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H T Robertson

Publications and source records attributed to H T Robertson.

At least 37 records · Page 2Linked to original sources

Conducting airway gas exchange: diffusion-related differences in inert gas elimination.

We studied CO2 and inert gas elimination in the isolated in situ trachea as a model of conducting airway gas exchange. Six inert gases with various solubilities and molecular weights (MW) were infused into the left atria of six pentobarbital-anesthetized dogs (group 1). The unidirectionally ventilated trachea behaved as a high ventilation-perfusion unit (ratio = 60) with no appreciable dead space. Excretion of higher-MW gases appeared to be depressed, suggesting a MW dependence to inert gas exchange. This was further explored in another six dogs (group 2) with three gases of nearly equal solubility but widely divergent MWs (acetylene, 26; Freon-22, 86.5; isoflurane, 184.5). Isoflurane and Freon-22 excretions were depressed 47 and 30%, respectively, relative to acetylene. In a theoretical model of airway gas exchange, neither a tissue nor a gas phase diffusion resistance predicted our results better than the standard equation for steady-state alveolar inert gas elimination. However, addition of a simple ln (MW) term reduced the remaining residual sum of squares by 40% in group 1 and by 83% in group 2. Despite this significant MW influence on tracheal gas exchange, we calculate that the quantitative gas exchange capacity of the conducting airways in total can account for less than or equal to 16% of any MW-dependent differences observed in pulmonary inert gas elimination.

Animals↗

Fractal modeling of pulmonary blood flow heterogeneity.

The heterogeneity of pulmonary blood flow is not adequately described by gravitational forces alone. We investigated the flow distributions predicted by two fractally branching vascular models to determine how well such networks could explain the observed heterogeneity. The distribution of flow was modeled with a dichotomously branching tree in which the fraction of blood flow from the parent to the daughter branches was gamma and 1-gamma repeatedly at each generation. In one model gamma was held constant throughout the network, and in the other model gamma varied about a mean of 0.5 with a standard deviation of sigma. Both gamma and sigma were optimized in each model for the best fit to pulmonary blood flow data from experimental animals. The predicted relative dispersion of flow from the two model fractal networks produced an excellent fit to the observed data. These fractally branching models relate structure and function of the pulmonary vascular tree and provide a mechanism to describe the spatially correlated distribution of flow and the gravity-independent heterogeneity of blood flow.

Animals↗

Applications of fractal analysis to physiology.

This review describes approaches to the analysis of fractal properties of physiological observations. Fractals are useful to describe the natural irregularity of physiological systems because their irregularity is not truly random and can be demonstrated to have spatial or temporal correlation. The concepts of fractal analysis are introduced from intuitive, visual, and mathematical perspectives. The regional heterogeneities of pulmonary and myocardial flows are discussed as applications of spatial fractal analysis, and methods for estimating a fractal dimension from physiological data are presented. Although the methods used for fractal analyses of physiological data are still under development and will require additional validation, they appear to have great potential for the study of physiology at scales of resolution ranging from the microcirculation to the intact organism.

Animals↗

Gravity is a minor determinant of pulmonary blood flow distribution.

Regional pulmonary blood flow in dogs under zone 3 conditions was measured in supine and prone postures to evaluate the linear gravitational model of perfusion distribution. Flow to regions of lung that were 1.9 cm3 in volume was determined by injection of radiolabeled microspheres in both postures. There was marked perfusion heterogeneity within isogravitational planes (coefficient of variation = 42.5%) as well as within gravitational planes (coefficient of variation = 44.2 and 39.2% in supine and prone postures, respectively; P = 0.02). On average, vertical height explained only 5.8 and 2.4% of the flow variability in the supine and prone postures, respectively. Whereas the gravitational model predicts that regional flows should be negatively correlated when measured in supine and prone postures, flows in the two postures were positively correlated, with an r2 of 0.708 +/- 0.050. Regional perfusion as a function of distance from the center of a lung explained 13.4 and 10.8% of the flow variability in the supine and prone postures, respectively. A linear combination of vertical height and radial distance from the centers of each lung provided a better-fitting model but still explained only 20.0 and 12.0% of the flow variability in the supine and prone postures, respectively. The entire lung was searched for a region of contiguous lung pieces (22.8 cm3) with high flow. Such a region was found in the dorsal area of the lower lobes in six of seven animals, and flow to this region was independent of posture. Under zone 3 conditions, neither gravity nor radial location is the principal determinant of regional perfusion distribution in supine and prone dogs.

Animals↗

Relative contribution of gravity to pulmonary perfusion heterogeneity.

We designed a series of experiments and analyses to quantify the contribution of gravity to pulmonary perfusion heterogeneity. Regional pulmonary perfusion was measured in five anesthetized and ventilated dogs in both supine and prone positions by use of radiolabeled microspheres injected during apnea at functional residual capacity. Measurements of flow were repeated in each position, and the sequence of positions was prospectively designed to nullify any effect of order. The lungs of each animal were excised, perfused with saline until clear, dried at an inflation pressure of 25 cmH2O, and cut into 1.9-cm3 pieces. Each piece was weighed and the radioactivity determined in a scintillation counter. Measurement errors were minimized by excluding lung pieces that had greater than 25% airway and weighed less than 10 mg or greater than 60 mg. Weight-normalized flows in each position and repetition were determined for each lung piece. An analysis of variance model was used to identify the percentage of variation in regional flow that was due to position (supine vs. prone), to random error and time (measurement and repetition), and to structure, where structure was defined as the component of flow that remained constant across position and replication. The contributions of position, error/time, and structure to the total variability of flow across the five dogs were 7.8 +/- 0.6, 8.4 +/- 8.3, and 83.8 +/- 8.4%, (SD), respectively. Because the contribution of position represents the additive effect of gravity between two opposite positions, the contribution of gravity to perfusion heterogeneity in one position may be as little as 4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients.

The objective of this study was to quantitate the improvement in exercise capacity produced in anemic chronic hemodialysis (HD) patients after correction of their anemia with recombinant human erythropoietin (rHuEPO). The maximal exercise capacity and quadriceps strength of 19 anemic HD patients was tested before and after correction of the anemia with rHuEPO. A progressive work exercise protocol (PWET) on a cycle ergometer was used to compare measurements of maximal oxygen uptake (VO2max), maximal heart rate, and subjective assessment of fatigue during the test. Measurements of quadriceps strength were performed before the cycle ergometer studies. At baseline, all patients had reduced VO2max (15.3 +/- 5.4 mL/kg/min) and maximal exercise heart rates (138.5 +/- 23.9 beats/min). rHuEPO increased the mean hematocrit from 21.2% to 35%, and this was associated with a 17% increase (P less than 0.0005) in the VO2max. At any specified work load, rHuEPO treatment decreased heart rate, minute ventilation, and the subjective perception of fatigue. Both isometric and isokinetic measurements of quadriceps strength were improved following administration of rHuEPO. The maximal exercise heart rate was decreased in comparison to the baseline measurements (P less than 0.04), suggesting that in contrast to normal subjects, HD patients stop exercise before oxygen transport limitations are reached. In this unselected group of chronic HD patients, rHuEPO produced clinically significant improvements in both aerobic exercise capacity and isometric and isokinetic quadriceps strength. The improvement in aerobic capacity was substantially less than would have been expected from the correction of a comparable degree of anemia in non-HD patients. None of the 19 treated patients attained the exercise performance level predicted for a sedentary normal subject.

Adult↗

Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects.

Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis, we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment. The trial, which lasted seven months (one month baseline, 6 months treatment) was multicenter, double blind, placebo controlled, and randomized. Eighty-two long-term hemodialysis patients, who were given either carnitine (N = 38) or placebo (N = 44), completed this study. In each group, clinical and biochemical parameters during treatment were compared with baseline values. Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group, while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups. Maximal oxygen consumption, measured during a progressive work exercise test, improved significantly in the carnitine group (111 +/- 50 ml/min. P less than 0.03) and was unchanged in the placebo group. L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen, creatinine and phosphorus (means +/- SEM, 101 +/- 4.5 to 84 +/- 3.9, 16.7 +/- 0.67 to 14.7 +/- 0.64, and 6.4 +/- 0.3 to 5.5 +/- 0.4 mg/dl, respectively, P less than 0.004). No significant changes in any of these variables were noticed in the placebo group. Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients. Calculated mid-arm muscle area increased in the carnitine patients (41.37 +/- 2.68 to 45.6 +/- 2.82 cm2, P = 0.05) and remained unchanged in the placebo patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Carnitine↗

Fractal properties of pulmonary blood flow: characterization of spatial heterogeneity.

The heterogeneity of pulmonary blood flow was examined using a fractal analytic procedure, and the results were compared with the traditional gravitational model of flow distribution. 99mTc-labeled macroaggregate was injected intravenously at functional residual capacity in six supine anesthetized dogs. The lungs were fixed in situ and sliced in transverse sections. The slices were imaged on a planar gamma camera, and a three-dimensional array of blood flow measurements was reconstructed for each lung. Fractal analysis was used to examine the spatial heterogeneity or RDs (relative dispersion = SD/mean) as a function of the number of pieces into which the flow array was subdivided. RDs was fractal and could be characterized by a fractal dimension (Ds) of 1.09 +/- 0.02, where a Ds of 1.0 reflects homogeneous flow and 1.5 indicates a random flow distribution. The data fit the fractal model exceptionally well with an average r = 0.98. RDs was examined in gravitational and isogravitational planes and as expected was greatest in the gravitational direction. However, the difference was small, suggesting that gravitation plays a secondary role to an underlying process producing heterogeneity. Within the limits of resolution attained by this study (piece volumes greater than 0.25 cm3), the heterogeneity of pulmonary blood flow is well characterized by a fractal model.

Animals↗

Physiologic and histologic determinants of gas exchange during induction of oleic acid pulmonary edema.

Five anesthetized mongrel dogs were studied during the induction of acute oleic acid pulmonary edema to determine the influence of cardiac output (Qt), extravascular lung water (ETV), and the degree of alveolar flooding on pulmonary gas exchange. Ot and ETV were measured by thermal dye dilution techniques, alveolar flooding was assesed by histologic studies, and gas exchange was quantitated by the multiple inert gas elimination technique (MIGET). Estimates of the inert gas venous admixture [(Qva/ Qt) IG%] were obtained at different experimental stages from the MIGET data to provide an index of overall gas exchange impairment. Pulmonary edema was produced by the intravenous (IV) infusion of oleic acid (0.08 mL/kg). Measurements of Qt, ETV and (Qva/Qt) IG% were made prior to lung injury and at 40, 80, and 120 minutes after injury. After death the lungs were inflated and frozen. Thirty cores of lung parenchyma (2 mL each) were obtained for histologic assessment of alveolar flooding. In the early phase of edema formation (0 to 80 minutes), (Ova/Qt) IG% increased as ETV increased. After 80 minutes, ETV stabilized and further changes in (Qva/ Qt) IG% were then primarily determined by changes in Qt (r = .94). The histologically assessed degree of alveolar flooding correlated well with ETV at the 120-minutes stage (r = .85). However, by use of multivariate analysis, the addition of the histologic information did not appreciably improve the prediction of gas exchange in acute oleic acid pulmonary edema.

Animals↗

The prone position improves arterial oxygenation and reduces shunt in oleic-acid-induced acute lung injury.

The arterial oxygen tension (PaO2) may increase when patients with the adult respiratory distress syndrome are turned from supine to prone. We sought to reproduce this observation in dogs with acute lung injury to study the physiologic mechanism by which the improvement in oxygenation might occur. Twenty anesthetized dogs were ventilated with a constant tidal volume (20 ml/kg) of 100% oxygen. Oleic acid (0.09 ml/kg) was injected into the right atrium while rotating the animals through 360 degrees in 4 stages. Animals in Group I (n = 5) remained supine for 10 to 120 min until the supine PaO2 fell below 200 mm Hg. Those in Group II (n = 4) were kept prone during this period. Dogs in Groups I and II were then turned supine or prone every 30 min 5 times. Cardiac output and pulmonary vascular pressures, functional residual capacity (helium dilution), and regional diaphragmatic motion (determined by dorsal and ventral diaphragmatic markers relative to markers on the chest wall seen on lateral chest radiographs taken at FRC and at end-inspiration) were obtained in each position. Eleven dogs were kept supine (Group III, n = 6) or prone (Group IV, n = 5) for 2 h after oleic acid infusion, after which intrapulmonary shunt (Qs/QT) and ventilation-perfusion heterogeneity were measured in the supine and prone positions using the multiple inert gas elimination technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Evaluation of breathlessness in asbestos workers. Results of exercise testing.

We studied 120 asbestos-exposed workers seeking compensation for asbestos-related ventilatory impairment who were referred to us for evaluation of their complaint of dyspnea. We reviewed history, chest radiographs, pulmonary function studies, and exercise tests. The workers were 59.9 +/- 9.5 (mean +/- SD) yr of age and their first asbestos exposure had been 34.4 +/- 10 yr prior to the study; 63% were smokers, 19% were ex-smokers, and 18% were nonsmokers. Chest radiographs were normal in 4%, showed only pleural disease in 35%, only parenchymal diseases in 5%, and pleuroparenchymal disease in 56%. Restrictive pulmonary function abnormalities were present in 25% of the workers, and obstructive abnormalities were present in 27%. Because the impairment of one of several organ systems (i.e., ventilatory, cardiac, pulmonary vascular, or peripheral circulatory) may limit exercise performance, we designed an exercise test score in an attempt to identify the system causing the limitation. No abnormal limitation was detectable in half (49.2%) of the subjects. Only 26% had a ventilatory limitation, which was much more frequent in smokers (32%) than in nonsmokers (9%) (p less than 0.05). Unexpectedly, rather more (37%) had a cardiac rather than a ventilatory limitation. We conclude that the complaint of dyspnea in these asbestos-exposed workers was usually not caused by a ventilatory dysfunction.

Asbestosis↗

Diffusion-related differences in elimination of inert gases from the lung.

Partial pressures of intravenously infused acetylene, Freon 22, and isoflurane (gases with similar solubilities in blood but differing molecular weights) were compared in arterial and mixed venous blood and mixed expired gas of 13 anesthetized mongrel dogs to determine whether gas molecular weight influenced gas exchange. Analysis of covariance was used to account for the variables of ventilation-perfusion ratio, partition coefficient, and experimental run before individual gas effects were sought. A gas effect difference was observed such that the arterial fractional retention of isoflurane (mol wt 184.5) would be 12% higher than that of acetylene (mol wt 26) if the two gases had identical partition coefficients. This effect was neither significantly increased by positive end-expiratory pressure nor decreased by high-frequency oscillatory ventilation. To test whether the individual gas effect was greater with gases with disparate erythrocyte and plasma partition coefficients, the exchange of ethyl iodide (erythrocyte-to-plasma solubility ratio 8.1) and diethyl ether (solubility ratio 0.95) was compared in five dogs. A larger difference between the elimination of the two gases was observed than predicted from the differences in molecular weight. The observed individual gas effect appears to be diffusion related, influenced both by the molecular weight of a gas and its erythrocyte-plasma partition coefficient ratio.

Acetylene↗

Distribution of ventilation and perfusion during positive end-expiratory pressure in the adult respiratory distress syndrome.

The response of respiratory gas exchange to incremental increases in positive end-expiratory pressure (PEEP) was studied in patients with the adult respiratory distress syndrome (ARDS). Fifty total changes in PEEP were studied in 19 PEEP trials performed in 16 patients. The initial patterns of ventilation-perfusion distribution as measured by the multiple inert gas elimination technique showed a large shunt flow (32 +/- 14% of total cardiac output), which was accompanied in half of the patients by perfusion to a region of low ventilation-perfusion ratio (VA/Q ratio less than 0.1). In 17 PEEP trials, there was an improvement in PaO2 (increase in PaO2 greater than 10 mmHg over control value) with at least one level of PEEP tested. In the 38 PEEP increments in these trials where PaO2 did improve, there was either a reduction in shunt alone, a reduction in ventilation-perfusion regions alone, or a redistribution in blood flow from shunt to regions of low or normal ventilation-perfusion ratio. In the increments where no increase was observed in PaO2, this reduction in blood flow to shunt or low VA/Q regions did not occur. In some instances, there was an increase in ventilation to unperfused alveoli and evidence of high ventilation-perfusion ratio (VA/Q greater than 10) as the level of PEEP increased. Because patients had an adequate pulmonary artery wedge pressure at the start of the PEEP trial (mean wedge pressure, 12.8 +/- 1.5 mmHg) improvements in oxygenation could usually be attained with only mild decreases in cardiac output.

Adult↗

A summary of preoperative and postoperative cardiorespiratory performance in patients undergoing pectus excavatum and carinatum repair.

Preoperative and postoperative pulmonary function tests and progressive work exercise performances were compared for fourteen pectus excavatum and five pectus carinatum patients who underwent operative repair. No changes could be documented in the pectus carinatum patients. The excavatum patients demonstrated a small improvement in total lung capacity (P less than .02) and a significant improvement in maximal voluntary ventilation (P less than .001). In addition, the exercise performances were improved for the excavatum patients postoperatively as quantitated both by the total exercise time and the maximal oxygen consumption (P less than .01). In addition, at any given work rate, the excavatum patient demonstrated a lower heart rate and higher minute ventilation after operation. These findings support the hypothesis that both the restricted cardiac stroke volume and the increased work of breathing that have been described in pectus excavatum patients can be ameliorated by operative intervention.

Adolescent↗

Pathophysiological patterns of resolution from acute oleic acid lung injury in the dog.

Lungs of mongrel dogs with permanent tracheostomies and implanted systemic pulmonary arterial catheters were injured by intravenous infusion of oleic acid (0.09 mg/kg). Injury resulted in extensive, multifocal, and nonrandomly distributed lung damage. Awake dogs were studied during a control period and 1, 4, and 7 days following injection of oleic acid. Standard gas exchange measurements, the inert gas elimination technique, and subsegmental bronchoalveolar lavage (BAL) were used. Five oleic acid dogs and two saline control dogs were killed after each study period for morphological evaluation. Control dogs did not develop significant gas exchange abnormalities but did have localized inflammatory reactions at the lavage site. The oleic acid dogs developed significant shunt at day 1 with resolution of shunt by day 7. The multifocal sites of oleic acid injury were virtually identical in appearance at a given time interval; they consisted of alveolar cell necrosis with varying amounts of hemorrhagic inflammatory exudation at day 1 followed by a proliferative reparative reaction resulting in substantial restoration of alveolar structure at day 7. BAL showed a suppurative inflammatory response with hemorrhage on day 1 and an increased number of macrophages by day 7. The oleic acid model of acute diffuse lung injury demonstrates several pathophysiological alterations that could be compared with pathomorphological changes during the acute injury phase and during the subsequent reparative phase.

Animals↗

Interaction of series and parallel dead space in the lung.

The volume of ventilation delivered to unperfused zones of the respiratory system (respiratory dead space) can be divided into the volume occupied by the conducting airways (series dead space) and the volume of unperfused alveolar space (parallel dead space). The effect of the interaction between these two components of dead space on steady-state gas exchange was first evaluated with a mathematical model. The presence of both parallel and series dead space was predicted to underestimate the dead space measured by the inert gas elimination technique (VDIG). This error was largest when the volumes of parallel and series dead space were equal. The size of the parallel dead space in the model could be calculated from measurements of VDIG made before and after adding a series dead space of known volume. In 16 anesthetized dogs series and parallel dead space were quantitated using the multiple inert gas elimination technique with addition of known volumes of series dead space. In five normal dogs, the series and parallel dead space averaged 20% and 13% of the tidal volume, respectively. In eleven dogs with the left pulmonary artery occluded the parallel dead space averaged 26%. This method represents the first means of quantitating these two anatomically separate components of wasted ventilation.

Animals↗

The effects of prophylactic expiratory positive airway pressure on the resolution of oleic acid-induced lung injury in dogs.

It is not known whether positive end-expiratory airway pressure (PEEP) merely improves gas exchange in patients with the adult respiratory distress syndrome (ARDS) or if it also affects the resolution of their lung injury. The present investigation was performed to determine whether expiratory positive airway pressure (EPAP), a form of PEEP, is prophylactic in preventing the lung injury induced by oleic acid in dogs or in enhancing its resolution. Arterial and mixed venous blood gases and functional residual capacity (FRC) were measured in 14 pairs of mongrel dogs with indwelling catheters and permanent tracheostomies. One member of each pair was treated with 10 cm H2O EPAP through a valve attached to the tracheostomy tube. Both dogs received 0.06 ml/kg oleic acid intravenously at hour 0. Measurements were made at three, 12, and 24 hours, when EPAP was discontinued, and over the next six days. Five dog pairs were sacrificed at 72 hours; the other surviving animals were sacrificed at 168 hours. FRC was higher at three, 12, and 24 hours in dogs receiving EPAP than in the untreated dogs. The arterial oxygen tension (PaO2) was higher and the venous admixture (Qva/Qt) was lower at three and 12 hours in the dogs receiving EPAP than in the untreated dogs. However, after 24 hours, no differences were noted between the two groups in FRC, PaO2, Qav/Qt, mortality, final lung compliance to initial lung compliance differences, lung water to dry lung weight ratios, or histology. It is concluded that EPAP improves gas exchange during its administration, but has no demonstrable prophylactic effect on the resolution of lung injury in the oleic acid model of human ARDS.

Animals↗