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 ⅐ kg Ϫ1 ⅐ d Ϫ1 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 [Ca 2ϩ ] i were measured with the indicator fluo 3 in myocytes from MI, MIϩGH, control, and normal animals treated with GH

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... (CϩGH) under stimulation at 0.5 Hz at 37°C. Cell length was similar in MI and MIϩGH rats (150Ϯ5 and 157Ϯ5 m) and was greater in these groups than in the control and CϩGH groups (140Ϯ4 and 139Ϯ4 m, PϽ0.05). At baseline perfusate calcium of 1.2 mmol/L, myocyte fractional shortening and [Ca 2ϩ ] 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 CϩGH groups, myocyte fractional shortening and peak systolic [Ca 2ϩ ] 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 [Ca 2ϩ ] i were depressed in the MI compared with the control groups. In contrast, myocyte fractional shortening (14.1Ϯ.9% versus 11.1Ϯ.9%, PϽ0.05) and peak systolic [Ca 2ϩ ] i (647Ϯ43 versus 509Ϯ37 nmol/L, PϽ0 .05) were significantly higher in MIϩGH than in MI rats and were comparable to controls. Left ventricular myocyte expression of sarcoplasmic reticulum Ca 2ϩ ATPase 2 (SERCA-2) and left ventricular SERCA-2 protein levels were increased in MIϩGH 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 [Ca 2ϩ ] i in myocytes from rats with postinfarction heart failure. (Circulation. 1999;99:127-134.)