Objective-To determine whether heart failure in rats is associated with altered expression of the skeletal muscle sarcoplasmic reticulum Ca 2+ -ATPase (SERCA). Methods-SERCA protein and mRNA were examined in the soleus muscles of eight female rats with heart failure induced by coronary artery ligation, six weeks after the procedure (mean (SEM) left ventricular end diastolic pressure 20.4 (2.2) mm Hg) and in six sham operated controls by western and northern analyses, respectively. Results-SERCA-2a isoform protein was reduced by 16% (112 000 (4000) v 134 000 (2000) arbitrary units, p < 0.001), and SERCA-2a messenger RNA was reduced by 59% (0.24 (0.06) v 0.58 (0.02) arbitrary units, p < 0.001). Although rats with heart failure had smaller muscles (0.54 mg/g v 0.66 mg/g body weight), no diVerence in locomotor activity was observed. Conclusions-These results may explain the previously documented abnormalities in calcium handling in skeletal muscle from animals with the same model of congestive heart failure, and could be responsible for the accelerated muscle fatigue characteristic of patients with heart failure. (Heart 1999;81:303-307) Keywords: skeletal muscle; gene expression; heart failure; calcium-ATPase Exercise intolerance is a common complaint in patients with congestive heart failure and is often their major limiting symptom. Although impaired cardiac output and peripheral blood flow may be partially responsible for this physiological limitation, many studies have identified abnormalities of skeletal muscle and these may also play an important role.1-4 These include atrophy, 5 6 altered fibre type composition, [7][8][9] and impaired oxidative metabolism. 3 7-12These observed abnormalities are not, however, likely to fully explain the pattern of muscle fatigue in patients, which is striking in its rapidity and severity and appears to reflect impaired excitation-contraction coupling. 9 13-15 In this regard, Perreault et al found that in rats with heart failure induced by coronary artery ligation, skeletal muscle fibres showed accelerated fatigue during electrical stimulation, associated with abnormal calcium transients characterised by a reduced amplitude and delayed rise and decline. 16 As reviewed by Arai et al, 17 similar abnormalities in calcium handling have been observed in cardiac muscle and have been associated with reduced expression of the sarcoplasmic reticulum Ca 2+ -ATPase (SERCA), which is responsible for calcium reuptake following contraction but also indirectly determines the amount of calcium availability for force development in both cardiac and skeletal muscle. Since we have recently observed that there are alterations in contractile protein and oxidative enzyme expression in skeletal muscle in rats with heart failure, 18 we hypothesised that SERCA expression might also be downregulated, thus providing a possible mechanism for the changes in muscle function. This study was therefore undertaken to determine whether heart failure in rats is associated with altered expression of ...
Enteroviruses have been considered to be a possible cause of idiopathic dilated cardiomyopathy. We used a polymerase chain reaction methodology for the identification of enteroviral RNA in an attempt to provide evidence of a role for enteroviruses in the pathogenesis of idiopathic dilated cardiomyopathy. The methodology was shown to identify a wide variety ofenteroviruses with a sensitivity up to 0.1-1 plaque-forming units/ gram of tissue. 5 of 11 cases (45%) of idiopathic dilated cardiomyopathy, as well as 9 of 24 cases (38%) of a wide variety of other cardiac conditions (including normal heart), were positive for enteroviral nucleic acid sequences; all eight control cases of breast carcinoma tested were negative. These results suggest that both the normal and abnormal heart may represent a site of latent or low-grade persistent enteroviral infection, and that the mere presence of enteroviral nucleic acid sequences is not specifically associated with idiopathic dilated cardiomyopathy. (J. Clin. Invest. 1992. 90:156-159.)
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