Biomedical subjects

H T Robertson

Publications and source records attributed to H T Robertson.

At least 19 recordsLinked to original sources

PubMed2001

Determination of regional ventilation and perfusion in the lung using xenon and computed tomography.

We propose a model to measure both regional ventilation (V) and perfusion (Q) in which the regional radiodensity (RD) in the lung during xenon (Xe) washin is a function of regional V (increasing RD) and Q (decreasing RD). We studied five anesthetized, paralyzed, mechanically ventilated, supine sheep. Four 2.5-mm-thick computed tomography (CT) images were simultaneously acquired immediately cephalad to the diaphragm at end inspiration for each breath during 3 min of Xe breathing. Observed changes in RD during Xe washin were used to determine regional V and Q. For 16 mm(3), Q displayed more variance than V: the coefficient of variance of Q (CV(Q)) = 1.58 +/- 0.23, the CV of V (CV(V)) = 0.46 +/- 0.07, and the ratio of CV(Q) to CV(V) = 3.5 +/- 1.1. CV(Q) (1.21 +/- 0.37) and the ratio of CV(Q) to CV(V) (2.4 +/- 1.2) were smaller at 1,000-mm(3) scale, but CV(V) (0.53 +/- 0.09) was not. V/Q distributions also displayed scale dependence: log SD of V and log SD of Q were 0.79 +/- 0.05 and 0.85 +/- 0.10 for 16-mm(3) and 0.69 +/- 0.20 and 0.67 +/- 0.10 for 1,000-mm(3) regions of lung, respectively. V and Q measurements made with CT and Xe also demonstrate vertically oriented and isogravitational heterogeneity, which are described using other methodologies. Sequential images acquired by CT during Xe breathing can be used to determine both regional V and Q noninvasively with high spatial resolution.

Algorithms↗

PubMed2000

Pulmonary NO synthase inhibition and inspired CO2: effects on V'/Q' and pulmonary blood flow distribution.

Inhaled carbon dioxide decreases ventilation/perfusion ratio (V'/Q') heterogeneity in dogs. The aim of this study was to test whether inhaled CO2 improves the V'/Q' by inhibition of nitric oxide production and whether inhibition of endogenous NO production in the lung alters gas exchange and V'/Q' matching. Eleven healthy dogs were anaesthetized and mechanically ventilated. The multiple inert gas elimination technique (MIGET) was used to measure V'/Q' heterogeneity and regional pulmonary blood flow heterogeneity was assessed in five dogs using fluorescent microspheres. In a separate set of five dogs, exhaled NO levels were measured via chemiluminescence. All dogs were studied before and after 4.8% inspired CO2, and then given the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg x kg(-1)) via nebulization, after which they were studied again with room air and inhaled CO2. CO2 and L-NAME improved arterial and alveolar oxygen tension, but the improvements with L-NAME did not reach statistical significance. Improved V'/Q' matching, as assessed by the MIGET, occurred under all experimental conditions. Exhaled NO levels were reduced by 40% with CO2 and 70% with L-NAME. The standard deviation of regional pulmonary blood flow assessed via microspheres decreased only with inhaled CO2. Fractal analysis of pulmonary blood flow distributions revealed that regional blood flow was highly correlated with flow to neighbouring pieces of lung in all four conditions with no changes in the fractal dimension. Inspired carbon dioxide improves ventilation perfusion ratio matching and is associated with a more homogeneous distribution of pulmonary blood flow. Although inspired carbon dioxide causes a reduction in exhaled nitric oxide, the differences in pulmonary perfusion distributions found between carbon dioxide and N(omega)-nitro-L-arginine methyl ester suggest that the carbon dioxide effect is not mediated by a reduction in nitric oxide production. The improved ventilation perfusion ratio matching with inhibition of nitric oxide synthase suggests the intriguing possibility requiring further study that endogenous production of nitric oxide in the lung does not subserve ventilation perfusion ratio regulation.

Administration, Inhalation↗

PubMed2000

Physiological implications of the fractal distribution of ventilation and perfusion in the lung.

Both regional ventilation and regional perfusion demonstrate progressive increases in heterogeneity as the resolution of measurement is improved. Because the efficiency of pulmonary gas exchange is dependent on the match between local ventilation and local perfusion, the correlation between these two parameters was examined over a range of scale. We marked regional ventilation and perfusion in three anesthetized pigs with aerosolized 1 microm fluorescent microspheres (FMS) and injected 15 microm FMS. The lungs were dried inflated, cut into approximately 2 cm3 cubes, and regional ventilation and blood flow were calculated from measurements of the fluorescence signals extracted from each piece. Adjacent pieces were clustered into successively larger aggregate volumes, and the averages of ventilation and of perfusion were calculated for each cluster size. While the coefficient of variation for both ventilation and perfusion increased predictably as the cluster size decreased, the correlation between ventilation and perfusion within clusters remained high, averaging between 0.82 and 0.92 among animals. Thus, while both ventilation and perfusion heterogeneity increase as the resolution of measurement improves, the strong correlation between these two parameters in a normal prone lung is nearly sample size invariant. This finding explains the observed efficiency of normal gas exchange in the face of the substantial degree of ventilation and perfusion heterogeneity observed in the normal lung with high-resolution measurement.

Administration, Inhalation↗

PubMed2000

Pulmonary blood flow remains fractal down to the level of gas exchange.

The spatial distribution of pulmonary blood flow is increasingly heterogeneous as progressively smaller lung regions are examined. To determine the extent of perfusion heterogeneity at the level of gas exchange, we studied blood flow distributions in rat lungs by using an imaging cryomicrotome. Approximately 150,000 fluorescent 15-microm-diameter microspheres were injected into tail veins of five awake rats. The rats were heavily anesthetized; the lungs were removed, filled with an optimal cutting tissue compound, and frozen; and the spatial location of every microsphere was determined. The data were mathematically dissected with the use of an unbiased random sampling method. The coefficients of variation of microsphere distributions were determined at varying sampling volumes. Perfusion heterogeneity increased linearly on a log-log plot of coefficient of variation vs. volume, down to the smallest sampling size of 0.53 mm(3). The average fractal dimension, a scale-independent measure of perfusion distribution, was 1.2. This value is similar to that of other larger species such as dogs, pigs, and horses. Pulmonary perfusion heterogeneity increases continuously and remains fractal down to the acinar level. Despite the large degree of perfusion heterogeneity at the acinar level, gases are efficiently exchanged.

Algorithms↗

PubMed2000

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity.

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Animals↗

PubMed2000

Vasomotor tone does not affect perfusion heterogeneity and gas exchange in normal primate lungs during normoxia.

To determine whether vasoregulation is an important cause of pulmonary perfusion heterogeneity, we measured regional blood flow and gas exchange before and after giving prostacyclin (PGI(2)) to baboons. Four animals were anesthetized with ketamine and mechanically ventilated. Fluorescent microspheres were used to mark regional perfusion before and after PGI(2) infusion. The lungs were subsequently excised, dried inflated, and diced into approximately 2-cm(3) pieces (n = 1,208-1,629 per animal) with the spatial coordinates recorded for each piece. Blood flow to each piece was determined for each condition from the fluorescent signals. Blood flow heterogeneity did not change with PGI(2) infusion. Two other measures of spatial blood flow distribution, the fractal dimension and the spatial correlation, did not change with PGI(2) infusion. Alveolar-arterial O(2) differences did not change with PGI(2) infusion. We conclude that, in normal primate lungs during normoxia, vasomotor tone is not a significant cause of perfusion heterogeneity. Despite the heterogeneous distribution of blood flow, active regulation of regional perfusion is not required for efficient gas exchange.

Animals↗

PubMed1999

Gravity is an important but secondary determinant of regional pulmonary blood flow in upright primates.

Original studies leading to the gravitational model of pulmonary blood flow and contemporary studies showing gravity-independent perfusion differ in the recent use of laboratory animals instead of humans. We explored the distribution of pulmonary blood flow in baboons because their anatomy, serial distribution of vascular resistances, and hemodynamic responses to hypoxia are similar to those of humans. Four baboons were anesthetized with ketamine, intubated, and mechanically ventilated. Different colors of fluorescent microspheres were given intravenously while the animals were in the supine, prone, upright (repeated), and head-down (repeated) postures. The animals were killed, and their lungs were excised, dried, and diced into approximately 2-cm3 pieces with the spatial coordinates recorded for each piece. Regional blood flow was determined for each posture from the fluorescent signals of each piece. Perfusion heterogeneity was greatest in the upright posture and least when prone. Using multiple-stepwise regression, we estimate that 7, 5, and 25% of perfusion heterogeneity is due to gravity in the supine, prone, and upright postures, respectively. Although important, gravity is not the predominant determinant of pulmonary perfusion heterogeneity in upright primates. Because of anatomic similarities, the same may be true for humans.

Algorithms↗

PubMed1998

Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation.

To explore mechanisms of hypoxemia after acute pulmonary embolism, we measured regional pulmonary blood flow and alveolar ventilation before and after embolization with 780-micrometers beads in five anesthetized, mechanically ventilated pigs. Regional ventilation and perfusion were determined in approximately 2.0-cm3 lung volumes by using 1-micrometers-diameter aerosolized and 15-micrometers-diameter injected fluorescent microspheres. Hypoxemia after embolization resulted from increased perfusion to regions with low ventilation-to-perfusion ratios. Embolization caused an increase in perfusion heterogeneity and a fall in the correlation between ventilation and perfusion. Correlation between regional ventilation pre- and postembolization was greater than correlation between regional perfusion pre- and postembolization. The majority of regional ventilation-to-perfusion ratio heterogeneity was attributable to changes in regional perfusion. Regional perfusion redistribution without compensatory changes in regional ventilation is responsible for hypoxemia after pulmonary vascular embolization in pigs.

Animals↗

PubMed1998

Pulmonary gas-exchange analysis by using simultaneous deposition of aerosolized and injected microspheres.

Numerical methods for determining end-capillary gas contents for ventilation-to-perfusion ratios were first developed in the late 1960s. In the 1970s these methods were applied to validate distributions of ventilation-to-perfusion ratios measured by the multiple inert-gas-elimination technique. We combined numerical gas analysis and fluorescent-microsphere measurements of ventilation and perfusion to predict gas exchange at a resolution of approximately 2.0-cm3 lung volume in pigs. Oxygen, carbon dioxide, and inert gas exchange were calculated in 551-845 compartments/animal before and after pulmonary embolization with 780-micrometers beads. Whole lung gas exchange was estimated from the perfusion- and ventilation-weighted end-capillary gas contents. Before lung injury, no significant difference existed between microsphere-estimated arterial PO2 and PCO2 and measured values. After lung injury, the microsphere method predicted a decrease in arterial PO2 but consistently underestimated its magnitude. Correlation between predicted and measured inert gas retentions was 0.99. Overestimation of low-solubility inert gas retentions suggests underestimation of areas with low ventilation-to-perfusion ratios by microspheres after lung injury. Regional deposition of aerosolized and injected microspheres is a valid method for investigating regional gas exchange with high spatial resolution.

Aerosols↗

PubMed1997

Spatial pattern of pulmonary blood flow distribution is stable over days.

Despite the heterogeneous distribution of regional pulmonary perfusion over space, local perfusion remains stable over short time periods (20-100 min). The purpose of this study was to determine whether the spatial distribution of pulmonary perfusion remains stable over longer time periods (1-5 days). Regional blood flow was measured each day for 5 days in five awake standing dogs. Fluorescent microspheres of different colors were injected into a limb vein over 30 s on each day. After the last microsphere injection, the dogs were killed, and lungs were flushed free of blood, excised, dried at total lung capacity, and diced into approximately 2-cm3 pieces (n = 1,296-1,487 per dog). Relative blood flow to each piece on each day was determined by extracting the fluorescent dyes and determining the concentrations of each color. We established that blood flow is spatially heterogeneous with a coefficient of variation of 29.5 +/- 2%. Blood flow to each piece is highly correlated with flow to the same piece on all days (r = 0.930 +/- 0.006). The temporal heterogeneity of regional perfusion as measured by the coefficient of variation is 6.9 +/- 0.7% over the 5 days and is nonrandom. The magnitude of spatial and temporal variation is significantly less than previously reported in a study in which anesthetized and mechanically ventilated dogs were used. We conclude that spatial distribution of pulmonary blood flow remains stable over days and we speculate that in the normal awake dog regional perfusion is determined primarily by a fixed structure such as the geometry of the pulmonary vascular tree rather than by local vasoactive regulators. Anesthesia and/or mechanical ventilation may increase the temporal variability in regional perfusion.

Animals↗

PubMed1997

High-resolution maps of regional ventilation utilizing inhaled fluorescent microspheres.

The regional deposition of an inhaled aerosol of 1.0-micron diameter fluorescent microspheres (FMS) was used to produce high-resolution maps of regional ventilation. Five anesthetized, prone, mechanically ventilated pigs received two 10-min inhalations of pairs of different FMS labels, accompanied by intravenous injection of 15.0-micron radioactive microspheres. The lungs were air dried and cut into 1.9-cm3 pieces, with notation of the spatial coordinates for each piece. After measurement of radioactive energy peaks, the tissue samples were soaked in 2-ethoxyethyl acetate, and fluorescent emission peaks were recorded for the wavelengths specific to each fluorescence label. The correlation of fluorescence activity between simultaneously administered inhaled FMS ranged from 0.98 to 0.99. The mean coefficient of variation for ventilation for all 10 trials (47.9 +/- 8.1%) was similar to that for perfusion (46.2 +/- 6.3%). No physiologically significant gravitational gradient of ventilation or perfusion was present in the prone animals. The strongest predictor of the magnitude of regional ventilation among all animals was regional perfusion (r = 0.77 +/- 0.13).

Administration, Inhalation↗

PubMed1995

A computer simulation of pulmonary perfusion in three dimensions.

Pulmonary perfusion is spatially correlated with neighboring regions of lung having similar magnitudes of flow and distant pieces exhibiting negative correlation. Although local correlation has been noted in a wide variety of natural processes, negative correlation has not and it may be unique to organ blood flow. We investigate the regional perfusion predicted by a three-dimensional branching vascular model to determine whether such a model can create negative correlation of perfusion. The distribution of flows is modeled by a dichotomously branching tree in which the fraction of flow from parent to daughter branches is gamma and 1-gamma at each bifurcation. The flow asymmetry parameter (gamma) is randomly chosen for each bifurcation from a normal distribution with a mean of 0.5 with an SD of sigma. The branches branch along one of three orthogonal directions to assure a space-filling structure. This model produces flow distributions similar to those observed in experimental animals, with perfusion being positively correlated locally and negatively correlated at distance. The model is refined by incorporating an effect of gravity, which redirects a fraction (delta), of the flow against gravity to the companion daughter branch in the gravitational direction. A flow bias in the "dorsal" direction is also introduced to account for differences in supine-prone perfusion gradients. In its final form, this three-dimensional branching model accounts for previously observed 1) spatial correlation of regional perfusion with negative correlation over distance, 2) isogravitational perfusion heterogeneity, 3) differences in supine and prone perfusion gradients, 4) positive correlation of flows between supine and prone postures, 5) relatively small contributions of gravity to perfusion heterogeneity, and 6) fractal distributions of flow. This three-dimensional branching vascular model relates the function and structure of the pulmonary vascular tree, offering an explanation for both heterogeneous and spatially correlated regional flows.

Animals↗

PubMed1995

Temporal heterogeneity of regional pulmonary perfusion is spatially clustered.

This study investigates temporal changes in regional pulmonary perfusion. Five dogs were studied with five or six different radiolabeled microspheres being injected via a central vein over 30 s every 20 min. The lungs of each animal were cubed into 1.9 cm3 pieces with spatial coordinates noted for each piece. Within individual pieces, the coefficient of variation of regional perfusion over time was 17.2 +/- 6.8% (SD) and across dogs accounted for 7.26 +/- 5.7% of total perfusion heterogeneity. Temporal variability or "twinkling" was not random. When lung pieces with similar temporal flow patterns were grouped together (regardless of spatial location), groups were more tightly clustered in space than expected by chance. Statistical clustering methods revealed regulation of blood flow on a large scale (lobar arteries), and fractal analyses suggested regulation existed on a smaller scale (arterioles). We conclude that regional pulmonary perfusion is heterogeneous over time in a nonrandom pattern and that pieces clustered by temporal patterns of perfusion are neighbors in the spatial domain.

Animals↗

PubMed1994

Pulmonary gas exchange during exercise in athletes. I. Ventilation-perfusion mismatch and diffusion limitation.

To investigate pulmonary gas exchange during exercise in athletes, 10 high aerobic capacity athletes (maximal aerobic capacity = 5.15 +/- 0.52 l/min) underwent testing on a cycle ergometer at rest, 150 W, 300 W, and maximal exercise (372 +/- 22 W) while trace amounts of six inert gases were infused intravenously. Arterial blood samples, mixed expired gas samples, and metabolic data were obtained. Indexes of ventilation-perfusion (VA/Q) mismatch were calculated by the multiple inert gas elimination technique. The alveolar-arterial difference for O2 (AaDO2) was predicted from the inert gas model on the basis of the calculated VA/Q mismatch. VA/Q heterogeneity increased significantly with exercise and was predicted to increase the AaDO2 by > 17 Torr during heavy and maximal exercise. The observed AaDO2 increased significantly more than that predicted by the inert gas technique during maximal exercise (10 +/- 10 Torr). These data suggest that this population develops diffusion limitation during maximal exercise, but VA/Q mismatch is the most important contributor (> 60%) to the wide AaDO2 observed.

Adult↗

PubMed1994

Effects of inspired carbon dioxide on ventilation-perfusion matching in normoxia, hypoxia, and hyperoxia.

We studied the effect of low concentrations (2 to 4%) of inspired CO2 on gas exchange and ventilation-perfusion (VA/Q) relationships in healthy normocapnic anesthetized dogs during constant mechanical ventilation by the multiple inert gas elimination technique (MIGET). One group was studied at normal tidal volumes (12 to 14 ml/kg) and rates (13 to 15/min) in normoxia, and the other in mild hyperoxia (FIO2 = 0.50) and hypoxia (FIO2 = 0.15). In normoxic dogs there were progressive increases in arterial PO2 and reductions in the alveolar-to-arterial PO2 and arterial-to-mixed expired PCO2 differences in response to increases in FICO2. This increased gas exchange efficiency was characterized by reductions in both dead space ventilation and VA/Q mismatch. Better VA/Q matching was characterized by reduction in the log standard deviation of ventilation (log SDV) without significant change in the log standard deviation of perfusion (log SDQ). Gas exchange parameters returned to baseline when dogs were returned to CO2-free inspired gas. In the second group, the effects of 3% inspired CO2 were of comparable magnitude in both mild hypoxia and hyperoxia. In this group (taking hyperoxic values as baseline), there were improved gas exchange and less VA/Q heterogeneity with inspired hypoxia, both with and without inspired CO2. In contrast to the effects of added inspired CO2, improved VA/Q matching with hypoxia was characterized by reductions in both log SDV and log SDQ.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1993

Effects of carbonic anhydrase inhibition on ventilation-perfusion matching in the dog lung.

Lung carbonic anhydrase (CA) permits rapid pH responses when changes in regional ventilation or perfusion alter airway and alveolar PCO2. These pH changes affect airway and vascular resistances and lung compliance to optimize the balance of regional ventilation (VA) and perfusion (Q) in the lung. To test the hypothesis that these or other CA-dependent mechanisms contribute to VA/Q matching, we administered acetazolamide (25 mg/kg intravenously) to six anesthetized and paralyzed dogs and measured VA/Q relationships before and after CA inhibition by the multiple inert gas elimination technique. Four other groups of dogs were studied to control for possible confounding effects of time under anesthesia and nonselective CA inhibition by acetazolamide: (a) saline placebo as a control for duration of anesthesia, (b) 4% CO2 inhalation to mimic systemic CO2 retention, (c) 1 mg/kg benzolamide (a selective renal CA inhibitor) or 0.5 meq/kg HCl to mimic systemic metabolic acidosis, and (d) 500 mg/kg 4,4'-dinitrostilbene-2,2'-disulfonate (an inhibitor of red cell band 3 protein) to mimic the respiratory acidosis arising from an intracapillary block to rapid mobilization of plasma HCO3- in CO2 exchange. Acetazolamide increased VA/Q mismatch and reduced arterial PO2 measured at equilibrium but these did not occur in the control group. There was no deterioration in VA/Q matching when systemic respiratory acidosis produced either by CO2 inhalation or 4,4'-dinitrostilbene-2,2'-disulfonate or metabolic acidosis (benzolamide or HCl) were imposed to mimic the effects of acetazolamide apart from its inhibition of lung CA. These results support the concept that lung CA subserves VA/Q matching in the normal lung.

Acetazolamide↗

PubMed1993

Effects of erythropoietin on strength and functional status of patients on hemodialysis.

The strength, endurance, and functional status of 15 anemic (HCT 21.2 +/- 4.6) hemodialysis patients was quantified prior to the administration of erythropoietin (epoetin) and after the anemia was partially corrected (HCT 35.4 +/- 2.3). Subjects showed significant increases in strength, measured isometrically (p < .01) and isokinetically (p < .01 at four of five speeds). They also demonstrated improved endurance and rated their functional ability higher. Anemia contributes to significant debilitation in hemodialysis patients and, when reversed with epoetin therapy, results in significantly improved muscle function and endurance.

Anemia↗

PubMed1992

Characteristics of peak aerobic capacity in symptomatic and asymptomatic subjects with left ventricular dysfunction. The Studies of Left Ventricular Dysfunction (SOLVD) Investigators.

Expired gas analysis was used to determine the aerobic exercise performance of subjects with depressed left ventricular (LV) systolic function and congestive heart failure (CHF). To determine whether subjects with no or minimal CHF have better aerobic exercise performance than do those with overt CHF, oxygen consumption (VO2) at anaerobic threshold (AT) and peak exercise was measured in 184 subjects with LV ejection fraction less than or equal to 0.35 who participated in the Studies of Left Ventricular Dysfunction. Subjects were divided into those with overt CHF needing treatment (treatment trial; n = 20) and those who had neither overt CHF nor treatment for CHF (prevention trial; n = 164). Treatment trial subjects had a lower LV ejection fraction (0.25 +/- 0.07) than did prevention trial ones (0.29 +/- 0.05; p = 0.001), but there were no differences in age, gender, body weight, resting heart rate and blood pressure. Treadmill exercise testing was performed after 2 to 3 weeks of placebo (no angiotensin-converting enzyme inhibitor) treatment. Treatment trial subjects exercised for a shorter time (493 +/- 160 seconds) and attained a lower peak VO2 (13 +/- 4 ml/kg/min) and VO2 at AT (11 +/- 4 ml/kg/min) than did prevention trial ones (842 +/- 277 seconds, and 20 +/- 6 and 16 +/- 5 ml/kg/min, respectively). Analysis of covariance showed that the differences in peak VO2 and VO2 at AT were statistically significant between the 2 trials after adjusting for age, gender, LV ejection fraction and New York Heart Association functional class.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗