Isolated myocytes from remodeled rat myocardium 6 weeks post-MI showed preserved beta-adrenergic receptor density compared to sham (24 vs 22.4 fmol/mg protein) and normal contractile response.
Absolute Event Rate: 19.1% vs 55.3%
p-value: p=<0.01
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.
Prahash et al. (2000) studied Myocardial Infarction. Myocardial Infarction (experimental model) vs. Sham operation was evaluated on Global fractional shortening (%) (p=<0.01). Isolated myocytes from remodeled rat myocardium 6 weeks post-MI showed preserved beta-adrenergic receptor density compared to sham (24 vs 22.4 fmol/mg protein) and normal contractile response.
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