Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women

Differences in Muscle Protein Synthesis and Anabolic Signaling in the Postabsorptive State and in Response to Food in 65–80 Year Old Men and Women

Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women

Impact of inactivity and exercise on the vasculature in humans

The effects of inactivity and exercise training on established and novel cardiovascular risk factors are relatively modest and do not account for the impact of inactivity and exercise on vascular risk. We examine evidence that inactivity and exercise have direct effects on both vasculature function and structure in humans. Physical deconditioning is associated with enhanced vasoconstrictor tone and has profound and rapid effects on arterial remodelling in both large and smaller arteries. Evidence for an effect of deconditioning on vasodilator function is less consistent. Studies of the impact of exercise training suggest that both functional and structural remodelling adaptations occur and that the magnitude and time-course of these changes depends upon training duration and intensity and the vessel beds involved. Inactivity and exercise have direct “vascular deconditioning and conditioning” effects which likely modify cardiovascular risk

The effects of shoulder load and pinch force on electromyographic activity and blood flow in the forearm during a pinch task

The object of the current study was to determine whether static contraction of proximal musculature has an effect on the blood flow more distally in the upper extremity. Static contractions of muscles in the neck shoulder region at three levels (relaxed, shoulders elevated and shoulders elevated loaded with 4.95 kg each) were combined with intermittent pinch forces at 0, 10 and 25% of the maximum voluntary contraction (MVC). Blood flow to the forearm was measured with Doppler ultrasound. Myoelectric activity of the forearm and neck-shoulder muscles was recorded to check for the workload levels. Across all levels of shoulder load, blood flow increased significantly with increasing pinch force (21% at 10% MVC and by 44% at 25% MVC). Blood flow was significantly affected by shoulder load, with the lowest blood flow at the highest shoulder load. Interactions of pinch force and shoulder load were not significant. The myoelectric activity of forearm muscles increased with increasing pinch force. The activation of the trapezius muscle decreased with increasing pinch force and increased with increasing shoulder load. The precise mechanisms accounting for the influence of shoulder load remains unclear. The results of this study indicate that shoulder load might influence blood flow to the forearm

Surgical repair of post infarction ventricular septa defects: a national experience

Obiectives: Ventricular septal rupture is a rare but feared complication after acute myocardial infarction. Most reports about outcome after surgical treatment are single center experiences. We investigated the results after surgical repair in all patients in Sweden during a 7-year period. Methods: All patients undergoing surgical repair 1992-1998 were identified with the aid of the Swedish Heart Surgery Registry. The patients (n = 189, 63% men, mean age 69 8 years) were operated at 10 different centers. Pre- and peri-operative variables were collected from the Registry and individual patient charts. Mortality was calculated and a Cox proportional hazards regression model was used to identify independent predictors for early and late mortality. Mean follow-up was 2.4 years. Results: Seventy-seven of the 189 patients died within 30 days (41%). Urgent repair (Risk Ratio 4.2 (2.0-8.9), P < 0.001) and posterior rupture (RR 2.1 (1.3-3.4), P = 0.002) were independent predictors of 30-day mortality. Total cumulative survival (Kaplan-Meyer) was 38% at 5 years. For patients that survived the first 30 days (n = 112), 5 year cumulative survival was 67%. Independent predictors for mortality after 30 days were number of concomitant coronary anastomoses (RR 1.5 (1.2-2.0), P = 0.001), residual postoperative shunt (RR 2.7 (1.4-5.4), P = 0.004) and postoperative dialysis (RR 3.4 (1.5-7.5), P = 0.003). Conclusions: Early mortality after surgical repair of post infarction septal rupture is still considerable. Early repair and posterior rupture are predictors of early mortality. Long-term survival in patients surviving the immediate postoperative period is limited by pre-existing coronary artery disease, postoperative renal failure and the presence of a residual postoperative shunt

Blunted sympathetic vasoconstriction in contracting skeletal muscle of healthy humans: is nitric oxide obligatory?

We tested the hypothesis that nitric oxide (NO) is responsible for blunting sympathetic α-adrenergic vasoconstriction in the active muscles of humans (functional sympatholysis). We measured forearm blood flow (Doppler ultrasound) and calculated the reductions in forearm vascular conductance (FVC) in response to α-adrenergic receptor stimulation during rhythmic handgrip exercise and during a control non-exercise vasodilator condition (intra-arterial adenosine), before and after local NO synthase (NOS) inhibition in healthy men. The forearm vasoconstrictor responses to endogenous noradrenaline release (intra-arterial tyramine) were significantly blunted during moderate exercise compared with adenosine, and these vasoconstrictor responses were not restored by NOS inhibition with NG-monomethyl-l-arginine (l-NMMA; n = 6) or NG-nitro-l-arginine methyl ester (l-NAME; n = 8). Similarly, l-NAME did not restore the vasoconstrictor responses to tyramine in contracting muscle during heavy rhythmic handgrip exercise (n = 4). In four additional subjects, we also found that the vasoconstrictor responses evoked by tyramine during exercise or adenosine were repeatable in the absence of NOS inhibition (i.e. time control). Finally, in five subjects the forearm vasoconstrictor responses to direct α1-adrenergic (phenylephrine) and α2-adrenergic (clonidine) receptor stimulation were blunted during moderate exercise compared with adenosine; these responses were also unaffected by l-NAME. Taken together, our results demonstrate that NO is not obligatory for functional sympatholysis in contracting skeletal muscles of healthy men