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J Solway

Publications and source records attributed to J Solway.

104 records · Page 6Linked to original sources

Pressure-flow relationships of endotracheal tubes during high-frequency ventilation.

We studied the pressure-flow relationships of various endotracheal tubes (ETT) at frequencies (f) and tidal volumes (VT) in the range used for high-frequency ventilation (HFV) (f: 2-32 Hz, VT: 15-100 ml). Sinusoidal flows were applied to ETT inserted into a rigid bottle or into the tracheae of three anesthetized paralyzed dogs, while pressure fluctuations were measured both proximal and distal to the ETT. The pressure drops in the ETT were nonlinearly related to the peak flow rate and were VT dependent, suggesting that turbulent frictional head loss and convective acceleration were important. The pressure drops measured in vitro were found to be in good agreement with the predictions of a nonlinear oscillatory pressure-flow equation (derived herein), which incorporate the effects of turbulent frictional losses, convective acceleration, inertance, and compliance. The pressure drops measured in situ were 30-50% higher than with the corresponding f-VT combinations in vitro. Possible explanations of these differences are junctional losses at the tip of the ETT or the nonrigid character of the trachea.

Animals↗

Differential inhibition of bronchoconstriction by the calcium channel blockers, verapamil and nifedipine.

Recent studies have demonstrated that the calcium channel blocking agents can inhibit experimentally induced bronchoconstriction in asthmatics, but their protective action has been variable. To clarify the influence of stimulus intensity and choice of calcium blocker on these reported differences in outcome, we performed noncumulative thermal stimulus-response curves using isocapnic hyperventilation of cold air in 8 asthmatics. Subjects received pretreatment with orally administered nifedipine (20 mg), intravenously administered verapamil (10 mg bolus followed by a continuous infusion), or appropriate placebos in a randomized, double-blind fashion. Verapamil afforded no consistent protection against the thermal challenges, whereas nifedipine significantly blunted the bronchoconstrictor response to stimuli of low (p less than 0.02) and middle (p less than 0.03) intensity. At the highest thermal burden, the effect of nifedipine was inconsistent and not significantly different from that of placebo. These results indicate that the protection from bronchoconstriction afforded by the calcium channel blockers depends on the choice of agent and the intensity of the bronchoconstricting stimulus, and they raise the possibility that the contribution of transmembrane calcium ion influx to the pathogenesis of bronchoconstriction may vary according to stimulus intensity.

Adult↗

Breathing pattern affects airway wall temperature during cold air hyperpnea in humans.

We studied the influence of flow rate on respiratory heat exchange in 9 healthy adult subjects using a new noninvasive technique, the single-breath temperature washout (SBTW) curve. The SBTW curve is a plot of exhaled gas temperature versus exhaled volume during a standard exhalation and consists of an initial rise (within the first 200 ml) to a plateau temperature that persists through the remainder of exhalation. We found that exhaled gas temperatures within the initial expirate were colder at every airway locus than corresponding intra-airway gas temperatures at end-inspiration, suggesting that heat exchange occurs between lumenal gas and the relatively cooler airway walls during exhalation. The SBTW plateau temperatures were: (1) lower after preconditioning the airways with rapid (80 L/min) isocapnic hyperpnea of frigid air than after less rapid (40 L/min) cold-air hyperpnea or after quiet breathing; (2) lower when, after identical airway preconditioning regimens, the SBTW exhalation was performed with a slower (0.5 versus 2.5 L/s) expiratory flow; and (3) lower when SBTW curves were obtained after airway preconditioning using respiratory patterns with larger inspiration-expiration duration (I:E) ratios (5:1 versus 1:5) at fixed minute ventilation and respiratory rate. Our results indicate that the global respiratory gas-wall heat transfer coefficient increases with velocity to the 0.9 power, a finding similar to that in previous studies of turbulent flow in rigid pipes.

Adult↗

Intra-airway gas mixing during high-frequency ventilation.

We examined the intra-airway gas transport mediated by high-frequency oscillations (HFO) in 10 nonintubated healthy volunteers using a method based on comparisons of single-breath N2-washout curves obtained after various durations of breath hold or high-frequency oscillations. With a mathematical analysis based on Fick's law of diffusion we computed the local transport parameter, effective diffusivity, during oscillations of frequency 2-24 Hz and tidal volume 10-120 ml and during breath hold alone. Local effective diffusivity increased with both oscillatory frequency and tidal volume at all levels in the tracheobronchial tree; the enhancing effect of tidal volume on local effective diffusivity was more pronounced than that of frequency so that effective diffusivity was greater with larger tidal volume at fixed frequency-tidal volume product (f . VT). The greatest enhancement of gas mixing within the lung during HFO (over breath hold) was seen in the central airways. In previous studies examining CO2 removal rate during HFO (J. Clin. Invest. 68: 1475, 1981), we found that CO2 output was also greater with larger tidal volume at fixed f . VT, and we attributed this to an end constraint imposed by a fresh gas bias flow. Results of the current study, performed without a bias flow, indicate that bias flow end constraint does not solely account for the observed dependence of CO2 output on frequency and tidal volume.

Adult↗

Gas mixing during high-frequency ventilation: an improved model.

A model for gas transport during high-frequency ventilation incorporating recently derived empirical forms for the effective diffusivity in oscillatory gas flow through a symmetrical branching network is proposed. The model accounts for the movement of gas among airways with changing cross-sectional area by using a moving-reference-frame analysis. The analysis technique incorporates the convective purging of the bias flow at the airway opening. The model predicts that although the cycle-averaged CO2 elimination rate (VCO2) depends most strongly on the product of frequency and tidal volume (VT), VT has an effect on its own, a finding consistent with published observations. This "VT effect" is due primarily to the oscillatory movement of gas from more central regions into peripheral regions where large cross-sectional areas promote efficient CO2 transport by molecular diffusion. Although the VT effect exists independent of the presence of a bias flow, placing the bias flow near the main carina can enhance the VT effect substantially. As VT is increased to values in the range of ordinary tidal breaths, VCO2 predicted by the model achieves close agreement with VCO2 deduced from conventional gas exchange theory.

Biological Transport↗

Influence of the endotracheal tube on CO2 transport during high-frequency ventilation.

Low-volume, high-frequency ventilation (HFV) delivered via an endotracheal tube can maintain eucapnia in both humans and animals. Because recent animal studies have suggested that a substantial fraction of the resistance to gas transport during HFV can be attributed to the presence of the endotracheal tube, we evaluated the importance of the endotracheal tube on carbon dioxide elimination (VCO2) during HFV in humans. We compared the effectiveness of delivering the fresh gas bias flow at the proximal and the distal end of an endotracheal tube. For each bias flow position, we ventilated patients using tidal volumes of 60 ml or less and frequencies from 0.5 to 12 Hz. In each case, VCO2 was approximately 50% greater when the fresh gas was introduced at the carinal end of the endotracheal tube. Thus, the endotracheal tube contributed about one third of the resistance to HFV-induced CO2 transport in these patients. These results indicate that the position of the fresh gas source strongly influences the effectiveness of HFV.

Adult↗

Influence of cromolyn sodium on airway temperature in normal subjects.

It is well established that cromolyn sodium attenuates the bronchoconstriction induced by airway cooling in both normal and asthmatic subjects. To determine whether this protection derives from a modification of the thermal events that transpire during the conditioning of inspired air, we first recorded the effect of cromolyn on the bronchoconstrictor response to hyperventilation with frigid air in 7 normal subjects. On a separate occasion, we imposed the same thermal burden and measured the temperature at multiple sites within the airways before and after pretreatment with cromolyn. The first cold air challenge produced a significant decrease in forced expiratory volume in one second (FEV1) of 5.5 +/- 0.9% (SEM) and these changes were significantly reduced by cromolyn (FEV1 = 2.8 +/- 0.9%; p less than 0.05). In concert with the improvement in mechanics, the temperatures (T) within the trachea (tr) and the anterior segment of the right lower lobe (AS-RLL) were significantly higher after cromolyn (Ttr = 1.3 +/- 0.2 degrees C; p less than 0.01; TAS-RLL = 1.0 +/- 0.4 degrees C; p = 0.05), and there was a direct positive relationship between the mechanical protection offered by the drug and the increase in airway temperature (Spearman's rank correlation coefficient = 0.83; p = 0.05). These data suggest that cromolyn modifies respiratory heat exchange in such a fashion as to limit airway cooling. The mechanism of this action is not presently known but may reflect a direct or indirect influence on the bronchial vasculature.

Adult↗

Calcium channel blocking agents in bronchial hyperreactivity.

A variety of clinical and animal bronchial challenge experiments have been undertaken to assess the efficacy and sites of action of the calcium channel blockers nifedipine and verapamil in blunting bronchoconstriction. Nifedipine appears to be the more effective of these agents, and it blunts the airways response to methacholine and histamine inhalation as well as the bronchoconstriction caused by exercise or cold air hyperpnea. The mechanism by which it acts is difficult to define with certainty because of the widely distributed role of calcium ion within the bronchoconstriction pathways, but nifedipine appears to exert a direct effect on airway wall smooth muscle as well as a possible influence on mast cell mediator release.

Airway Resistance↗

Lung inflation during high-frequency ventilation.

We investigated the relationship between mean airway pressure and lung volume during low-tidal-volume, high-frequency ventilation (HFV). Eight patients requiring mechanical ventilatory support for treatment of respiratory insufficiency were studied by imposing rapid (60 to 600 breaths/min) oscillations with low tidal volumes (50 to 150 ml) at a constant mean airway pressure of 5 cm H2O. Despite this constant mean airway pressure, lung volume increased substantially during the oscillation period in 7 of 8 subjects, as indicated both by an increase in thoracoabdominal dimensions and by an increase in respiratory system relaxation pressures after the oscillations were stopped. For each patient in whom these changes occurred, the degree of lung inflation rose progressively with increases in either frequency or tidal volume. Given this dissociation between lung volume and mean airway pressure, some index of lung volume or alveolar pressure should be monitored to minimize the likelihood of adverse effects during HFV.

Adult↗

Biosynthesis of glycosylated hemoglobins in the monkey.

We have investigated the in vivo biosynthesis of the minor hemoglobin components in the rhesus monkey. The elution profile of rhesus hemolysate on BioRex 70 cation exchange resin was analogous to that of human hemolysate. The rhesus Hb Alc peak was identified with the TBA test, which revealed a carbohydrate content identical to that of human Hb A1c. A rhesus monkey was injected with autologous 55Fe-bound transferrin, and the specific activity of each of the minor and major components was followed for over 70 days. As previously shown in man, rhesus Hb alc accumulated specific activity almost linearly over the erythrocyte life-span, indicative of slow and continuous conversion of Hb A0 to Hb Alc. This study revealed two new findings. (1) The specific activity of rhesus Hb Alb was always significantly less than that of Hb Alc. This result suggested that HB Alb is made by further posttranslational modification of Hb Alc. (2) The first portion of rhesus Hb A0 to be eluted on BioRex 70 contained a significant amount of carbohydrate and lower initial specific radioactivity than did the latter portion. This unexpected heterogeneity in the major hemoglobin component reflects slow, nonenzymatic glycosylation at sites other than at the N-terminus of the beta-chain.

Animals↗

Glycosylated minor components of human adult hemoglobin. Purification, identification, and partial structural analysis.

Human hemolysate contains several minor components designated Hb A1a, Hb A1b, Hb A1c, which are post-translational modifications of the major hemoglobin component A0. Individuals with diabetes mellitus have elevated levels of Hb A1c, a hemoglobin modified with a glucose moiety at the NH2 terminus of each beta chain. A new chromatographic technique using Bio-Rex 70 is described which not only allows complete separation of Hb A1a from Hb A1b but also resolution of Hb A1a into two components, designated Hb A1a1 and Hb A1a2. Carbohydrate determinations with the thiobarbituric acid procedure revealed that Hb A1a1, Hb A1a2, and Hb A1b as well as Hb A1c were glycosylated. Total phosphate analysis revealed 2.06 and 1.01 mol of phosphorus/alphabeta dimer for Hb A1a1 and Hb A1a2 respectively; Hb A1b and Hb A1c contained no detectable phosphate. Hemoglobin incubated with D-[14C]glucose-6-P co-chromatographs precisely with Hb A1a2, strongly suggesting that Hb A1a2 is glucose-6-P hemoglobin. Levels of Hb A1a1 and Hb A1a2 are normal in individuals with diabetes mellitus. Furthermore, diabetic red cells contain normal levels of glucose-6-P. Therefore, glucose-6-P hemoglobin does not serve as a significant precursor to Hb A1c. Instead Hb A1c is formed by the direct reaction of hemoglobin with glucose. This suggests that hemoglobin can serve as a model system for nonenzymatic glycosylation of protein.

Adult↗