A J Prahash1, S Gupta, I S Anand. 1. Department of Medicine and Division of Cardiology, University of Minnesota and VA Medical Center, Minneapolis, MN 55417, USA.
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. Beta-adrenergic receptor (beta-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. beta-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. beta-AR receptor density (B(max) 24+/-1.5 versus 22.4+/-1.6 fmol/mg protein) and beta-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 beta-AR stimulation. beta-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.
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. Beta-adrenergic receptor (beta-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. beta-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. beta-AR receptor density (B(max) 24+/-1.5 versus 22.4+/-1.6 fmol/mg protein) and beta-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 beta-AR stimulation. beta-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.
Authors: Rômulo D Novaes; Arlete R Penitente; Reggiani V Gonçalves; André Talvani; Clóvis A Neves; Izabel R S C Maldonado; Antônio J Natali Journal: Int J Exp Pathol Date: 2011-07-08 Impact factor: 1.925
Authors: Yanan Liu; Shelley L Baumgardt; Juan Fang; Yang Shi; Shigang Qiao; Zeljko J Bosnjak; Jeannette Vásquez-Vivar; Zhengyuan Xia; David C Warltier; Judy R Kersten; Zhi-Dong Ge Journal: Sci Rep Date: 2017-06-08 Impact factor: 4.379