Impaired contractile function due to decreased cardiac myosin binding protein C content in the sarcomere.

Mutations in cardiac myosin binding protein C (MyBP-C) are a common cause of familial hypertrophic cardiomyopathy (FHC). The majority of MyBP-C mutations are expected to reduce MyBP-C expression; however, the consequences of MyBP-C deficiency on the regulation of myofilament function, Ca²âº homeostasis, and in vivo cardiac function are unknown. To elucidate the effects of decreased MyBP-C expression on cardiac function, we employed MyBP-C heterozygous null (MyBP-C+/-) mice presenting decreases in MyBP-C expression (32%) similar to those of FHC patients carrying MyBP-C mutations. The levels of MyBP-C phosphorylation were reduced 53% in MyBP-C+/- hearts compared with wild-type hearts. Skinned myocardium isolated from MyBP-C+/- hearts displayed decreased cross-bridge stiffness at half-maximal Ca²âº activations, increased steady-state force generation, and accelerated rates of cross-bridge recruitment at low Ca²âº activations (<15% and <25% of maximum, respectively). Protein kinase A treatment abolished basal differences in rates of cross-bridge recruitment between MyBP-C+/- and wild-type myocardium. Intact ventricular myocytes from MyBP-C+/- hearts displayed abnormal sarcomere shortening but unchanged Ca²âº transient kinetics. Despite a lack of left ventricular hypertrophy, MyBP-C+/- hearts exhibited elevated end-diastolic pressure and decreased peak rate of LV pressure rise, which was normalized following dobutamine infusion. Furthermore, electrocardiogram recordings in conscious MyBP-C+/- mice revealed prolonged QRS and QT intervals, which are known risk factors for cardiac arrhythmia. Collectively, our data show that reduced MyBP-C expression and phosphorylation in the sarcomere result in myofilament dysfunction, contributing to contractile dysfunction that precedes compensatory adaptations in Ca²âº handling, and chamber remodeling. Perturbations in mechanical and electrical activity in MyBP-C+/- mice could increase their susceptibility to cardiac dysfunction and arrhythmia.

Effects of active and passive recovery on lactate removal and subsequent isokinetic muscle function.

The effect of active and passive recovery on the removal of accumulated blood lactate and subsequent muscle function were tested using five male subjects. The experimental protocol consisted of two exercise sessions performed on a mechanical brake cycle ergometer at 150% VO2max for 60 seconds. Termination of the supramaximal work bouts were followed by a 20 minutes active recovery period cycling at 30% VO2max and a 20 minutes passive recovery period sitting quietly. Following the recovery modes, isokinetic measures of peak torque, total work output and fatigue were evaluated in the dominant quadricep muscle group. During the control test, exercise performance was limited to that of isokinetic evaluation. The order of the experimental and control tests were randomly assigned. Postexercise blood lactate levels prior to the isokinetic muscle test were 9.2 and 9.1 mM during the active and passive recovery conditions respectively. Blood lactate concentration during the control test was .4 mM prior to the isokinetic muscle test. The rate of blood lactate disappearance was significantly greater during active recovery (3.5 mM) when compared with passive recovery (7.2 mM). Blood lactate concentration during the control test was significantly lower (.4 mM) in comparison to both active and passive lactate concentrations prior to the isokinetic muscle test. Despite significant differences in blood lactate between active and passive recovery conditions, there was no difference in isokinetic measures of maximal strength, work output and muscle fatigue between recovery modes. Further indication that lactate is unrelated to muscle function was the nonsignificant finding in muscle function between the control and experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Caffeine ingestion and isokinetic strength.

The purpose of this study was to investigate the effects of caffeine on maximum voluntary contractions of the dominant knee extension and flexion muscles in 12 male intercollegiate track sprinters. Caffeine (5 mg.kg-1) and placebo (225 mg methylcellulose) gelatin capsules were administered orally in randomly assigned order. Muscle function was measured isokinetically by a Cybex II dynamometer interfaced with a data reduction computer. Six repetitions maximum of the extensors and flexors were performed at three sequential ordered speeds (30 degrees, 150 degrees and 300 degrees s-1) with a one-minute rest between varying velocities. Peake torque and power were than assessed after treatment conditions, as well as a fatigue index calculated from a series of 60 repetitions maximum ato 150 degrees s-1. Results of the 2 X 3 ANOVA and paired t-test indicated no difference in measures of peak torque and power at the varying contracting velocities and fatigue index after caffeine ingestion. These findings indicate the ingestion of caffeine in a small dose exerts no ergogenic effect on muscle function under anaerobic conditions.