Mitochondrial protein synthesis is increased in oxidative skeletal muscles of rats with cardiac cachexia.

Since cardiac cachexia could be associated with alterations in muscular mitochondrial metabolism, we hypothesized that the expected alterations in the activities of mitochondrial oxidative enzymes could be associated with changes in mitochondrial protein synthesis in oxidative skeletal muscles. Cardiac cachexia was provoked in male rats by the ligation of the left coronary artery. Six cachectic and 6 control rats were age-paired, and their food intake was observed. The synthesis of mitochondrial proteins was measured by [1-13C]-valine infusion in soleus, tibilais, myocardium, and liver. Muscles (soleus, gastrocnemius, and tibialis anterior), heart, kidneys, liver, and visceral adipose tissue were weighed. Mitochondrial cytochrome c oxydase IV as well as citrate synthase and myosin ATPase activities were measured. As expected, decreased food intake was observed in the cachectic group. Heart, kidney, and liver weights were higher in the cachectic group, while the visceral adipose tissue weight was lower (P < .01). No changes in muscle weights were observed. Soleus mitochondrial proteins fractional synthesis rate was higher in the cachectic group (P = .054). Cytochrome c oxydase IV activity was reduced (P = .009) and increased (P = .038) in the soleus and liver of the cachectic rats, respectively. No change in citrate synthase activity was observed. Myosin ATPase activity was reduced in the gastrocnemius of the cachectic group (P < .01). Mitochondrial protein synthesis is increased in the soleus of rats with cardiac cachexia, suggesting a compensatory mechanism of the impaired oxidative mitochondrial function. Further work should assess whether the mitochondrial protein synthesis is altered in chronic heart failure patients with cardiac cachexia, and whether this is the cause or the consequence of cachexia.

Can erythropoietin improve skeletal myoblast engraftment in infarcted myocardium?

The benefits of skeletal myoblast transplantation are limited by the high rate of early cell death which is partly of ischemic origin. We, therefore, assessed whether graft survival could be improved by the additional use of the angiogenic cytokine erythropoietin (EPO). Thirty-five Lewis rats underwent coronary artery ligation and, two weeks later, were randomized to receive in-scar injections of control medium, skeletal myoblasts (5x10(6)) or skeletal myoblasts with EPO started the day before transplantation and continued for two weeks (500 U/kg three times a week). A fourth group was treated by EPO alone without injections. Function was assessed by 2D echocardiography before transplantation and one month thereafter. Compared with controls and hearts treated by EPO-alone, those transplanted with myoblasts yielded a significantly better recovery of LV ejection fraction, irrespective of whether they had received EPO or not. Neither the area of myoblast engraftment, nor angiogenesis differed between the myoblast-alone and the myoblast+EPO groups. Apoptosis was hardly detectable and, therefore, unaffected by EPO therapy. In this model, EPO failed to improve myoblast engraftment and postinfarction LV function. These negative findings justify to pursue the search for alternate cell survival-enhancing strategies.