-3 PUFAs) can alter ventricular myocyte calcium handling, these fatty acids could adversely affect cardiac contractile function, particularly following myocardial infarction. Therefore, 4 wk after myocardial infarction, dogs were randomly assigned to either placebo (corn oil, 1 g/day, n = 16) or n-3 PUFAs supplement [docosahexaenoic acid (DHA) + eicosapentaenoic acid (EPA) ethyl esters; 1, 2, or 4 g/day; n = 7, 8, and 12, respectively] groups. In vivo, ventricular function was evaluated by echocardiography before and after 3 mo of treatment. At the end of the 3-mo period, hearts were removed and in vitro function was evaluated using right ventricular trabeculae and isolated left ventricular myocytes. The treatment elicited significant ( P < 0.0001) dose-dependent increases (16.4-fold increase with 4 g/day) in left ventricular tissue and red blood cell n-3 PUFA levels (EPA + DHA, placebo, 0.42 ± 0.04; 1 g/day, 3.02 ± 0.23; 2 g/day, 3.63 ± 0.17; and 4 g/day, 6.97 ± 0.33%). Regardless of the dose, n-3 PUFA treatment did not alter ventricular function in the intact animal (e.g., 4 g/day, fractional shortening: pre, 42.9 ± 1.6 vs. post, 40.1 ± 1.7%; placebo: pre, 39.2 ± 1.3 vs. post, 38.4 ± 1.6%). The developed force per cross-sectional area, changes in length- and frequency-dependent behavior in contractile force, and the inotropic response to β-adrenoceptor activation were also similar for trabeculae obtained from placebo- or n-3 PUFA-treated dogs. Finally, calcium currents and calcium transients were the same in myocytes from n-3 PUFA- and placebo-treated dogs. Thus dietary n-3 PUFAs did not adversely alter either in vitro or in vivo ventricular contractile function in dogs with healed infarctions.

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Tài liệu tham khảo

10.1056/NEJMoa012918

10.1093/ajcn/33.12.2657

10.1016/j.pharmthera.2006.01.002

10.1152/ajpendo.00021.2009

10.1152/ajpheart.1990.258.3.H896

10.1152/japplphysiol.01328.2005

10.1073/pnas.91.10.4427

10.1152/jappl.1985.59.3.890

10.1152/ajpheart.01220.2005

10.1139/o59-099

Boden WE, Krone RJ, Kleiger RE, Oakes D, Greenberg H, Dwyer EJ, Jr, Miller JP, Abrams J, Coromilas J, Goldstein R. Electrocardiographic subset analysis of diltiazem on long-term outcome after acute myocardial infarction. The Multicenter Diltiazem Post-Infarction Trial Research Group.Am J Cardiol63: 70–79, 1991.

Brouwer IA, Riatt MH, Dullemeijer C, Kraemer DF, Zock PL, Morris C, Katan MB, Connor WE, Camm JA, Schouten EG, McAnulty J. Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators.Eur Heart J30: 820–826, 2009.

10.1007/s00232-005-0784-1

10.1016/S0140-6736(89)90828-3

10.1038/sj.ejcn.1601539

10.1136/bmj.312.7032.677

10.1161/01.CIR.0000084542.64687.97

10.1056/NEJM199704103361502

10.1161/CIRCULATIONAHA.107.733329

10.1007/s00228-004-0758-8

10.1016/j.cardiores.2007.07.002

10.1093/cvr/cvn310

Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR. Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis?Lancet2: 117–119, 1978.

10.1016/S0008-6363(02)00275-4

10.1016/S0002-8703(03)00808-1

10.1016/S0140-6736(08)61239-8

10.1007/s10557-006-0295-z

Hanson JF. Treatment with verapamil during and after acute myocardial infarction: a review based upon the Danish verapamil infarction trials I and II.J Cardiovasc Pharmacol19, Suppl 6: S20–S25, 1991.

10.1016/j.ypmed.2004.02.030

10.1016/j.amjcard.2006.06.033

10.1007/s11745-007-3036-6

10.1161/01.CIR.0000142292.10048.B2

10.1016/S0014-2999(98)00484-1

10.1007/s00232-003-0628-9

Hooper L, Thompson RL, Harrison RA, Summerbell CD, Moore H, Worthington HV, Durrington PN, Ness AR, Capps NE, Davey Smith G, Riemersma RA, Ebrahim SB. Omega–3 fatty acids for prevention and treatment of cardiovascular disease.Cochrane Database Syst Rev4: CD003177, 2004.

10.1152/jappl.2001.91.4.1627

10.1161/01.ATV.0000057393.97337.AE

Kromhout D, Bosschieter EB, de Lezenne CC. The inverse relation between fish consumption and 20-year mortality from coronary heart disease.N Engl J Med1985;312: 1205–1209, 1985.

León H, Shibata MC, Sivakumaran S, Dorgan M, Chatterley T, Tsuyuki RT. Effect of fish oil on arrhythmias and mortality: systematic review.Br Med J338: a2931, 2009.

10.1016/S0008-6363(02)00859-3

10.1161/CIRCULATIONAHA.107.712984

10.1055/s-2007-973047

10.1161/01.CIR.0000014682.14181.F2

10.1093/cvr/26.9.871

Morrison WR, Smith LM. Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride-methanol.J Lipid Res5: 600–608, 1964.

10.1016/j.jacc.2006.03.048

10.1161/CIRCULATIONAHA.107.732826

10.1161/CIRCULATIONAHA.105.556886

10.1111/j.1469-7793.2000.t01-1-00367.x

10.1016/j.amjcard.2005.11.025

10.1111/j.1527-5299.2007.07135.x

10.1113/jphysiol.2001.013015

10.1152/japplphysiol.00446.2006

Porges SW. Respiratory sinus arrhythmia: physiological basis, quantitative methods and clinical implications. In:Cardiac, Respiratory, and Cardiosomatic Psychophysiology.New York: Plenum, 1986, p. 101–115.

10.1161/01.CIR.102.22.2677

10.1161/CIRCULATIONAHA.107.704759

10.1001/jama.1995.03530170043030

Skou HA, Toft E, Christensen JH, Hansen JB, Dyerberg J, Schmidt EB. N-3 fatty acids and cardiac function after myocardial infarction in Denmark.Int J Circumpolar Health60: 360–365, 2001.

10.1152/ajpregu.90583.2008

10.1016/S0008-6363(03)00545-5

10.1016/j.cardiores.2005.05.018

10.1161/01.CIR.93.5.1043

10.1152/ajpheart.00778.2006

10.1016/j.cardiores.2006.02.022

10.1016/j.hrthm.2009.07.024

10.1016/j.cardiores.2006.08.019

10.1073/pnas.94.8.4182

10.1016/0002-8703(93)90524-D

10.1016/S0140-6736(07)60527-3

10.1080/07853890802698834

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American Journal of Physiology - Heart and Circulatory Physiology

Tập 298 Số 4

H1219-H1228

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