Citations

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)

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.

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.

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.

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 inspiratio

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.

Abstract 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 &lt; 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 &lt; 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 &lt; 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 &lt; 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

AbstractBackground: Positive control materials for clinical diagnostic molecular genetic testing are in critically short supply. High-quality DNA that closely resembles DNA isolated from patient specimens can be obtained from Epstein–Barr virus (EBV)–transformed peripheral blood lymphocyte cell lines. Here we report the development of a process to (a) recover residual blood samples with clinically important mutations detected during routine medical care, (b) select samples likely to provide viable lymphocytes for EBV transformation, (c) establish stable cell lines and confirm the reported mutation(s), and (d) validate the cell lines for use as positive controls in clinical molecular genetic testing applications.Methods: A network of 32 genetic testing laboratories was established to obtain anonymous, residual clinical samples for transformation and to validate resulting cell lines for use as positive controls. Three panel meetings with experts in molecular genetic testing were held to evaluate results and formulate a process that could function in the context of current common practices in molecular diagnostic testing.Results: Thirteen laboratories submitted a total of 113 residual clinical blood samples with mutations for 14 genetic disorders. Forty-one EBV-transformed cell lines were established. Thirty-five individual point and deletion mutations were shown to be stable after 20 population doublings in culture. Thirty-three cell lines were characterized for specific mutations and validated for use as positive controls in clinical diagnostic applications.Conclusions: A process for producing and validating positive control cell lines from residual clinical blood samples has been developed. Sustainable implementation of the process could help alleviate the current shortage of positive control materials.