Decreased [³H]ouabain binding sites in skeletal muscle of rats with chronic heart failure

Abstract

Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.

Na+-K+-ATPase properties in rat heart and skeletal muscle 3 mo after coronary artery ligation

“…Our findings of the effects of CHF on Na ϩ -K ϩ -ATPase content (␤ max ) are similar to what has been reported previously in the Sol muscles of rats with CHF (22,38,45). Interestingly, the absolute values we report for ␤ max in Sol in Con rats and rats with severe CHF are nearly identically to those previously published (38).…”

“…A unique feature of our study, which does not appear to have been properly addressed in previous studies examining skeletal muscle Na 45), it was expected that changes in the catalytic activity of the enzyme would parallel the changes in Na ϩ -K ϩ -ATPase content. However, we have found that only in the case of the LV was the association maintained in CHF.…”

“…Similar to the study by Helwig et al (22) and Musch et al (38), we report increases in the ratios of LV/body mass, RV/body mass, and lung/body mass of a similar magnitude. These ratios appear to offer a reasonable measure of the severity of CHF as assessed by more direct techniques, such as left ventricular end-diastolic pressure (LVEDP) and myocardial infarct size (13,38,45). In previous research involving experimental CHF in rats, the oxidative potential, as measured by CS, has been reported to decrease in Sol, RG, and WG in severe but not moderate stages of the disease (13).…”

Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

“…This may explain why a tissue distal from the heart is also affected. This is the case for skeletal muscle from rats subjected to MI in which ouabain sites were reduced even though their affinity was not different (36,39). Furthermore, our results demonstrate that the inotropic response to ouabain was Ca 2+ -dependent in the Sham group.…”

Membrane Excitability, Weakness, and Fatigue

“…To date only a few studies have examined muscle Na + -K + -ATPase changes with the disease. There is evidence that in experimental CHF in rats, Na + -K + -pump content (βmax), as measured with [ 3 H] ouabain binding, is decreased in muscles composed primarily of slow-oxidative and fast-oxidative glycolytic fibres, but not in muscles composed of fast-glycolytic fibres (Musch et al, 2002;Pickar et al, 1997). The reductions in βmax occurred in the absence of changes in the dissociation constant (K d ) (Musch et al, 2002;Pickar et al, 1997), suggesting that there is no change in Na + -K + -ATPase enzyme population type.…”