Myocyte response to β-adrenergic stimulation is preserved in the noninfarcted myocardium of globally dysfunctional rat hearts after myocardial infarction

Arun J.C. Prahash; Sudhir Gupta; Inder S. Anand

doi:10.1161/01.CIR.102.15.1840

Myocyte response to β-adrenergic stimulation is preserved in the noninfarcted myocardium of globally dysfunctional rat hearts after myocardial infarction

Arun J.C. Prahash, Sudhir Gupta, Inder S. Anand

Medicine - Veteran's Administration Medical Center

Research output: Contribution to journal › Article › peer-review

27 Scopus citations

Abstract

Background - Cellular mechanisms underlying the diminished inotropic response of remodeled hearts after myocardial infarction (MI) remain unclear. Methods and Results - Left ventricular (LV) remodeling and function were assessed by 2D echocardiography and isolated perfused heart studies in 6-week post-MI and sham-operated rats. LV myocytes from sham and noninfarcted MI hearts were used for morphometric and functional studies. β-Adrenergic receptor (β-AR) agonist isoproterenol (ISO)-induced contractile response was measured in isolated hearts. The effects of ISO and forskolin on contractile function and calcium transients of isolated myocytes were recorded. ISO-induced cAMP generation was compared in sham and MI myocytes. β-AR density was measured by radioligand binding. MI hearts were remodeled (LV diameter 8.5±0.3 versus 5.7±0.3 mm, P<0.001) and showed global (% fractional shortening 19.1±2.5 versus 55.3±2.2, P<0.01) and regional contractile dysfunction of noninfarcted myocardium (% systolic posterior wall thickening 37±4 versus 62±10, P<0.01). Isolated heart function (LV developed pressure 58±2 versus 72±3 mm Hg, P=0.004) and ISO concentration response were reduced in MI hearts. Myocytes from the noninfarcted LV were structurally remodeled (32% longer and 18% wider), but their contractile response and intracellular calcium kinetics to ISO and forskolin were not diminished. β-AR receptor density (B(max) 24±1.5 versus 22.4±1.6 fmol/mg protein) and β-AR agonist-stimulated cAMP were similar in both groups. Conclusions - Isolated myocytes from the remodeled and dysfunctional myocardium are structurally modified but contract normally under basal conditions and in response to β-AR stimulation. β-AR density is preserved in remodeled myocytes. Nonmyocyte factors may be more important in the genesis of contractile dysfunction in the remodeled rat heart up to 6 weeks after MI.

Original language	English (US)
Pages (from-to)	1840-1846
Number of pages	7
Journal	Circulation
Volume	102
Issue number	15
DOIs	https://doi.org/10.1161/01.CIR.102.15.1840
State	Published - Oct 10 2000

Keywords

Myocardial infarction
Myocytes
Receptors, adrenergic, beta

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@article{abbb09df0b6e4f4ca728195b4ef71b86,

title = "Myocyte response to β-adrenergic stimulation is preserved in the noninfarcted myocardium of globally dysfunctional rat hearts after myocardial infarction",

abstract = "Background - Cellular mechanisms underlying the diminished inotropic response of remodeled hearts after myocardial infarction (MI) remain unclear. Methods and Results - Left ventricular (LV) remodeling and function were assessed by 2D echocardiography and isolated perfused heart studies in 6-week post-MI and sham-operated rats. LV myocytes from sham and noninfarcted MI hearts were used for morphometric and functional studies. β-Adrenergic receptor (β-AR) agonist isoproterenol (ISO)-induced contractile response was measured in isolated hearts. The effects of ISO and forskolin on contractile function and calcium transients of isolated myocytes were recorded. ISO-induced cAMP generation was compared in sham and MI myocytes. β-AR density was measured by radioligand binding. MI hearts were remodeled (LV diameter 8.5±0.3 versus 5.7±0.3 mm, P<0.001) and showed global (% fractional shortening 19.1±2.5 versus 55.3±2.2, P<0.01) and regional contractile dysfunction of noninfarcted myocardium (% systolic posterior wall thickening 37±4 versus 62±10, P<0.01). Isolated heart function (LV developed pressure 58±2 versus 72±3 mm Hg, P=0.004) and ISO concentration response were reduced in MI hearts. Myocytes from the noninfarcted LV were structurally remodeled (32% longer and 18% wider), but their contractile response and intracellular calcium kinetics to ISO and forskolin were not diminished. β-AR receptor density (B(max) 24±1.5 versus 22.4±1.6 fmol/mg protein) and β-AR agonist-stimulated cAMP were similar in both groups. Conclusions - Isolated myocytes from the remodeled and dysfunctional myocardium are structurally modified but contract normally under basal conditions and in response to β-AR stimulation. β-AR density is preserved in remodeled myocytes. Nonmyocyte factors may be more important in the genesis of contractile dysfunction in the remodeled rat heart up to 6 weeks after MI.",

keywords = "Myocardial infarction, Myocytes, Receptors, adrenergic, beta",

author = "Prahash, {Arun J.C.} and Sudhir Gupta and Anand, {Inder S.}",

year = "2000",

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doi = "10.1161/01.CIR.102.15.1840",

language = "English (US)",

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pages = "1840--1846",

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TY - JOUR

T1 - Myocyte response to β-adrenergic stimulation is preserved in the noninfarcted myocardium of globally dysfunctional rat hearts after myocardial infarction

AU - Prahash, Arun J.C.

AU - Gupta, Sudhir

AU - Anand, Inder S.

PY - 2000/10/10

Y1 - 2000/10/10

N2 - Background - Cellular mechanisms underlying the diminished inotropic response of remodeled hearts after myocardial infarction (MI) remain unclear. Methods and Results - Left ventricular (LV) remodeling and function were assessed by 2D echocardiography and isolated perfused heart studies in 6-week post-MI and sham-operated rats. LV myocytes from sham and noninfarcted MI hearts were used for morphometric and functional studies. β-Adrenergic receptor (β-AR) agonist isoproterenol (ISO)-induced contractile response was measured in isolated hearts. The effects of ISO and forskolin on contractile function and calcium transients of isolated myocytes were recorded. ISO-induced cAMP generation was compared in sham and MI myocytes. β-AR density was measured by radioligand binding. MI hearts were remodeled (LV diameter 8.5±0.3 versus 5.7±0.3 mm, P<0.001) and showed global (% fractional shortening 19.1±2.5 versus 55.3±2.2, P<0.01) and regional contractile dysfunction of noninfarcted myocardium (% systolic posterior wall thickening 37±4 versus 62±10, P<0.01). Isolated heart function (LV developed pressure 58±2 versus 72±3 mm Hg, P=0.004) and ISO concentration response were reduced in MI hearts. Myocytes from the noninfarcted LV were structurally remodeled (32% longer and 18% wider), but their contractile response and intracellular calcium kinetics to ISO and forskolin were not diminished. β-AR receptor density (B(max) 24±1.5 versus 22.4±1.6 fmol/mg protein) and β-AR agonist-stimulated cAMP were similar in both groups. Conclusions - Isolated myocytes from the remodeled and dysfunctional myocardium are structurally modified but contract normally under basal conditions and in response to β-AR stimulation. β-AR density is preserved in remodeled myocytes. Nonmyocyte factors may be more important in the genesis of contractile dysfunction in the remodeled rat heart up to 6 weeks after MI.

AB - Background - Cellular mechanisms underlying the diminished inotropic response of remodeled hearts after myocardial infarction (MI) remain unclear. Methods and Results - Left ventricular (LV) remodeling and function were assessed by 2D echocardiography and isolated perfused heart studies in 6-week post-MI and sham-operated rats. LV myocytes from sham and noninfarcted MI hearts were used for morphometric and functional studies. β-Adrenergic receptor (β-AR) agonist isoproterenol (ISO)-induced contractile response was measured in isolated hearts. The effects of ISO and forskolin on contractile function and calcium transients of isolated myocytes were recorded. ISO-induced cAMP generation was compared in sham and MI myocytes. β-AR density was measured by radioligand binding. MI hearts were remodeled (LV diameter 8.5±0.3 versus 5.7±0.3 mm, P<0.001) and showed global (% fractional shortening 19.1±2.5 versus 55.3±2.2, P<0.01) and regional contractile dysfunction of noninfarcted myocardium (% systolic posterior wall thickening 37±4 versus 62±10, P<0.01). Isolated heart function (LV developed pressure 58±2 versus 72±3 mm Hg, P=0.004) and ISO concentration response were reduced in MI hearts. Myocytes from the noninfarcted LV were structurally remodeled (32% longer and 18% wider), but their contractile response and intracellular calcium kinetics to ISO and forskolin were not diminished. β-AR receptor density (B(max) 24±1.5 versus 22.4±1.6 fmol/mg protein) and β-AR agonist-stimulated cAMP were similar in both groups. Conclusions - Isolated myocytes from the remodeled and dysfunctional myocardium are structurally modified but contract normally under basal conditions and in response to β-AR stimulation. β-AR density is preserved in remodeled myocytes. Nonmyocyte factors may be more important in the genesis of contractile dysfunction in the remodeled rat heart up to 6 weeks after MI.

KW - Myocardial infarction

KW - Myocytes

KW - Receptors, adrenergic, beta

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C2 - 11023941

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SN - 0009-7322

VL - 102

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JO - Circulation

JF - Circulation

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ER -

Myocyte response to β-adrenergic stimulation is preserved in the noninfarcted myocardium of globally dysfunctional rat hearts after myocardial infarction

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