Grossman J D, Bishop A, Travers K E, Perreault C, Woolf J, Hampton T, Rasgado-Flores H, Gonzalez-Serratos H, Morgan J P
Cardiovascular Division, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
J Card Fail. 1996 Dec;2(4 Suppl):S105-11. doi: 10.1016/s1071-9164(96)80065-0.
Deficient myocardial cyclic AMP concentrations contribute to abnormal Ca2+ handling and systolic and diastolic dysfunction in chronic heart failure (CHF). We tested the hypothesis that decreased cyclic AMP in skeletal muscle of animals with failure may contribute to the weakness and easy fatiguability also common in patients with CHF. We compared intracellular Ca2+ signaling and contractility in skeletal muscle preparations from rats 6 weeks after myocardial infarction-induced CHF versus sham-operated controls. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control and CHF rats. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches. Treatment with 2mM dibutyryl cyclic AMP returned tension and Ca2+ towards normal levels. There was no evidence of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling that could be reversed with cyclic AMP supplementation as previously reported for the heart. This suggests that deficient cyclic AMP levels may contribute to both cardiac and skeletal muscle dysfunction in CHF.
心肌环磷酸腺苷（cAMP）浓度不足会导致慢性心力衰竭（CHF）时异常的Ca2+处理以及收缩和舒张功能障碍。我们检验了这样一个假设：心力衰竭动物骨骼肌中环磷酸腺苷减少可能导致CHF患者也常见的虚弱和易疲劳。我们比较了心肌梗死诱导的CHF大鼠与假手术对照组大鼠6周后骨骼肌标本中的细胞内Ca2+信号传导和收缩性。从对照大鼠和CHF大鼠的趾长伸肌（EDL）中解剖出100至200个细胞的束。与对照肌肉相比，CHF大鼠的肌肉在抽搐时张力发展受到抑制。用2mM二丁酰环磷酸腺苷处理可使张力和Ca2+恢复到正常水平。没有证据表明CHF大鼠存在细胞萎缩。总之，CHF大鼠的EDL骨骼肌在兴奋-收缩偶联方面存在内在异常，如先前在心脏中报道的那样，补充环磷酸腺苷可使其逆转。这表明环磷酸腺苷水平不足可能导致CHF时心脏和骨骼肌功能障碍。
