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These experiments tested the capacity of theophylline to improve diaphragm strength (maximal force development) and endurance (maintenance of force output during repeated contractions). Rodent diaphragm strips were mounted at optimal length in oxygenated Krebs-Ringer solution (37 degrees C, pH 7.37). Direct stimuli used supramaximal current density, 0.2-ms pulses, and 250-ms tetanic trains. Theophylline (500 mg/ml) increased force development at low stimulation frequencies but did not increase maximal force [25.7 +/- 0.5 for theophylline vs. 26.0 +/- 0.4 (SE) N/cm2 for control (n = 34)]. During repeated submaximal (25–36 Hz) tetanic contractions, theophylline did not affect endurance. During repeated maximal (160 Hz) tetanic contractions theophylline reduced endurance, accelerating the fall of developed force. Theophylline also inhibited recovery of force after endurance trials ended. We conclude that theophylline does not increase maximal tetanic force and can reduce diaphragm endurance in vitro.

The effects of nifedipine (30 ug/ml) on isometric force production of in-vitro rat diaphragm were studied during direct and indirect modes of muscle activation. During direct muscle stimulation, nifedipine potentiated isometric force during twitch and unfused tetanic stimulation. Indirectly elicited responses, evoked by stimulation of the phrenic nerve, were uniformly depressed following nifedipine. Inhibition of indirect force production increased with time, while force potentiation with direct activation remained constant. We conclude that inhibitory effects of nifedipine on the phrenic nerve-diaphragm preparation are specific for nerve or neuromuscular junction.

We recorded the responses of 21 slowly adapting pulmonary stretch receptors (PSRs) and 8 rapidly adapting pulmonary stretch receptors (RARs) from the vagi of anesthetized open-chest dogs to high-frequency ventilation (HFV) at 15 Hz, at constant mean end-expiratory lung volume, and constant end-tidal PCO2. HFV applied in this way has been shown to prolong expiration. The responses of pulmonary afferents during HFV at constant mean volume have not been described. In the present experiments, receptor discharge during HFV was compared with that during the end-expiratory pause of normal-frequency ventilation. Average PSR discharge increased when HFV was applied, although not all PSRs exhibited increases. RARs were generally silent during normal and high-frequency ventilation at functional residual capacity and above. However, at low lung volumes, RAR discharge increased greatly when HFV was applied. We conclude that PSR discharge is increased during HFV in the absence of increased lung volume and that increases in PSR discharge during HFV are sufficient to explain the reflex that prolongs expiration in dogs.

The existence of a compact nonthermal radio source at the galactic centre was first suggested by Lynden-Bell and Rees1 as the possible signature of a black hole. Such a source was detected unambiguously by Balick and Brown2.Very long baseline interferometry (VLBI) observations of the structure of this source, hereafter referred to as Sgr A*, have been made for several years3,4. In all previous experiments, the visibility amplitudes, measured over a restricted (U, V) range, could be fitted only to the simplest model of brightness distribution, that is, to a circular gaussian. We have re-observed Sgr A* at λ3.6 cm and λ 1.35 cm with many baselines, using the more sensitive receivers and VLBI recording terminals now available. These observations set an upper limit of 20 AU (3 × l014 cm) to the diameter of Sgr A* at λ 1.35 cm and reveal for the first time an elongated structure at λ 3.6 cm, with the position angle of the long axis almost parallel to the rotation axis of the Galaxy. Sgr A* is unique in our Galaxy, but resembles most closely the compact radio sources at the centre of external galaxies. Observations of the central 4 arc s (0.2 pc) at radio and other wavelengths are best explained by a single massive collapsed object at the galactic centre.

We have determined the mechanical effects of immersion to the neck on the passive chest wall of seated upright humans. Repeated measurements were made at relaxed end expiration on four subjects. Changes in relaxed chest wall configuration were measured using magnetometers. Gastric and esophageal pressures were measured with balloon-tipped catheters in three subjects; from these, transdiaphragmatic pressure was calculated. Transabdominal pressure was estimated using a fluid-filled, open-tipped catheter referenced to the abdomen's exterior vertical surface. We found that immersion progressively reduced mean transabdominal pressure to near zero and that the relaxed abdominal wall was moved inward 3–4 cm. The viscera were displaced upward into the thorax, gastric pressure increased by 20 cmH2O, and transdiaphragmatic pressure decreased by 10–15 cmH2O. This lengthened the diaphragm, elevating the diaphragmatic dome 3–4 cm. Esophageal pressure became progressively more positive throughout immersion, increasing by 8 cmH2O. The relaxed rib cage was elevated and expanded by raising water from hips to lower sternum; this passively shortened the inspiratory intercostals and the accessory muscles of inspiration. Deeper immersion distorted the thorax markedly: the upper rib cage was forced inward while lower rib cage shape was not systematically altered and the rib cage remained elevated. Such distortion may have passively lengthened or shortened the inspiratory muscles of the rib cage, depending on their location. We conclude that the nonuniform forcing produced by immersion provides unique insights into the mechanical characteristics of the abdomen and rib cage, that immersion-induced length changes differ among the inspiratory muscles according to their locations and the depth of immersion, and that such length changes may have implications for patients with inspiratory muscle deficits.

The isometric contractile response of the directly-stimulated rat diaphragm was studied before and following addition of the calcium channel blocker, nifedipine. Nifedipine (10 micrograms/ml and 30 micrograms/ml bath concentrations) significantly increased isometric force output during twitch and unfused tetanic stimulation. Force potentiation during unfused tetanic stimulation was equivalent during either high or low voltage stimulation. Nifedipine had no effect on the time to peak force, half relaxation time, or relaxation time during twitch stimulation; thus, both activation and relaxation rates were increased. The force potentiating actions of nifedipine persisted in a calcium-free bathing solution and were enhanced by d-tubocurarine. In contrast to the force enhancing effects found with twitch and unfused tetanic stimulation, nifedipine caused a small but significant reduction in isometric force during maximal fused tetanic stimulation. It is concluded that the force potentiating effects of nifedipine on rat diaphragm are not due to fiber recruitment, enhancement of neuromuscular excitation, or altered inward trans-sarcolemmal calcium flux, but may result from a direct effect of the drug on the rate of activation of the contractile apparatus.

In the present study, we measured fiber types and fiber diameters in canine respiratory muscles and examined regional variation within the diaphragm. Samples of eight diaphragm regions, internal intercostals, external intercostals, transversus abdominis, and triceps brachii were removed from eight adult mongrel dogs, frozen, and histochemically processed for standard fiber type and fiber diameter determinations. The respiratory muscles were composed of types I and IIa fibers; no IIb fibers were identified. Fiber composition differed between muscles (P less than 0.0001). Normal type I percent (+/- SE) were: diaphragm 46 +/- 2, external intercostal 85 +/- 6, internal intercostals 48 +/- 3, transversus abdominis 53 +/- 1, and triceps 33 +/- 7. The diaphragm also contained a type I subtype [6 +/- 1% (SE)] previously thought only to occur in developing muscle. Fiber composition varied between diaphragm regions (P less than 0.01). Most notably, left medial crus contained 64% type I fibers. Fiber size also varied systematically among muscles (P less than 0.025) and diaphragm regions (P less than 0.0005). External intercostal fiber diameter was largest (47–50 microns) and diaphragm was smallest (34 microns). Within diaphragm, crural fibers were larger than costal (P less than 0.05). We conclude that there are systematic differences in fiber composition and fiber diameter of the canine respiratory muscles.

When immersion alters inspiratory muscle operating lengths, spontaneously breathing humans maintain a constant tidal volume by reflex adjustment of inspiratory muscle activation (Reid et al. J. Appl. Physiol. 58: 1136–1142, 1985). We term this the operational length compensation reflex. The present experiment demonstrates that similar adjustments occur during voluntary respiratory maneuvers. Each of seven naive subjects sat in a tank with water at hip level. We trained them to reproduce an inspired volume (+/- 10%) at constant inspiratory duration. They received verbal feedback during training but not during the experiment. We measured surface electromyograms (EMGs) of diaphragm and intercostal muscles and tidal volume. After the subjects were trained, we made repeated measurements of 10 trained breaths with water at the hip and then again after raising water level to the xiphoid (which decreases lung volume and increases operating length of the diaphragm). In 30 of 42 trials there was a substantial fall in peak diaphragm EMG. In 10 trials this was sufficient to prevent any change in tidal volume. Inspiratory flow was more closely regulated than tidal volume. Subjects were not aware of making adjustments in drive.

High frequency (15 Hz), low volume (approximately 40 ml) oscillation of the respiratory system lengthens expiration in anesthetized dogs even in the absence of changes in mean expiratory lung volume or blood gases (Banzett et al ., 1983). Although vagotomy abolishes this response, we felt it might mask the reflex rather than interrupt the afferent pathway. To ascertain whether pulmonary and airway afferents alone are capable of evoking this reflex, we confined the oscillatory stimulus to the lung by widely opening the chest. The dogs were paralyzed but breathed ‘spontaneously’ by means of a solenoid valve opened and closed by the phrenic neurogram. End-expiratory lung volume and P CO2 were held constant. All eight dogs that were tested after thoracotomy lengthened expiration during oscillation. Although quantitative comparisons of responses before and after thoracotomy are not entirely reliable, we could see no consistent change in the strength of response with paralysis or with thoracotomy. We conclude that the principal afferent limb of the ventilatory reflex response to oscillation arises in the lungs and intrathoracic airways.

Chronic ethanol consumption alters the structure and function of human respiratory muscle. We have examined its effect on the active and passive mechanical properties of rat diaphragm strips in vitro. We conditioned eight rats using a liquid diet containing ethanol as 36% of calories. Eight control rats were pair-fed an isocaloric, ethanol-free liquid diet. Rats were killed after 23 wk. Two strips from the left hemidiaphragm were suspended in Krebs-Ringers solution at 25 degrees C, equilibrated with 5% CO2–95% O2. Isometric stresses were calculated from force transducer measurements. Strips were stimulated directly at supramaximal voltage. Twitch stress (Pt), measured at optimal length (Lo), was greater in ethanol-conditioned strips: 5.1 vs. 3.8 N/cm2. Times to peak Pt and twitch half-relaxation times were equal. Tetanic stress at Lo (Po) was also greater after ethanol conditioning: 17.2 vs. 12.8 N/cm2. Pt/Po ratios were equal. Expressed as %Po, tetanic stress-stimulation frequency curves and tetanic stress-length curves were identical. Ethanol-conditioned strips were marginally less compliant when passively stretched to lengths between Lo and 130% Lo. We postulate that ethanol may have increased active stress development by reducing intracellular free water.

We measured tidal volume (VT), chest wall dimensions, end-tidal PCO2, and respiratory muscle electromyograms as seated subjects were immersed in water. We studied nine spontaneously breathing subjects; five were uninformed. Raising the water to xiphoid level pushed the abdomen in and expanded the rib cage at end expiration. This increased the diaphragm's operating length, giving it a contractile advantage, and shortened the inspiratory intercostals, giving them a contractile disadvantage. Peak inspiratory activities of both muscle groups decreased; inspiratory time (TI), respiratory frequency (f), and VT were unchanged. The experiments thus demonstrated operational length compensation during immersion and further showed that inspiratory muscle activation is not adjusted locally, according to changes in each muscle's length, but rather that the response is global. Xiphoid-to-shoulder immersion was less easily interpreted, since both rib cage and abdomen were compressed, lengthening both inspiratory muscles. Our subjects continued to maintain VT, f, and TI. Peak inspiratory activities of both muscles were further reduced. We do not attribute the change in inspiratory muscle activation to altered chemical drive or to voluntary response. Rather, the response appears to be a mechanoreceptive reflex that employs afferent information from the lungs or diaphragm to adjust all inspiratory muscle activities.

The relationship between parasternal intercostal length and rib cage cross-sectional area was examined in nine supine dogs during passive inflation and during quiet breathing before and after phrenicotomy. Parasternal intercostal length (PSL) was measured with a sonomicrometry technique, and rib cage cross-sectional area (Arc) was measured with a Respitrace coil placed around the middle rib cage. During active inspiration as well as during passive inflation, PSL decreased as Arc increased. However, the relationship between PSL and Arc during active inspiration, whether in the intact or phrenicotomized animal, was almost invariably different from that during passive inflation, so that the same increase in Arc was associated with a greater decrease in PSL in the former than in the latter instance. This difference between passive inflation and active inspiration is probably due to the active contraction of the parasternals during inspiration and the consequent caudal displacement of the sternum. In upright humans, the sternum moves cephalad and not caudad during inspiration, so the relationship between PSL and Arc during active breathing might be similar to that during passive inflation.

Purpose: The present study examined the effects of endurance training on the contractile and biochemical properties of the rat costal diaphragm in vitro. Methods: Sixty-four rats were divided into two groups: exercise trained (T) and control (C). Training consisted of treadmill running 5 d wk(-1), 60 min.d(-1) at similar to 70% of (V) over dotO(2max), over a 10-wk period. Results: Control diaphragm strips produced an average of 12% less force from minute 15 to 50 of a 60-min in vitro fatigue protocol, compared with the T diaphragm strips (P < 0.01). T diaphragms had 10.1% higher citrate synthase (CS) and 12.1% higher superoxide dismutase (SOD) activities compared with the C (P < 0.05). Despite a significant decrease (P < 0.05) in Type IIb myosin heavy chains (MHC) and an increase (P < 0.05) in Type I MHC in T diaphragms, maximal shortening velocity (V-max) in the diaphragm was not different between T and C animals. No differences were observed in specific force or the relative proportions of myosin light chains between groups. Conclusions: These findings suggest that endurance training reduces the rate of diaphragm fatigue in vitro but has no effect on V-max or specific force.