TY - JOUR
T1 - Myocyte contractile function is intact in the post-infarct remodeled rat heart despite molecular alterations
AU - Gupta, Sudhir
AU - Prahash, Arun J.C.
AU - Anand, Inder S.
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 2000/10
Y1 - 2000/10
N2 - Objective: To investigate the cellular mechanisms underlying global and regional LV dysfunction in the post-infarct (MI) remodeled rat hearts. Methods: LV remodeling and function were quantified by echocardiography, morphometry, in vivo hemodynamics, and isolated perfused heart studies in 6 weeks post-MI and sham-operated rats. LV myocytes from sham and MI hearts were used for morphometric and functional studies. Myocyte contractile function and intracellular calcium kinetics were measured at different stimulation frequencies (0.2-2 Hz), temperatures (30 and 37°C), and external viscous load (1, 15, 200 and 300 centipoise). Myocyte apoptosis was measured by DNA laddering; BCL-2, BAX, Na+ -Ca2+ exchanger, and SERCA-2 proteins by western blot; and brain natriuretic peptide (BNP), SERCA-2 mRNA by RT-PCR. Results: MI hearts were remodeled (Echo LV diameter 7.3 ± 0.38 vs. 5.9 ± 0.16 mm, P < 0.03), and showed global (Echo % fractional shortening 30 ± 2.4 vs. 58 ± 3, P < 0.001), and regional contractile dysfunction of non- infarcted myocardium (Echo % systolic posterior wall thickening 36 ± 2 vs. 57 ± 1.7, P < 0.001). In vivo hemodynamic and isolated heart function studies confirmed depressed LV systolic and diastolic function and increased volumes. Whereas, myocytes isolated from infarcted hearts were remodeled (40% longer and 10% wider), their contractile function and calcium kinetics under basal conditions and at high stimulation frequency, temperature and viscous load were similar to sham myocytes. The mRNA for BNP was increased whereas that for SERCA-2 decreased, but the SERCA-2 protein was normal. Despite myocyte hypertrophy, ventricular septal thickness was reduced in infarcted hearts (2.2 ± 0.1 vs. 2.6 ± 0.07 mm, P < 0.01), and showed increased apoptosis. Conclusions: Myocytes from remote non-infarcted myocardium of the remodeled hearts have normal contractile function, despite structural remodeling and altered gene expression. Non-myocyte factors may be more important in genesis of contractile dysfunction in the remodeled heart, for up to 6 weeks after MI. (C) 2000 Elsevier Science B.V.
AB - Objective: To investigate the cellular mechanisms underlying global and regional LV dysfunction in the post-infarct (MI) remodeled rat hearts. Methods: LV remodeling and function were quantified by echocardiography, morphometry, in vivo hemodynamics, and isolated perfused heart studies in 6 weeks post-MI and sham-operated rats. LV myocytes from sham and MI hearts were used for morphometric and functional studies. Myocyte contractile function and intracellular calcium kinetics were measured at different stimulation frequencies (0.2-2 Hz), temperatures (30 and 37°C), and external viscous load (1, 15, 200 and 300 centipoise). Myocyte apoptosis was measured by DNA laddering; BCL-2, BAX, Na+ -Ca2+ exchanger, and SERCA-2 proteins by western blot; and brain natriuretic peptide (BNP), SERCA-2 mRNA by RT-PCR. Results: MI hearts were remodeled (Echo LV diameter 7.3 ± 0.38 vs. 5.9 ± 0.16 mm, P < 0.03), and showed global (Echo % fractional shortening 30 ± 2.4 vs. 58 ± 3, P < 0.001), and regional contractile dysfunction of non- infarcted myocardium (Echo % systolic posterior wall thickening 36 ± 2 vs. 57 ± 1.7, P < 0.001). In vivo hemodynamic and isolated heart function studies confirmed depressed LV systolic and diastolic function and increased volumes. Whereas, myocytes isolated from infarcted hearts were remodeled (40% longer and 10% wider), their contractile function and calcium kinetics under basal conditions and at high stimulation frequency, temperature and viscous load were similar to sham myocytes. The mRNA for BNP was increased whereas that for SERCA-2 decreased, but the SERCA-2 protein was normal. Despite myocyte hypertrophy, ventricular septal thickness was reduced in infarcted hearts (2.2 ± 0.1 vs. 2.6 ± 0.07 mm, P < 0.01), and showed increased apoptosis. Conclusions: Myocytes from remote non-infarcted myocardium of the remodeled hearts have normal contractile function, despite structural remodeling and altered gene expression. Non-myocyte factors may be more important in genesis of contractile dysfunction in the remodeled heart, for up to 6 weeks after MI. (C) 2000 Elsevier Science B.V.
KW - Calcium (cellular)
KW - Contractile function
KW - Gene expression
KW - Heart failure
KW - Hypertrophy
KW - Infarction
KW - Myocytes
KW - Remodeling
KW - Ventricular function
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U2 - 10.1016/S0008-6363(00)00160-7
DO - 10.1016/S0008-6363(00)00160-7
M3 - Article
C2 - 11033110
AN - SCOPUS:0033772623
SN - 0008-6363
VL - 48
SP - 77
EP - 88
JO - Cardiovascular Research
JF - Cardiovascular Research
IS - 1
ER -