Search PubMed⌕ Search

Biomedical subjects

G A Farkas

Publications and source records attributed to G A Farkas.

At least 37 records · Page 2Linked to original sources

Metabolic characteristics of primary inspiratory and expiratory muscles in the dog.

These experiments examined the metabolic properties of the canine respiratory muscles. Because the costal diaphragm (COD), crural diaphragm (CRD), parasternal intercostals (PI), triangularis sterni (TS), and transversus abdominis (TA) are active during quite breathing in the dog, we hypothesized that these muscles would have different metabolic profiles (i.e., higher oxidative and antioxidant enzyme activities) compared with ventilatory muscles recruited only at increased ventilatory requirements [e.g., scalene (SC) and external oblique (EO)] and locomotor muscles [e.g., deltoid (DEL)]. To test this hypothesis, muscle samples were removed from six healthy adult dogs and analyzed to determine the activities of citrate synthase (CS), phosphofructokinase (PFK), 3-hydroxyacyl-CoA dehydrogenase (HADH), and superoxide dismutase (SOD). The activities of these enzymes were interpreted as relative measures of metabolic capacities, and enzyme activity ratios were considered as representing relationships between different metabolic pathways. Analysis revealed that CS and HADH activities were significantly higher (P < 0.05) in the PI, COD, CRD, and TS compared with those in all other muscles. Muscles with the lowest CS, HADH, and SOD activities (i.e., SC, TA, EO, DEL) generally had the highest PFK activities, Furthermore, the PFK/CS ratio was significantly lower in the PI, COD, CRD, and TS compared with that in all other muscles studied. These data support the notion that the canine PI, COD, CRD, and TS are metabolically different from other key ventilatory muscles.

3-Hydroxyacyl CoA Dehydrogenases↗

Histochemical and mechanical properties of diaphragm muscle in morbidly obese Zucker rats.

The purpose of the present study was to evaluate the effects of chronic mass loading produced by obesity on the structural and functional characteristics of the diaphragm in lean and obese Zucker rats. The trapezius muscle served as an internal control. The studies were carried out on 17 lean (303 +/- 24 g) and 16 obese (698 +/- 79 g) Zucker rats. We observed that the diaphragms from obese animals were restructured such that the overall contribution of type I and IIa fibers was significantly increased. As a consequence of this remodeling, overall diaphragm thickness was selectively greater in obese animals. In small isolated diaphragm bundles studied in vitro, we also detected a reduction in specific force in obese animals that was not detected in the trapezius muscle. In vitro fatigue resistance, assessed by repeated stimulation, was similar in muscles of lean and obese animals. Diaphragm fiber oxidative capacity (succinate dehydrogenase activity) was also comparable in lean and obese animals. We conclude that in obesity the diaphragm undergoes modest remodeling that may be beneficial in enhancing force generation.

Animals↗

Pulmonary ventilation and mechanics in morbidly obese Zucker rats.

The obese Zucker rat, an autosomally genetic model of obesity, represents a good model of relatively early onset human obesity. Although factors associated with the control of metabolism and thermoregulation have been studied extensively in these animals, pulmonary mechanics and ventilation have not been documented and form the basis of this investigation. Studies were carried out in 16 obese and 18 lean female littermates (698 +/- 79 versus 304 +/- 24 g, p < 0.001). Pulmonary function, including lung volumes and respiratory system compliance, was evaluated in supine anesthetized animals. With the exception of residual volume, all other lung volumes, including function residual capacity, total lung capacity, expiratory reserve volume, and inspiratory capacity, were significantly reduced (p < 0.05 or better) in the obese phenotype compared with volumes in the lean littermates. Pressure-volume relationships of the intact respiratory system and the excised lung were also determined. Although lung compliance was similar between the phenotypes, respiratory system compliance was significantly lower (0.85 +/- 0.06 versus 0.67 +/- 0.09 ml/cm H2O, p < 0.01) in the obese rats. Oxygen consumption and ventilatory parameters (including respiratory rate, tidal volume, minute ventilation, inspiratory time, and expiratory time) were similar between phenotypes breathing room air, and the minute ventilation in response to hypoxia was similar in both groups. In marked contrast, obese animals exhibited a blunted ventilatory response to hypercapnia (221 +/- 38 versus 135 +/- 44 ml/min, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Functional significance of expiratory muscles during spontaneous breathing in anesthetized dogs.

Recent electromyographic studies in awake and anesthetized dogs have demonstrated that spontaneous breathing in prone dogs is associated with an increased activation of the expiratory muscles compared with that recorded in supine dogs. On the basis of these observations, one would infer that the mechanical role and contribution of the expiratory musculature to the act of breathing are enhanced in the prone posture. The changes in length associated with these postural increases in expiratory muscle electrical activity, however, have not been investigated and formed the basis of our investigation. We examined the active and passive changes in length of expiratory muscles during spontaneous breathing in supine and prone anesthetized dogs and assessed the relative role of the expiratory musculature in the generation of tidal volume. The experiments were performed on eight mongrel dogs anesthetized with pentobarbital sodium. In all eight animals, spontaneous breathing in the prone posture was associated with an increased activation (electromyogram) of the triangularis sterni, external oblique, and transversus abdominis muscles compared with that recorded in the supine posture. We quantitated the role of the expiratory muscles in both postures by measuring the volume difference between relaxation volume of the respiratory system and the end-expiratory lung volume. In the supine animal, 93 ml were attributed to the expiratory musculature, whereas in the prone animal, we noted that 186 ml (P < 0.01) were displaced during expiration, representing 43 and 52% (NS) of tidal volume, respectively. During spontaneous breathing in the supine or prone posture, all three expiratory muscles underwent significant length changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Diaphragm mechanics in dogs with unilateral emphysema.

We studied dogs with unilateral papain-induced emphysema to answer two questions: (1) Do emphysema lung-apposed hemidiaphragm (DiE) and normal lung-apposed hemidiaphragm (DiN) have equal capacities for lowering lung surface pressure? and (2) Are side-to-side differences in intrathoracic pressure the result of unequal force outputs by DiE and DiN or are they caused by differences in their mechanical efficiency as pressure generators? After the airways of the emphysematous and normal lungs were intubated with a dual lumen endotracheal tube, both phrenic nerves were maximally stimulated at rates between 1 and 50 Hz and the changes in airway occlusion pressure (delta PaoE,N) and diaphragm length (sonomicrometry) were recorded. In all animals, delta PaoN exceeded delta PaoE. Differences in pressure ranged from 1.2 +/- 0.6 cm H2O during a twitch to 6.0 +/- 2.9 cm H2O during a 50-Hz tetanus. Midcostal bundles of DiE shortened less than corresponding bundles of DiN, but both reached the same active length relative to their optimal lengths, which were measured in vitro. There was no significant difference in fiber type distribution, fiber cross-sectional area, or maximal isometric tetanic tensions among midcostal regions of DiE and DiN. We conclude that unilateral hyperinflation impairs the mechanical efficiency of the apposing hemidiaphragm as a pressure generator.

Animals↗

Mechanical characteristics and functional length of canine expiratory muscles.

The expiratory muscles of the abdominal region actively contribute to breathing. In dogs, the transversus abdominis appears to be the main abdominal muscle of expiration. The in vitro mechanical properties of the transversus abdominis have not been reported to date, and formed the basis of the present investigation. Moreover, in order to understand better the nature of the mechanical interplay between the various abdominal muscle groups, we also evaluated the effects of posture on the operational length of canine transversus abdominis and external oblique muscles and related their in situ length to optimal length. The experiments were performed on twelve mongrel dogs, anesthetized with pentobarbital sodium. Contractile properties of excised transversus abdominis muscle strips were evaluated at 37 degrees C and revealed similar twitch, force-frequency and length-tension properties as previously reported in canine external oblique (Farkas and Rochester, J. Appl. Physiol. 65: 2427-2433, 1988). In the supine posture, we noted that external oblique was operating at 88% Lo, while the transversus abdominis was operating at a significantly shorter length of 74% Lo. Thus, in the supine posture, the external oblique is better situated than the transversus abdominis to generate tension. In the prone posture, however, we noted that both abdominal muscles were located at similar positions along their length-tension curve, operating at a length of roughly 77% Lo. Since both muscles share common length-tension characteristics, the present results indicate that the tension generating potential of both muscles in prone dogs is equal for a given neural input. However, we conclude that the preferential recruitment of the transversus abdominis in prone animals must be related to factors other than simple tension generation.

Abdominal Muscles↗

Predictability of ventilatory muscle optimal length based on excised dimensions.

The purpose of the present study was to assess the relationship between excised length (unstressed length of excised muscle; Lex) and optimal force-generating length (Lo) in a variety of respiratory muscles, with the goal of establishing a reliable method whereby Lo could be rapidly and easily estimated with a high level of accuracy. Experiments were conducted on 111 muscle bundles obtained from 18 mongrel dogs. Segments of costal diaphragm, parasternal intercostal, scalene, sternomastoid, triangularis sterni, rectus abdominis, external oblique, and transversus abdominis muscles were studied. We noted a linear relationship between the distance measured between two fixed points in excised bundles (Lex) and at the muscles' Lo. Correlation coefficients ranged from 0.83 (P less than 0.01) for the transversus abdominis to 0.92 (P less than 0.01) for the triangularis sterni and external oblique muscles. Pooled Lex for all muscles averaged 61.4 +/- 6.3% (SD) Lo, with specific values ranging from 55.5 +/- 3.9% Lo for triangularis sterni bundles to 63.0 +/- 5.1% Lo for external oblique bundles. In three additional dogs, we verified the usefulness of this relationship and prospectively estimated Lo from excised length in 10 costal diaphragm bundles and 10 transversus abdominis bundles and then measured Lo directly. Predicted Lo averaged 100.0 +/- 6.0% Lo for diaphragm and 97.6 +/- 5.9% Lo for transversus abdominis muscle. We conclude that Lo can be conveniently and accurately estimated from excised dimensions. This rapid estimation technique should prove valuable for future studies in respiratory muscle physiology.

Animals↗

Mechanics of acutely shortened canine diaphragm muscle in vitro.

Acute changes in lung volume, as might be seen in an airway-obstructed patient, may lead to different amounts of shortening of the various inspiratory muscles, of which the diaphragm is the most important. The purpose of this study is to investigate the twitch and contractile characteristics of acutely shortened canine diaphragm muscle in vitro during isometric contraction. We found that with diaphragmatic muscle shortening from Lo (optimal length, defined as being that length at which peak twitch tension was generated) to 70% Lo, the time-to-peak tension, half relaxation time and twitch tension were significantly reduced. The force-frequency curves, obtained from different muscle lengths, disclosed that shorter muscles generate disproportionately less force during low-frequency stimulation. These factors may, at least in part, contribute to the vulnerability to fatigue of those with shorter diaphragmatic muscle length.

Animals↗

Mechanical properties of respiratory muscles in primates.

We examined the in-vitro mechanical characteristics of the diaphragm and parasternal intercostal muscles in adult baboons. At optimal length (Lo) the parasternal intercostal muscles were consistently faster than the diaphragm as judged by a shorter time-to-peak tension and a reduced twitch-to-tetanus ratio. However, maximal absolute force at Lo, corrected for cross-sectional area, revealed that the inherent strengths of both inspiratory muscles were identical (31.5 +/- 3.2 N/cm2 for diaphragm vs 29.5 +/- 1.1 N/cm2 for parasternal intercostals). Moreover, at submaximal stimulation rates, the parasternal intercostals produced significantly less tension at Lo than the diaphragm. At lengths less than Lo, however, the parasternal intercostal muscles generated significantly less tetanic tension than the diaphragm. These differences are similar to previously reported values in dogs (Farkas et al. (1985) J. Appl. Physiol. 59: 528-535). Thus, based on our findings, it appears that within a given species, the parasternal intercostals are quite different in mechanical terms from the diaphragm. Since both muscles are recruited at all levels of ventilation, including quiet breathing, these differences do not appear to be related to the activation levels. Moreover, since the present results were similar to those in dogs, the differences between both muscles do not appear to be affected or altered by body habitus.

Animals↗

Mechanical role of expiratory muscle recruitment during eupnea in supine anesthetized dogs.

To assess the mechanical role of the expiratory musculature during eupnea, we recorded the electromyographic (EMG) activity of the triangularis sterni, the external oblique, and the transversus abdominis in eight supine lightly anesthetized dogs and have measured the volume generated by the phasic activation of the expiratory muscles. Activation of the expiratory muscles was invariably associated with a decrease in lung volume below the relaxed position of the respiratory system, a volume equal to 41.3 +/- 8.4 ml. This volume represented roughly 20% of tidal volume generated during spontaneous breathing. The fractional expiratory contribution to the tidal volume was unrelated to the size of the animal. Traction on the forelimbs (limb extension), however, tended to enhance the phasic expiratory activation of both the triangularis sterni and the transversus abdominis in the majority of animals. Moreover, after limb extension, the fractional contribution of tidal volume attributed to the phasic activation of the expiratory muscles increased in all but one animal. During spontaneous breathing with the forelimbs extended, roughly 25% of tidal volume was found to be due directly to phasic expiratory muscle contraction. The present observations firmly establish that in supine lightly anesthetized dogs breathing at rest the expiratory component of tidal volume represents a substantial contribution.

Anesthesia↗

Linkage between parasternals and external intercostals during resting breathing.

To assess the mechanical coupling between the parasternal and external intercostals in the cranial portion of the rib cage, we measured the respiratory changes in length and the electromyograms of the two muscles in the same third or fourth intercostal space in 24 spontaneously breathing dogs. We found that 1) the amount of inspiratory shortening of the external intercostal was considerably smaller than the amount of shortening of the parasternal; 2) after selective denervation of the parasternal, the inspiratory shortening of both the parasternal and the external intercostal was almost abolished; 3) on the other hand, after selective denervation of the external intercostal, the inspiratory shortening of the parasternal was unchanged, and the inspiratory shortening of the external intercostal was reduced but not suppressed; and 4) this persistent shortening of the external intercostal was reversed into a clear-cut inspiratory lengthening when the parasternal was subsequently denervated. We conclude that in the dog 1) the inspiratory contraction of the external intercostals in the cranial portion of the rib cage is agonistic in nature as is the contraction of the parasternals; 2) during resting breathing, however, the changes in length of these external intercostals are largely determined by the action of the parasternals. These observations are consistent with the idea that in the dog, the parasternals play a larger role than the external intercostals in elevating the ribs during resting inspiration.

Animals↗

Effects of body position and lung volume on in situ operating length of canine diaphragm.

The performance of the diaphragm is influenced by its in situ length relative to its optimal force-generating length (Lo). Lead markers were sutured to the abdominal surface of the diaphragm along bundles of the left ventral, middle, and dorsal regions of the costal diaphragm and the left crural diaphragm of six beagle dogs. After 2-3 wk postoperative recovery, the dogs were anesthetized, paralyzed, and scanned prone and supine in the Dynamic Spatial Reconstructor (DSR) at a total lung capacity (TLC), functional residual capacity (FRC), and residual volume (RV). The location of each marker was digitized from the reconstructed DSR images, and in situ lengths were determined. After an overdose of anesthetic had been administered to the dogs, each marked diaphragm bundle was removed, mounted in a 37 degrees C in vitro chamber, and adjusted to Lo (maximum tetanic force). The operating length of the diaphragm, or in situ length expressed as percent Lo, varied from region to region at the lung volumes studied; variability was least at RV and increased with increasing lung volume. At FRC, all regions of the diaphragm was shorter in the prone posture compared with the supine, but there was no clear gravity-dependent vertical gradient of in situ length in either posture. Because in vitro length-tension characteristics were similar for all diaphragm regions, regional in vivo length differences indicate that the diaphragm's potential to generate maximal force is nonuniform.

Animals↗

Mechanical role of expiratory muscles during breathing in prone anesthetized dogs.

The purpose of the present study was to assess the mechanical role of the expiratory muscles during spontaneous breathing in prone animals. The electromyographic (EMG) activity of the triangularis sterni, the rectus abdominis, the external oblique, and the transversus abdominis was studied in 10 dogs light anesthetized with pentobarbital sodium. EMGs were recorded during spontaneous steady-state breathing in supine and prone suspended animals both before and after cervical vagotomy. We also measured the end-expiratory lung volume [functional residual capacity (FRC)] in supine and prone positions to assess the mechanical role of expiratory muscle activation in prone dogs. Spontaneous breathing in the prone posture elicited a significant recruitment of the triangularis sterni, the external oblique, and the transversus abdominis (P less than 0.05). Bilateral cervical vagotomy eliminated the postural activation of the external oblique and the transversus abdominis but not the triangularis sterni. Changes in posture during control and after cervical vagotomy were associated with an increase in FRC. However, changes in FRC, on average, were 132.3 +/- 33.8 (SE) ml larger (P less than 0.01) postvagotomy. We conclude that spontaneous breathing in prone anesthetized dogs is associated with a marked phasic expiratory recruitment of rib cage and abdominal muscles. The present data also indicate that by relaxing at end expiration the expiratory muscles of the abdominal region are directly responsible for generating roughly 40% of the tidal volume.

Anesthesia, General↗

Effect of midline laparotomy on the cough reflex in dogs.

The present studies were designed to test the hypothesis that midline laparotomy promotes selective inhibition of the transversus abdominis muscle during cough as it does during expiratory threshold loading. Anesthetized dogs were studied in the supine posture, and cough was induced by mechanical stimulation of the airways. Midline laparotomy had virtually no effect on the cough-induced activation of the triangularis sterni or the external oblique. On the other hand, the activation of the transversus abdominis was markedly reduced in all animals. Despite this marked inhibition, however, peak pleural pressure and expiratory flow were preserved. This suggests that this inhibition does not play a significant role in determining the occurrence of bronchopulmonary infection after abdominal surgery.

Abdominal Muscles↗

Passive shortening of canine parasternal intercostals during breathing.

We have previously demonstrated that the shortening of the canine parasternal intercostals during inspiration results primarily from the muscles' own activation (J. Appl. Physiol. 64: 1546-1553, 1988). In the present studies, we have tested the hypothesis that other inspiratory rib cage muscles may contribute to the parasternal inspiratory shortening. Eight supine, spontaneously breathing dogs were studied. Changes in length of the third or fourth right parasternal intercostal were measured during quiet breathing and during single-breath airway occlusion first with the animal intact, then after selective denervation of the muscle, and finally after bilateral phrenicotomy. Denervating the parasternal virtually eliminated the muscle shortening during quiet inspiration and caused the muscle to lengthen during occluded breaths. After phrenicotomy, however, the parasternal, while being denervated, shortened again a significant amount during both quiet inspiration and occluded breaths. These data thus confirm that a component of the parasternal inspiratory shortening is not active and results from the action of other inspiratory rib cage muscles. Additional studies in four animals demonstrated that the scalene and serratus muscles do not play any role in this phenomenon; it must therefore result from the action of intrinsic rib cage muscles.

Animals↗

Mechanical arrangement of the parasternal intercostals in the different interspaces.

When the parasternal intercostal in a single interspace is selectively denervated in dogs with diaphragmatic paralysis, it continues to shorten during both quiet and occluded inspiration. In the present studies, we have tested the hypothesis that this passive parasternal inspiratory shortening is due to the action of the other parasternal intercostals. Changes in length of the denervated third right parasternal were measured in eight supine phrenicotomized animals. We found that 1) the inspiratory muscle shortening increased after denervation of the third left parasternal but gradually decreased with denervation of the parasternals situated in the second, fourth, and fifth interspaces; 2) the muscle, however, always continued to shorten during inspiration, even after denervation of all the parasternals; 3) stimulating selectively the third left parasternal caused a muscle lengthening; and 4) bilateral stimulation of the parasternals in the second or the fourth interspace produced a muscle shortening. We conclude that 1) the two parasternals situated in the same interspace on both sides of the sternum are mechanically arranged in series, whereas the parasternals located in adjacent interspaces are mechanically arranged in parallel; and 2) if a denervated parasternal continues to shorten during inspiration, this is in part because of the action of the parasternals in the adjacent interspaces and in part because of other inspiratory muscles of the rib cage, possibly the external intercostals and the levator costae.

Animals↗

Effects of midline laparotomy on expiratory muscle activation in anesthetized dogs.

Abdominal surgery has a marked inhibitory influence on the diaphragm, but its effect on the expiratory muscles is not known. Therefore, we have recorded the electromyograms of the triangularis sterni, abdominal external oblique, and transversus abdominis before and after a midline laparotomy in 10 anesthetized, spontaneously breathing dogs. Measurements were obtained during quiet breathing in the supine posture, during breathing against expiratory threshold loads, during head-up tilting, and during hyperoxic hypercapnia. Expiratory activation of the transversus abdominis in all conditions was considerably reduced after laparotomy. This reduction was real, as no change in the compound muscle action potential during single pulse stimulation was observed. In contrast, expiratory recruitment of either the triangularis sterni or the abdominal external oblique was maintained or increased. We therefore conclude that laparotomy inhibits not only activation of the diaphragm during inspiration but also activation of the transversus abdominis during expiration. Visceral afferents thus affect in concert the two respiratory muscles lining the peritoneum. The present findings also emphasize the important fact that the pattern of activation of a particular abdominal muscle is not necessarily representative of the entire abdominal musculature.

Anesthesia, General↗

Expiratory muscle contribution to tidal volume in head-up dogs.

A change from the supine to the head-up posture in anesthetized dogs elicits increased phasic expiratory activation of the rib cage and abdominal expiratory muscles. However, when this postural change is produced over a 4- to 5-s period, there is an initial apnea during which all the muscles are silent. In the present studies, we have taken advantage of this initial silence to determine functional residual capacity (FRC) and measure the subsequent change in end-expiratory lung volume. Eight animals were studied, and in all of them end-expiratory lung volume in the head-up posture decreased relative to FRC [329 +/- 70 (SE) ml]. Because this decrease also represents the increase in lung volume as a result of expiratory muscle relaxation at the end of the expiratory pause, it can be used to determine the expiratory muscle contribution to tidal volume (VT). The average contribution was 62 +/- 6% VT. After denervation of the rib cage expiratory muscles, the reduction in end-expiratory lung volume still amounted to 273 +/- 84 ml (49 +/- 10% VT). Thus, in head-up dogs, about two-thirds of VT result from the action of the expiratory muscles, and most of it (83%) is due to the action of the abdominal rather than the rib cage expiratory muscles.

Animals↗