Diaphragmatic relaxation rate after voluntary contractions and uni- and bilateral phrenic stimulation

We compared the rate of relaxation of the diaphragm (RRdi) after unilateral phrenic nerve stimulation, bilateral phrenic nerve stimulations, and short sharp voluntary contractions (sniffs). RRdi was measured as the maximum rate of decline in transdiaphragmatic pressure (Pdi) corrected for the change in Pdi [maximum relaxation rate (MRR)/delta Pdi], the time constant (tau) of the later exponential decline in Pdi, and the time to half relaxation (1/2 RT). In five subjects there was no difference in mean RRdi apart from a smaller MRR/delta Pdi (P less than 0.05) for left unilateral compared with either right unilateral or bilateral needle stimulation. However, RRdi varied unpredictably between unilateral and bilateral stimulation of the phrenic nerve in individual subjects. In the same five subjects, sniffs were found to have a slower RRdi than bilateral stimulations (MRR/delta Pdi 0.0064 +/- 0.0007 vs. 0.0074 +/- 0.0018/ms, tau 57.2 +/- 8.7 vs. 48.2 +/- 7.4 ms, 1/2 RT 108.9 +/- 10.9 vs. 73.9 +/- 6.0 ms; all P less than 0.05). The application and inflation of an abdominal binder to an external pressure of 60 mmHg resulted in a decrease in functional residual capacity (-710 +/- 70 ml), but there was no effect on relaxation parameters. Our findings suggest that in the evaluation of RRdi 1) unilateral hemidiaphragmatic stimulations may not accurately reflect the in vivo contractile properties of the diaphragm, 2) sniff maneuvers are not voluntary equivalents of phrenic nerve stimulations, and 3) RRdi is not affected by abdominal binder inflation up to 60 mmHg.     

Central components of diaphragmatic fatigue assessed by phrenic nerve stimulation

The extent to which diaphragmatic fatigue results from failure of neural drive has been investigated using twitch occlusion. Fatigue was induced by repeatedly generating transdiaphragmatic pressures (Pdi) of either 50 or 75% maximum Pdi (Pdimax) until approximately 10 min after the target Pdi could no longer be reached (Tlim). Maximal bilateral shocks delivered periodically to the phrenic nerves elicited Pdi twitches between breaths (Tr) and superimposed on the voluntary contractions (Ts). The ratio [1 - Ts/Tr], which provides an index of the degree of central nervous system muscle activation, increased as fatigue developed. However, superimposed twitches were still detectable at and beyond Tlim when all contractions involved maximal efforts. They were not seen in maximal contractions of the unfatigued muscle. Initially, the diaphragm electromyogram increased, but then declined. No impairment of neuromuscular transmission was seen. We conclude that at and beyond Tlim about one-half of the reduction in Pdimax resulted from reduced central motor drive; the remainder resulted from peripheral muscle contractile failure. No fatigue was evident during 50% Pdimax dynamic contractions.     

Determinants of transdiaphragmatic pressure in dogs

We measured the transdiaphragmatic pressure (Pdi) during bilateral phrenic nerve stimulation and evaluated the determinants of its change with lung volume, chest wall geometry, and respiratory system impedance in supine dogs. Four rows of radiopaque markers were sewn onto muscle bundles of the costal and crural diaphragm between their origin on the central tendon and their insertion on the rib cage and spine. The length of the diaphragm (L) was determined from the projection images of marker rows using biplane fluoroscopy. Measurements were made at lung volumes between total lung capacity and functional residual capacity before and after the infusion of Ringer lactate solution into the abdominal cavity. In contrast to relaxation, during tetanic stimulation the active lengths of the muscle bundles were similar at all volumes, but the diaphragm assumed different shapes. Although the small differences in active muscle length with volume and liquid loads are consistent with only small changes in muscle force output, Pdi varied by a factor of greater than or equal to 5. There was no single L/Pdi curve that fitted all data during 50-Hz stimulations. We conclude that under these experimental conditions Pdi is not a unique measure of the force produced by the diaphragm and that lung volume, chest wall geometry, and respiratory system impedance are important determinants of the mechanical efficiency of the diaphragm as a pressure generator.     

Mechanics of the canine diaphragm in ascites: a CT study.

Ascites causes an increase in the elastance of the abdomen and impairs the lung-expanding action of the diaphragm, but its overall effects on the pressure-generating ability of the muscle remain unclear. In the present study, radiopaque markers were attached to muscle bundles in the midcostal region of the diaphragm in five dogs, and the three-dimensional locations of the markers during relaxation and during phrenic nerve stimulation in the presence of increasing amounts of ascites were determined using a computed tomographic scanner. From these data, accurate measurements of muscle length and quantitative estimates of diaphragm curvature were obtained, and the changes in transdiaphragmatic pressure (Pdi) were analyzed as functions of muscle length and curvature. With increasing ascites, the resting length of the diaphragm increased progressively. In addition, the amount of muscle shortening during phrenic nerve stimulation decreased gradually. When ascites was 100 ml/kg body wt, therefore, the muscle during contraction was longer, leading to a 20-25% increase in Pdi. As ascites increased further to 200 ml/kg, however, muscle length during contraction continued to increase, but Pdi did not. This absence of additional increase in Pdi was well explained by the increase in the diameter of the ring of insertion of the diaphragm to the rib cage and the concomitant increase in the radius of diaphragm curvature. These observations indicate that the pressure-generating ability of the diaphragm is determined not only by muscle length as conventionally thought but also by muscle shape.     

Aminophylline and human diaphragm strength in vivo

The transdiaphragmatic pressure (Pdi) twitch response to single shocks from supramaximal bilateral phrenic nerve stimulation was studied before and after acute intravenous infusions of aminophylline [14.9 +/- 3.1 (SD) micrograms/ml] in nine normal subjects. Stimulation was performed with subjects in the sitting position against an occluded airway from end expiration. Baseline gastric pressure and abdominal and rib cage configuration were kept constant. There was no significant difference in peak twitch Pdi from the relaxed diaphragm between control (38.8 +/- 3.3 cmH2O) and aminophylline (40.2 +/- 5.2 cmH2O) experiments. Other twitch characteristics including contraction time, half-relaxation time, and maximum relaxation rate were also unchanged. The Pdi-twitch amplitude at different levels of voluntary Pdi was measured with the twitch occlusion technique, and this relationship was found to be similar under control conditions and after aminophylline. With this technique, maximum Pdi (Pdimax) was calculated as the Pdi at which stimulation would result in no Pdi twitch because all motor units are already maximally activated. No significant change was found in mean calculated Pdimax between control (146.9 +/- 27.0 cmH2O) and aminophylline (149.2 +/- 26.0 cmH2O) experiments. We conclude from this study that the acute administration of aminophylline at therapeutic concentrations does not significantly affect contractility or maximum strength of the normal human diaphragm in vivo.     

Diaphragm motor unit recruitment during ventilatory and nonventilatory behaviors

The forces generated by the cat diaphragm (DIA) during different ventilatory and nonventilatory behaviors were determined by measuring transdiaphragmatic pressures (Pdi). The Pdi generated during eupnea was only approximately 12% of the maximum Pdi (Pdimax) generated by bilateral phrenic nerve stimulation. When the animals breathed a gas mixture of 10% O2 and 5% CO2, the Pdi increased to approximately 28% of Pdimax. During total airway occlusion, the Pdi generated by the diaphragm increased to approximately 49% of Pdimax. Only during the gag reflex and sneezing did Pdi reach maximal levels. A model for diaphragm motor unit recruitment during these different behaviors was presented based on the proportion of different motor unit types within the diaphragm, the relative tetanic tensions produced by each unit type, and the assumption of an orderly pattern of motor unit recruitment.     

Use of motor cortex stimulation to measure simultaneously the changes in dynamic muscle properties and voluntary activation in human muscles.

Force responses to transcranial magnetic stimulation of motor cortex (TMS) during exercise provide information about voluntary activation and contractile properties of the muscle. Here, TMS-generated twitches and muscle relaxation during the TMS-evoked silent period were measured in fresh, heated, and fatigued muscle. Subjects performed isometric contractions of elbow flexors in two studies. Torque and EMG were recorded from elbow flexor and extensor muscles. One study (n = 6) measured muscle contraction times and relaxation rates during brief maximal and submaximal contractions in fresh and fatigued muscle. Another study (n = 7) aimed to 1) assess the reproducibility of muscle contractile properties during brief voluntary contractions in fresh muscle, 2) validate the technique for contractile properties in passively heated muscle, and 3) apply the technique to study contractile properties during sustained maximal voluntary contractions. In both studies, muscle contractile properties during voluntary contractions were compared with the resting twitch evoked by motor nerve stimulation. Measurement of muscle contractile properties during voluntary contractions is reproducible in fresh muscle and reveals faster and slower muscle relaxation rates in heated and fatigued muscle, respectively. The technique is more sensitive to altered muscle state than the traditional motor nerve resting twitch. Use of TMS during sustained maximal contractions reveals slowing of muscle contraction and relaxation with different time courses and a decline in voluntary activation. Voluntary output from the motor cortex becomes insufficient to maintain complete activation of muscle, although slowing of muscle contraction and relaxation indicates that lower motor unit firing rates are required for fusion of force.     

Optimal diaphragmatic blood perfusion.

The intrabreath time course of phrenic artery blood perfusion (Qpha) was studied in five anesthetized dogs. The diaphragm was paced with submaximal levels of stimulation at various duty cycles (DC) to achieve tension-time index below and above the fatigue threshold (0.03-0.60). Left Qpha was measured via Doppler technique during control (inactive diaphragm) and during two submaximal levels of bilateral phrenic nerve stimulation sustained for 1 min. Measurements were done when Qpha reached steady state in each run. The frequency of pacing of each run was 10/min, and the DC ranged from 0.1 to 0.9 in 0.1 increments. Shortening of costal and crural segments was measured by sonomicrometry. It was found that Qpha during the diaphragmatic contraction phase (QphaC) was a sigmoidal function of DC and was not affected by the levels of transdiaphragmatic pressure (Pdi) explored (34-64% of maximal Pdi). Qpha during the diaphragmatic relaxation phase (QphaR) was a parabolic function of the DC, reaching an optimal value at DC of approximately 0.3 at any given Pdi. QphaR increased significantly with the preceding level of Pdi. QphaT (the sum of QphaC and QphaR) was a parabolic function of DC, reaching peak values at DC of 0.4-0.6 and then decreasing. This function was similar at two levels of Pdi. Post-pacing hyperemia was directly related to tension-time index greater than 0.20.     

Influence of acute lung volume change on contractile properties of human diaphragm

The effect of stimulus frequency on thein vivo pressure generating capacity of the human diaphragm is unknownat lung volumes other than functional residual capacity. Thetransdiaphragmatic pressure (Pdi) produced by a pair of phrenic nervestimuli may be viewed as the sum of the Pdi elicited by the first (T1Pdi) and second (T2 Pdi) stimuli. We used bilateral anteriorsupramaximal magnetic phrenic nerve stimulation and a digitalsubtraction technique to obtain the T2 Pdi at interstimulus intervalsof 999, 100, 50, 33, and 10 ms in eight normal subjects at lung volumesbetween residual volume and total lung capacity. The reduction in T2Pdi that we observed as lung volume increased was greatest at long interstimulus intervals, whereas the T2 Pdi obtained with short interstimulus intervals remained relatively stable over the 50% ofvital capacity around functional residual capacity. For all interstimulus intervals, the total pressure produced by the pair decreased as a function of increasing lung volume. These data demonstrate that, in the human diaphragm, hyperinflation has a disproportionately severe effect on the summation of pressure responseselicited by low-frequency stimulations; this effect isdistinct from and additional to the known length-tension relationship.

     

Effect of digitalis on the diaphragm in anesthetized dogs

We examined the effect of digitalis on diaphragmatic contractility and fatigability in 19 anesthetized mechanically ventilated dogs. The diaphragmatic force was assessed from transdiaphragmatic pressure (Pdi) developed at functional residual capacity against an occluded airway during cervical phrenic nerve stimulation. In a first group of five dogs, Pdi-stimulus frequency relationships were compared before and after administration of ouabain in doses of 0.01, 0.02, and 0.04 mg/kg. In a second group, diaphragmatic fatigue was produced by bilateral phrenic nerve stimulation at 30 Hz. Ten seconds of stimulation and 15 s of mechanical ventilation were repeated for 30 min. The rates of decrease in Pdi were compared between two groups, one of 0.05 mg/kg deslanoside-treated dogs (n = 7) and one of nontreated dogs (n = 7). After ouabain administration Pdi was significantly greater at each frequency in a dose-dependent manner. On the other hand, the rate of decrease in Pdi in the deslanoside group was significantly smaller than that in the nontreated group, whereas deslanoside did not greatly change the Pdi-frequency curves in fresh diaphragm. We conclude that ouabain improves contractility of the fresh diaphragm and that deslanoside has a protective effect against fatigability.     

Effect of acute nutritional deprivation on diaphragm structure and function

The influence of 90 h of acute nutritional deprivation (ND) on the cross-sectional areas of muscle fibers and the contractile and fatigue properties of the adult rat diaphragm were determined. Isometric contractile properties and fatigue resistance of the diaphragm were measured by means of an in vitro nerve-muscle strip preparation. Contractions were evoked by using phrenic nerve stimulation (left hemidiaphragm) or direct muscle stimulation (right hemidiaphragm) in the presence of curare. Acute ND resulted in a 20% reduction in body weight. No significant decrements in diaphragm or soleus weights were noted in the ND animals compared with controls (CTL), whereas the weight of the medial gastrocnemius was reduced by 20% in the ND animals. Peak twitch and tetanic tensions (normalized for the weight of the diaphragm strip) were not reduced in ND compared with CTL animals after either nerve or muscle stimulation. The fatigue index of the diaphragm was significantly reduced in ND animals only after nerve stimulation. After the fatigue test, there was rapid recovery of the additional fatigue noted with nerve stimulation. The proportions of type I and II muscle fibers of the diaphragm were similar in the CTL and ND animals. No differences in diaphragm cross-sectional areas were noted for either type I or II muscle fibers in the CTL and ND animals. It is concluded that acute ND has no effect on diaphragm contractility or morphometry and only an inconsequential influence on diaphragm fatigue.     

Relative strengths of the chest wall muscles

We hypothesized that during maximal respiratory efforts involving the simultaneous activation of two or more chest wall muscles (or muscle groups), differences in muscle strength require that the activity of the stronger muscle be submaximal to prevent changes in thoracoabdominal configuration. Furthermore we predicted that maximal respiratory pressures are limited by the strength of the weaker muscle involved. To test these hypotheses, we measured the pleural pressure, abdominal pressure (Pab), and transdiaphragmatic pressure (Pdi) generated during maximal inspiratory, open-glottis and closed-glottis expulsive, and combined inspiratory and expulsive maneuvers in four adults. We then determined the activation of the diaphragm and abdominal muscles during selected maximal respiratory maneuvers, using electromyography and phrenic nerve stimulation. In all subjects, the Pdi generated during maximal inspiratory efforts was significantly lower than the Pdi generated during open-glottis expulsive or combined efforts, suggesting that rib cage, not diaphragm, strength limits maximal inspiratory pressure. Similarly, at high lung volumes, the Pab generated during closed-glottis expulsive efforts was significantly greater than that generated during open-glottis efforts, suggesting that the latter pressure is limited by diaphragm, not abdominal muscle, strength. As predicted, diaphragm activation was submaximal during maximal inspiratory efforts, and abdominal muscle activation was submaximal during open-glottis expulsive efforts at midlung volume. Additionally, assisting the inspiratory muscles of the rib cage with negative body-surface pressure significantly increased maximal inspiratory pressure, whereas loading the rib cage muscles with rib cage compression decreased maximal inspiratory pressure. We conclude that activation of the chest wall muscles during static respiratory efforts is determined by the relative strengths and mechanical advantage of the muscles involved.     

Contractile and fatigue properties of the rat diaphragm musculature during the perinatal period.

The following two hypotheses regarding diaphragm contractile properties in the perinatal rat were tested. First, there is a major transformation of contractile and fatigue properties during the period between the inception of inspiratory drive transmission in utero and birth. Second, the diaphragm muscle properties develop to functionally match changes occurring in phrenic motoneuron electrophysiological properties. Muscle force recordings and intracellular recordings of end-plate potentials were measured by using phrenic nerve-diaphragm muscle in vitro preparations isolated from rats on embryonic day 18 and postnatal days 0-1. The following age-dependent changes occurred: 1) twitch contraction and half relaxation times decreased approximately two- and threefold, respectively; 2) the tetanic force levels increased approximately fivefold; 3) the ratio of peak twitch force to maximum tetanic force decreased 2.3-fold; 4) the range of forces generated by the diaphragm in response to graded nerve stimulation increased approximately twofold; 5) the force-frequency curve was shifted to the right; and 6) the propensity for neuromuscular transmission failure decreased. In conclusion, the diaphragm contractile and phrenic motoneuron repetitive firing properties develop in concert so that the full range of potential diaphragm force recruitment can be utilized and problems associated with diaphragm fatigue are minimized.     

Diaphragm curvature modulates the relationship between muscle shortening and volume displacement

During physiological spontaneous breathing maneuvers, the diaphragm displaces volume while maintaining curvature. However, with maximal diaphragm activation, curvature decreases sharply. We tested the hypotheses that the relationship between diaphragm muscle shortening and volume displacement (VD) is nonlinear and that curvature is a determinant of such a relationship. Radiopaque markers were surgically placed on three neighboring muscle fibers in the midcostal region of the diaphragm in six dogs. The three-dimensional locations were determined using biplanar fluoroscopy and diaphragm VD, curvature, and muscle shortening were computed in the prone and supine postures during spontaneous breathing (SB), spontaneous inspiration efforts after airway occlusion at lung volumes ranging from functional residual capacity (FRC) to total lung capacity, and during bilateral maximal phrenic nerve stimulation at those same lung volumes. In supine dogs, diaphragm VD was approximately two- to three-fold greater during maximal phrenic nerve stimulation than during SB. The contribution of muscle shortening to VD nonlinearly increases with level of diaphragm activation independent of posture. During submaximal diaphragm activation, the contribution is essentially linear due to constancy of diaphragm curvature in both the prone and supine posture. However, the sudden loss of curvature during maximal bilateral phrenic nerve stimulation at muscle shortening values greater than 40% (ΔL/L(FRC)) causes a nonlinear increase in the contribution of muscle shortening to diaphragm VD, which is concomitant with a nonlinear change in diaphragm curvature. We conclude that the nonlinear relationship between diaphragm muscle shortening and its VD is, in part, due to a loss of its curvature at extreme muscle shortening.     

Functional adaptation of diaphragm to chronic hyperinflation in emphysematous hamsters

Costal strips of diaphragmatic muscle obtained from animals with elastase-induced emphysema generate maximum tension at significantly shorter muscle fiber lengths than muscle strips from control animals. The present study examined the consequences of alterations in the length-tension relationship assessed in vitro on the pressure generated by the diaphragm in vivo. Transdiaphragmatic pressure (Pdi) and functional residual capacity (FRC) were measured in 22 emphysematous and 22 control hamsters 4-5 mo after intratracheal injection of pancreatic elastase or saline, respectively. In 12 emphysematous and 12 control hamsters Pdi was also measured during spontaneous contractions against an occluded airway. To allow greater control over muscle excitation, Pdi was measured during bilateral tetanic (50 Hz) electrical stimulation of the phrenic nerves in 10 emphysematous and 10 control hamsters. Mean FRC in the emphysematous hamsters was 183% of the value in control hamsters (P less than 0.01). During spontaneous inspiratory efforts against a closed airway the highest Pdi generated at FRC tended to be greater in control than emphysematous hamsters. When control hamsters were inflated to a lung volume approximating the FRC of emphysematous animals, however, peak Pdi was significantly greater in emphysematous animals (70 +/- 6 and 41 +/- 8 cmH2O; P less than 0.05). With electrophrenic stimulation, the Pdi-lung volume curve was shifted toward higher lung volumes in emphysematous hamsters. Pdi at all absolute lung volumes at and above the FRC of emphysematous hamsters was significantly greater in emphysematous compared with control animals. Moreover, Pdi continued to be generated by emphysematous hamsters at levels of lung volume where Pdi of control subjects was zero.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contractile properties of feline genioglossus, sternohyoid, and sternothyroid muscles.

Despite a wealth of information about the respiratory behavior of pharyngeal dilator muscles such as the genioglossus, sternohyoid, and sternothyroid muscles, little is known about their contractile and endurance properties. Strips of these muscles (as well as of the diaphragm) were surgically removed from anesthetized cats and studied in vitro at 37 degrees C. The isometric contraction times of the muscles were 38 +/- 1, 31 +/- 1, 28 +/- 2, and 35 +/- 1 ms for genioglossus, sternothyroid, sternohyoid, and diaphragm, respectively. Contraction times were significantly longer for the genioglossus than for the sternohyoid and sternothyroid muscles and significantly longer for the diaphragm than for the sternohyoid muscle. Twitch-to-tetanic ratios were largest for the diaphragm and lowest for the sternohyoid muscle, and the force-frequency relationship of the sternohyoid was most rightward positioned and that of the diaphragm was most leftward positioned. During repetitive stimulation, the decrement in force was greatest for the diaphragm and least for the genioglossus muscle, with the force loss of the two hyoid muscles being intermediate in magnitude. The Burke fatigue index was significantly greater for the genioglossus than for the diaphragm, despite similar tension-time indexes during repetitive stimulation. These data indicate heterogeneity among pharyngeal dilator muscles in their contractile and endurance properties, that certain pharyngeal dilator muscle properties differ from diaphragmatic properties, and that pharyngeal muscles have relatively fast contractile kinetics yet reasonable endurance characteristics.     

Effect of inspiratory resistive loaded breathing and hypoxemia on diaphragmatic function in the piglet.

The combined effects of inspiratory resistive loaded breathing (IRL) and hypoxemia on transdiaphragmatic pressure (Pdi) in nine 1-mo-old Yorkshire piglets were studied. IRL was adjusted to increase spontaneously generated Pdi five to six times above baseline but maintain arterial PCO2 < 70 Torr to prevent hypercapnic depression of diaphragmatic contractility. Measurements of ventilation, blood gases and pH, Pdi, diaphragmatic electromyogram, Pdi during phrenic nerve stimulation, diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 2 h of IRL, and then after 1 h of hypoxemia (arterial PO2 approximately 40 Torr) combined with IRL. Diaphragmatic muscle samples were obtained after study completion and immediately frozen in liquid nitrogen for determination of tissue ATP, phosphocreatine, lactate, and glycogen levels. Ten 1-mo-old piglets were subjected to IRL alone and served as controls. IRL alone resulted in significant impairment of Pdi generation. The addition of hypoxemia for 1 h did not further compromise Pdi in comparison to control animals who were subjected to IRL alone. Blood flow to both the costal and crural segments of the diaphragm increased significantly during IRL; the addition of the hypoxemic stress resulted in further significant augmentation of blood flow to both segments of the diaphragm. No differences were noted in diaphragmatic muscle tissue ATP, phosphocreatine, or glycogen between control and IRL animals or between control and IRL plus hypoxemia animals. Muscle lactate levels increased significantly in the IRL plus hypoxemia animals only. The data from this study suggest that moderate hypoxemia during resistive-loaded breathing in the piglet does not accentuate diaphragmatic fatigue.     

Diaphragmatic contractility after upper abdominal surgery

Postoperative dysfunction of the diaphragm has been reported after upper abdominal surgery. This study was designed to determine whether an impairment in diaphragmatic contractility was involved in the genesis of the diaphragmatic dysfunction observed after upper abdominal surgery. Five patients undergoing upper abdominal surgery were studied. The following measurements were performed before and 4 h after surgery: vital capacity (VC), functional residual capacity (FRC), and forced expiratory volume in 1 s. Diaphragmatic function was also assessed using the ratio of changes in gastric pressure (delta Pga) over changes in transdiaphragmatic pressure (delta Pdi). Finally contractility of the diaphragm was determined by measuring the change in delta Pdi generated during bilateral electrical stimulation of the phrenic nerves (Pdi stim). Diaphragmatic dysfunction occurred in all the patients after upper abdominal surgery as assessed by a marked decrease in delta Pga/delta Pdi from 0.480 +/- 0.040 to -0.097 +/- 0.152 (P less than 0.01) 4 h after surgery compared with preoperative values. VC also markedly decreased after upper abdominal surgery from 3,900 +/- 630 to 2,060 +/- 520 ml (P less than 0.01) 4 h after surgery. In contrast, no change in FRC and Pdi stim was observed 4 h after surgery. In contrast, no change in FRC and Pdi stim was observed 4 h after upper abdominal surgery compared with the preoperative values. We conclude that contractility of the diaphragm is not altered after upper abdominal surgery, and diaphragmatic dysfunction is secondary to other mechanisms such as possible reflexes arising from the periphery (chest wall and/or peritoneum), which could inhibit the phrenic nerve output.     

Fatigue of isolated rat diaphragm: role of impaired neuromuscular transmission

We compared the contributions of impaired neuromuscular transmission (transmission fatigue) and impaired muscle contractility (contractile fatigue) to fatigue of the isolated rat diaphragm. To make this comparison, we measured the differences in active tension elicited by direct muscle stimulation and by indirect (phrenic nerve) stimulation before and after fatigue induced by indirect supramaximal stimulation at varying frequencies and durations. Transmission fatigue was observed after all experimental protocols. Although significant contractile fatigue was not demonstrated after brief periods of low-frequency stimulation (6 min, 15 Hz, 25% duty cycle), it was present after longer or higher frequency stimulation. We repeated the direct stimulation in the presence of neuromuscular blockade with 6 microM d-tubocurarine to demonstrate that a reduced response to stimulation of intramuscular branches of the phrenic nerve during direct stimulation was not responsible for the apparent contractile fatigue. Since we found significant decreases in the response to direct stimulation even after neuromuscular blockade, we could verify the presence of contractile fatigue. We conclude that both contractile and transmission fatigue can occur in the isolated rat diaphragm and that transmission fatigue is a much more important factor after brief periods of fatiguing contractions.     

Model-generated decomposition of unfused tetani of motor units evoked by random stimulation

Unfused tetani of motor units (MUs) evoked by stimulation at variable interpulse intervals at mean frequencies of 20, 25, 33, 40 and 50 Hz were studied using ten functionally isolated fast-type MUs from the medial gastrocnemius muscle of adult Wistar rats. A previously proposed algorithm and computer program for mathematical decomposition of unfused tetani into a series of twitches, representing responses to individual pulses, were used. Analysis of the parameters of the decomposed twitches showed considerable variability in force of successive contractions. These twitches were extremely variable with up to 2-fold higher forces and longer contraction times than a single twitch evoked by one stimulus. However, when the stimulation frequency was decreased, the decomposed twitches became similar to the single twitch with respect to amplitude and contraction time. It was found that the basic contractile parameters of decomposed twitches could be predicted with high accuracy on the basis of the tetanus force level at which the next contraction begins. This analysis of the parameters of decomposed twitches demonstrated that the contractile responses of the muscle fibers to successive action potentials generated by motoneurons are highly variable and depend on the previous MU state.