André De Troyer

In an attempt to explain the clinical efficacy of aminophylline, we studied its effect on diaphragmatic function in eight normal subjects. The relation between the electrical activity of the diaphragm and the pressure generated by the diaphragm was assessed during voluntary contractions before and after aminophylline infusion. Aminophylline shifted the electrical activity/pressure curve to the left; the pressure at a given electrical activity increased an average of 15 per cent (P less than 0.001). In four subjects, pressure was also measured during stimulation of the phrenic nerve at various frequencies before and after diaphragmatic fatigue was produced by resistive breathing, with and without aminophylline infusion. Pressure increased after fatigue at all stimulation frequencies with aminophylline, as compared with the pressure after identical fatigue runs at the same stimulation frequencies without aminophylline. The mean plasma aminophylline concentration associated with these responses was 13 +/- 0.9 mg per liter. We conclude that aminophylline improves the diaphragm's contractility and renders it less susceptible to fatigue.

The mechanical advantages of the external and internal intercostals depend partly on the orientation of the muscle but mostly on interspace number and the position of the muscle within each interspace. Thus the external intercostals in the dorsal portion of the rostral interspaces have a large inspiratory mechanical advantage, but this advantage decreases ventrally and caudally such that in the ventral portion of the caudal interspaces, it is reversed into an expiratory mechanical advantage. The internal interosseous intercostals in the caudal interspaces also have a large expiratory mechanical advantage, but this advantage decreases cranially and, for the upper interspaces, ventrally as well. The intercartilaginous portion of the internal intercostals (the so-called parasternal intercostals), therefore, has an inspiratory mechanical advantage, whereas the triangularis sterni has a large expiratory mechanical advantage. These rostrocaudal gradients result from the nonuniform coupling between rib displacement and lung expansion, and the dorsoventral gradients result from the three-dimensional configuration of the rib cage. Such topographic differences in mechanical advantage imply that the functions of the muscles during breathing are largely determined by the topographic distributions of neural drive. The distributions of inspiratory and expiratory activity among the muscles are strikingly similar to the distributions of inspiratory and expiratory mechanical advantages, respectively. As a result, the external intercostals and the parasternal intercostals have an inspiratory function during breathing, whereas the internal interosseous intercostals and the triangularis sterni have an expiratory function.

We used a high-resolution ultrasound to make electrical recordings from the transversus abdominis muscle in humans. The behavior of this muscle was then compared with that of the external oblique and rectus abdominis in six normal subjects in the seated posture. During voluntary efforts such as expiration from functional residual capacity, speaking, expulsive maneuvers, and isovolume "belly-in" maneuvers, the transversus in general contracted together with the external oblique and the rectus abdominis. In contrast, during hyperoxic hypercapnia, all subjects had phasic expiratory activity in the transversus at ventilations between 10 and 18 l/min, well before activity could be recorded from either the external oblique or the rectus abdominis. Similarly, inspiratory elastic loading evoked transversus expiratory activity in all subjects but external oblique activity in only one subject and rectus abdominis activity in only two subjects. We thus conclude that in humans 1) the transversus abdominis is recruited preferentially to the superficial muscle layer of the abdominal wall during breathing and 2) the threshold for abdominal muscle recruitment during expiration is substantially lower than conventionally thought.

We investigated pulmonary mechanics in 25 patients, 9 to 55 years of age, with a variety of generalised neuromuscular diseases and variable degrees of respiratory muscle weakness. The average degree of inspiratory muscle force was 39.2% (range 8-83%) of predicted. The lung volume restriction far exceeded that expected for the degree of muscle weakness: the observed decrement in respiratory muscle force should, theoretically, decrease vital capacity to 78% of its control value, while the mean VC in our patients was only 50% of predicted. Analysis of lung pressure-volume curves indicated that the two principal causes of the disproportionate loss of lung volume were a reduction in lung distensibility probably caused by widespread microatelectasis, and a decrease in the outward pull of the chest wall. Because it reflects both direct (loss of distending pressure) and secondary (alterations in the elastic properties of the lungs and chest wall) effects of respiratory muscle weakness on lung function, we conclude that, in these patients, the vital capacity remains the most useful measurement to follow evolution of the disease process or response to treatment.

Patients with severe chronic obstructive pulmonary disease (COPD) have a greater neural drive to the parasternal intercostal and scalene muscles and greater inspiratory expansion of the rib cage than do healthy individuals. However, such patients also have a reduced outward displacement or a paradoxical inward displacement of the ventral abdominal wall during inspiration. This has led to the suggestion that they may have less use of the diaphragm, possibly secondary to chronic muscle fatigue. To assess the effect of COPD on the neural drive to the diaphragm, we inserted needle electrodes into the costal part of the right hemidiaphragm in eight patients with severe disease (mean [+/- SD] FEV1: 0.82 [+/- 0.27] L) and six control subjects of similar age, and measured the discharge frequencies of single motor units during resting breathing. A total of 115 diaphragmatic motor units were recorded in the control subjects and 122 in the patients. All motor units discharged rhythmically in phase with inspiration. However, whereas 95% of the units in the control subjects had a peak discharge frequency between 7 and 14 Hz, 79% of the units in the COPD patients had a peak discharge frequency greater than 15 Hz. As a result, the discharge frequency of all units averaged 10.5 [+/- 2.4] Hz in the control subjects, but 17.9 [+/- 4.3] Hz in the patients (p < 0.001). These observations indicate that patients with severe COPD have an increased neural drive not only to the rib cage inspiratory muscles, but also to the diaphragm. Consequently, the reduced inspiratory expansion of the abdomen in severe COPD results from mechanical factors alone.