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Biomedical subjects

D A Rickaby

Publications and source records attributed to D A Rickaby.

49 records · Page 3Linked to original sources
PubMed1984

Influence of plasma protein on the inhibitory effects of indocyanine green and bromcresol green on pulmonary prostaglandin E1 extraction.

The purpose of this study was to examine the influence of plasma protein on the inhibitory effects of the anionic dyes indocyanine green and bromcresol green on prostaglandin E1 (PGE1) uptake by the lungs. Dog lung lobes were isolated and perfused with either autologous plasma or Krebs-Ringer bicarbonate solution (KRB) containing no protein but with dextran used as a colloid. PGE1 uptake was determined by injecting a bolus, containing radiolabelled PGE1 into the lobar artery and then analysing ethanolic extracts of the venous effluent for radioactivity in PGE1 and PGE1 metabolites by thin layer chromatography and scintillation counting. When the lobes were perfused with KRB, bromcresol green at an average initial concentration of 28.5 microM, reduced PGE1 by an average of 56%. When the lobes were perfused with plasma, similar concentrations of bromcresol green reduced the uptake by less than 2%. A similar result was obtained with indocyanine green, which at an average initial concentration of 17.5 microM reduced uptake by about 70% when the lobes were perfused with KRB, but when the lobes were perfused with plasma similar concentrations of the dye reduced uptake by less than 3.5%. The results suggest that plasma protein binding interferes with the inhibitory effects of these dyes on PGE1 uptake in the lungs.

Alprostadil↗
PubMed1984

Influence of embolism and imipramine on kinetics of serotonin uptake by dog lung.

We previously presented a model from which the kinetic parameters Km and Vmax for serotonin uptake by the lung can be obtained from multiple indicator-dilution data. The purpose of the present study was to determine whether experimentally induced changes in lung endothelial function would be revealed in the kinetic parameters calculated using the model. In experiments using isolated dog lung lobes, embolization with 550-microns glass beads was used to reduce the vascular volume and perfused surface area. Imipramine was used to inhibit the serotonin uptake mechanism. In addition, we studied the influence of the vasodilator papaverine, which in previous studies had been used to block the serotonin-induced vasoconstriction. Embolization, imipramine, and papaverine all significantly reduced percentage uptake of serotonin. The kinetic analysis revealed a significant decrease in the maximum serotonin uptake rate (Vmax) with all three experimental manipulations. In addition, imipramine significantly increased Km. The results indicate that the kinetic parameters obtained from the model do respond to transport inhibition and changes in endothelial surface area, further supporting their usefulness as indexes of endothelial function.

Animals↗
PubMed1984

Lung serotonin uptake kinetics from indicator-dilution and constant-infusion methods.

The kinetics of the pulmonary endothelial uptake of serotonin (5-HT) were evaluated in isolated dog lung lobes using three methods. In method A serotonin was infused at various constant rates to provide a range of capillary concentrations that included Km. The arterial and venous concentrations measured by high-performance liquid chromatography were then used to determine the effect of concentration on the rate of 5-HT uptake. In method B trace doses of 5-[3H]HT and a reference indicator (indocyanine green dye) were injected during each constant infusion of unlabeled 5-HT to provide a measure of unidirectional 5-HT uptake at each background concentration. In method C boluses containing different amounts of unlabeled 5-HT, along with the 5-[3H]HT and the dye, were injected such that each bolus resulted in a range of concentrations and provided a measure of the unidirectional uptake at each concentration. Each method provided the data needed to calculate the maximum uptake rate (Vmax) and the concentration at Vmax/2 (Km), assuming that the uptake kinetics can be represented by the Michaelis-Menten equation. However, the mathematical model underlying each method involved different assumptions about the returning flux of the 5-HT which entered the endothelial cell and the heterogeneity of vascular transit times. The results obtained, considered in light of the different assumptions involved, indicate that all three methods can provide reasonable estimates of the mass transfer kinetic constants if the constant infusions of 5-HT are of short duration and/or the boluses are adequately dispersed prior to reaching the capillary bed.

Animals↗
PubMed1984

Kinetics of serotonin uptake by the dog lung is pH independent in the physiological range.

Given the strong pH dependence of platelet serotonin uptake, the many similarities between platelet and pulmonary endothelial serotonin uptake and the potential importance of a pH dependence on the interpretation of changes in pulmonary endothelial serotonin uptake in diseased lungs, we examined the influence of pH on the kinetics of serotonin uptake in isolated dog lung lobes using a multiple indicator technique. A range of pH values from about 7.2 to 8.0 were obtained by ventilating the lobes with gas containing different concentrations of CO2. Over the pH range studied, no significant changes in serotonin uptake were observed, nor were significant changes detected in the kinetic parameters, Km and Vmax, for the uptake process. The lack of a significant pH effect represents a difference between platelet and lung endothelial serotonin uptake. It also indicates that correlations between PCO2 and serotonin uptake which might occur in diseased lungs do not imply causality.

Animals↗
PubMed1982

Distribution of vascular resistance and compliance in a dog lung lobe.

We have modeled the left lower dog lung lobe as three serial compartments, each containing resistance (R) and compliance (C). The intracompartmental arrangement of R and C was chosen to permit their evaluation from pressure data obtained following occlusion of the venous outflow. We found that two mathematically distinct models permitted evaluation of the distribution of R and C. The models were complementary in that when used together the R and C of the three compartments could be determined. The central compartment had 46% of the lobar vascular resistance and 75% of the lobar vascular compliance under control conditions. We found that serotonin and histamine, which increased the resistance proximal and distal to the central compartment, respectively, did not increase the central resistance. Therefore, we conclude that the central compartment includes the capillary bed. The equilibrium pressure (Pd), obtained when arterial inflow and venous outflow were simultaneously occluded, was in close agreement with the average preocclusion pressure of the central compartment, indicating that Pd is close to the pulmonary microvascular pressure.

Animals↗
PubMed1982

Influence of blood and plasma flow rate on kinetics of serotonin uptake by lungs.

Serotonin extraction following a bolus injection of serotonin and a nonpermeating indicator into the pulmonary artery can be evaluated using a model that represents the saturable uptake of serotonin by Michaelis-Menten kinetics. By use of this model Km, Vmax, and a perfusion parameter, alpha, can be determined by multiple linear regression analysis of the time-concentration data. Kinetic and perfusion parameters were obtained using data from isolated dog lung lobes in which plasma flow rate was changed by changing the pump flow rate in blood- or plasma-perfused lobes or by keeping the pump flow rate constant and removing the blood cells. The calculated Vmax was reproducible and flow independent over the range of flow rates used in the study. The calculated Km was more sensitive than Vmax to small variations in experimental data and was independent of flow at flow rates greater than about one-half the normal cardiac output per gram of lung tissue. The perfusion parameter alpha was lower in the plasma-perfused lobes, reflecting more homogeneous perfusion in the absence of cells. The results suggest that this approach will be useful for separating changes in the kinetics of serotonin uptake by endothelial cells from effects of changes in flow and perfusion heterogeneity.

Animals↗
PubMed1981

A computer program for calculating respiratory anatomic dead space.

The Fowler technique for estimating anatomic dead space (VD -- the volume of the airway conducting system) on the basis of CO2 changes in the expired air of a single breath was adapted to computer analysis. The areas above and below the sigmoid CO2 curve in the region of transition from inspired to alveolar concentration were simultaneously integrated (forward and backward) on a time base until the sum of the two integrated values equalled the total area representing the transition. The point on the CO2 curve was defined as the CO2 midpoint. Expiratory flow was then integrated with time from its beginning to the CO2 midpoint, and the resultant volume represented VD for that breath. The computer program was able to compensate for differences in response time between the gas monitor and the flow measuring device and was able to integrate the areas rapidly. The program provided a rapid calculation of VD, which compared well with values calculated by tedious, manual methods.

Carbon Dioxide↗
PubMed1981

Kinetics of serotonin uptake in the dog lung.

A bolous containing [3H]serotonin and indocyanine green dye was rapidly introduced into the pulmonary artery on an isolated blood-perfused left lower dog lung lobe. Sequential samples of the venous effluent were collected for approximately 25 s following the injections. The lung intake of the injected [3H]serotonin was inversely proportional to the injected dose, ranging from about 70% for a 10-nmol injection to about 38% for a 100-nmol injection. Less than 2% of the injected 3H, which appeared in the venous effluent over the sampling interval, was in the form of [3H]5-hydroxyindoleacetic acid; and during the bolous transit through the lung lobe, uptake of serotonin by platelets was negligible. The serotonin extraction ratio curves exhibited dose-dependent characteristic shapes that we have interpreted using a model in which it is assumed that serotonin uptake follows Michaelis-Menten kinetics and flow through the capillary bed is heterogeneous. Using this model and a multiple regression analysis, the outflow dye and 3H concentration vs. time curves were used to estimate Km and Vmax for serotonin uptake by the lungs.

Animals↗
PubMed1980

Pulmonary inactivation of serotonin and site of serotonin pulmonary vasoconstriction.

To determine whether the site of serotonin-induced pulmonary vasoconstriction is influenced by serotonin uptake and inactivation within the lung, we utilized an isolated perfused left lower lobe of the dog lung, which could be perfused with flow in the normal direction (i.e., blood flowing into the lobar artery) or in the retrograde direction (i.e., blood flowing into the lobar vein). To localize the site of vasoconstriction, we utilized an outflow occlusion technique in which the changes in lobar vascular resistance were divided into changes in arterial and venous resistances. Serotonin infusion constricted vessels on the arterial side of the site of serotonin uptake during both forward and retrograde perfusion while having much less influence on the venous side. However, during retrograde perfusion the serotonin infusion rate required to produce a given increase in arterial resistance was approximately 85 micrograms/min greater than during forward perfusion. Thus, it would appear that serotonin was primarily an arterial constrictor in this preparation and that, although the lung removed a substantial quantity of serotonin, the uptake and inactivation within the lung had relatively little influence on the site of serotonin vasoconstriction.

Animals↗
PubMed1980

Adrenal component to pulmonary hypertension caused by nicotine administration in the dog.

In this study, we investigated the possibility that the adrenal gland contributes to nicotine-induced pulmonary hypertension using a canine left lower lung lobe (LLL) preparation that was pump-perfused with mixed venous blood at constant flow and outflow pressure. Main pulmonary artery, left atrial, and LLL arterial pressures were monitored to assess the responses of the animal's intact right lung and isolated LLL. With the adrenal venous return intact, injection of 10-26 micrograms/kg nicotine into the left ventricle or ascending aorta resulted in a 42% increase in LLL arterial pressure and a 70% increase in the pulmonary arterial-left atrial pressure gradient (Ppa-Pla). When the adrenal venous return was interrupted, the increases in LLL arterial pressure and Ppa-Pla were reduced to 6 and 10%, respectively. The LLL response could be eliminated by alpha-adrenergic receptor blockade, suggesting that adrenal catecholamines may contribute to the pulmonary hypertension induced by nicotine infusion.

Adrenal Glands↗
PubMed1977

Acoustic helium analyzer for closing volume measurement.

An acoustic gas analyzer was developed to measure helium during the closing volume (CV) test. It is based on the principle that altering the composition of a gas mixture will change the velocity at which sound is transmitted through the gas. The change in transit time for an acoustic burst across an in-line (breathe-through) cell is measured as a function of He concentration in the expired air during the CV test. Although CO2 and H2O vapor affect the signal, so it is not specific for He, the system provides good records of CV. A comparison of measurements in 21 normal subjects demonstrated no differences for CV measured in the same breath by the bolus technique using the acoustic gas analyzer and by the resident gas method using a nitrogen analyzer. Differences in closing volumes measured by the He bolus technique and the resident gas method might exist in patients with some kinds of pulmonary disease, and the suggestion is made that CV measurements by the two methods might assist in describing pulmonary alterations in patients with bronchopulmonary disease.

Closing Volume↗
PubMedDate not supplied

Whole-body hyperthermia combined with hyperfractionated irradiation of the thorax in dog: acute physiological response.

Whole-body hyperthermia has potential as an adjuvant treatment with chemotherapy and radiation therapy for diseases such as lung cancer which require both local and systemic control. The acute toxicity of whole-body hyperthermia combined with whole-thorax irradiation was studied in dogs. Twenty-eight dogs received three 2-h whole-body hyperthermia (WBH) treatments at 42.0 degrees C deep rectal temperature. Twenty-four of these dogs were also randomized to receive radiation doses of 18, 22.5, 27, 31.5, 40.5 or 45 Gy. Irradiation was given in 1.5 Gy fractions over 6 weeks. Three WBH treatments were given to 28 dogs with all dogs surviving treatment. WBH was given on days 1, 22 and 40 of the 6-week interval. Thirty-one dogs received radiation doses of 18-49.5 Gy without WBH. Deep rectal temperature was maintained at 41.9 +/- 0.3 degrees C over 2 h with an average of 20 min outside the chamber for irradiation. Two dogs required intervention with emergency medications during WBH treatment. One of the two dogs developed permanent neurological injury. Continuous physiological monitoring was necessary for successful WBH. WBH plus thoracic irradiation was well tolerated. All dogs survived all treatments. A significant but transient increase in peripheral blood leucocytes and a decrease in platelet counts occurred after each WBH treatment. The addition of thoracic irradiation up to 45 Gy in 1.5 Gy fractions did not appear to alter the acute toxicity of WBH with the exception of an increase in the protein content of lung lavage fluids. In conclusion, multiple WBH treatments of 2 h at a target temperature of 42 degrees C in addition to thoracic irradiation up to 45 Gy in 1.5 Gy fractions was administered with only mild acute toxicities occurring. Core temperature could be maintained for up to 20 min outside of the WBH chamber which allowed irradiation to be given concurrently with hyperthermia at a core temperature of 42 degrees C +/- 0.1 degree C.

Animals↗