Quantitative graphical description of portocentral gradients in hepatic gene expression by image analysis

The work loop technique was used to measure the mechanical performance in situ of the latissimus dorsi (LD) muscles of rabbits maintained under fentanyl anesthesia. After 3 wk of incrementally applied stretch the LD muscles were 36% heavier, but absolute power output (195 mW/muscle) was not significantly changed relative to that of external control muscle (206 mW). In contrast, continuous 10-Hz electrical stimulation reduced power output per kilogram of muscle >75% after 3 or 6 wk and muscle mass by 32% after 6 wk. When combined, stretch and 10-Hz electrical stimulation preserved or increased the mass of the treated muscles but failed to prevent an 80% loss in maximum muscle power. However, this combined treatment increased fatigue resistance to a greater degree than electrical stimulation alone. These stretched/stimulated muscles, therefore, are more suitable for cardiomyoplasty. Nonetheless, further work will be necessary to find an ideal training program for this surgical procedure.     

Chronic implantation of a skeletal muscle energy convertor for cardiac assist devices: a preliminary report

An efficient energy convertor capable of driving a variety of cardiac assist devices is being developed in goats. Muscle work in a linear configuration is converted to hydraulic energy and transmitted to an external test system that controls muscle loads during shortening contractions. This investigation focuses on the variation of muscle characteristics and optimal power output during muscle conditioning. The energy convertor was mounted on the rib cage, the latissimus dorsi insertion reattached to the device, and percutaneous hydraulic lines exited near the spine. Following device, stimulator, and intramuscular electrode implantation, a progressive conditioning protocol was initiated. Weekly biomechanical muscle characterization was performed in the conscious animal, with single twitch and tetanic contractions performed under isometric and isotonic conditions. The characterization data provide a measure of available power, as well as inputs, for a computer simulation that predicts optimal muscle power output and operating conditions. These ongoing implants provide insight into the available muscle power and suggest an implantable energy convertor is feasible. Development of an energy convertor is an important step toward tether free skeletal muscle powered cardiac assist. These studies will be expanded in number and duration to further investigate the effects of conditioning and identify improvements in device development.     

Functional MRI study of the cognitive generation of affect

BACKGROUND: Cardiomyoplasty is a new surgical alternative therapy for CHF. Although conditioning of muscle for cardiomyoplasty has a positive effect on fatigue resistance it also produces negative effects. In this study we assessed the effect of salbutamol, a beta2-agonist, on both the positive and the negative effects of conditioning. METHODS: In a control group of six animals one latissimus dorsi was subject to chronic, 1 Hz, low-frequency stimulation (CLFS) while the other served as a control. The experimental group of seven dogs received a continuous SC infusion of salbutamol and one latissimus dorsi was subjected to CLFS. The other muscle demonstrated the effects of salbutamol per se. After 42 days the animals were anesthetized and fatigue resistance, muscle mass, and mechanical properties of the muscles were evaluated. RESULTS: Salbutamol increased muscle mass, tetanic tension, and rate of rise and fall of tetanic tension. It diminished fatigue resistance and had no effect on shortening velocity. Chronic stimulation decreased muscle mass, tetanic tension, rate of rise and fall of tetanic tension, and muscle shortening velocity in both groups of dogs. Salbutamol diminished the declines in muscle mass, rate of tension development, and rate of muscle shortening due to CLFS, but did not change the effects of CLFS on tetanic tension and the rate of fall of tetanic tension. Salbutamol did not alter the increase in fatigue resistance induced by CLFS. CONCLUSIONS: The favorable effect of CLFS on fatigue resistance was unaffected by salbutamol. The unfavorable effects of CLFS on loss of muscle mass, rate of tension development, and decline in shortening velocity were partially blocked by salbutamol, improving the ability of the latissimus dorsi to augment cardiac systole.     

Long-term survival after treatment of malignant colonic polyps

For the application of the latissimus dorsi muscle (LDM) to circulatory assist, the muscle is stimulated with co- or counterpulsation during the cardiac cycle. The purpose of this study was to evaluate the blood supply to the LDM and its muscular performance during each respective stimulation. The origin of the LDM was connected to a tension gauge, a potentiometer, and 1 kg of weight in series. The LDM was stimulated at a ratio of 1:1 of heart to muscle contraction for 10 min. Copulsatile stimulation made thoracodorsal arterial flow (TDF) predominant during cardiac diastole. In counterpulsatile stimulation, TDF occurred predominantly during cardiac systole. Between the 2 patterns of stimulation, no significant differences were observed in the mean TDF rate during 1 cardiac cycle. The maximal force, maximal contraction length, and power of the LDM also did not differ significantly. These results suggest that despite the difference of the TDF profile, LDM performance may be comparable between co- and counterpulsatile stimulation for the application of the LDM to circulatory assist.     

Contractile properties of aged avian muscle after stretch-overload

The effects of ageing on muscle contractile adaptations to stretch-overload was examined in the anterior latissimus dorsi (ALD) muscle of 12 old (90 weeks of age) and 12 young adult (10 weeks of age) Japanese quails. A weight corresponding to 12% of the birds' body weight was attached to one wing for 30 days, while the contralateral wing served as the intra-animal control. In vitro contractile measurements were made at 25 degrees C by indirect stimulation of the ALD by its nerve (pulse 0.2 ms). Compared with young adult twitch characteristics, aged muscles had significantly greater contraction time (149 +/- 9 ms vs. 174 +/- 16 ms). Stretch-overload increased contraction time to 162 +/- 7 ms in young muscles and 215 +/- 14 ms in old muscles. Ageing and overload resulted in a greater fusing of twitches at stimulation frequencies of 5 and 10 Hz which resulted in a leftward shift of the force-frequency curve at these frequencies, relative to young adult control muscles. Maximal shortening velocity (Vmax) decreased from 2.6 +/- 0.3 to 1.2 +/- 0.1 muscle lengths/s in young muscles after overload. Vmax in old control muscles was similar to young muscles after stretch, but stretch further decreased Vmax in old muscles to 0.8 muscle lengths/s. Maximal tetanic force and specific force were similar in young and old muscles, both before and after stretch. These data indicate that ageing induces a slowing of both twitch contractile characteristics and shortening velocity in the ALD, without affecting maximal force capabilities.     

Delayed stimulation of the latissimus dorsi may result in disuse atrophy

BACKGROUND: The latissimus dorsi is usually left unstimulated for 2 weeks after cardiomyoplasty to allow the muscle to recover from the loss of the collateral circulation. To determine whether the 2-week delay may cause muscle atrophy, we randomized 15 mongrel dogs to a control group or a disuse atrophy group. METHODS: The collateral circulation to the latissimus dorsi was ligated in all animals before cardiomyoplasty to reduce the risk of ischemic injury to the muscle during mobilization. Two weeks after collateral ligation, the atrophy group had the tendinous attachment of the latissimus dorsi severed and then 2 weeks later underwent cardiomyoplasty. The control group had a 2-week delay after collateral ligation followed by cardiomyoplasty. Biopsies were performed before collateral ligation and before cardiomyoplasty. After heart failure was induced, hemodynamic function was assessed during synchronized contraction of the latissimus dorsi by measuring the maximum systolic elastance, stroke volume, preload recruitable stroke work index, and diastolic compliance. RESULTS: Comparison of muscle morphology between the two groups demonstrated the presence of muscle atrophy in those animals that had been randomized to the atrophy protocol. During synchronized contraction of the latissimus dorsi, there was no significant increase in maximum systolic elastance in either group. However, both stroke volume and pulmonary recruitable stroke work index were significantly higher in the control animals during assisted beats. The left ventricle was less compliant in the atrophy group, suggesting that muscle atrophy had adversely affected diastolic function. CONCLUSIONS: Delayed electrical stimulation of the latissimus dorsi may result in atrophy and loss of function.     

Is it possible to perform immediate cardiac assist using untrained latissimus dorsi muscle in a work-rest regimen?

The authors investigated what contractile force (CF) could be obtained from unconditioned latissimus dorsi muscle immediately after mobilization and for the 2 week vascular period of recovery. Latissimus dorsi muscle mobilization was performed on seven adult (4 experimental and 3 control) sheep leaving only the pedicle and the peripheral muscle intact. Telectronics stimulators (Myostim 7220; Teletronics Pacing Systems, Inc, Englewood, CO) were implanted. Immediately after mobilization 11-35% of the initial CF was lost. A 30 min fatigue test was performed 1 hr after mobilization (20 g/kg preload, 10 V, 10 Hz, 15 BPM, 6 impulses per burst) using a 1 min work-1 min rest regimen. Two sheep lost 2-12% of initial CF; two increased CF by 14-24%. At the end of the fatigue test, CF consisted of 74-89% of immobilized CF. Electrical stimulation training of the muscle was then initiated with the following regimen in the experimental animals only: 15 BPM, single impulses, 5 V, 10 Hz. Every day the muscle was exercised using a work-rest regimen to mimic cardiac assist, starting with 20 min on day 2, and increasing by 2 min per day until a total of 50 min was reached on day 16. All animals were retested for CF using a 42 min fatigue test on days 6, 11, and 16. On day 6, there was no fatigue evident in the experimental group during the 42 min test. CF after testing was 59-81% (mean 67%) of initial data. In the control group (animals with no electrical stimulation training protocol), CF decreased by 11% (from 64 to 53%). On day 11, there was no fatigue evident in the experimental group; CF in all animals increased by 2-8%. On day 16, there was also no fatigue evident in the experimental group; CF increased by 0-9%. An additional 20 min of continuous contraction (15 BPM) fatigue testing was performed on the muscle without rest between the tests. No fatigue was evident at the end of testing. Light microscopic analysis of latissimus dorsi muscle biopsy specimens taken on the days of testing showed no evidence of necrotic damage. Our investigations suggest that it may be possible to start muscle transformation immediately after mobilization and use the untrained latissimus dorsi muscle for cardiac assist immediately after surgery for short periods.     

Activity-rest stimulation of latissimus dorsi for cardiomyoplasty: 1-year results in sheep

BACKGROUND: In dynamic cardiomyoplasty electro-stimulation achieves full transformation of the latissimus dorsi (LD); therefore, its slowness limits the systolic support. Daily activity-rest could maintain partial transformation of the LD. METHODS: Sheep LD were burst-stimulated either 10 or 24 hours/day. Before and 2, 4, 6, and 12 months after stimulation, LD power output, fatigue resistance, and tetanic fusion frequency were assessed. Latissimus dorsi were biopsied at 6 months, and sheep sacrificed at 12 months. RESULTS: After 1 year of 10 hours/day stimulation LD was substantially conserved and contained large amounts of fast type myosin. From 2 months to 1 year of stimulation the power per muscle of the daily rested LD was greater than that of the left ventricle, being three to four times higher than in the 24-hour/day stimulation. CONCLUSIONS: If extended to humans, these results could be the rationale for the need of a cardiomyostimulator, whose discontinuous activity could offer to patients the long-standing advantage of a faster and powerful muscle contraction.     

Evaluation of the effects of bioadhesive substances as addition to oral contrast media: an experimental study

The primary restraint preventing humeral head translation is the capsuloligamentous system. Muscle forces can also decrease translation; however, the timing and magnitude of muscle response has not been previously reported. Fine wire electromyographic analysis of the biceps long head, anterior deltoid, pectoralis major, latissimus dorsi, and rotator cuff muscles was performed after an anterior translation force was applied to 15 normal shoulders. The reflex response time (time to 5% maximal muscle test), the protection response time (time to 20% maximal muscle test), the duration of the protection response, and the magnitude of the protection response were calculated. The shoulder reaction data showed 2 consistent patterns. Activation of the anteriorly located muscles preceded the posteriorly located muscles, and the rotator cuff muscles fired with greater magnitude than the more peripherally located muscles.     

Cardiomyoplasty - improvement of muscle fibre type transformation by an anabolic steroid (metenolone)

Dynamic cardiomyoplasty, a method to support ventricular function by the chronically stimulated latissimus dorsi muscle wrapped around the heart is accompanied by a loss of mass and force of the transplanted muscle. These effects and the fast-to-slow transformation of the muscle could be possibly influenced by the additional administration of anabolic steroids. In this study, the left latissimus dorsi muscles of 12 sheep were electrically conditioned (group A). In 12 other animals (group B), stimulation was combined with the administration of metenolone (100 mg/week). Biopsies were taken from the right and left muscles at the beginning and after 6 and 12 weeks of treatment, frozen and cross-sectioned. The muscle fibre type composition was studied enzymhistochemically (SDH-staining and Myosin-ATPase-reaction) and immunocytochemically (using antibodies against different myosin heavy chains, MHC). Furthermore, the expression of different MHC isoforms was investigated electrophoretically. The untreated latissimus dorsi muscle contains 20% type I fibres expressing slow MHC and 80% type II fibres expressing fast MHC. After 6 weeks, the respective fibre type composition was 42 and 58% (group A) and 80 and 20% (group B). After 12 weeks, the percentage of the type I fibres rose in group A to 59% and in group B to 98%. In accordance with these morphological results, the MHC pattern determined electrophoretically showed a corresponding shift from the fast to the slow isoform. Therefore, the administration of metenolone avoids severe muscle atrophy, and improves and accelerates fast to slow fibre type conversion necessary for successful cardiomyoplasty.     

Clinical features of relative focal hyperfusion in patients with intracerebral hemorrhage detected by contrast-enhanced xenon CT

Optimization of the skeletal muscle contraction during cardiac assist is important to achieve maximal cardiac assist and yet avoid overstimulation that may injure skeletal muscle. Dynamic cardiomyoplasty suffers from lack of an objective, reproducible, and accurate technique to measure skeletal muscle shortening fraction after wrap and training of the muscle. A recruitment curve is considered the best way to select the proper stimulation level to achieve supramaximal contraction without overstimulating the muscle. A fluoroscopic technique of determining latissimus dorsi recruitment curve was evaluated in five goats undergoing dynamic cardiomyoplasty with an anterior cardio-subcutaneous wrap. Two pairs of stainless steel targets (0.5 and 1 cm of diameter) were implanted on each side of the muscle wrap. One pair of sonomicrometer crystals was also implanted. Displacement of the targets was measured under fluoroscopy at five different stimulation levels. Correlation coefficients between targets on the inside surface of the wrap and the sonomicrometer crystals, and targets on the outside surface of the wrap and the sonomicrometer crystals were 0.71 (P < 0.05) and 0.60 (P < 0.05), respectively. Targets on the inside surface of the wrap were more accurate than targets on the outside surface of the wrap for measurement of skeletal muscle shortening fraction and establishment of a recruitment curve. Adverse effects from the targets were not observed.     

Quantification of early damage in latissimus dorsi muscle grafts

Acute damage in the latissimus dorsi muscle may account for variable clinical results following dynamic cardiomyoplasty and an ischemic cause has been suggested. Using established techniques, we set out to demonstrate and to quantify the acute muscle damage in a rodent model. The left latissimus dorsi muscle of 5 Sprague-Dawley rats was mobilized on its thoracodorsal vascular pedicle, thus interrupting the regional blood supply to its distal part. The undisturbed contralateral muscle served as a matched control. After 24 hours, the muscle was excised and divided into proximal, middle, and distal thirds. Damage was graded histologically and quantified by nitroblue tetrazolium macrohistochemistry. Both methods of assessment correlated well (r=-0.936; P < 0.001) and demonstrated significant damage, principally in the middle and the distal regions of the ischemic muscles. Therefore, the rodent model appears to be useful for investigating the pathogenesis and prevention of acute ischemic damage in the latissimus dorsi graft under conditions resembling the clinical scenario.     

Targeted disruption of the TGA3 locus in Arabidopsis thaliana

BACKGROUND: Severe latissimus dorsi muscle damage may compromise cardiomyoplasty performance. We analyzed factors underlying the damage produced in 20 sheep latissimus dorsi muscles by isolating the influences of electrical stimulation, mobilization (with some loss of vascular supply), loss of normal resting tension, or a combination of these. METHODS: In group I (n = 3), the muscle was mobilized except for its neurovascular pedicle and reattached at normal resting length. In group II (n = 3), the muscle was mobilized and reattached at about 80% of resting length. Groups III (n = 6) and IV (n = 4) were as groups I and II except that continuous indirect stimulation at 2 Hz was added after 2 weeks. In group V (n = 4), the undisturbed muscle received stimulation alone. After 10 to 12 weeks, muscle samples were taken for morphometric analysis. RESULTS: Loss of resting muscle tension appeared to be the single most damaging intervention, though mobilization and stimulation had further deleterious effects. The worst damage was seen when all three factors were combined, when 60% of the muscle cross section was occupied by connective tissue and fat. The changes were significantly more severe in the distal than in the proximal part of the muscle, implicating ischemia as a contributory factor. CONCLUSIONS: Fiber damage reduces the effectiveness of muscle grafts used for cardiac assistance and merits further systematic investigation.     

Use of ultrasonography to evaluate muscle thickness and blood flow in free flaps

The purpose of this study was to investigate the common belief that a microvascular transfer of a non-innervated free muscle flap loses muscle bulk over time. Sixteen patients (latissimus dorsi = 8, rectus abdominis = 7, and gracilis muscle = 1) were evaluated an average of 41 months after free flap transfer. Latissimus dorsi and lower extremity flaps displayed significantly more swelling than the other flaps. Flap bulk was measured by ultrasound. The mean thickness of upper extremity flaps was 10.3 +/- 1.8 mm (control muscles 11.8 +/- 2.8), lower-extremity 14.5 +/- 3.7 mm (control muscles 10.9 +/- 0.7), latissimus dorsi 14.3 +/- 2.2 mm (control muscles 10.3 +/- 0.8, P = 0.018), and rectus abdominis 11.2 +/- 1.2 mm (control muscles 12.4 +/- 1.9). Color Doppler ultrasonography was used to detect the pedicles of the free flaps and also to measure the peak velocity of blood flow intramuscularly and in the pedicles. In the upper extremities (n = 5) the pedicles could be found in only 20% of cases whereas in the lower extremities (n = 11) 91% of pedicles were located. (P = 0.013). Peak flow within the free flaps was significantly higher in the lower extremity (50% of the peak flow of the common femoral artery) than in the upper extremity (5% of the peak flow of the common femoral artery, P = 0.013). This study demonstrated that non-innervated free muscle flaps in the extremities maintain the original muscle thickness, although lower extremity and latissimus dorsi flaps have a trend to be thicker. Most pedicles of free muscle flaps in the upper extremities could not be located by ultrasound. However, flaps in the lower extremities most often have patent pedicles and also more vigorous intramuscular blood flow.     

Consequences of the combined deficiency in dystrophin and utrophin on the mechanical properties and myosin composition of some limb and respiratory muscles of the mouse

The mechanical properties and the myosin isoform composition were studied in three isolated muscles (EDL, soleus, diaphragm) of mutant mice lacking both dystrophin and utrophin (dko). They were compared with the corresponding muscles of the normal and the dystrophin-deficient (mdx) and the utrophin-deficient (uko) mice. In comparison with mdx muscles, dko muscles show a significant reduction of the normalized isometric force, confirmed by the reduced muscular activity of the whole animal. Kinetics parameters (twitch time-to-peak and half-relaxation time) were slightly reduced, and the maximal speed of shortening of soleus, Vmax, was reduced by 30%. The maximal power output (muW/mm3) was reduced by 50% in dko soleus. In the three muscles studied, the relative myosin heavy chains (MHC) composition showed a shift towards slower isoforms. dko EDL presented a dramatic decrease of the resistance ot tetanic contraction with forced lengthenings (eccentric contractions), while muscle lacking only utrophin (uko mutants) display a normal resistance to this exacting mechanical challenge. These experiments suggest that lack of both dystrophin and utrophin is very detrimental to the mice and that mechanical properties of the muscles may explain the overall phenotype. Moreover these results bring some support to the idea that the expression of utrophin in mdx muscle compensates, to some extent, for the lack of dystrophin.     

Developmental transitions in the myosin patterns of two fast muscles

Transitions in myosin patterns were examined in situ by immunofluorescence in two fast muscles of the developing chicken, the pectoralis and the posterior latissimus dorsi. Myosin isoforms were localized using stage-specific monoclonal antibodies against the heavy chain of pectoralis myosin. Two antibodies (12C5 and 10H10) recognize adult and late embryonic myosin. They reacted weakly with both the pectoralis and posterior latissimus dorsi at 10 days in ovo, but intensely at 18 days in ovo. Both muscles were completely unreactive with an adult-specific antibody (5C3), indicating that the staining with 12C5 and 10H10 at 18 days in ovo reflects embryonic myosin. Thus two different embryonic isoforms are expressed sequentially in each muscle. Both 12C5 and 10H10 reacted weakly again with these muscles after hatching. The reappearance of a strong positive response to both antibodies, at 28 days in the pectoralis and after 60 days in the posterior latissimus dorsi, correlated well with the first appearance of a response to the adult-specific antibody, 5C3, signalling the beginning of the adult pattern. Both muscles reacted strongly with an antibody (5B4) specific for 'neonatal' myosin between 18 days in ovo and 60 days after hatching. In the pectoralis, embryonic was replaced by neonatal myosin in most fibres by 14 days after hatching; by 28 days, both adult and neonatal myosin were expressed in most fibres; and in the adult, neonatal myosin was replaced entirely by the adult isoform. In contrast, many fibres in the posterior latissimus dorsi still expressed both embryonic and neonatal myosins up to at least 60 days post-hatch, and the remaining fibres expressed the neonatal isoform; the neonatal isoform was present in some fibres even in the adult posterior latissimus dorsi. We have therefore demonstrated in situ four different heavy chain isoforms in two different fast muscles. 'Early embryonic', 'late embryonic', 'neonatal' and eventually 'adult' isoforms are expressed in each muscle and more than one isoform often coexists in the same fibre.     

Mechanical advantage of skeletal muscle as a cardiac assist power source

The insertion of unconditioned latissimus dorsi muscle at the humerus was reattached in anesthetized goats to the first stage piston of a two stage mechanical-to-hydraulic energy convertor for a skeletal muscle powered ventricular assist device. To study a range of forces, pistons of different cross sectional areas were evaluated during thoracodorsal nerve stimulation. Each energy convertor piston was coupled hydraulically to an actuator on a Thoratec VAD (Thoratec Laboratories, Berkeley, CA) in a mock circulatory loop. Maximum force (70.1 +/- 10.8 N) was greatest for the largest piston, and stroke length (4.0 +/- 0.7 cm) was greatest for the smallest piston. However, maximum stroke work (1.2 +/- 0.5 J) and muscle powered VAD ejected stroke volume (45 +/- 17 ml) were greatest for the middle size piston. These results are consistent with a biomechanical model of whole muscle contraction that predicts that there is an optimum force that produces maximum cycle work. Thus, with a two stage energy convertor, by changing the ratio of the cross sectional areas of the energy convertor and muscle powered VAD actuator pistons, the effective mechanical advantage for the muscle can be optimized to produce more work output and muscle powered VAD flow. Skeletal muscle powered devices using such an energy convertor could provide completely implantable circulatory support free from batteries and other power conditioning hardware required with electromechanical systems.     

Effects of load and tone on the mechanics of isolated human bronchial smooth muscle

Isotonic and isometric properties of nine human bronchial smooth muscles were studied under various loading and tone conditions. Freshly dissected bronchial strips were electrically stimulated successively at baseline, after precontraction with 10(-7) M methacholine (MCh), and after relaxation with 10(-5) M albuterol (Alb). Resting tension, i.e., preload determining optimal initial length (Lo) at baseline, was held constant. Compared with baseline, MCh decreased muscle length to 93 +/- 1% Lo (P < 0.001) before any electrical stimulation, whereas Alb increased it to 111 +/- 3% Lo (P < 0.01). MCh significantly decreased maximum unloaded shortening velocity (0.045 +/- 0.007 vs. 0.059 +/- 0.007 Lo/s), maximal extent of muscle shortening (8.4 +/- 1.2 vs. 13.9 +/- 2.4% Lo), and peak isometric tension (6.1 +/- 0.8 vs. 7.2 +/- 1.0 mN/mm2). Alb restored all these contractile indexes to baseline values. These findings suggest that MCh reversibly increased the number of active actomyosin cross bridges under resting conditions, limiting further muscle shortening and active tension development. After the electrically induced contraction, muscles showed a transient phase of decrease in tension below preload. This decrease in tension was unaffected by afterload levels but was significantly increased by MCh and reduced by Alb. These findings suggest that the cross bridges activated before, but not during, the electrically elicited contraction may modulate the phase of decrease in tension below preload, reflecting the active part of resting tension.     

Effects of chronic low frequency stimulation on contractile and elastic properties of hindlimb suspended rat soleus muscle

Chronic low frequency stimulation (10 Hz, 8 h x day[-1]) was used in this study to prevent the changes in the contractile and elastic properties of rat soleus muscles induced by 3 weeks of hindlimb suspension (HS). Results showed that electrostimulation was able to counteract in part the decrease in soleus muscle mass and tension output induced by unweighting. On the other hand, the increases in maximal shortening velocity and twitch speed following HS were not prevented by stimulation. Unweighting was responsible for an increase in series elastic compliance of soleus muscle. Chronic stimulation successfully counteracted this increase in series compliance probably by changing the properties of the tendon. The partial recovery of muscle mass and tension output as a result of stimulation enhanced the role of contractile activity in preventing muscle atrophy. Moreover, the inefficiency of the tonic activity imposed by stimulation in preventing the increase in twitch speed of soleus muscle during HS demonstrated the primacy of neuronal activity. Discrepant results concerning changes in contraction kinetics deduced from the twitch could have been due to the fact that such myograms also depend on the series compliance.     

Function of the diaphragm during exercise]

We evaluated the effect of global inspiratory muscle fatigue (GF) on respiratory muscle control during exercise at 30%, 60%, and 90% of maximal power output in normal subjects. Fatigue was induced by breathing against a high inspiratory resistance until exhaustion. Respiratory pressures, breathing pattern, and perceived breathlessness were measured. Induction of GF had no effect on the ventilatory parameters during mild and moderate exercise. It altered, however, ventilatory response to heavy exercise by increasing breathing frequency and minute ventilation, with minor changes in tidal volume. This was accompanied by an increase in perceived breathlessness. GF significantly increased both the tonic and phasic activities of abdominal muscles that allowed 1) the diaphragm to maintain its function while developing less pressure, 2) the same tidal volume with lesser shortening of the rib cage inspiratory muscles, and 3) relaxation of the abdominal muscles to contribute to lung inflation. The increased work performed by the abdominal muscles may, however, lead to a reduction in their strength. GF may impair exercise performance in some healthy subjects that is probably not related to excessive breathlessness or other ventilatory factors. The respiratory system is remarkably adaptable in maintaining ventilation during exercise even with impaired inspiratory muscle contractility.