Effect of theophylline on the velocity of diaphragmatic muscle shortening

The present study examined the effect of theophylline on the shortening velocity of submaximally activated diaphragmatic muscle (i.e., muscles were activated by the use of a level of stimulation, 50 Hz, within the range of phrenic neural firing frequencies achieved during breathing, whereas maximum activation is achieved at 300 Hz). Experiments were performed in vitro on strips of diaphragmatic muscle obtained from 21 Syrian hamsters. Muscle shortening velocity was assessed during isotonic contractions against a range of afterloads, and Hill's characteristic equation was used to calculate velocity at zero load. In addition, unloaded shortening velocity was also measured by the slack test, i.e., from the time required for muscles to take up slack after a sudden reduction in muscle length. Theophylline (160 mg/l) increased the velocity of muscle shortening against a wide range of external loads (0-14 N/cm2) and increased the extrapolated unloaded velocity of shortening from 6.4 +/- 0.9 to 7.9 +/- 1.1 (SE) lengths/s (P less than 0.01). Theophylline reduced the time required to take up slack for any given step change in muscle length, increasing the unloaded velocity of shortening assessed by the slack test from 7.6 +/- 0.9 to 9.3 +/- 1.1 lengths/s (P less than 0.002). The effect of theophylline on diaphragmatic shortening velocity was evident at concentrations as low as 40 mg/l and increased progressively as theophylline concentrations were increased to 320 mg/l. Theophylline increased the shortening velocity of fatigued as well as fresh muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of lung inflation on lung blood volume and pulmonary venous flow

Phasic changes in lung blood volume (LBV) during the respiratory cycle may play an important role in the genesis of the respiratory wave in arterial pressure, or pulsus paradoxus. To better understand the effects of lung inflation on LBV, we studied the effect of changes in transpulmonary pressure (delta Ptp) on pulmonary venous flow (Qv) in eight isolated canine lungs with constant inflow. Inflation when the zone 2 condition was predominant resulted in transient decreases in Qv associated with increases in LBV. In contrast, inflation when the zone 3 condition was predominant resulted in transient increases in Qv associated with decreases in LBV. These findings are consistent with a model of the pulmonary vasculature that consists of alveolar and extra-alveolar vessels. Blood may be expelled from alveolar vessels but is retained in extra-alveolar vessels with each inflation. The net effect on LBV and thus on Qv is dependent on the zone conditions that predominate during inflation, with alveolar or extra-alveolar effects being greater when the zone 3 or zone 2 conditions predominate, respectively. Lung inflation may therefore result in either transiently augmented or diminished Qv. Phasic changes in left ventricular preload may therefore depend on the zone conditions of the lungs during the respiratory cycle. This may be an important modulator of respiratory variations in cardiac output and blood pressure.     

Effect of lung inflation on regional lung expansion in supine and prone rabbits

At functional residual capacity, lung expansion is more uniform in the prone position than in the supine position. We examined the effect of positive airway pressure (Paw) on this position-dependent difference in lung expansion. In supine and prone rabbits postmortem, we measured alveolar size through dependent and nondependent pleural windows via videomicroscopy at Paw of 0 (functional residual capacity), 7, and 15 cmH2O. After the chest was opened, alveolar size was measured in the isolated lung at several transpulmonary pressures (Ptp) on lung deflation. Alveolar mean linear intercept (Lm) was measured from the video images taken in situ. This was compared with those measured in the isolated lung to determine Ptp in situ. In the supine position, the vertical Ptp gradient increased from 0.52 cmH2O/cm at 0 cmH2O Paw to 0.90 cmH2O/cm at 15 cmH2O Paw, while the vertical gradient in Lm decreased from 2.17 to 0.80 microns/cm. In the prone position, the vertical Ptp gradient increased from 0.06 cmH2O/cm at 0 cmH2O Paw to 0.35 cmH2O/cm at 15 cmH2O Paw, but there was no change in the vertical Lm gradient. In anesthetized paralyzed rabbits in supine and prone positions, we measured pleural liquid pressure directly at 0, 7, and 15 cmH2O Paw with dependent and nondependent rib capsules. Vertical Ptp gradients measured with rib capsules were similar to those estimated from the alveolar size measurements. Lung inflation during mechanical ventilation may reduce the vertical nonuniformities in lung expansion observed in the supine position, thereby improving gas exchange and the distribution of ventilation.     

Effect of lung inflation on fluid flux in zone 1 lungs

Because of conflicting data in the literature, we studied the effect of positive-pressure inflation on transvascular fluid filtration in zone 1 lungs. Lungs from New Zealand White rabbits (n = 10) were excised, perfused with saline and autologous whole blood (1:1), ventilated, and continuously weighed. Pulmonary arterial and venous pressures (Pvas) were referenced to the most dependent part of the lung. A change in vascular volume (delta Vvas) and a fluid filtration rate (FFR) were calculated from the change in lung weight that occurred from 0 to 30 s and from 3 to 5 and 5 to 10 min, respectively, after changing alveolar pressure (PA). FFR's and delta Vvas's were measured with Pvas equal to 2 or 10 cmH2O and PA changing from 15 to 30 cmH2O when the lungs were normal and after they were made edematous. When Pvas = 2 cmH2O, increasing PA increased the Vvas and the FFR in both normal and edematous lungs. However, when Pvas = 10 cmH2O, increasing PA only slightly changed the Vvas and reduced the FFR in the normal lungs, and decreased Vvas and markedly decreased the FFR in the presence of edema. Inflating zone 1 lungs by positive pressure has an effect on transvascular fluid flux that depends on the Pvas. The results suggest that the sites of leakage in zone 1 also vary depending on Pvas and PA.     

Effect of fatigue on diaphragmatic function at different lung volumes.

The transdiaphragmatic pressure twitches (PdiT) in response to single maximal shocks delivered bilaterally to the phrenic nerves were recorded as a function of lung volume when the diaphragm was fresh and when fatigued. All relationships were linear and negatively sloped (all r greater than 0.85). From these relationships PdiT was found to decrease with fatigue more rapidly and to recover more quickly at high than at low lung volumes. Complete recovery of PdiT at all lung volumes was greater than 1 h. Contraction and relaxation rate constants of PdiT did not change significantly with fatigue. We conclude that fatigue affects diaphragm contractility more at high than at low lung volumes and that changes in diaphragm contractility are best reflected in the measurement of PdiT as a function of lung volume.     

Sonomicrometric regional diaphragmatic shortening in awake sheep after thoracic surgery

Through a right thoracotomy in seven sheep we chronically implanted sonomicrometry crystals and electromyographic electrodes in the costal and crural diaphragmatic regions. Awake sheep were studied during recovery for 4-6 wk, both during quiet breathing (QB) and during CO2 rebreathing. Tidal volume, respiratory frequency, and esophageal and gastric pressures were studied before and after surgery. Normalized resting length (LFRC) was significantly decreased for the costal segment on postoperative day 1 compared with postoperative day 28. Fractional costal shortening both during QB and at 10% end-tidal CO2 (ETCO2) increased significantly from postoperative days 1 to 28, whereas crural shortening did not change during QB but progressively increased at 10% ETCO2. Maximal costal shortening during electrophrenic stimulation was constant at 40% LFRC during recovery, although maximal crural shortening increased from 23 to 32% LFRC. Minute ventilation, tidal volume, and transdiaphragmatic pressure at 10% ETCO2 increased progressively after thoracotomy until postoperative day 28. Our results suggest there is profound diaphragmatic inhibition after thoracotomy and crystal implantation in sheep that requires at least 3-4 wk for stable recovery.     

Effect of lung inflation on the respiratory frequency and heart rate of premature neonates

Changes in the respiratory frequency and heart rate in response to 10 seconds' inflation of the lungs with oxygen by the CPAP method were studied in 32 premature neonates. Elevation of the pressure in the airways and lungs of 0.25, 0.49, 0.73 and 0.98 kPa led to a slower respiration rate or to apnoea. The incidence of apnoea rose in proportion to the pressure. When inflation was started, forced inspiratory efforts (a gasp reflex) occurred. The incidence of the efforts was higher at higher inflation pressures, but their intensity was not correlated to the size of the pressure. They were manifested in a drop in oesophageal pressure to a mean -2.0 +/- 0.2 kPa and their mean duration was 169 +/- 8 ms. The administration of oxygen without an increase in pressure produced neither apnoea nor forced inspiratory reactions. Neither an increase in the pressure in the airways and lungs to the above values, nor the plain administration of oxygen, produced any significant changes in the instantaneous heart rate.