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Biomedical subjects

R E Parker

Publications and source records attributed to R E Parker.

At least 19 recordsLinked to original sources
PubMed1998

Optical measurement of isolated canine lung filtration coefficients after alloxan infusion.

In this study, lung filtration coefficient (Kfc) was measured in eight isolated canine lung preparations by using three methods: standard gravimetric (Std), blood-corrected gravimetric (BC), and optical. The lungs were held in zone III conditions and were subjected to an average venous pressure increase of 8.79 +/- 0.93 (mean +/- SD) cmH2O. The permeability of the lungs was increased with an infusion of alloxan (75 mg/kg). The resulting Kfc values (in milliliters . min-1 . cmH2O-1 . 100 g dry lung weight-1) measured by using Std and BC gravimetric techniques before vs. after alloxan infusion were statistically different: Std, 0.527 +/- 0.290 vs. 1. 966 +/- 0.283; BC, 0.313 +/- 0.290 vs. 1.384 +/- 0.290. However, the optical technique did not show any statistical difference between pre- and postinjury with alloxan, 0.280 +/- 0.305 vs. 0.483 +/- 0. 297, respectively. The alloxan injury, quantified by using multiple-indicator techniques, showed an increase in permeability and a corresponding decrease in reflection coefficient for albumin (sigmaf). Because the optical method measures the product of Kfc and sigmaf, this study shows that albumin should not be used as an intravascular optical filtration marker when permeability is elevated. However, the optical technique, along with another means of measuring Kfc (such as BC), can be used to calculate the sigmaf of a tracer (in this study, sigmaf of 0.894 at baseline and 0.348 after injury). Another important finding of this study was that the ratio of baseline-to-injury Kfc values was not statistically different for Std and BC techniques, indicating that the percent contribution of slow blood-volume increases does not change because of injury.

Alloxan↗
PubMed1997

Optical measurement of isolated canine lung filtration coefficients at normal hematocrits.

In this study, lung filtration coefficient (Kfc) values were measured in eight isolated canine lung preparations at normal hematocrit values using three methods: gravimetric, blood-corrected gravimetric, and optical. The lungs were kept in zone 3 conditions and subjected to an average venous pressure increase of 10.24 +/- 0.27 (SE) cmH2O. The resulting Kfc (ml . min-1 . cmH2O-1 . 100 g dry lung wt-1) measured with the gravimetric technique was 0.420 +/- 0.017, which was statistically different from the Kfc measured by the blood-corrected gravimetric method (0.273 +/- 0.018) or the product of the reflection coefficient (sigmaf) and Kfc measured optically (0. 272 +/- 0.018). The optical method involved the use of a Cellco filter cartridge to separate red blood cells from plasma, which allowed measurement of the concentration of the tracer in plasma at normal hematocrits (34 +/- 1.5). The permeability-surface area product was measured using radioactive multiple indicator-dilution methods before, during, and after venous pressure elevations. Results showed that the surface area of the lung did not change significantly during the measurement of Kfc. These studies suggest that sigmafKfc can be measured optically at normal hematocrits, that this measurement is not influenced by blood volume changes that occur during the measurement, and that the optical sigmafKfc agrees with the Kfc obtained via the blood-corrected gravimetric method.

Animals↗
PubMed1996

Effects on pulmonary physiology of reamed femoral intramedullary nailing in an open-chest sheep model.

We have recently developed an open-chest sheep model to monitor and study the effects of major orthopedic procedures on pulmonary physiology. In this pilot study, we focused on reamed intramedullary femoral nailing in animals without pulmonary injury. Details of the model are described herein. The control group consisted of sheep that underwent thoracotomy and invasive monitoring only, while the study group also underwent femoral osteotomy, reaming, and intramedullary nailing. Baseline, postthoracotomy, and post-reaming/nailing values were recorded for mean pulmonary arterial pressure, central venous pressure, left arterial pressure, dynamic compliance, arterial blood gas, mixed venous O2, cardiac index, and mean arterial pressure so that hemodynamic and oxygen transport data could be calculated. Postprocedure values were recorded at hourly intervals for 4 h. A physiologically stable, reproducible model was created. No statistically significant differences were found between the control and experimental groups, indicating no adverse effect of femoral reaming/nailing. In one animal, using echocardiography, pulmonary embolization was documented while reaming and inserting the intramedullary nail. Reamed femoral intramedullary nailing is not detrimental to sheep with otherwise normal lungs. This finding suggests that femoral reaming and nailing in trauma patients without associated pulmonary injuries and otherwise normal lungs may be carried out without risk of inducing significant respiratory complications.

Analysis of Variance↗
PubMed1995

Effects of flow heterogeneity on the measurement of capillary exchange in the lung.

The effects of flow heterogeneity on the measurement of transcapillary escape of small molecules for perfused in situ sheep lungs were evaluated. Lungs were studied at five flows (1.5-5.0 l/min) ranging from zone 1 to zone 3 conditions. At each flow, multiple indicator-dilution curves were collected using 14C-labeled urea (U) or butanediol (B) as the diffusing tracer, and radiolabeled 15-microns microspheres were injected. The lungs were removed, dried, sectioned, weighed, and counted for microsphere radioactivity. Flow heterogeneity expressed as relative dispersion, decreased with increasing flow, from 0.838 +/- 0.179 (mean +/- SD, n = 8) to 0.447 +/- 0.119 (n = 6). We applied homogeneous flow models of capillary exchange to compute permeability-surface area product (PS) and a related parameter, D1/2S, for diffusing tracers. (D is effective diffusivity of capillary exchange.) PS and D1/2S increased to a maximum with increasing flow, but the ratio of D1/2SU to D1/2SB remained constant. A new model incorporating flow heterogeneity and recruitment (the variable recruitment model) was used. The variable recruitment model described the effects of flow on capillary recruitment, but incorporating heterogeneity into the computation did not alter D1/2S values from those computed assuming homogeneous flow.

Animals↗
PubMed1995

Noninvasive measures of radiolabeled dextran transport in in situ rabbit lung.

UNLABELLED: Dextrans are nontoxic and can be obtained in a wide variety of molecular weights. The purpose of this study was to label 6-kDa and 40-kDa dextrans with gamma- (99mTc) and positron- (18F) emitting radioisotopes and monitor their transport across the pulmonary microvascular barrier. METHODS: External scan measurements for radiolabeled uncharged dextrans, albumin and red blood cells were obtained in eight blood-perfused in situ rabbit lung preparations. After 3 hr of external scanning, the lungs were removed for postmortem and extravascular distribution volume calculations. Extravascular distribution volumes were obtained in six additional rabbits following 4 hr of dextran perfusion to compare the effect of time. The normalized slope index (NSI), a measure of transvascular transport rate, was calculated for each diffusible tracer. RESULTS: The mean NSI for albumin (0.001676 +/- 0.000537 min-1) was significantly lower than NSI for the 40-kDa dextran (0.002303 +/- 0.0005426 min-1) as well as the 6-kDa dextran (0.004312 +/- 0.001134 min-1). The difference between the 6-kDa and the 40-kDa dextrans was also significant. After 4 hr of equilibration, distribution volumes were not significantly different than those obtained at 3 hr. CONCLUSION: Dextrans can be radiolabeled with gamma and positron emitters and small dextrans traverse the lung microvascular barrier more rapidly than albumin. Our results suggest that the use of small dextrans rather than albumin can reduce scan times in clinical applications and minimize motion artifact associated with the noninvasive gamma detection method.

Animals↗
PubMed1994

Evaluation of perilla ketone-induced unilateral lung injury using external gamma scanning.

We used a modified external gamma scanning technique to quantitate right and left lung permeability changes to iodinated sheep albumin before and after perilla ketone (PK)-mediated unilateral lung injury in seven anesthetized sheep. Three portable gamma scintillation probes containing 2-in. NaI crystals detected radioactivities of 51Cr-labeled red blood cells and 125I-labeled albumin over the right and left lungs and blood, respectively. Radioactivities were monitored for 1 h before and 3 h after infusion of 25 mg/kg PK into a single lung. Calculation of normalized slope index (NSI) (Roselli and Riddle, J. Appl. Physiol. 67: 2343-2350, 1989) over the 30-min interval before PK and over the 60- to 90-min interval after PK for each lung revealed a four- to five-fold NSI increase in lungs receiving PK (0.00237 +/- 0.00065 to 0.0109 +/- 0.0016 min-1) and no increase in contralateral control lungs (0.00214 +/- 0.00065 to 0.00201 +/- 0.00032 min-1). Observed changes in NSI were consistent with postmortem evaluations of each lung. Lungs receiving PK had significantly higher wet-to-dry lung weight ratios and extravascular lung water volumes than contralateral control lungs. Measured bloodless wet-to-dry lung weight ratios were 5.68 +/- 0.39 and 3.27 +/- 0.27 (P < 0.05) for PK and control lungs, respectively.

Animals↗
PubMed1994

Pulmonary vascular resistance distribution and recruitment of microvascular surface area.

To test the hypothesis that the distribution of hemodynamic resistance is involved in the control of pulmonary capillary surface area, we measured permeability-surface area product (PS) and longitudinal resistance distribution (LRD) as functions of perfusion rate in isolated rabbit lungs under zone II conditions (n = 10) and through the zone II-III transition (n = 4). PS, considered to be indicative of functioning capillary surface area, was measured with the aid of the diffusion-limited tracer [14C]propanediol, whereas LRD was determined using a viscous bolus technique. LRD was seen to change character with increasing flow and increasing PS/surface area, becoming bimodal with low central resistance as full capillary recruitment was approached in zone III. Effects of hypoxic ventilation were studied in zone II in five lungs; it was found that hypoxia altered the LRD and eradicated the normoxic dependence of PS/surface area on perfusion rate. It was concluded that LRD is involved in the determination of functioning capillary surface area.

Animals↗
PubMed1994

Protection of rabbit lungs from endotoxin injury by in vivo hyperexpression of the prostaglandin G/H synthase gene.

A recombinant prostaglandin G/H (PGH) synthase gene has been expressed in vitro in bovine pulmonary artery endothelial cells and in vivo in rabbits by transfection with a plasmid using cationic liposomes. Transfection of bovine pulmonary artery endothelial cells with the PGH synthase cDNA resulted in increased intracellular PGH synthase protein (determined by Western blot analysis) and increased release of prostacyclin. Rabbits intravenously transfected with the PGH synthase gene had increased plasma levels of prostacyclin and PGE2, and their lungs produced increased amounts of the same eicosanoids. In an in situ, perfused preparation of PGH synthase transfected rabbit lungs, the pressor response to endotoxin was markedly attenuated. In addition, pulmonary edema and release of thromboxane B2 into the perfusate after endotoxin infusion were markedly decreased in transfected lungs compared to controls (animals transfected with a pCMV4 construct that did not contain a cDNA insert). The data suggest that augmented endogenous production of prostacyclin and PGE2, achieved by liposome-mediated gene transfer, protects the lungs from endotoxin. This may be caused in part by suppression of endotoxin-stimulated thromboxane B2 production. Modification of lipid mediator responses by in vivo transfection is a potential approach to the therapy of acute lung injury.

Animals↗
PubMed1993

Effect of a 5-lipoxygenase inhibitor on endotoxin-induced pulmonary dysfunction in awake sheep.

We studied the effects of a 5-lipoxygenase inhibitor, SC-45662, on endotoxin-induced pulmonary dysfunction in chronically instrumented unanesthetized sheep. Each sheep was studied with endotoxin alone, SC-45662 alone, and endotoxin after SC-45662 pretreatment. Endotoxin did not cause consistent increases in plasma or lung lymph concentrations of leukotriene B4 (LTB4). Ex vivo stimulation of whole blood from sheep before and after treatment with SC-45662 demonstrated no inhibition of cyclooxygenase metabolism but an approximately 80% inhibition of LTB4 production. At drug concentrations obtained in vivo, SC-45662 did not significantly inhibit in vitro A23187-stimulated whole blood thromboxane B2 production but did inhibit LTB4 production from ionophore-stimulated sheep granulocytes. SC-45662 attenuated the early changes in lung mechanics and pulmonary hypertension but did not attenuate the later increase in lung fluid and solute exchange observed after endotoxemia. We conclude that 5-lipoxygenase products are not measurably involved in the later increase in lung fluid and solute exchange observed after endotoxemia in sheep.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Effects of air embolism on sheep lung fluid volumes.

Changes in lung fluid volumes and hyaluronan clearance were measured in six awake sheep during increased microvascular permeability induced by pulmonary air embolism (AE). After a 1- to 2-h baseline, filtered room air was infused through a proximal port of a Swan-Ganz catheter for 2 h at a rate sufficient to double pulmonary vascular resistance. The air infusion was discontinued, and the sheep were monitored for an additional 2 h (recovery). Lung lymph flow and protein flux increased during air infusion and continued to increase during recovery. During AE, lymph-to-plasma ratio for albumin decreased while lymph-to-plasma ratio for large protein remained the same. This would suggest that both microvascular pressure and microvascular permeability increase during AE. Protein clearance increased similarly for all protein sizes during AE and recovery. After 2 h of recovery, interstitial and extravascular volumes were elevated with no change in cellular volume. The volume of the interstitium available to albumin was more than twice control. The fraction of the interstitium that excludes albumin was calculated to be 0.32 +/- 0.04, with a 51% reduction in absolute excluded volume 2 h after AE. Clearance of hyaluronan by the lymphatics (normalized to baseline) increased 6- to 10-fold during and after AE. It was estimated that < 2% of the total hyaluronan in the lung would be cleared in 24 h under baseline conditions. This amount increased to approximately 11% under AE conditions and approximately 15% under recovery conditions. Changes in lung fluid volumes and protein clearance indicate increased microvascular permeability 2 h after AE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Pressure and flow changes in the pulmonary circulation in exercising sheep: evidence for elevated microvascular pressure.

The purpose of this study was to measure hemodynamic and transvascular filtration changes in the lung during strenuous exercise in sheep. The specific goals were (1) to determine the nature of the reduction in pulmonary arterial pressure (Ppa) after its initial peak rise with onset of exercise; (2) to use a pulmonary artery catheter distal wedge technique ("microwedge") to better assess longitudinal changes in resistance in the pulmonary circulation with exercise; and (3) to compare lung lymph flow and protein concentration changes at comparable estimated microvascular pressure (Pmv) (mean Ppa - mean left atrial pressure) (Pla) x 0.4 + mean Pla) during exercise versus passive left atrial hypertension to determine whether exercise causes a higher than expected lymph flow. We found that cardiac output rises quickly and thereafter remains constant with constant-rate exercise, and, thus, the secondary reduction in Ppa was due to vasodilation and/or recruitment. The microwedge pressure rose more than did Pla, suggesting that actual Pmv was probably higher than that estimated. With hypoxia, most of the change in pulmonary vascular resistance was in upstream vessels (arteries and capillaries), as was most of the exercise-induced vasodilation. Lymph flow rose more quickly and was much higher during brief exercise than during left atrial hypertension at a comparable calculated Pmv, and lymph protein content decreased more quickly. The data point to a Pmv with strenuous exercise that is higher than expected.

Animals↗
PubMed1992

Hydrostatic pulmonary edema in sheep. Effects of bronchial artery embolization on the plain chest radiograph.

RATIONALE AND OBJECTIVES: The bronchial circulation may influence pulmonary edema. This study evaluates possible effects of bronchoesophageal artery embolization on the plain film manifestations of hydrostatic pulmonary edema in sheep. METHODS: Anteroposterior and lateral chest radiographs were obtained during the induction of pulmonary edema both before and after embolization of the bronchoesophageal artery in six adult sheep. Interstitial lines and perivascular, segmental bronchial, proximal bronchial, carinal, tracheal, and parenchymal edema were evaluated. RESULTS: Only parenchymal edema was graded consistently. Though edema increased with left atrial pressure before embolization (P < .001), there was no similar change afterward. The embolized animals tended to be more edematous by the first film. CONCLUSION: Rather than any protective effect, bronchoesophageal artery embolization may increase edema. This model may be inappropriate for further investigation of the bronchial circulation in the development of human pulmonary edema.

Animals↗
PubMed1992

Evaluating flux of labeled albumin into the pulmonary interstitium of sheep lungs.

A noninvasive method was used to measure the movement of 131I-labeled albumin across the pulmonary microvascular barrier of a blood-perfused in situ sheep lung lymph preparation. After injection of labeled albumin into the blood, external measurements of gamma activity were taken for 2 h. The interstitial concentrations were calculated by applying the external activities and sampled lung lymph concentrations to a mass transport model. For the external activities and lymph activities to yield the same quantitative results, two modifications were necessary. First, lymph concentrations were corrected for transport delay from the lymphatic system. Second, externally detected radioactivity had to be corrected for the contribution of unbound nuclide. Application of a mathematical model to the data indicated the extravascular distribution volume for albumin was 79% of the pulmonary blood volume, and the extravascular distribution volume for radiolabeled iodide was 4.42 times greater than the pulmonary blood volume. The permeability-surface area product for iodide in the lung was estimated to be 0.274 ml.min-1.g blood-free dry lung wt-1. The transport delay in the lymphatic system was approximately 30-45 min and represented a volume of 1.44-2.80 ml.

Albumins↗
PubMed1992

Effects of Perilla ketone on the in situ sheep lung.

We studied the effects of three different doses (15, 20, and 25 mg/kg) of Perilla ketone (PK) on the blood-perfused in situ sheep lung while obtaining external measurements of lung transvascular protein flux. Lymph flow and lymphatic protein clearance increased significantly after all doses of PK. Severe pulmonary edema was confirmed by high postmortem wet-to-dry lung weight ratios and increased extravascular lung water from multiple indicator-dilution studies. Urea permeability-surface area product and effective diffusivity from multiple indicator-dilution studies also increased after PK infusion. Because we observed no evidence of increased capillary pressure or increased microvascular surface area after PK, we conclude that PK significantly increased pulmonary microvascular permeability. Certain aspects of the in situ PK response appeared to be dose dependent. The lungs responded rather quickly to high doses of PK, but an apparent latency period was noted with low doses of PK. Postmortem wet-to-dry lung weight ratios were always high but did not suggest dose dependence. However, times of postmortem measurements were not the same for all doses of PK. The external scan technique appeared to be sensitive to changes that occurred in the lung after PK. Externally detected albumin interstitial-to-plasma mass (mass I/P) ratios were substantially higher after PK than during control in situ studies. In some experiments, final mass I/P ratios increased above 4 approximately 2.0 h after PK compared with control values of 0.2 and 0.4. A delay time between injection and change in mass I/P slope was also observed, which decreased with increasing dose of PK. PK causes a permeability injury in the in situ sheep lung and provides a useful model for studying the sensitivity of permeability measurement techniques such as the external gamma-ray detection method.

Albumins↗
PubMed1992

Canine pulmonary filtration coefficient calculated from optical, radioisotope, and weight measurements.

Three independent methods were used to estimate filtration coefficient (Kf) in isolated dog lungs perfused with low-hematocrit (Hct) blood. Pulmonary vascular pressure was increased by 12-23 cmH2O to induce fluid filtration. Average Kf (ml.min-1 x cmH2O-1 x 100 g dry wt-1) for six lungs was 0.26 +/- 0.05 (SE) with use of equations describing conservation of optically measured protein labeled with indocyanine green. Good agreement was found when a simplified version of the multiequation theory was applied to the data (0.24 +/- 0.05). Both optical estimates were lower than those predicted by constant slope (0.55 +/- 0.07) or extrapolation (1.20 +/- 0.15) techniques, which are based on changes in total lung weight. Subsequent studies in five dog lungs investigated whether the higher Kf from weight analyses could be caused by prolonged pulmonary vascular filling. We found that 51Cr-labeled red blood cells (RBCs), monitored over the lung, continued to accumulate for 30 min after vascular pressure elevations of 9-16 cmH2O.Kf was determined by subtracting computed vascular filling from total weight change (0.28 +/- 0.06) and by perfusate Hct changes determined from radiolabeled RBCs (0.23 +/- 0.04). These values were similar to those obtained from analysis of optical data with the complete model (0.30 +/- 0.06), the simplified version (0.26 +/- 0.05), and from optically determined perfusate Hct (0.16 +/- 0.03). However, constant slope (0.47 +/- 0.04) and extrapolation (0.57 +/- 0.07) computations of Kf were higher than estimates from the other methods. Our studies indicate that prolonged blood volume changes may accompany vascular pressure elevations and produce overestimates of Kf with standard weight measurement techniques. However, Kf computed from optical measurements is independent of pulmonary blood volume changes.

Albumins↗