Zinc-induced alterations in contractile properties of rat diaphragm muscle in vitro

The effect of zinc ions on the isometric contraction of rat diaphragm muscles in the presence and in the absence of external calcium was studied. Using a transducer, the isometric force was measured as a function of supramaximal electrical stimulation, either directly or indirectly applied to the muscle. The following parameters were measured: peak twitch tension, PT, twitch contraction time, CT, relaxation half-time, RT-1/2, and peak rates of tension increase and decrease, +dP/dt and -dP/dt. The following zinc-induced alterations were observed: an increase of the PT; a decrease of the RT-1/2; an increase in the +dP/dt and -dP/dt. The CT was not changed significantly. Our results suggest that zinc ions have a positive inotropic effect on isolated diaphragm muscle. The increase in PT may be explained by a zinc-activated Ca²⁺ uptake by sarcoplasmic reticulum. This was followed by an increase in the rate of rise of tension development, which was secondary to increased -dP/dt. The mechanism(s) by which extracellular Ca²⁺ contributes to this action of zinc is not known.     

Effects of prior dynamic leg exercise on static effort of the elbow flexors

The isometric endurance of the elbow flexors was determined in a control condition and subsequent to a maximal effort exercise bout on a cycle ergometer in seven subjects. Maximum voluntary contraction (MVC), peak rate of tension development (+dP/dt), peak rate of tension relaxation (-dP/dt), one-half contraction time, and one-half relaxation time were also measured. Each subject was tested on four occasions: two control and two experimental sessions. During the control sessions each subject held 40% of MVC to exhaustion, whereas the experimental session included a 1-min maximal effort exercise bout on a cycle ergometer 6 min prior to the isometric endurance task. Arterialized blood samples were drawn and analyzed for lactate, pH, PCO2, and PO2. Plasma bicarbonate was calculated from the Henderson-Hasselbalch equation. Subsequent to the cycle ergometer bout, blood lactate concentration rose from 0.8 to 11 mM, pH decreased from 7.43 to 7.20, PCO2 decreased from 40 to 32 Torr, and plasma bicarbonate decreased from 26 to 12 mM. When compared with the control values, no significant changes were evident for any muscle contractile properties following the cycle ergometer bout. However, isometric endurance was significantly reduced from 115.0 +/- 7.2 to 86.3 +/- 7.3 s.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of {beta}-adrenoceptor signaling in the hearts of 4-wk simulated weightlessness rats.

The modulation of beta-adrenoceptor signaling in the hearts of hindlimb unweighting (HU) simulated weightlessness rats has not been reported. In the present study, we adopted the rat tail suspension for 4 wk to simulate weightlessness; then the effects of simulated microgravity on beta-adrenoceptor signaling were studied. Mean arterial blood pressure (ABP), left ventricular pressure (LVP), systolic function (+dP/dtmax), and diastolic function (-dP/dtmax) were monitored in the course of the in vivo experiment. Single rat ventricular myocyte was obtained by the enzymatic dissociation method. Hemodynamics, myocyte contraction, and cAMP production in response to beta-adrenoceptor stimulation with isoproterenol or adenylyl cyclase stimulation with forskolin were measured, and Gs protein was also determined. Compared with the control group, no significant changes were found in heart weight, body weight and ABP, while LVP and +/-dP/dtmax were significantly reduced. The ABP decrease, LVP increase, and +/-dP/dtmax in response to isoproterenol administration were significantly attenuated in the HU group. The effects of isoproterenol on electrically induced single-cell contraction and cAMP production in myocytes of ventricles in the HU rats were significantly attenuated. The biologically active isoform, Gsalpha (45 kDa) in the heart, was unchanged. Both the increased electrically induced contraction and cAMP production in response to forskolin were also significantly attenuated in the simulated weightlessness rats. Above results indicated that impaired function of adenylyl cyclase causes beta-adrenoceptor desensitization, which may be partly responsible for the depression of cardiac function.     

Inhibition of PLC improves postischemic recovery in isolated rat heart

The Ca2+-dependent PLC converts phosphatidylinositol 4,5-bisphosphate to diacylglycerol (DAG) and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Because these products modulate Ca2+ movements in the myocardium, PLC may also contribute to a self-perpetuating cycle that exacerbates cardiomyocyte Ca2+-overload and subsequent cardiac dysfunction in ischemia-reperfusion (I/R). Although we have reported that I/R-induced changes in PLC isozymes might contribute to cardiac dysfunction, the present study was undertaken to examine the beneficial effects of the PLC inhibitor, U-73122, as well as determining the role of Ca2+ on the I/R-induced changes in PLC isozymes. Isolated rat hearts were subjected to global ischemia 30 min, followed by 5 or 30 min of reperfusion. Pretreatment of hearts with U-73122 (0.5 microM) significantly inhibited DAG and Ins(1,4,5)P3 production in I/R and was associated with enhanced recovery of cardiac function as indicated by measurement of left ventricular (LV) end-diastolic pressure (EDP), LV diastolic pressure (LVDP), maximum rate of pressure development (+dP/dtmax), and maximum rate of LV pressure decay (-dP/dtmax). Verapamil (0.1 microM) partially prevented the increase in sarcolemmal (SL) PLC-beta1 activity in ischemia and the decrease in its activity during the reperfusion phase as well as elicited a partial protection of the depression in SL PLC-delta1 and PLC-gamma1 activities during the ischemic phase and attenuated the increase during the reperfusion period. Although these changes were associated with an improved myocardial recovery after I/R, verapamil was less effective than U-73122. Perfusion with high Ca2+ resulted in the activation of the PLC isozymes studied and was associated with a markedly increased LVEDP and reduced LVDP, +dP/dtmax, and -dP/dtmax. These results suggest that inhibition of PLC improves myocardial recovery after I/R.     

Fatigue from incompletely fused tetanic contractions in skeletal muscle in situ

The purpose of this study was to investigate the contractile response of skeletal muscle in situ when stimulation results in an unfused tetanic contraction. The left gastrocnemius-plantaris muscle group of anesthetized (pentobarbital sodium) dogs (n = 16) was connected to an isometric lever and stimulated indirectly for 30 min. During 10-Hz stimulation, total tension (the peak of each oscillation in tension) increased during the first 2 min of stimulation (staircase), then decreased during the remaining 28 min of stimulation. Since relaxation was incomplete at this rate of stimulation, the developed tension, the difference between peak tension and the lowest tension between successive contractions, did not follow the same pattern of staircase and fatigue as the peak tension did. Developed tension (delta T) decreased during the staircase response then increased from 2 to 10 min before finally decreasing again during the last 20 min, ending at 56 +/- 15 (mean +/- SE) % of the initial (first contraction) delta T. At 2 min of 10-Hz contractions, half-relaxation time (1/2 RT) was too long to measure (insufficient relaxation between contractions), but later, 1/2 RT decreased from greater than 65 ms to less than 40 ms. Increased 1/2 RT has been associated with reduced energy availability. If an increased 1/2 RT is an indication of insufficient energy, then it can be concluded that fatigue continued in spite of a recovery of energy supplies. This suggests a possible dissociation of fatigue and energy availability.     

Decreased left ventricular function, myocarditis, and coronary arteriolar medial thickening following monocrotaline administration in adult rats.

Decreased right as well as left ventricular function can be associated with pulmonary hypertension (PH). Numerous investigations have examined cardiac function following induction of pulmonary hypertension with monocrotaline (MCT) assuming that MCT has no direct cardiac effect. We tested this assumption by examining left ventricular function and histology of isolated and perfused hearts from MCT-treated rats. Experiments were performed on 50 male Sprague-Dawley rats [348 +/- 6 g (SD)]. Thirty-seven rats received MCT (50 mg/kg sc; MCT group) while the remainder did not (Control group). Three weeks later, pulmonary artery pressure was assessed echocardiographically in 20 MCT and 8 Control rats. The hearts were then excised and perfused in the constant pressure Langendorff mode to determine peak left ventricular pressure (LVP), the peak instantaneous rate of pressure increase (+dP/dtmax) and decrease (-dP/dtmax), as well as the rate pressure product (RPP). Histological sections were subsequently examined. Pulmonary artery pressure was higher in the MCT-treated group compared with the Control group [12.9 +/- 6 vs. 51 +/- 35.3 mmHg (P < 0.01)]. Left ventricular systolic function and diastolic relaxation were decreased in the MCT group compared with the Control group (+dP/dtmax 4,178 +/- 388 vs. 2,801 +/- 503 mmHg/s, LVP 115 +/- 11 vs. 83 +/- 14 mmHg, RPP 33,688 +/- 1,910 vs. 23,541 +/- 3,858 beats x min(-1) x mmHg(-1), -dP/dtmax -3,036 +/- 247 vs. -2,091 +/- 389 mmHg/s; P < 0.0001). The impairment of cardiac function was associated with myocarditis and coronary arteriolar medial thickening. Similarly depressed ventricular function and inflammatory infiltration was seen in 12 rats 7 days after MCT administration. Our findings appear unrelated to the degree of PH and indicate a direct cardiotoxic effect of MCT.     

Electrically evoked isometric and isokinetic properties of the triceps surae in young male subjects

The relationship between electrically evoked isometric and isokinetic properties of the triceps surae have been studied in 11 healthy male subjects. The results showed that the time to peak tension (TPT) and half relaxation time (1/2 RT) of the maximal twitch were 110 +/- 11 ms and 82 +/- 11 ms respectively, and the peak rates of rise of contraction (delta P50, delta P200) and relaxation (delta PR50, delta PR200) at 50 and 200 Hz were 0.36 +/- 0.07, 0.48 +/- 0.08 and 1.27 +/- 0.33, 1.25 +/- 0.27% Po ms-1 respectively. The decline in force during a fatigue test was significantly (P less than 0.02) associated with the decrease in maximal relaxation rate (r = 0.79). The TPT was significantly (P less than 0.05) and inversely related to delta P50 and delta P200. The mean angle specific torque-velocity relationship for the 11 subjects was adequately described by the empirical exponential equation of the form: V = 16.5 (e-P/30.8-e-84.3/30.8) where V = velocity (rads s-1) and P = torque (Nm). The only significant association found between the isometric and isokinetic properties of the muscle was between delta PR200 and the torque expressed at a given velocity of 4 rads s-1. This lack of association between the two variables is difficult to explain with certainty but it is suggested that it may be due to the differential effects of Ca2+ release and uptake and cross-bridge turnover rate in the two situations.     

兔膈肌力学模式对慢性电刺激的适应性改变和细胞外Ca …

目的：研究兔膈肌肌条力学对不同频率慢性电刺激（ＣＥＳ）的适应性变化特征和细胞外Ｃａ＾２＋变化夺其力学特征的影响。方法：测定正常对照组和ＣＥＳ组的颤搐收缩张力（Ｐｔ）、峰值张力时间（ＴＰＴ）、１／２松弛时间（１／２ＲＴ）、强直颤搐收缩张力（Ｐｏ）、疲劳指数（ＦＩ）和疲劳恢复指数（ＦＲＩ）;观察在无Ｃａ＾２＋Ｈａｎｋ’ｓ液和标准Ｈａｎｋ’ｓ液时肌条收缩张力消失和恢复的时间差异。结果：①同对照组作比较,     

Isometric or dynamic training: differential effects on mechanical properties of a human muscle

This work compares the specific effects of 3 mo of moderate, isometric, or dynamic voluntary exercises on the contractile properties of human adductor pollicis muscle. Isometric training consisted of 10 daily contractions of 5-s duration at the frequency of one contraction per minute. Dynamic training consisted of 10 daily series of 10 fast contractions (less than 0.5-s duration) moving a load of one-third of the maximal muscle strength at a frequency of one series per minute. Both training programs produced a concomitant increase in maximal tetanic tension and in peak rate of tension development (Ro). A larger increase (P less than 0.05) was found after isometric training (20 vs. 11% after dynamic exercises), whereas Ro augmented more (P less than 0.05) after dynamic contractions (31 vs. 18% after isometric training). Enhancements of twitch force (Pt), rates of twitch tension development (Rt), and of relaxation (St) were, respectively, 20, 20, and 12% after isometric training. There was no modification of contraction time and time of half relaxation (T 1/2R). Conversely, dynamic training produced increases of Rt (25%) and St (16%), associated with an apparently paradoxical decrease of Pt (10%) and reductions of contraction time (11%) and T 1/2R (9%). Maximal shortening velocity was only increased after dynamic training (21%), whereas the maximal muscle power presented a large increase (P less than 0.05) after isometric exercises (51 vs. 19% after dynamic exercises) and a shift of its optimal peak toward heavier loads. This study suggests that human muscle adapts differently to isometric or to dynamic training programs and provides evidence that its contractile kinetics can be altered by exercises performed in physiological conditions.     

Inhibition of PKC phosphorylation of cTnI improves cardiac performance in vivo

Protein kinase C (PKC) modulates cardiomyocyte function by phosphorylation of intracellular targets including myofilament proteins. Data generated from studies on in vitro heart preparations indicate that PKC phosphorylation of troponin I (TnI), primarily via PKC-epsilon, may slow the rates of cardiac contraction and relaxation (+dP/dt and -dP/dt). To explore this issue in vivo, we employed transgenic mice [mutant TnI (mTnI) mice] in which the major PKC phosphorylation sites on cardiac TnI were mutated by alanine substitutions for Ser(43) and Ser(45) and studied in situ hemodynamics at baseline and increased inotropy. Hearts from mTnI mice exhibited increased contractility, as shown by a 30% greater +dP/dt and 18% greater -dP/dt than FVB hearts, and had a negligible response to isoproterenol compared with FVB mice, in which +dP/dt increased by 33% and -dP/dt increased by 26%. Treatment with phenylephrine and propranolol gave a similar result; FVB mouse hearts demonstrated a 20% increase in developed pressure, whereas mTnI mice showed no response. Back phosphorylation of TnI from mTnI hearts demonstrated that the mutation of the PKC sites was associated with an enhanced PKA-dependent phosphorylation independent of a change in basal cAMP levels. Our results demonstrate the important role that PKC-dependent phosphorylation of TnI has on the modulation of cardiac function under basal as well as augmented states and indicate interdependence of the phosphorylation sites of TnI in hearts beating in situ.     

The effect of 5, 10, and 20 repetition maximums on the recovery of voluntary and evoked contractile properties

Maximal strength training has been reported to emphasize neural adaptations. The main objective of this study was to detect differences in muscle activation between 5, 10, and 20 repetition maximum (RM) sets. Fourteen subjects performed elbow flexion with 5, 10, and 20RM. Subjects were tested for maximum isometric force (maximal voluntary contraction [MVC]), twitch amplitude (peak twitch [Pt]), time to peak twitch (TPT), half relaxation time ((1/2) RT), electromyography (EMG), and muscle activation (interpolated twitch). Subjects were tested preexercise and 30 seconds, 1, 2, and 3 minutes postexercise. There were no significant differences in MVC, muscle activation, or antagonist/agonist EMG after 5, 10, or 20RM. However, greater RM did have a greater detrimental effect on twitch properties than fewer RM. Peak twitch was significantly (p = 0.004) less (32.08%) for the 20 than for the 5RM, whereas TPT shortened (p < 0.05) by 7.3 and 11.1% with 10 and 20RM vs. 5RM, respectively. Half relaxation time at 20RM was shortened (p < 0.05) by 20.6 and 25.4% compared with that at 5 and 10RM, respectively. MVC, muscle activation, and temporal twitch properties did not recover within 3 minutes of recovery. In conclusion, whereas 5RM did not produce greater muscle inactivation, twitch contractile properties were affected to a greater degree by a higher number of RM.     

Modulation of stimulation frequency responses and calcium dependency of functional parameters in hyperthyroid rat ventricular papillary muscles

The effects of stimulation frequency (0.2-1.5 Hz) and extracellular calcium concentration ([Ca2+]o) (0.6-15.0 mM) on the contractile function of thin papillary muscles of euthyroid and hyperthyroid rats were studied. Hyperthyroidism led to a decrease in developed tension (DT) and time to peak tension (TPT), but it exhibited no influence on the maximal rates of contraction (+dT/dt) and relaxation (-dT/dt). Also, the mean rates of contraction were similar in euthyroid and hyperthyroid muscle groups. The increase in stimulation frequency brought about a marked decrease in DT, +dT/dt, and -dT/dt of euthyroid papillary muscles at lower frequencies in comparison to papillary muscles in the hyperthyroid group. At stimulation frequencies above 1.0 Hz, the absolute and relative levels of DT and -dT/dt of hyperthyroid myocardium were elevated over euthyroid preparations. At the same time, TPT was unchanged in any of the muscle groups. Hyperthyroidism modulated the relationships between contractile parameters and [Ca2+]o. At a [Ca2+]o of 1.0-4.0 mM, the DT of hyperthyroid papillary muscles was lower than in euthyroid muscle. At 4.0 and 8.0 mM of [Ca2+]o, the equal values of maximal DT were registered for euthyroid and hyperthyroid papillary muscles, respectively. An increase in the [Ca2+]o in the range of 1.0-15.0 mM was accompanied by an increase in TPT of both muscle groups, but to a greater extent in hyperthyroid myocardium. In conclusion, the myocardium of hyperthyroid rat appeared to exhibit decreased sensitivity to calcium as well as to the negative inotropic effect of enhanced stimulation frequency. Alterations of the processes of transsarcolemmal movement and intracellular recycling of Ca2 may be implicated.     

Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy

Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.     

Effect of a low sodium medium, ouabain and noradrenaline on relaxation of the myocardium of the perfused rabbit heart

Random stimulation of the perfused heart allows relationships between the rate of contractions (dP/dtmax), the size of contraction (Pmax) and the rate of relaxation (dP/dtmin) of contractions of varying intensity to be studied. The present study concerns these relationships during perfusion with ouabain, a low sodium medium and noradrenaline. Isolated rabbit hearts were perfused with Tyrode solution (O2 95%, CO2 5%, 36.4 degrees C), the isovolumic contractions of the left ventricle were recorded and the right ventricle was stimulated at random for 30 s (pulse width 10 ms, voltage double the threshold value). Perfusion was then switched over to perfusion with ouabain solution (10(-6) mol.l-1), with noradrenaline solution (10(-6) mol.l-1) or with low sodium solution (with 31% of the normal Na concentration). When spontaneous contraction size had attained a stable level, random stimulation was repeated. During random stimulation, dP/dtmin was directly proportional to Pmax (dP/dtmin = k1.P max) and to dP/dtmax (dP/dtmin = k2.dP/dtmax). Ouabain and low sodium did not change k1 or k2 and noradrenaline did not change k2. The increase in k1 during noradrenaline perfusion corresponds to shorter duration of contraction. It was found that dP/dtmax, which corresponds to the sarcoplasmic calcium concentration at the outset of activation, was the main factor determining the relaxation rate during ouabain, noradrenaline and low sodium perfusion.     

Electrically evoked contractions of the triceps surae during and following 21 days of voluntary leg immobilization

The effects of 21 days voluntary leg (plaster) immobilization on the mechanical properties of the triceps surae have been studied in 11 young female subjects, mean age 19.4 years. The results show that during the period of immobilization the mean time to peak tension (TPT) and half relaxation time (1/2RT) and tension (Pt) of the maximal twitch increased significantly (p less than 0.001) but the effects were short lived. Maximal tension and contraction times of the twitch recovered within 2-14 days following the removal of the plaster cast. The electrically evoked tetanic tensions at 10 Hz and 20 Hz did not change significantly (P greater than 0.1) during immobilization, but the 50 Hz tetanic tension (Po50) and maximal voluntary contraction (MVC) were reduced (p less than 0.05). The fall in Po50 and MVC was associated with 10% decrease in the estimated muscle (plus bone) cross-sectional area. The relative (%) change in Po50 and MVC following immobilization was related to the initial physiological status (as indicated by the response of the triceps surae to a standard fatigue test prior to immobilization) of the muscle. The rate of rise and recovery fall of the tetanus were slightly but significantly (p less than 0.01) reduced on day 7 of immobilization, but thereafter remained constant. The isokinetic properties of the triceps surae as reflected in the measured torque/velocity relation of the muscle in 4 subjects did not change significantly if account was taken of the slight degree of atrophy present following immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Continuum rheology of muscle contraction and its application to cardiac contractility.

A set of constitutive equations is proposed to describe the mechanics of contraction of skeletal and heart muscle. Fiber tension is assumed to depend on the degree of chemical activation, the stretch ratio, and the rate of stretching of the fibers. The time rate of change of activation is governed by a differential equation. The proposed constitutive equations are used to model the time courses of isotonic and isometric twitches during contraction and relaxation phases of the muscle response to stimulation. Various contractility indices of the left ventricle are considered next by using the proposed constitutive equations. The present analysis introduces a new interpretation of the index of contractility (dP/dt)/P used in cardiac literature. It is shown that this index may not be related at all to the maximum speed of shortening and that it may be dependent on both preload and afterload. The development of pressure during isovolumetric contraction of the left ventricle is shown to be governed by a differential equation describing the time rate of change of tension during isometric contraction of myocardium fibers.     

Mechanomyographic amplitude and mean power frequency versus torque relationships during isokinetic and isometric muscle actions of the biceps brachii.

The purpose of this investigation was to determine the mechanomyographic (MMG) amplitude and mean power frequency (MPF) versus torque (or force) relationships during isokinetic and isometric muscle actions of the biceps brachii. Ten adults (mean +/- SD age = 21.6 +/- 1.7 years) performed submaximal to maximal isokinetic and isometric muscle actions of the dominant forearm flexors. Following determination of isokinetic peak torque (PT) and the isometric maximum voluntary contraction (MVC), the subjects randomly performed submaximal step muscle actions in 10% increments from 10% to 90% PT and MVC. Polynomial regression analyses indicated that MMG amplitude increased linearly with torque during both the isokinetic (r2 = 0.982) and isometric (r2 = 0.956) muscle actions. From 80% to 100% of isometric MVC, however, MMG amplitude appeared to plateau. Cubic models provided the best fit for the MMG MPF versus isokinetic (R2 = 0.786) and isometric (R2 = 0.940) torque relationships, although no significant increase in MMG MPF was found from 10% to 100% of isokinetic PT. For the isometric muscle actions, however, MMG MPF remained relatively stable from 10% to 50% MVC, increased from 50% to 80% MVC, and decreased from 80% to 100% MVC. The results demonstrated differences in the MMG amplitude and MPF versus torque relationships between the isokinetic and isometric muscle actions. These findings suggested that the time and frequency domains of the MMG signal may be useful for describing the unique motor control strategies that modulate dynamic versus isometric torque production.     

Disruption of protein kinase A interaction with A-kinase-anchoring proteins in the heart in vivo: effects on cardiac contractility, protein kinase A phosphorylation, and troponin I proteolysis

Protein kinase A (PKA)-dependent phosphorylation is regulated by targeting of PKA to its substrate as a result of binding of regulatory subunit, R, to A-kinase-anchoring proteins (AKAPs). We investigated the effects of disrupting PKA targeting to AKAPs in the heart by expressing the 24-amino acid regulatory subunit RII-binding peptide, Ht31, its inactive analog, Ht31P, or enhanced green fluorescent protein by adenoviral gene transfer into rat hearts in vivo. Ht31 expression resulted in loss of the striated staining pattern of type II PKA (RII), indicating loss of PKA from binding sites on endogenous AKAPs. In the absence of isoproterenol stimulation, Ht31-expressing hearts had decreased +dP/dtmax and -dP/dtmin but no change in left ventricular ejection fraction or stroke volume and decreased end diastolic pressure versus controls. This suggests that cardiac output is unchanged despite decreased +dP/dt and -dP/dt. There was also no difference in PKA phosphorylation of cardiac troponin I (cTnI), phospholamban, or ryanodine receptor (RyR2). Upon isoproterenol infusion, +dP/dtmax and -dP/dtmin did not differ between Ht31 hearts and controls. At higher doses of isoproterenol, left ventricular ejection fraction and stroke volume increased versus isoproterenol-stimulated controls. This occurred in the context of decreased PKA phosphorylation of cTnI, RyR2, and phospholamban versus controls. We previously showed that expression of N-terminal-cleaved cTnI (cTnI-ND) in transgenic mice improves cardiac function. Increased cTnI N-terminal truncation was also observed in Ht31-expressing hearts versus controls. Increased cTnI-ND may help compensate for reduced PKA phosphorylation as occurs in heart failure.     

Opposite actions of caffeine and creatine on muscle relaxation time in humans.

The effect of creatine and caffeine supplementation on muscle torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (T(max)), contraction time (CT) from 0.25 to 0.75 of T(max), and relaxation time (RT) from 0.75 to 0.25 of T(max) were measured during an exercise test consisting of 30 intermittent contractions of musculus quadriceps (2 s stimulation, 2 s rest) that were induced by electrical stimulation. According to a double-blind randomized crossover design, subjects (n = 10) performed the exercise test before (pretest) and after (posttest) creatine supplementation (Cr, 4 x 5 g/day, 4 days), short-term caffeine intake (Caf, 5 mg x kg(-1) x day(-1), 3 days), creatine supplementation + short-term caffeine intake (Cr+Caf), acute caffeine intake (ACaf, 5 mg/kg) or placebo. Compared with placebo, Cr shortened RT by approximately 5% (P < 0.05). Conversely, Caf increased RT (+ approximately 10%, P < 0.05), in particular as RT increased because of fatigue. RT was not significantly changed by either Cr+Caf or ACaf. T(max) and CT were similar during all experimental conditions. Initial T(max) was approximately 20% of voluntary maximal isometric contraction force, which was not different between treatments. It is concluded that Caf intake (3 days) prolongs muscle RT and by this action overrides the shortening of RT due to creatine supplementation.     

In vivo changes in the human patellar tendon moment arm length with different modes and intensities of muscle contraction

The purpose of this study was to examine the effect of different muscle contraction modes and intensities on patellar tendon moment arm length (d(PT)). Five men performed isokinetic concentric, eccentric and passive knee extensions at an angular velocity of 60 deg/s and six men performed gradually increasing to maximum effort isometric muscle contractions at 90( composite function) and 20( composite function) of knee flexion. During the tests, lateral X-ray fluoroscopy imaging was used to scan the knee joint. The d(PT) differences between the passive state and the isokinetic concentric and extension were quantified at 15( composite function) intervals of knee joint flexion angle. Furthermore, the changes of the d(PT) as a function of the isometric muscle contraction intensities were determined during the isometric knee extension at 90( composite function) and 20( composite function) of knee joint flexion. Muscle contraction-induced changes in knee joint flexion angle during the isometric muscle contraction were also taken into account for the d(PT) measurements. During the two isometric knee extensions, d(PT) increased from rest to maximum voluntary muscle contraction (MVC) by 14-15%. However, when changes in knee joint flexion angle induced by the muscle contraction were taken into account, d(PT) during MVC increased by 6-26% compared with rest. Moreover, d(PT) increased during concentric and eccentric knee extension by 3-15%, depending on knee flexion angle, compared with passive knee extension. These findings have important implications for estimating musculoskeletal loads using modelling under static and dynamic conditions.