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Sepsis has been shown to impair ventilatory muscle function. To determine whether this can be attributed to direct effects of inflammatory mediators on muscle fibers, we carried out in vitro studies on hamster costal diaphragm. Baseline measurements included supramaximal peak twitch (Pt) and tetanic tension (Po), twitch half relaxation time (1/2RT) and time-to-peak tension (TTP), and force frequency response (15 to 80 Hz). Fatigability was evaluated using 60-Hz stimulations at a duty cycle of 0.4 until tension fell to 50% of baseline. Preparations were then incubated in one of the following for 60 min: (1) Krebs solution (n = 5), (2) nonstimulated monocyte supernatant (n = 5), or (3) lipopolysaccharide-stimulated monocyte supernatant (n = 5). Baseline Pt, Po, 1/2RT, TTP, force frequency response, and fatigue profile were similar between groups. After incubation there was a significant fall in Pt (mean +/- SD, 538 +/- 65 to 288 +/- 13 g/cm2, p < 0.05) and Po (1,268 +/- 132 to 921 +/- 64 g/cm2, p < 0.05) in the LPS group, with no change in the other groups. There was no change in TTP; however, 1/2RT was lower in the LPS-stimulated group after incubation (p < 0.05). There was a rightward shift in the force frequency response for the LPS-stimulated group (p < 0.05). When normalizing for initial Po, there was no significant change in the time to fatigue for any of the three groups. This study demonstrated that monocyte secretory products impair diaphragmatic contractility in vitro by a direct effect on muscle fibers.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the regenerative capacity of mdx skeletal muscle, changes in contractile properties of the fast-twitch extensor digitorum longus (EDL) of normal and mdx mice were studied at 7 and 16 weeks of age, following denervation and devascularization (DD) at 4 weeks of age. At 7 weeks, DD EDL of both strains showed significantly decreased isometric twitch and tetanus tensions compared with their non-DD controls. By 16 weeks, normal operated muscle exhibited a recovery of 57% and 58% of absolute tetanus and twitch tensions while the mdx EDL recovered remarkably to 96% and 99% of 7-week values. At 7 weeks, the DD EDL of both strains exhibited significantly slower time-to-peak (TTP) and one-half relaxation time (1/2RT). By 16 weeks, TTP and 1/2RT of the mdx DD EDL no longer differed from non-DD controls, but the normal EDL showed slowed TTP. No differences were found in the maximum velocity of shortening (Vo) or in posttetanic potentiation (PTP). Following DD, there was an increase in resistance to fatigue in both strains at 7 weeks. This resistance persisted at 16 weeks in the normal mouse, but the operated mdx EDL returned to normal. It would appear that following a denervation/devascularization insult, the mdx EDL is able to recover contractile characteristics to a remarkably larger extent than normal EDL.

Isometric tension and instantaneous stiffness were measured in frog semitendinosus single muscle fibers in both isotonic and hypotonic Ringer solution. In 0.7 and 0.5 x normal Ringer tension increased 17 and 20%, respectively. There was no corresponding increase in the measured stiffness. The increase in tension in hypotonic Ringer could be reversed by the addition of an osmotic equivalent of sucrose to the bathing solution. These findings suggest that the potentiated tension observed in hypotonic Ringer is due to an increased tension per cross-bridge and not to an increase in the number of attached cross-bridges.

The isometric contractile properties of frog (Rana pipiens) and toad (Bufo bufo) sartorii have been studied over the temperature range from 0 to 20 degrees C. The isometric twitch tension was found to vary considerably between these two species and between muscles in the same species. Between 0 and 4 degrees C there was very little change in maximum isometric twitch tension. Between 4 and 12 degrees C several muscles from frog or toad showed a potentiation of twitch tension whereas others showed a decline. Over this temperature range the toad sartorii consistently demonstrated a greater potentiation. By 12 degrees C a steady decline in twitch tension in both muscles was seen as the temperature range the toad sartorii consistently demonstrated a greater potentiation. By 12 degrees C a steady decline in twitch tension in both muscles was seen as the temperature approached 20 degrees C. The maximum isometric tetanic tension recorded between 18 and 20 degrees C increased fractionally to an average of 1.504 +/- 0.029 (n = 4) for frog sartorii and to 1.377 +/- 0.008 (n = 5) for toad sartorii. The time to peak twitch tension and the half-relaxation time decreased markedly with an increase in temperature. Moreover, the half-relaxation time was reduced by a greater proportion than the time to peak twitch tension. Measurements of instantaneous stiffness by controlled velocity releases from the plateau of isometric tetani revealed that the large increase in isometric tetanus tension as the muscle was warmed was not accompanied by a corresponding increase in the total number of active cross-bridges. The possibility that a decreased availability of intracellular Ca2+ ions at the contractile sites contributing to the fall of isometric twitch tension at elevated temperatures is discussed. The possibility exists that at elevated temperatures a change inthe intrinsic contractile ability of the muscle occurs which produces an increased tension per cross-bridge.

1. The method of controlled releases was used to obtain tension-extension curves in toad (Bufo bufo) sartorii under a variety of conditions at 0 degrees C.2. The curves obtained were approximately linear over a considerable range of force (0.4P(0) to P(0)) if the releases were given from the plateau of tetanic tension. The slope of this linear region was little affected by changes of release velocity in the range 10-120 mm/sec.3. Such changes as did occur with alterations in release velocity could be quantitatively accounted for in terms of the internal shortening predicted by A. V. Hill's two-component model.4. As the muscles were stretched above l(0), we found that the maximum stiffness of the tetanized muscles fell in much the same way as the maximum developed force, P(0).5. In another series of experiments we found a rapid change in the overall shape of the tension-extension curve during the early phase of force development in an isometric tetanus. The stiffness of the muscle increased with increasing developed force during this period.6. The force-velocity curve in these muscles was measured by two methods, both giving a similar result. Surprisingly, toad muscle appears to have about the same intrinsic speed as frog muscle at 0 degrees C. The a.b product from our experiments is considerably greater than the reported values for the maintenance heat rate at 0 degrees C in these muscles.7. The probable site of the variable compliance in active muscle is discussed. It seems most likely that this is within the A-band, perhaps in the cross-bridges themselves.

Changes in contractile properties of developing fast-twitch skeletal muscle of the C57/BL6J mouse were studied following neonatal denervation. A sciatic neurectomy was performed at 1 day of age and then denervated and control muscles were examined at 7, 14, and 21 days postdenervation. In addition, normal muscles were studied at 1 day of age. The denervated muscles exhibited prolongation of time-to-peak twitch tension and half-relaxation time, a slowing of the maximum velocity of shortening, and a marked increase in resistance to fatigue compared with controls. Isometric tetanus tension was reduced compared to the control muscle both in absolute terms and when expressed relative to body weight at all ages studied. The absolute isometric twitch tension was reduced at 7 and 14 days, but was reduced only at 21 days when expressed as a fraction of the muscle weight. Post-tetanic twitch potentiation failed to appear in the denervated muscle. It would appear that neonatal denervation results in an uncoupling of the developmental pattern of skeletal muscle.

1. A study has been carried out of the tension responses of single fibres from frog semitendinosus muscle at 4 degrees C which occur in response to rapid lengthening and shortening steps throughout the isometric tetanus. 2. Instantaneous stiffness values were calculated as the ratio of the tension change to the length change. 3. Stiffness was seen to increase more rapidly than the tension during the initial development of force and was constant during the tetanus plateau. During the relaxation phase of tension, stiffness declined more slowly than the force up to the shoulder; thereafter both declined rapidly and with a nearly similar time course. 4. Throughout the initial rise of force, the period of maximum force development and the early phase of relaxation, a rapid stretch produced a significantly greater tension change than a rapid release. The fibres appeared 'stiffer' during a stretch. 5. The experimental results are shown to be consistent with the suggestion that cross-bridges may detach during a small rapid shortening step but remain attached during a similar lengthening step.

Our primary aim was to determine if there exists a preferential involvement of the fast-twitch or slow-twitch skeletal muscle fibers in the dy2J/dy2J strain of murine dystrophy. The changes in the contractile properties of the slow-twitch soleus (SOL) and the fast-twitch extensor digitorum longus (EDL) muscles of normal and dystrophic mice were studied at 4, 8, 12, and 32 weeks of age. Isometric twitch and tetanus tension were decreased in the 4- and 8-week-old dystrophic EDL compared with controls, this situation being reversed in the older animals. At 12 weeks, the dystrophic EDL generated 15% more tetanic tension than normal EDL and by 32 weeks no significant difference was seen between normal and dystrophic EDL twitch or tetanus tension. By 8 weeks, dystrophic EDL exhibited a prolonged time-to-peak twitch tension (TTP) and half-relaxation time (1/2RT) of the isometric twitch which continued to 32 weeks. For the dystrophic SOL, decreased twitch and tetanus tension was observed from 4 to 32 weeks. At 8 and 12 weeks, TTP and 1/2RT of dystrophic SOL were prolonged. However, by 32 weeks there was no longer a significant difference seen in TTP or 1/2RT between normal and dystrophic SOL. Our results appear to indicate that a loss of the primary control which is determining the fiber composition of the individual muscles is occurring as the dystrophic process advances.

In this study, conducted on mice of the C57BL/6J+/+ strain, we investigated the differential effects of denervation on the isometric contractile properties of the extensor digitorum longus (EDL) and soleus (SOL) muscles. The contractile properties were studied at 1, 28, 84, and 210 days following unilateral section of the sciatic nerve at 12 weeks of age. When isometric tetanus tension was expressed relative to wet weight, the denervated SOL showed an earlier and more pronounced loss in tension generating capacity than the EDL. Both the denervated SOL and EDL showed potentiation of the twitch tension at 28 days postdenervation. The time to peak twitch tension (TTP) and the time to half-relaxation (1/2RT) were prolonged by 28 days postdenervation in both muscles. This trend continued to the oldest age-groups studied in the EDL, but reached an apparent plateau in the SOL at 84 days postdenervation. In response to fatigue, the denervated SOL showed a marked decrease in resistance to fatigue at 1 day but a relatively normal response thereafter, whereas the denervated EDL showed an increase in resistance to fatigue at and beyond the 28-day period. In spite of the fact that the total contraction time of both muscles increased following denervation, the predominantly oxidative SOL remained a slower contracting muscle than the more glycolytic EDL.

The instantaneous elasticity and maximum isometric tetanic tension of isolated frog and toad sartorii have been measured in hypertonic Ringer solution. Although the mechanical response of contraction muscle continued to decrease as the tonicity of the bathing solution was increased to 1.26 X R, 1.52 X R, and 2.04 X R, a similar change in the instantaneous stiffness could not be shown. This finding was not expected on the basis of our current model of the cross-bridge mechanism which predicts that the instantaneous stiffness is a measure of the total number of tension-generating cross-bridges formed in a stimulated muscle. The compatability of our findings with an electrostatic theory of the cross-bridge mechanism proposed by Iwazumi (1970) is discussed.

The stiffness-tension relationship has been studied during the isometric twitch. All experiments were carried out at 0 degrees C using small fiber bundles from frog semitendinosus. Rapid shortening and lengthening steps of 3-6 nm/hs, complete in 500 mu sec were given at various times during the twitch. Instantaneous stiffness was measured as the ratio of delta P to delta L and expressed as a relative change to the maximum values recorded at the plateau of an isometric tetanus. The time course of the stiffness changes followed the tension for both releases and stretches. However, the stiffness measured with a rapid stretch was higher than when measured with a rapid release. This raises the possibility that the instantaneous elasticity is non-linear in stretches.

Tension responses to ramp shortening of varying speed in whole muscle or single fibres from the plateau of an isometric tetanus, revealed at least two distinct phases. There was a fast initial drop in tension followed by a change of slope and a definite inflexion on the tension record. As the velocity of the imposed length change was increased, the inflexion point appeared at a lower tension. Similar inflexions were not observed during ramp releases to an elastic band or a segment of semitendinosus tendon. The tension records obtained with moderately fast ramp length changes to contracting muscle reflect the T1 and T2 phases of the tension transients.

Presents information pertaining to the inhibition of the contractility of the milrinone in skinned skeletal muscle fibers. Information on the capabilities of milrinone; Attachment of clipped fibers; Estimation of the maximal shortening velocity.