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(Circulation. 2000;102:1840.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Myocyte Response to ß-Adrenergic Stimulation Is Preserved in the Noninfarcted Myocardium of Globally Dysfunctional Rat Hearts After Myocardial Infarction

Presented in part at the 47th Annual Scientific Sessions of the American College of Cardiology, Atlanta, Ga, March 29 to April 1, 1998, and 71st Scientific Sessions of the American Heart Association, Dallas, Tex, November 8 to 11, 1998.

Arun J. C. Prahash, MD; Sudhir Gupta, PhD; Inder S. Anand, MD, DPhil, (Oxon)

From the Department of Medicine and Division of Cardiology, University of Minnesota and VA Medical Center, Minneapolis, Minn.

Correspondence to Inder S. Anand, MD, DPhil (Oxon), VA Medical Center 111-C, Minneapolis MN 55417. E-mail anand001{at}tc.umn.edu

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. ß-Adrenergic receptor (ß-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. ß-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. ß-AR receptor density (B_max 24±1.5 versus 22.4±1.6 fmol/mg protein) and ß-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 ß-AR stimulation. ß-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.

Key Words: myocardial infarction • myocytes • receptors, adrenergic, beta

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