Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO 3 −), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22–79 year of age and weighing 52.1–114.9 kg were studied using a randomized, double‐blind, placebo‐controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO 3 −. Plasma NO 3 − and nitrite (NO 2 −) were measured as indicators of NO bioavailability and maximal knee extensor speed (V max), power (P max), and fatigability were determined via isokinetic dynamometry. On average, dietary NO 3 − increased (P < 0.05) P max by 4.4 ± 8.1%. Individual changes, however, ranged from −9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO 3 − dose per kg), body mass index (surrogate for body composition) or placebo trial V max or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO 2 − concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO 3 −‐induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO 2 − and possibly female sex.

ObjectiveTo determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF).MethodsA primary cohort (N=12) with HFpEF and obesity underwent echocardiography, magnetic resonance spectroscopy before, and 3- and 6-mos after bariatric surgery. Plasma lipidomics were performed on pre- and 3-mo post-surgery in the primary cohort and confirmed in a validation cohort (N=22).ResultsAfter surgery-induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, < 0.001, = 0.007); echo-derived e′ increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate.ConclusionsSurgery-induced weight loss in women with HFpEF and obesity is associated with improved symptoms, reverse cardiac remodeling and improved relaxation. While weight loss associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. Our study results suggest that gastric bypass ameliorates obesity-related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.

Acute dietary NO intake increases VOpeak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO also improves muscle contractile function, suggest that dietary NO supplementation may be a valuable means of enhancing exercise capacity in this population.

AM, Chan TO. Myocardial injury after ischemia-reperfusion in mice deficient in Akt2 is associated with increased cardiac macrophage density. Am J Physiol Heart Circ Physiol 301: H1932-H1940, 2011. First published September 2, 2011; doi:10.1152/ajpheart.00755.2010.-Akt2 protein kinase has been shown to promote cell migration and actin polymerization in several cell types, including macrophages. Because migrating macrophages constitute an important inflammatory response after myocardial ischemia, we determined cardiac macrophage expression after ischemia-reperfusion (I/R) injury and cryo-injury in mice lacking Akt2 (Akt2-KO). At 7 days post-I/R, Akt2-KO cardiac tissues showed an increase in immunohistochemical staining for macrophage markers (Galectin 3 and F4/80) compared with wild-type (WT) mice, indicating macrophage density was increased in the injured Akt2-KO myocardium. This change was time dependent because macrophage density was similar between WT and Akt2-KO myocardium at 3 days post-I/R, but by 7 and 14 days post-I/R, macrophage density was significantly increased in Akt2-KO myocardium. Concomitantly, infarct size was larger and cardiac function was reduced in Akt2-KO mice subjected to I/R. However, when cryo-infarction produced similar infarct sizes in the anterior wall in both WT and Akt2-KO mice, macrophage density remained higher in Akt2-KO mouse myocardium, suggesting Akt2 regulates myocardial macrophage density independent of infarct size. Consistently, bone marrow from Akt2-KO mice enhanced myocardial macrophage density in both C57/B6 WT and Akt2-KO recipient mice. Finally, reciprocal ex-vivo coculturing of macrophages and cardiac myocytes showed that activated Akt2-KO peritoneal macrophages had reduced mobility and adhesion when compared with WT littermate controls. Thus, although Akt-2 KO mice did not affect the initial inflammation response after injury and Akt2 deficiency has been shown to impair cell migration or motility in macrophages, our data suggested a novel mechanism in which increasing retention of Akt2-KO macrophages resulted in increasing cardiac Akt2-KO macrophage density in the myocardial space.heart; protein kinase B; cryo-infarction; inflammation; peritoneal macrophages AKT SERINE-THREONINE kinase, also known as protein kinase B, is composed of a family of three highly homologous members: Akt1, Akt2, and Akt3. The three Akt isotypes share over 85% homology with similar catalytic characteristics and can block cell apoptosis and enhance cell growth and metabolism (37). Interestingly, Akt1 and Akt2 functions diverge at cell migration. Activated Akt1 inhibits cell migration by inhibiting nuclear factor of activated T-cells, ERK, and tuberous sclerosis protein 2 signals (5). On the other hand, activated Akt2 promotes cell migration through ␤ 1 integrin in breast cancer cells (21) or through phosphorylation of girdin or cofilin in glioma cells and macrophages (39,40). In the heart, viralmediated gene transfer of activated Akt1 protein kinase into rodent myocardium protected against is...

No abstract