Treatment with growth hormone enhances contractile reserve and intracellular calcium transients in myocytes from rats with postinfarction heart failure

Article

关键词: CONVERTING ENZYME-INHIBITION;    LARGE MYOCARDIAL-INFARCTION;    FACTOR-I;    DEFICIENT ADULTS;    CARDIAC-HYPERTROPHY;    NITRIC-OXIDE;    STIMULATION;    MUSCLE;    SYSTEM;    HYPERSECRETION;   

DOI  :  10.1161/01.CIR.99.1.127

来源: SCIE

【 摘 要 】

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 flue 3 in myocytes from MI, MI+GH, control, and normal animals treated with GH (C+GH) under stimulation at 0.5 Hz at 37 degrees C. Cell length was similar in MI and MI+GH rats (150+/-5 and 157+/-5 mu m) and was greater in these groups than in the control and C+GH groups (140+/-4 and 139+/-4 mu m, 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.

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