Maximum Isometric Tetanic Tension Research Articles

The effect of mesenchymal stem cells in a PEGylated fibrin gel seeded on an extracellular matrix on skeletal muscle recovery in a volumetric muscle loss model

This study investigated the effect of mesenchymal stem cells (MSCs) in a PEGylated fibrin gel (PEG) seeded into an acellular extracellular matrix (ECM) on recovery of skeletal muscle following volumetric muscle loss (VML) injury. Approximately 1/3 of the mass of the lateral gastrocnemius (LGAS) was removed from 6–9 month male Sprague‐Dawley rats, and immediately replaced with an ECM of the same dimensions. One week later, animals were injected with: saline (SAL), MSCs, PEG, or MSCs in PEG (PEG+MSC). Fifty‐six days after injury, LGAS maximal isometric tetanic tension (Po) of the PEG+MSC treated group was significantly higher compared to all other treatments due to greater mass. The specific tension (N/cm2) however, was only significantly higher compared to SAL and PEG groups. Myofiber cross‐sectional area (CSA) was evaluated throughout the implanted scaffold. Cell‐treated groups trended towards a greater percentage of larger myofibers compared to SAL and PEG groups. These findings suggest that MSCs provide the main regenerative stimulus when infused at 7 days, and demonstrates their importance in regeneration in VML injury models. Functional assessments via neural stimulation demonstrated neural regeneration, however long–term viability is yet to be determined.

Efficacy and evaluation of safety of sclerosants for intramuscular venous malformations: Clinical and experimental studies

Excision of intramuscular venous malformations may damage intact functional muscles, and sclerotherapy is an alternative way of relieving symptoms. Several sclerosants are available, but selection of the optimal one is controversial. We report our clinical experiences of sclerotherapy, and experimental studies in rats that investigated muscular damage after injection of various sclerosants. For the clinical study, 10 patients with intramuscular venous malformations were reviewed who had been treated by sclerotherapy using ethanolamine oleate. The rate by which the volume reduced was assessed quantitatively using findings from magnetic resonance imaging (MRI). Pain was cured or improved in all cases, and volume reduced on imaging analysis. There were no severe complications such as renal failure or thromboembolism. For the experimental study, 62 Wistar rats were used to investigate the toxicity of sclerosants on the intact-muscle by injecting three types of sclerosants (100% ethanol, 5% ethanolamine oleate, and 1% polidocanol). After the injection of each sclerosant into the anterior tibial muscle, the daily measurement of the circumference of the legs, histological and morphological alterations in the muscles, and maximal isometric tetanic tension, were investigated. Swelling was most prominent with ethanolamine oleate, while destruction and atrophy of the muscle were most prominent after injection of ethanol. In the clinical study, the efficacy of 5% ethanolamine oleate was at least equivalent or possibly superior to that of 100% ethanol. In the experimental study, ethanol had a more detrimental effect on muscles than the other agents. We consider that ethanolamine oleate is the most suitable sclerosant for the treatment of intramuscular venous malformations.

Skeletal Muscle Transection Injury with Tissue Loss

Despite skeletal muscle’s regenerative capacity, injuries resulting in transection of the fibers and muscle tissue loss can lead to permanent functional loss. Studies with skeletal muscle transection injury-induced functional loss and recovery generally only use laceration models. Many severe skeletal muscle injuries however, result in the loss of muscle tissue. In order to determine the functional deficit following an injury with tissue loss, a model was developed in which portions of the lateral gastrocnemius (GAS) of Sprague-Dawley rats were removed. Maximal isometric tetanic tension and twitch tension were measured following the removal of either a 0.5cm × 1.0cm (SDEF) or a 1.0cm × 1.0cm (LDEF) piece of the GAS. The maximal force produced immediately after creation of the defect was 88.3 +/− 2.0% of the non-operated contralateral GAS force for SDEF and 76.9 +/− 3.2% for LDEF. Fourteen days post-defect, the maximal force produced was 88.1 +/− 5.6% for SDEF and 80.7 +/− 3.5% for LDEF of the control. Twenty-eight days post-defect, the maximal force produced was 80.9 +/− 1.0% for LDEF. These data suggest that little to no functional regeneration occurs in the defected muscle in the first four weeks.

The contribution of contractile pre-activation to loss of function after a single lengthening contraction

Purpose: Some muscle injuries are the result of a single lengthening contraction. Our goal was to evaluate the contributions of angular velocity, arc of motion, and timing of contractile activation relative to the onset of joint motion in an animal model of muscle injury using a single lengthening contraction. Methods: The intact tibialis anterior (TA) muscle of rats was activated while lengthened, preceded by a maximal isometric contraction of 0, 25, 50, 100, or 200ms. The lengthening contraction was performed at two different angular velocities (300 or 900°/s) and through two different arcs of motion (90° or 45°). Results: Muscle contractile function, as measured by maximal isometric tetanic tension, was significantly decreased only when the TA was activated at least 50ms prior to the motion, regardless of angular velocity or arc of motion. Conclusion: The data indicated that the duration of an isometric contraction prior to a single lengthening contraction determined the extent of muscle injury irrespective of two different angular velocities.

Length-tension relationship of the feline thyroarytenoid muscle

Vocal fold tension during phonation is generated by coordinated contraction of the intrinsic laryngeal muscles. The thyroarytenoid muscle has been found to have increased stiffness at various levels of strain when compared with other intrinsic laryngeal muscles. The objective here is to test the hypothesis that the thyroarytenoid muscle exhibits high passive tension during maximal isometric tetanic force generation, and to test the hypothesis that the thyroarytenoid maintains the ability to generate contractile force at high levels of strain more effectively than other skeletal muscle. The thyroarytenoid muscles (n = 9) and digastric muscle strips (n = 7) were removed from adult random-bred cats. Maximal isometric tension and passive tension at optimum length were measured from each muscle in vitro. Active and passive length-tension curves were constructed for each muscle. The contractile properties of the thyroarytenoid group were compared with those of the digastric muscle group. The thyroarytenoid muscle group required on average 140 mN of passive tension to generate maximal isometric tetanic tension. This represented 39% of the average maximal isometric tetanic tension generated by the muscles. These results were significantly higher than the digastric muscle group, which required on average 28 mN of passive tension (9% of maximal isometric tetanic tension, p<0.05). At 110% of optimum length, the thyroarytenoid muscle maintained 89.8% of maximal isometric tetanic force, whereas the digastric muscle group maintained 67.7% of maximal isometric tetanic force ( p<0.05). The thyroarytenoid muscle exhibits higher passive tension when generating maximal isometric tension than the digastric muscle control group. The thyroarytenoid muscle maintains higher levels of active tension at high strain than the digastric muscle control group. We conclude that these findings are related to the ability of the thyroarytenoid muscle to function as a fine tensor of the vocal fold in a high strain environment.

Use of Anabolic Steroids to Attenuate the Effects Glucocorticoids on the Rat Diaphragm

Administration of glucocorticoids results in atrophy and contractile dysfunction in the rat diaphragm. Anabolic steroids may be useful in preventing atrophy and contractile dysfunction. The purpose of this study was to assess the effects of simultaneous administration of testosterone and glucocorticoids on morphological and contractile properties of the rat diaphragm. Eighty-eight adult female Sprague-Dawley rats were divided into 1 of 4 groups: a control group that was given sham injections for 13 days (CONT group, n=23), a group that was given prednisolone injections (0.5 mg/100 g) for 10 days (PRED group, n=23), a group that was given testosterone injections (0.5 mg/100 g) for 13 days (TEST group, n=18), and a group that was given a combination of prednisolone and testosterone injections (0.5 mg/100 g) for 10 and 13 days, respectively (COMBO group, n=23). The animals were weighed daily, and drug doses were adjusted to changes in body mass. Twenty-four hours following the final injection, animals were weighed and sacrificed and the diaphragm was removed and weighed. A small strip of diaphragm was attached to a force transducer to determine normalized maximal isometric tetanic tension (PO). Body weights in the PRED group were decreased by 26% as compared with body weights in the CONT group, and body weights in the COMBO group were decreased by 11% as compared with body weights in the CONT group. Diaphragm weights in the PRED and COMBO groups were decreased by 22% and 12%, respectively, as compared with diaphragm weights in the CONT group. Normalized maximal isometric tetanic tension was decreased by 11% in the PRED group as compared with PO in both the CONT and TEST groups and was decreased by 13% as compared with PO in the COMBO group. There was no difference in PO among the CONT, TEST, and COMBO groups. The results support the hypothesis that simultaneous administration of testosterone with glucocorticoids would prevent a decrease in PO. The results indicate that simultaneous administration of testosterone with glucocorticoids prevented the loss in body weight and partially attenuated the loss in diaphragm weight that is commonly observed when glucocorticoids are given alone. These data support the notion that testosterone may be useful in the prevention of glucocorticoid-induced atrophy.

Muscle impairment occurs rapidly and precedes inflammatory cell accumulation after mechanical loading.

Modified muscle use can result in muscle atrophy and impairment. We tested whether inflammatory cell concentrations correlate temporally with muscle impairment during modified loading periods. Rat hindlimbs were unloaded for 10 days followed by reloading. The density of neutrophils and ED1+ macrophages was significantly increased by 16.5- and 9.8-fold, respectively, after 1 day of reloading. ED2+ macrophage concentration was not significantly increased until 3 days of reloading. Maximal isometric tetanic tension (P(o); N/cm2) decreased during hindlimb suspension (HS), which was followed by a second drop in P(o) after 2 h of reloading. This latter loss in muscle force was uncoupled with the significant elevation in muscle inflammatory cell concentrations. Experiments where HS soleus muscles were incubated with caffeine revealed that at least 40% of the P(o) decrement at 2 h could be associated with a loss of efficiency of the excitation-contraction (E-C) coupling process. These data suggest that an important mechanism for the early loss in force is the inability to activate the contractile machinery likely caused by a failure in the E-C coupling process during the reloading period.

Effect of chronic K+ deficiency on contractile properties of soleus muscle in rats: evidence of sex differences.

1. Alterations in skeletal muscle function of chronically K(+)-depleted male and female rats were investigated in isolated soleus muscles. 2. By 16 weeks K+ deficiency, plasma K+ concentrations in both male and female rats were reduced to approximately 2 mEq/L, which was accompanied by an approximate 50% reduction in muscle K+ content and a marked increase in muscle Na+ content. These changes were similar in both males and females. 3. Plasma creatine phosphokinase activity progressively increased with time in K(+)-depleted male rats, whereas only a slight increase was observed in female rats. 4. Maximum isometric twitch tension (Pt) and tetanic tension (Po) of K(+)-depleted soleus muscles from male rats was markedly suppressed; this was not seen for soleus muscles obtained from female rats. 5. After exposure to insulin in low-K+ solution, the contractile tension of soleus from the K(+)-depleted male rats was suppressed to a greater extent. 6. All alterations in muscle function during chronic K+ depletion were restored to normal after 2 weeks K+ repletion. 7. The results suggest that there is a preponderance for male over female rats in developing alterations in skeletal muscle function during chronic K+ deficiency. The changes may be associated with abnormalities of muscle membrane permeability and cellular function.

Behavior and muscle performance in heterothermic bats.

Body temperatures of winter-resident Korean bats typically range from 10 degrees to 40 degrees C between August and September and from 3 degrees to 15 degrees C between January and April. To learn how behavior and the motor systems of heterothermic bats respond to this body-temperature variation, we examined whole-organism performance and the temperature-dependence of contractile properties of flight muscle in Murina leucogaster ognevi. In winter and midspring, the lowest limits of body temperature were 8 degrees C for biting and crawling, 16 degrees C for visually observable shivering, 22 degrees C for wing flapping (without powered flight), and 28 degrees C for aerial flight. In summer, the lowest temperature limits changed little for biting and wing flapping, but the temperature limits increased about 3 degrees C for crawling, shivering, and flight. Maximum isometric tetanic tension of the isolated biceps brachii muscle was almost insensitive to tissue temperatures between 10 degrees and 40 degrees C, with an average temperature coefficient of 1.02 in summer and of 0.96 in winter. Rate of tetanic tension production between 10 degrees and 40 degrees C and shortening velocity and power between 15 degrees and 25 degrees C were temperature sensitive, with average temperature coefficients of 1.3-2.3. Seasonal differences in contractile properties within each temperature were not significant, except for maximum tetanic tension at 30 degrees - 40 degrees C. Thus, the motor system of the bats had functional capacity over the range of body temperature experienced in winter to summer. The temperature-dependence of behavior was consistent with muscle physiology. The defensive behaviors, like biting and crawling, observed at 8 degrees - 12 degrees C body temperature could be exerted by using temperature-independent tetanic tension, whereas activities, such as flight, that require power generation would be restricted to higher body temperatures by temperature-sensitive rate properties. Some rate processes appeared to be more temperature sensitive in summer than in winter.

Modulation of myosin isoform expression by mechanical loading: role of stimulation frequency.

This study tested for the hypothesis that mechanical loading, not stimulation frequency per se, plays a key role in determining the plasticity of myosin heavy chain (MHC) protein isoform expression in muscle undergoing resistance training. Female Sprague-Dawley rats were randomly assigned to resistance-training programs that employed active 1) shortening (n = 7) or 2) lengthening contractions (n = 8). The medial gastrocnemius (MG) muscles in each group trained under loading conditions that approximated 90-95% of maximum isometric tetanic tension but were stimulated at frequencies of 100 and approximately 25 Hz, respectively. Lengthening and shortening contractions were produced by using a Cambridge ergometer system. The MG muscles trained every other day, performing a total of 16 training session. Both training programs produced significant (P < 0.01) and similar reductions in the fast type IIB MHC protein isoform in the white MG muscle, reducing its relative content to approximately 50% of the total MHC protein isoform pool. These changes were accompanied by increases in the relative content of the fast type IIX MHC protein isoform that were of similar magnitude for both groups. The results of this study clearly demonstrate that stimulation frequency does not play a key role in modulating MHC isoform alterations that result from high-resistance training.

Upper airway collapsibility, and contractile and metabolic characteristics of musculus uvulae

Physiologic, metabolic, and histochemical characteristics of one upper airway (UA) dilator muscle (musculus uvulae; MU) differ between sleep apnea hypopnea syndrome (SAHS) and nonapneic snorers. We hypothesized that these differences in MU characteristics could result from the cumulative effects of the diurnal and nocturnal intermittent contractions of UA muscles in order to compensate for a permanent increase in UA collapsibility. The aim of this study was to determine the influence of UA collapsibility on MU characteristics. Seventeen SAHS and three nonapneic snorers, who underwent an uvulo-palato-pharyngoplasty as a treatment for snoring or SAHS, participated in the study. Awake and sleeping UA critical pressure (Pcrit) was measured during continuous positive or negative airway pressure trials by analysis of the relationship between maximal inspiratory flow and the upstream pressure of flow-limited breathing cycles. Maximum isometric twitch (Pt) and tetanic tension (Po), fatigability measurements, activities of marker enzymes for anaerobic and aerobic-oxidative profile, and fiber type proportions and areas of MU were determined. There was a significant positive relationship between Pt, Po, and Pcrit measured during wakefulness and sleep. The fatigability index was negatively correlated with awake Pcrit values (r = -0.79). Activity level of the anaerobic enzymes as well as the percentage of surface occupied by type I and type IIA muscle fibers as correlated witb awake Pcrit. We conclude that the differences in awake UA collapsibility help to determine the contractile properties and metabolic and histochemical characteristics of MU.

Materials fatigue initiates eccentric contraction-induced injury in rat soleus muscle.

1. The initiation of exercise-induced muscle injury is thought to be the result of high tensile stresses produced in the muscle during eccentric contractions. Materials science theory suggests that high tensile stresses could initiate the injury during the first eccentric contraction (normal stress theory) or after multiple eccentric contractions (materials fatigue). It was the objective of this study to investigate the two possibilities. 2. Rat soleus muscles (n = 66; 11 protocols with 6 muscles per protocol) were isolated, placed in an oxygenated Krebs-Ringer buffer at 37 degrees C, and baseline measurements were made. The muscle then performed an injury protocol which consisted of between zero and ten eccentric contractions (muscle starting length = 0.90 soleus muscle length, L0; length change = 0.25 L0; velocity = 1.5 L0/s; peak force = 180% maximal isometric tetanic tension (P0); time between contractions = 4 min; total duration of the injury protocol = 40 min). At the end of the injury protocol, the muscle was incubated in buffer for 1 h; every 15 min, an isometric twitch and tetanus were performed and lactate dehydrogenase (LDH) release was measured. Total muscle [Ca2+] was measured at the end of the incubation. 3. Change-point regression analysis indicates that at 0 min into the incubation, declines in P0, maximal rate of tension development (+dP/dt), maximal rate of relaxation (-dP/dt), and muscle stiffness (dP/dx) became significantly greater after eight eccentric contractions (p < or = 0.05). No relation was found between the number of eccentric contractions performed and the LDH activity at 0 min into the incubation, although after 60 min of incubation, LDH activity in the buffer was linearly related to eccentric contraction number (p = 0.01). There was no relationship between total muscle [Ca2+] and eccentric contraction number. These findings support the materials fatigue hypothesis of exercise-induced muscle injury.

Effects of hyperphosphatemia on diaphragmatic strength and endurance.

Effects of an infusion of Na2HPO4 on diaphragm strength, endurance, and magnitude of recovery were evaluated in in situ canine diaphragm strips. Results showed no effect on maximal isometric tetanic tension. Twitch tension and tension in the low- (10-Hz) frequency range were significantly increased (P less than 0.01). Time to fatigue (endurance) increased by 38 +/- 4.5% in the group that received phosphorus compared with its control and decreased by 18.5 +/- 2.5% in the group that received dextrose compared with its control (P less than 0.005). Recovery from fatigue was also significantly improved after the phosphorus infusion. Serum ATP and 2,3-diphosphoglycerate levels were unchanged throughout the experiment. The results of this study support the notion that hyperphosphatemia improves diaphragmatic endurance and recovery from fatigue. The mechanisms involved may in part be due to the phosphate-buffering effects, which limit the extent of the muscle intracellular acidosis produced with fatigue.

Myotrophic effects of an anabolic steroid in rabbit limb muscles.

There has been no reliable evidence that the actions of anabolic steroids extend to limb muscles. In this study, female rabbits were treated with anabolic steroid (nandrolone decanoate) or arachis oil placebo for 4 weeks or 12 weeks. After 12 weeks, tibialis anterior muscles of treated animals showed highly significant increases in wet weight (38%), twitch tension (66%), maximum isometric tetanic tension (48%), maximum cross-sectional area (27%), and specific tension (17%). Fiber type composition showed a significant trend toward a less oxidative metabolic character. The experiments provided clear physiological and morphological evidence of a steroid-induced hypertrophy that was not attributable to fluid retention or changes in body weight. Of the muscles examined, the myotrophic effect was confined to the tibialis anterior muscle; extensor digitorum longus, plantaris, and soleus muscles showed no significant response. The work establishes an experimental model for the responses of limb muscles to anabolic compounds.

Mechanical Properties of Sensitized Airway Smooth Muscle: Shortening Capacity

Fig. 1. Schematic drawing of Voigt's model. SEC::: series elastic component; CE ::: contractile element; PEC ::: parallel elastic component. Importance of Maximal Shortening Capacity of Airway Smooth Muscle Because of the nonspecificity of the increased contractile response of antigen-sensitized airway smooth muscle (SASM), the idea has developed that the primary cause of allergic bronchospasm resides in the contractile apparatus of the SASM (1). In 1979 we studied this possibility and reported (2) that in the ovalbumin-sensitized SASM, both the capacity to shorten (~lmax) and the maximal velocity of shortening (V0) were significantly greater than in the control airway smooth muscle. Interestingly, maximal isometric tetanic tension (Po) remained normal in the SASMs that had been obtained from 2-month-old pups. We concluded that Po is a poor and tardy index of altered contractility. The important finding emerging from this study was the increased ~lmax because it represented the important in vitro analogue to in vivo bronchospasm. It indicated that elucidation of bronchospasm must necessarily focus on mechanisms controlling extent of shortening. Although V0 also increased, suggesting that changes had occurred in the myosin molecule and its enzymatic properties, these did not relate directly to allergic bronchospasm. Recently, we conducted studies (3) on tracheal smooth muscle (TSM) from rats with congenitally hyperreactive airways and obtained similar results. We now describe the results of studies we have reported in the past (4) that deal with

Contractile properties of cat skeletal muscle after repetitive stimulation.

The isometric and force-velocity properties of the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles were investigated immediately after and during recovery from a fatiguing stimulus regime (40 Hz for 330 ms every second for 180 s) in the anesthetized cat. The amplitude of the isometric twitch of FDL was unaffected but in soleus it remained depressed for much of the recovery period. Immediately after stimulation the twitch time to peak of FDL increased to 140% of the control (prefatigue) value and then reverted to control values. The maximum isometric tetanic tension (Po) developed by FDL was reduced to 67% of control values immediately after the stimulus regime, whereas soleus declined to 93% of control. Recovery of maximum force development was achieved after 45 min in FDL and after 15 min in soleus. The maximum speed of shortening of FDL was reduced to 63% of control values immediately after fatigue; despite some recovery within the first 30 min, it remained depressed during the remainder of the recovery period (up to 300 min). Maximum speed of shortening was unaltered in soleus. The a/Po value transiently increased to 176% of control values in FDL immediately after the fatigue regime but promptly returned to control values. Force-velocity properties of soleus were not affected by the stimulus regime. It is concluded that in FDL changes in the maximum speed of shortening and maximum isometric tension as a result of the stimulus regime are attributable to changes in the intrinsic behavior of cross-bridges and the metabolic status of the fibers, particularly in the fast-twitch fatigue-resistant fibers.

Force-velocity properties of fatigue-resistant units in cat fast-twitch muscle after fatigue.

The isometric and force-velocity properties of an identified and uniform population of fast-twitch, fatigue-resistant (FR) fibers within the flexor digitorum longus (FDL) muscle were investigated before, immediately after, and during recovery from a fatiguing repetitive isometric stimulus regime (40 Hz for 330 ms every s for 180 s) in the anesthetized cat. It was necessary to determine the smallest fraction of muscle that had the same force-velocity properties as the whole muscle. This was approximately 15% for FDL; if the fraction was less, the maximum speed of shortening was depressed and the a/Po value increased. Motor units were enlarged by partial denervation of the muscle, causing the intact motoneurons to sprout and incorporate more muscle fibers; FR units showed the greatest increase. Immediately after the fatigue regime, maximum isometric tetanic tension declined to 67% but subsequently recovered to 90% of the control value by the end of the 60-min recovery period. Maximum speed of shortening dropped to 71% of the control but after 30 min had recovered and did not differ significantly from control values. It is concluded that the capacity for recovery from fatigue is greater for FR units than for a whole muscle, which also contains fast-fatiguable units, and that the mechanisms involved in the recovery of the maximum isometric tension and maximum speed of shortening are independently regulated.

Force-velocity constants in smooth muscle: afterloaded isotonic and quick-release methods.

In using pharmacologic stimuli, force-velocity (FV) curves are usually obtained by the method of quick release (QR) and redevelopment of shortening at peak tetanic tension; the advantage of the method being that the active state is at maximum. However, the QR may itself reduce the intensity of the active state and result in reduced values of FV constants. We tested this by delineating FV curves in canine tracheal smooth muscle using both conventional afterloaded isotonic contractions (ALI), and redevelopment of shortening after QR methods. For both these studies a supramaximal tetanizing electrical stimulus was used. The analysis of 11 experiments revealed that the latter method resulted in statistically significant reductions of all FV constants except for Po (maximum isometric tetanic tension). The means and standard errors for the sets of constants for the ALI and QR, respectively, are as follows: Vmax (maximum velocity of shortening) = 0.275 lo (optimal muscle length)/s +/- 0.024 (SE), and 0.216 lo/s + 0.023; a (hyperbolic constant with units of force) = 294 g/cm2 +/- 35 and 236 g/cm2 +/- 32; b (hyperbolic constant with units of velocity) = 0.059 lo +/- 0.004 and 0.039 lo/s +/- 0.005; a/Po = 0.214 +/- 0.028 and 0.182 +/- 0.026; and Po = 1.362 kg/cm2 +/- 0.106 and 1.294 kg/cm2 +/- 0.097. These data clearly show that the quick-release method for measuring force-velocity relationships in canine smooth muscle results in significant underestimates of muscle shortening properties.

Characteristics of cat skeletal muscles grafted with intact nerves or with anastomosed nerves

Grafting of 3-g extensor digitorum longus (EDL) muscles of cats may be made with (i) severence of the nerve with spontaneous reinnervation, termed standard grafts (ii) severence of the nerve with reinnervation facilitated by anastomosis of the nerve, termed nerve-anastomosed grafts; and (iii) preservation of the nerve, termed nerveintact grafts. In previous studies, standard grafts developed a maximum isometric tetanic tension (P 0) that was 22% of the value for control EDL muscles. We hypothesized that the low values of P 0 resulted from incomplete reinnervation of muscle fibers. To test this hypothesis, EDL muscles were grafted in cats with nerves intact and with nerves anastomosed. In standard grafts differences were observed in both structure and function at 120 compared with 240 days after grafting. Characteristics of the nerve-intact and nerve-anastomosed grafts did not change significantly between 120 and 240 days and the data were pooled for comparisons with control EDL muscles. Nerve-anastomosed and nerve-intact grafts developed P 0 values that were 34 and 64% of the control values, respectively. Nerve-intact grafts had a mass and fiber cross-sectional area not different from control EDL muscles. Compared with control values, all grafts had fewer fibers, more connective tissue, lower absolute and normalized P 0, reduced capillary density, and increased fatigability. The greater P 0 of nerve-intact compared with standard and nerve-anastomosed grafts supported our hypothesis that the degree of reinnervation is a factor that limits graft development. The presence of a necrotic core and the low tension development of even the nerve-intact grafts suggested that revascularization is a significant limitation as well.

Mechanics and energetics of lengthening of active airway smooth muscle.

For smooth muscle in general there appears only one report dealing with force-velocity (FV) relationships of active muscle subjected to forcible elongation by application of loads (P) greater than its maximum isometric tetanic tension (Po); for airway smooth muscle (ASM) there is none. Since ASM may be subjected to increasing stretch during inspiration, the relationship is important and was therefore studied with canine tracheal smooth muscle (TSM) as a model. FV data for P less than Po could be fitted by Hill's hyperbolic equation. For P greater than Po, lengthening velocity was greater than predicted by the equation. However at equivalent velocities, the muscle during elongation could support a load three times greater than during shortening; in this it resembled skeletal muscle. From this it may be speculated that distension of the airway during inspiration would not be associated with mechanical instability. With reference to energy requirements of the elongating TSM it was shown, as has been for skeletal muscle, that the net rate of energy liberation (assessed by measuring tissue levels of adenosine triphosphate and creatine phosphate) in an elongating active muscle is less than that of a muscle contracting isometrically.