Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine.
Cardiac hypertrophy in response to hypertension or myocardial infarction is a pathological indicator associated with heart failure (HF). A central component of the remodeling process is the loss of cardiomyocytes via cell death pathways regulated by the mitochondrion. Recent evidence has indicated that exercise training can attenuate or reverse pathological remodeling, creating a physiological phenotype. The purpose of this study was to examine left ventricular (LV) function, remodeling, and cardiomyocyte mitochondrial function in aortic-banded (AB) sedentary (HFSED; n = 6), AB exercise-trained (HFTR, n = 5), and control sedentary (n = 5) male Yucatan miniature swine. LV hypertrophy was present in both AB groups before the start of training, as indicated by increases in LV end-diastolic volume, LV end-systolic volume (LVESV), and LV end-systolic dimension (LVESD). Exercise training (15 wk) prevented further increases in LVESV and LVESD (P < 0.05). The heart weight-to-body weight ratio, LV + septum-to-body weight ratio, LV + septum-to-right ventricle ratio, and cardiomyocyte cross-sectional area were increased in both AB groups postmortem regardless of training status. Preservation of LV function after exercise training, as indicated by the maintenance of fractional shortening, ejection fraction, and mean wall shortening and increased stroke volume, was associated with an attenuation of the increased LV fibrosis (23%) and collagen (36%) observed in HFSED animals. LV mitochondrial dysfunction, as measured by Ca(2+)-induced mitochondrial permeability transition, was increased in HFSED (P < 0.05) but not HFTR animals. In conclusion, low-intensity interval exercise training preserved LV function as exemplified by an attenuation of fibrosis, maintenance of a positive inotropic state, and inhibition of mitochondrial dysfunction, providing further evidence of the therapeutic potential of exercise in a clinical setting.
Emter
Craig A
CA
Dept. of Biomedical Science, Univ. of Missouri, 1600 E. Rollins, E117 Veterinary Medicine, Columbia, MO 65211, USA. emterc@missouri.edu
Baines
Christopher P
CP
D000818:Animals; D001013:Aorta, Thoracic; D016923:Cell Death / Q000502:physiology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling / Q000502:physiology*
J Physiol. 2009 Aug 1;587(Pt 15):3899-910
19505981
J Clin Invest. 2005 Mar;115(3):565-71
15765138
Eur J Clin Invest. 1999 May;29(5):380-6
10354194
Am J Physiol. 1997 Jul;273(1 Pt 2):H487-93
9249522
Hypertension. 2009 Apr;53(4):701-7
19255362
Cardiovasc Res. 2009 Feb 15;81(3):465-73
18779231
Cardiovasc Res. 2003 Dec 1;60(3):617-25
14659807
Nature. 2005 Mar 31;434(7033):652-8
15800626
JAMA. 2000 Jun 21;283(23):3095-101
10865304
Circ Heart Fail. 2009 Sep;2(5):437-45
19808374
Circulation. 2007 Jun 19;115(24):3086-94
17548726
Physiol Rev. 2007 Jan;87(1):99-163
17237344
Cardiovasc Res. 2004 Feb 15;61(3):372-85
14962470
Hypertension. 2007 Aug;50(2):410-6
17592073
Cardiovasc Res. 2005 Jul 1;67(1):21-9
15896727
Am J Physiol Heart Circ Physiol. 2000 Dec;279(6):H2994-3002
11087257
J Biol Chem. 2001 Jan 26;276(4):2571-5
11073947
Circulation. 2009 Aug 18;120(7):577-84
19652094
Hypertension. 2008 Apr;51(4):1096-102
18259016
N Engl J Med. 1997 Apr 17;336(16):1131-41
9099657
Circulation. 1979 Dec;60(6):1308-16
498456
Circulation. 2003 Feb 25;107(7):984-91
12600911
FASEB J. 2006 Apr;20(6):791-3
16459353
J Biol Chem. 2002 Sep 20;277(38):34793-9
12095984
Circ Res. 2006 Mar 3;98(4):540-8
16439687
Physiology (Bethesda). 2007 Feb;22:56-64
17289931
Nature. 2005 Mar 31;434(7033):658-62
15800627
Am J Cardiol. 1976 Jan;37(1):7-11
1244736
J Clin Invest. 2007 Sep;117(9):2431-44
17694179
J Appl Physiol (1985). 2005 Jul;99(1):204-9
15774698
FASEB J. 2008 Aug;22(8):2862-71
18417547
Am J Physiol Heart Circ Physiol. 2008 Feb;294(2):H928-35
18083894
J Appl Physiol (1985). 1989 Sep;67(3):1140-9
2551878
Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2030-8
15994855
Cardiovasc Res. 2008 Jan 15;77(2):334-43
18006487
Apoptosis. 2009 Apr;14(4):536-48
19142731
N Engl J Med. 1996 Oct 17;335(16):1182-9
8815940
Hypertension. 2000 Nov;36(5):755-9
11082139
Annu Rev Physiol. 2010;72:61-80
20148667
Circulation. 1972 Mar;45(3):602-11
4258936
Am J Physiol Regul Integr Comp Physiol. 2004 Aug;287(2):R247-9
15789454
Circulation. 1978 Dec;58(6):1072-83
709763
J Clin Invest. 2003 May;111(10):1497-504
12750399
Cardiol Clin. 1998 Nov;16(4):691-710, ix
9891598
Am J Physiol Heart Circ Physiol. 2007 Aug;293(2):H903-4
17513492
Circ Res. 1999 Oct 29;85(9):856-66
10532954
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1322-3
17630343
Hypertension. 2009 Apr;53(4):708-14
19221208
Circulation. 2003 Aug 5;108(5):554-9
12860904
J Mol Cell Cardiol. 2009 Mar;46(3):420-30
19094991
Histochem J. 1979 Jul;11(4):447-55
91593
FASEB J. 2004 Jul;18(10):1150-2
15132982