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Biomedical subjects

G A Farkas

Publications and source records attributed to G A Farkas.

54 records · Page 3Linked to original sources

Inspiratory function of the levator costae and external intercostal muscles in the dog.

The shortening of the canine parasternal intercostals during inspiration may have a passive component, and we have previously speculated that this might result from the actions of the levator costae and external intercostals (J. Appl. Physiol. 66: 1421-1429, 1989). The present studies were designed, therefore, to evaluate the pattern of activation of these muscles in the dog and to define their action on the rib cage during breathing. The results indicate that 1) the levator costae and external intercostals in the cranial part of the rib cage are active during inspiration, both in the supine and in the prone posture; 2) the inspiratory activation of the two muscles is increased after bilateral phrenicotomy; 3) it is increased even more when the parasternal intercostals in the different interspaces are also denervated; and 4) when the levator costae and external intercostals are the only muscles active during inspiration, the ribs continue to move cranially, and the sternum, rather than moving caudally as it does in the intact animal, moves cranially as well. Therefore, we conclude that the levator costae and external intercostals in the dog have a true inspiratory function. When needed, they are capable of causing a significant expansion of the rib cage and the lung during breathing.

Animals↗

Mechanism of rib cage inspiratory muscle recruitment in diaphragmatic paralysis.

Paralysis of the diaphragm promotes an increase in the activation of the rib cage inspiratory muscles, and previous studies have suggested that this compensation is primarily due to vagal mechanisms (6). To test this hypothesis, we have assessed the effect of diaphragmatic paralysis on the electrical response of 19 parasternal intercostal muscles in eight anesthetized, vagotomized, spontaneously breathing dogs in the supine posture. Complete diaphragmatic paralysis was induced by section of the C5, C6, and C7 phrenic nerve roots in the neck. With the animals breathing room air, diaphragmatic paralysis resulted in a mean 94% increase in the peak height of integrated parasternal activity (p less than 0.001) associated with a 14 mm Hg decrease in arterial PO2 (p less than 0.05) and an 8 mm Hg increase in arterial PCO2 (p less than 0.001). The augmented parasternal activity was unrelated to the duration of inspiration and persisted when the animals were given a hyperoxic gas mixture. Thus the rib cage inspiratory muscles still compensate for diaphragmatic paralysis in the absence of vagal signals and of hypoxemia. This compensation probably results from the considerably augmented CO2 load placed on the extradiaphragmatic muscles.

Animals↗

Effects of a chronic wasting infection on skeletal muscle size and contractile properties.

To evaluate the effects of chronic infection on skeletal muscle dimensions and contractile properties, we used a hamster model of visceral leishmaniasis, a parasitic infection of the reticuloendothelial system produced by Leishmania donovani (LD). To distinguish between effects of reduced caloric intake and infection per se, we also studied healthy control animals and noninfected animals subjected to caloric restriction. Three muscles were tested in vitro: plantaris, soleus, and diaphragm. Both caloric restriction and LD infection caused loss of body weight and reduced muscle cross-sectional areas and wet weights. The interventions had variable effects on in vitro contractile properties, the most pronounced being reduction in peak tension in response to tetanic stimulation. Tension loss was 35-45%, except for a loss of 65% in plantaris of LD-infected animals. We conclude that chronic LD infection affects skeletal muscles in both indirect and direct ways. 1) Reduced caloric intake due to anorexia decreases muscle size and active tension. Disuse probably enhances this effect in limb muscles. 2) Infection produces profound weakness of inactive fast-twitch muscle by unknown mechanisms.

Animals↗

Mechanical role of expiratory muscles during breathing in upright dogs.

To examine the mechanical effects of the abdominal and triangularis sterni expiratory recruitment that occurs when anesthetized dogs are tilted head up, we measured both before and after cervical vagotomy the end-expiratory length of the costal and crural diaphragmatic segments and the end-expiratory lung volume (FRC) in eight spontaneously breathing animals during postural changes from supine (0 degree) to 80 degrees head up. Tilting the animals from 0 degree to 80 degrees head up in both conditions was associated with a gradual decrease in end-expiratory costal and crural diaphragmatic length and with a progressive increase in FRC. All these changes, however, were considerably larger (P less than 0.005 or less) postvagotomy when the expiratory muscles were no longer recruited with tilting. Alterations in the elastic properties of the lung could not account for the effects of vagotomy on the postural changes. We conclude therefore that 1) by contracting during expiration, the canine expiratory muscles minimize the shortening of the diaphragm and the increase in FRC that the action of gravity would otherwise introduce, and 2) the end-expiratory diaphragmatic length and FRC in upright dogs are thus actively determined. The present data also indicate that by relaxing at end expiration, the expiratory muscles make a substantial contribution to tidal volume in upright dogs; in the 80 degrees head-up posture, this contribution would amount to approximately 60% of tidal volume.

Abdominal Muscles↗

Mechanics of the parasternal intercostals during occluded breaths in dogs.

The electrical activity and the respiratory changes in length of the third parasternal intercostal muscle were measured during single-breath airway occlusion in 12 anesthetized, spontaneously breathing dogs in the supine posture. During occluded breaths in the intact animal, the parasternal intercostal was electrically active and shortened while pleural pressure fell. In contrast, after section of the third intercostal nerve at the chondrocostal junction and abolition of parasternal electrical activity, the muscle always lengthened. This inspiratory muscle lengthening must be related to the fall in pleural pressure; it was, however, approximately 50% less than the amount of muscle lengthening produced, for the same fall in pleural pressure, by isolated stimulation of the phrenic nerves. These results indicate that 1) the parasternal inspiratory shortening that occurs during occluded breaths in the dog results primarily from the muscle inspiratory contraction per se, and 2) other muscles of the rib cage, however, contribute to this parasternal shortening by acting on the ribs or the sternum. The present studies also demonstrate the important fact that the parasternal inspiratory contraction in the dog is really agonistic in nature.

Animals↗

Vagal afferents, diaphragm fatigue, and inspiratory resistance in anesthetized dogs.

This study tests three hypotheses regarding mechanisms that produce rapid shallow breathing during a severe inspiratory resistive load (IRL): 1) an intact vagal afferent pathway is necessary; 2) diaphragm fatigue contributes to tachypnea; and 3) hypoxia may alter the pattern of respiration. We imposed a severe IRL on pentobarbital sodium-anesthetized dogs, followed by bilateral vagotomy, then by supplemental O2. IRL alone produced rapid shallow breathing associated with hypercapnia and hypoxia. After the vagotomy, the breathing pattern became slow and deep, restoring arterial PCO2 but not arterial PO2 toward the control values. Relief of hypoxia had no effect, and at no time was there any evidence of fatigue of the diaphragm as measured by the response to phrenic nerve stimulation. We conclude that an intact afferent vagal pathway is necessary for the tachypnea resulting from a severe IRL, neither hypoxia nor diaphragm fatigue played a role, and, although we cannot rule out stimulation of vagal afferents, the simplest explanation for the increased frequency in our experiments is increased respiratory drive due to hypercapnia.

Afferent Pathways↗

Functional characteristics of canine costal and crural diaphragm.

We estimated the in situ force-generating capacity of the costal and crural portions of the canine diaphragm by relating in vitro contractile properties and diaphragmatic dimensions to in situ lengths. Piezoelectric crystals were implanted on right costal and left crural diaphragms of anesthetized dogs, via midline laparatomy. With the abdomen reclosed, diaphragm lengths were recorded at five lung volumes. Contractile properties of excised muscle bundles were then measured. In vitro force-frequency and length-tension characteristics of the costal and crural diaphragms were virtually identical; their optimal force values were 2.15 and 2.22 kg/cm2, respectively. In situ, at residual volume, functional residual capacity (FRC), and total lung capacity the costal diaphragm lay at 102, 95, and 60% of optimal length (Lo), whereas the crural diaphragm lay at 88, 84, and 66% of Lo. Muscle cross-sectional area was 40% greater in costal than in crural diaphragms. Considering in situ lengths, cross-sectional areas, and in vitro length-tension characteristics at FRC, the costal diaphragm could exert 60% more force than the crural diaphragm.

Animals↗

Characteristics and functional significance of canine abdominal muscles.

To assess the characteristics and function of the muscles of the anterolateral abdominal wall, we have examined the isometric contractile properties of bundles of canine rectus abdominis (RA) and external oblique (EO) muscles. In addition, we have related the lengths of these muscles measured sonometrically in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We also investigated the action of the abdominal muscles on the displacement of costal and crural diaphragm. We found that 1) contraction time of RA was longer and that the RA developed greater force than the EO at submaximal stimulation frequencies; 2) maximal tetanic force and the active length-tension curves were similar in both abdominal muscles; 3) on passive stretch, the compliance of the RA was one-third that of the EO; 4) at supine FRC, the EO is operating at 83% of Lo, whereas the RA is operating at 105% of Lo; 5) stimulation of either RA or EO (abdominal pressure of 15 cmH2O) lengthened the costal and crural diaphragm toward their Lo values, with greater crural excursion occurring than costal. We conclude that the RA is well suited for restraining the abdominal viscera in prone quadrupeds, whereas the EO is better designed to assist expiration. Stimulation of both muscles improves in situ diaphragmatic operating length.

Abdominal Muscles↗

The increased expiratory muscle use in upright dogs: role of cardiovascular receptors.

A change from the supine to upright posture in anesthetized dogs promotes increased expiratory muscle use during breathing. To examine the role of cardiovascular receptors in eliciting this expiratory muscle recruitment, the electromyographic (EMG) activity of the triangularis sterni (TS) and abdominal external oblique (EO) muscles was recorded in seven spontaneously breathing animals during head up tilting and during occlusion of the inferior vena cava. Head up tilting was associated with a reduction in cardiac output, a transient fall in systemic blood pressure, and considerable increases in TS and EO expiratory EMG activity. On an average (mean +/- SE), the amount of TS and EO expiratory activity in the supine posture was 44.7 +/- 12.9 and 10.3 +/- 7.3%, respectively, of the activity recorded in the 80 degree head up posture. When occlusion of the inferior vena cava in the supine animals induced a reduction in cardiac output and a fall in systemic blood pressure that were comparable to those measured during head up tilting, the TS and EO expiratory EMG activity also increased. This activity, however, always remained smaller than that recorded during breathing in the upright posture; for the seven animals, the amount of TS and EO expiratory activity during vena cava occlusion was only 58.4 +/- 5.7 and 17.9 +/- 10.4% of the activity in upright posture, respectively (P less than 0.001 for both muscles). We conclude, therefore, that the reduced venous return and systemic hypotension of the upright posture are not the critical sensory events for promoting the increased expiratory muscle use in this posture. It must, therefore, be elicited by respiratory receptors.

Animals↗

The ventral rib cage muscles in the dog: contractile properties and operating lengths.

To have some insight into the mechanical interplay between the parasternal intercostal and triangularis sterni muscles during breathing, we have examined the isometric contractile properties of these two muscles in the dog. Using piezoelectric crystals, we have also measured the respiratory changes in muscle length in eight spontaneously breathing animals in the supine posture, and we have compared the in situ relaxation length (Lr) of these two muscles to their respective in vitro optimal force-producing length (Lo). The triangularis sterni and parasternal intercostals had similar isometric twitch, force-frequency, and length-tension characteristics. These two muscles, therefore, are intrinsically similar. In supine dogs, however, they operate on quite distinct segments of their length-tension curve. Whereas Lr for the parasternals corresponded to 117% Lo, Lr for the triangularis sterni was only 75% Lo. This suggests that the triangularis sterni in supine dogs operates on a poorly advantageous portion of its length-tension curve. However, shortening of the parasternals during inspiration causes considerable passive distension of the muscle. As a result, the triangularis sterni is much closer to its optimal length when it starts contracting in early expiration.

Animals↗

Contractile characteristics and operating lengths of canine neck inspiratory muscles.

The neck inspiratory muscles are recruited to support breathing under numerous conditions. To gain insight into their synergistic actions we examined the isometric contractile properties of bundles from canine scalene and sternomastoid muscles. In addition, we also related the length of the neck muscles, measured sonomicrometrically in vivo at different lung volumes and body positions, to their optimal force-producing length (Lo) determined in vitro. We found that the speed of the sternomastoid is somewhat faster than that of the scalene owing to a shorter relaxation rate; the sternomastoid generates higher forces at submaximal stimulation frequencies than the scalene; the maximal tetanic force corrected for cross-sectional area is the same for both neck muscles; the neck muscles are significantly faster than the canine costal diaphragm; at supine functional residual capacity (FRC), the scalene is operating at a length corresponding to 85% Lo, whereas the sternomastoid is significantly shorter at 75% Lo; increasing lung volume shortens both muscles slightly, the length at supine total lung capacity being approximately 5% shorter than at FRC; and in the upright posture, both neck muscles lengthen toward their Lo, with the sternomastoid lengthening more than the scalene. We conclude that the scalene is a more effective force generator than the sternomastoid with the animal lying supine; the neck muscles appear to maintain their force-generating potential regardless of the lung volume; and the force-generating potential of the neck muscles is greatly enhanced with the animal in the upright vs. the supine position. This may contribute to the augmented rib cage motion characteristic of breathing in the upright posture.

Animals↗

Contractile properties of intercostal muscles and their functional significance.

To have some insight into the functional coupling between the parasternal intercostals (PS) and the diaphragm (DPM), we have examined the isometric contractile properties of bundles from canine PS and DPM muscles. Bundles of external (EXT) and internal (INT) interosseous intercostals were studied for comparison. In addition we have related sonometrically measured length of the intercostals in vivo at supine functional residual capacity (FRC) to in vitro optimal force-producing length (Lo). We found that 1) intercostal twitch speed is significantly faster than DPM, thus displacing their relative force-frequency curve to the right of that of the DPM; 2) the ascending limb of the active length-tension curve of all intercostals lies below the DPM curve; i.e., at 85% Lo, PS force is 46% of maximal force (Po), whereas DPM force is still 87% Po; 3) for any given length change beyond Lo, all intercostals generate greater passive tension than the DPM; 4) Po is greater for the intercostals than the DPM; and 5) at supine FRC, both EXT and INT in dogs are nearly operating at Lo, whereas the PS are operating at a length greater than Lo. We conclude that 1) PS produce less force than DPM during breathing efforts involving low- (10-20 Hz) stimulation frequencies, but they generate more force than DPM when high- (greater than 50 Hz) stimulation frequencies are required; and 2) the pressure-generating ability of the PS is better preserved than that of the DPM with increases in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Changes in heart rate during breathing interrupted by recurrent apneas in humans.

Heart rate varies with breathing patterns, especially in sleep apnea. To assess the effects on heart rate of recurrent apneas interrupting tidal breathing, we studied five normal awake male subjects. These subjects voluntarily changed their breathing pattern from regular tidal breathing to tidal breathing interrupted by breath holding at end expiration. This recurrent apneic breathing pattern did not change mean heart rate but increased its variance significantly. In addition, the variations in heart rate formed a cyclic pattern of oscillation with a mean cycle length identical to both arterial O2 saturation (SaO2) (R = 0.95; P less than 0.01) and ventilation (R = 0.92; P less than 0.01). Cyclic changes in either SaO2 or ventilation reproduced the oscillatory patterns of heart rate seen with tidal breathing interrupted by multiple apneas, but the amplitude of the variance in heart rate was smaller. Finally, preventing the cyclic declines in SaO2 with supplemental O2 did not significantly alter the heart rate changes seen in tidal breathing interrupted by apneas.

Adult↗

Acute diaphragmatic shortening: in vitro mechanics and fatigue.

In acute hyperinflation, the occurrence of diaphragmatic shortening may alter the contractile characteristics and function of the diaphragm. The aim of this study was to investigate the effects of acute passive diaphragmatic shortening on in vitro mechanical properties and fatigability. Optimal diaphragmatic length (Lo) was defined as being that length at which peak twitch-tension occurred. Acute shortening (85% Lo, 70% Lo) altered the twitch characteristics. At shorter lengths, the time-to-peak tension and the half-relaxation time were significantly reduced (p less than 0.05). These alterations led to marked alterations in the shape of the force-frequency curve at shorter lengths and in the length-tension properties when assessed at different stimulation frequencies. When normalized with respect to maximal tension, a disproportionate decrease in the generated tension was observed at shorter lengths. Fatigability was assessed by repeatedly stimulating the diaphragmatic bundles and observing the drop in tension with respect to time. For a given fatigue regimen, i.e., same stimulation frequency, the shorter diaphragm (70% Lo) generated more absolute force at any given time period. When the initial tensions were matched at Lo and 70% Lo by increasing the stimulation frequency used to fatigue the shorter muscle, the acutely shortened diaphragm generated less absolute force following 60 s of the fatigue regimen. We conclude that alterations in the contractile characteristics of the diaphragm during acute passive shortening are such that a disproportionately greater excitability is required in order to reach a given submaximal tension as at Lo. This factor may partly account for increased diaphragmatic fatiguability in the acutely shortened state.

Animals↗

Histochemical and biochemical correlates of ventilatory muscle fatigue in emphysematous hamsters.

Histochemical and biochemical characteristics of the ventilatory muscles were evaluated in control and elastase-induced emphysematous hamsters. The emphysematous group was divided into sedentary and endurance-trained groups. Endurance training consisted of treadmill running, 1 h a day, 7 d a week. The experimental period lasted 24 wk. Histochemically, the diaphragm from the sedentary emphysematous hamsters revealed a selective fast fiber atrophy which was prevented by endurance training. Training also led to a hypertrophy of the slow, high oxidative fibers. The external intercostals from both emphysematous groups revealed an increased proportion of fast oxidative fibers at the expense of a decreased number of fast glycolytic fibers. However, the fast fibers in both emphysematous groups were significantly atrophied as compared with controls. The internal intercostals revealed no adaptive changes in either size or proportion distribution of the various fiber types. Biochemically, the diaphragm of the emphysematous animals had a significantly improved oxidative potential as measured by citrate synthase, and a reduced glycolytic capacity as indicated by phosphofructokinase activity, compared with controls. The magnitudes of the biochemical changes were similar in both emphysematous groups and were consistent for diaphragmatic samples taken from the costal and crural segments. The combined internal and external intercostals also underwent significant biochemical increases in their oxidative capacity. In addition, training of the emphysematous group led to an increased glycolytic potential of the intercostals.

Animals↗

Respiratory factors limiting exercise.

The question of respiratory factors limiting exercise has been examined in terms of possible limitations arising from the function of gas exchange, the respiratory mechanics, the energetics of the respiratory muscles, or the development of respiratory muscle fatigue. Exercise capacity is curtailed in the presence of marked hypoxia, and this is readily observed in patients with chronic airflow limitation and interstitial lung disease and in some athletes at high intensities of exercise. In patients with interstitial lung disease, gas exchange abnormality--partly the result of diffusion disequilibrium for oxygen transfer--occurs during exercise despite abnormally high ventilations. In contrast, in certain athletes arterial hypoxemia has been documented during heavy exercise, apparently as a result of relative hypoventilation. During strenuous exercise the maximum expiratory flow volume curves are attained both by patients with chronic airflow limitation and by normal subjects, in particular when they breathe dense gas, so that a mechanical constraint is imposed on further increases in ventilation. Similarly, the force velocity characteristics of the inspiratory muscles may also impose a constraint to further increases in inspiratory flows that affects the ability to increase ventilation. In addition, the oxygen cost of maintaining high ventilations is large. Analysis of results from blood flow experiments reveal a substantial increase in blood flow to the respiratory muscles during exercise, with the result that oxygen supply to the rest of the body may be lessened. Alternatively, high exercise ventilations may not be sustained indefinitely owing to the development of respiratory muscle fatigue that results in hypoventilation and reduced arterial oxygen tension.

Animals↗

Diaphragm in emphysematous hamsters: sarcomere adaptability.

We investigated whether the shift in the diaphragmatic length-tension curve of emphysematous animals was due to changes in either sarcomere number or sarcomere length. In vitro length-tension characteristics of the diaphragm were evaluated in control and emphysematous hamsters. Emphysema was induced by a single endotracheal instillation of elastase. Functional residual capacity, measured by means of a plethysmograph, was about twice that measured in emphysematous animals compared with control animals. Small diaphragmatic bundles were isolated and evaluated for their length-tension characteristics. The length-tension curve of diaphragms from emphysematous animals was displaced toward the left. Maximal tetanic tensions were similar in both groups, whereas optimal bundle length was significantly decreased in the emphysematous animals. Sarcomere number and sarcomere length at optimal length were then calculated for the diaphragmatic bundles. The bundles from emphysematous animals were found to have a significantly reduced number of sarcomeres, as well as a significantly decreased sarcomere length at optimal compared with control values. The total number of sarcomeres were also found to be significantly negatively correlated with the animal's functional residual capacity. From these results, we conclude that the decrease in diaphragmatic length, seen with hyperinflation, is due mainly to a loss of sarcomeres and possibly to a small decrease in sarcomere length measured at optimal bundle length.

Adaptation, Physiological↗

Adaptability of the hamster diaphragm to exercise and/or emphysema.

In vitro contractile properties of the diaphragm were measured in four groups of inbred adult hamsters (greater than 40wk), randomly divided into sedentary control (SC), exercise control (EC), sedentary emphysematous (SE), and exercise emphysematous (EE) groups. Emphysema was induced by a single endotracheal instillation of elastase. Exercise consisted of running 1 h/day, 7 days/wk for 20 wk. Functional residual capacity (FRC), measured by means of a pressure box, was approximately 2.5 times greater in both emphysematous groups compared with control groups. Small diaphragmatic bundles were then isolated and subjected to in vitro analysis of isometric contractile properties. No differences were observed among the four groups in time to peak tension, half-relaxation time, and shape of the force-frequency curve. The diaphragmatic length-tension curve of emphysematous animals was displaced toward the left; maximal tetanic tension was similar in all groups, while optimal length (Lo), defined as the length at which maximal twitch tension occurred, was significantly shorter in both emphysematous groups. The Lo was negatively correlated with the FRC. Exercise tended to increase the in vitro endurance of the diaphragm bundles in control animals only. Diaphragms from both emphysematous groups, however, did show the greatest resistance to fatigue. It is concluded that 1) daily running for 1 h does not influence the diaphragmatic contractile properties in the hamster, but fatigue was reduced; 2) the load of chronic emphysema decreased the hamster's diaphragm fatiguability; and 3) the diaphragms of emphysematous hamsters chronically adapt by decreasing diaphragmatic length in proportion to the degree of hyperinflation and thus probably continue to operate at an Lo.

Adaptation, Physiological↗