(Circulation. 1999;99:127-134.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Treatment With Growth Hormone Enhances Contractile Reserve and Intracellular Calcium Transients in Myocytes From Rats With Postinfarction Heart Failure
From the Charles A. Dana Research Institute, the Harvard-Thorndike Laboratory, and the Department of Medicine (Cardiovascular Division), Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Mass (M.T., E.O.W., J.B., B.H.L.), and the Department of Cardiovascular Research, Genentech, Inc (H.J., R.Y., N.F.P.), South San Francisco, Calif.
Correspondence to Beverly H. Lorell, MD, Cardiovascular Division, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215. E-mail blorell{at}bidmc.harvard.edu
Background—Recombinant human growth hormone (GH) improves in vivo cardiac function in rats with postinfarction heart failure (MI). We examined the effects of growth hormone (14 days of 3.5 mg · kg-1 · d-1 begun 4 weeks after MI) on contractile reserve in left ventricular myocytes from rats with chronic postinfarction heart failure.
Methods and Results—Cell shortening and [Ca2+]i were measured with the indicator fluo 3 in myocytes from MI, MI+GH, control, and normal animals treated with GH (C+GH) under stimulation at 0.5 Hz at 37°C. Cell length was similar in MI and MI+GH rats (150±5 and 157±5 µm) and was greater in these groups than in the control and C+GH groups (140±4 and 139±4 µm, P<0.05). At baseline perfusate calcium of 1.2 mmol/L, myocyte fractional shortening and [Ca2+]i transients were similar among the 4 groups. We then assessed contractile reserve by measuring the increase in myocyte fractional shortening in the presence of high-perfusate calcium of 3.5 mmol/L. In the control and C+GH groups, myocyte fractional shortening and peak systolic [Ca2+]i were similarly increased in the presence of high-perfusate calcium. In the presence of high-perfusate calcium, both myocyte fractional shortening and peak systolic [Ca2+]i were depressed in the MI compared with the control groups. In contrast, myocyte fractional shortening (14.1±.9% versus 11.1±.9%, P<0.05) and peak systolic [Ca2+]i (647±43 versus 509±37 nmol/L, P<0.05) were significantly higher in MI+GH than in MI rats and were comparable to controls. Left ventricular myocyte expression of sarcoplasmic reticulum Ca2+ ATPase 2 (SERCA-2) and left ventricular SERCA-2 protein levels were increased in MI+GH compared with MI rats.
Conclusions—Calcium-dependent contractile reserve is depressed in myocytes from rats with postinfarction heart failure. Long-term growth hormone therapy increases contractile reserve by restoring normal augmentation of systolic [Ca2+]i in myocytes from rats with postinfarction heart failure.
Key Words: growth hormone • myocardial infarction • myocytes • calcium • heart failure
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