Oral administration of amino acidic supplements improves protein and energy profiles in skeletal muscle of aged rats: elongation of functional performance and acceleration of mitochondrial recovery in adenosine triphosphate after exhaustive exertion.

Sarcopenia is an inevitable age-related degenerative process chiefly characterized by decreased synthesis of muscle proteins and impaired mitochondrial function, leading to progressive loss of muscle mass. Here, we sought to probe whether long-term administration of oral amino acids (AAs) can increase protein and adenosine triphosphate (ATP) content in the gastrocnemius muscle of aged rats, enhancing functional performance. To this end, 6- and 24-month-old male Fisher 344 rats were divided into 3 groups: group A (6-month-old rats) and group B (24-month-old rats) were used as adult and senescent control group, respectively, while group C (24-month-old rats) was used as senescent treated group and underwent 1-month oral treatment with a mixture of mainly essential AAs. Untreated senescent animals exhibited a 30% reduction in total and fractional protein content, as well as a 50% reduction in ATP content and production, compared with adult control rats (p <0.001). Long-term supplementation with mixed AAs significantly improved protein and high-energy phosphate content, as well as the rate of mitochondrial ATP production, conforming their values to those of adult control animals (p <0.001). The improved availability of protein and high-energy substrates in the gastrocnemius muscle of treated aged rats paralleled a significant enhancement in functional performance assessed by swim test, with dramatic elongation of maximal exertion times compared with untreated senescent rats (p <0.001). In line with these findings, we observed that, after 6 hours of rest following exhaustive swimming, the recovery in mitochondrial ATP content was approximately 70% in adult control rats, approximately 60% in senescent control rats, and normalized in treated rats as compared with animals of the same age unexposed to maximal exertion (p <0.001). In conclusion, nutritional supplementation with oral AAs improved protein and energy profiles in the gastrocnemius of treated rats, enhancing functional performance and accelerating high-energy phosphate recovery after exhaustive exertion.

Amino acid supplementation differentially modulates STAT1 and STAT3 activation in the myocardium exposed to ischemia/reperfusion injury.

We have previously demonstrated that the transcription factor STAT1 plays a critical role in promoting apoptotic cell death, whereas the related STAT3 family member may antagonize STAT1 and protect cardiac myocytes from ischemia/reperfusion (I/R) injury. More recently we demonstrated that long-term nutritional supplementation with mixed amino acids (AAs) can enhance myocyte survival by preserving mitochondrial functional capacity during I/R injury. We therefore investigated whether short-term nutritional supplementation with the same AA mixture has any effects on STAT1 or STAT3 activation in the Langendorff perfused rat heart exposed to I/R injury. In Sprague-Dawley rats given a single oral dose of a mixture of mainly essential l-AA (1 g/kg), and exposed, after 6 hours, to 35 minutes of ischemia, followed by 120 minutes of reperfusion, AA supplementation prolonged STAT3 activation/phosphorylation, while STAT1 activation was reduced. Enhanced STAT3 phosphorylation paralleled a reduction in expression of Fas, a known STAT1 target gene and proapoptotic marker that is upregulated after I/R. Moreover, abrogation of STAT3 activation by means of the JAK inhibitor AG490, reduced, but did not abolish, the cardioprotective effects of AA supplementation after I/R. These results show that modulation of the functional balance between STAT3 and STAT1, with preferential activation of prosurvival STAT3 over the proapoptotic STAT1, represents a mechanism by means of which short-term oral supplementation with mixed AAs protects the heart from I/R injury.

Peripartum cardiomyopathy: a comprehensive review.

Peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular dysfunction and symptoms of heart failure occur in the peripartum period in previously healthy women. Incidence of PPCM ranges from 1 in 1300 to 1 in 15,000 pregnancies. The etiology of PPCM is unknown, but viral, autoimmune, and idiopathic causes may contribute. The diagnostic criteria are onset of heart failure in the last month of pregnancy or in first 5 months postpartum, absence of determinable cause for cardiac failure, and absence of a demonstrable heart disease before the last month of pregnancy. Risk factors for PPCM include advanced maternal age, multiparity, African race, twinning, gestational hypertension, and long-term tocolysis. The clinical presentation of patients with PPCM is similar to that of patients with dilated cardiomyopathy. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Treatment is similar to medical therapy for other forms of dilated cardiomyopathy. About half the patients of PPCM recover without complications. The prognosis is poor in patients with persistent cardiomyopathy. Persistence of disease after 6 months indicates irreversible cardiomyopathy and portends worse survival.