Biomedical subjects

L E Olson

Publications and source records attributed to L E Olson.

At least 19 recordsLinked to original sources

PubMed2004

A chromosome 21 critical region does not cause specific Down syndrome phenotypes.

The "Down syndrome critical region" (DSCR) is a chromosome 21 segment purported to contain genes responsible for many features of Down syndrome (DS), including craniofacial dysmorphology. We used chromosome engineering to create mice that were trisomic or monosomic for only the mouse chromosome segment orthologous to the DSCR and assessed dysmorphologies of the craniofacial skeleton that show direct parallels with DS in mice with a larger segmental trisomy. The DSCR genes were not sufficient and were largely not necessary to produce the facial phenotype. These results refute specific predictions of the prevailing hypothesis of gene action in DS.

Animals↗

PubMed2004

Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes.

Two mouse models are widely used for Down syndrome (DS) research. The Ts65Dn mouse carries a small chromosome derived primarily from mouse chromosome 16, causing dosage imbalance for approximately half of human chromosome 21 orthologs. These mice have cerebellar pathology with direct parallels to DS. The Ts1Cje mouse, containing a translocated chromosome 16, is at dosage imbalance for 67% of the genes triplicated in Ts65Dn. We quantified cerebellar volume and granule cell and Purkinje cell density in Ts1Cje. Cerebellar volume was significantly affected to the same degree in Ts1Cje and Ts65Dn, despite that Ts1Cje has fewer triplicated genes. However, dosage imbalance in Ts1Cje had little effect on granule cell and Purkinje cell density. Several mice with dosage imbalance for the segment of the Ts65Dn chromosome not triplicated in Ts1Cje had phenotypes that contrasted with those in Ts1Cje. These observations do not readily differentiate between two prevalent hypotheses for gene action in DS.

Animals↗

PubMed2000

Surfactant treatment impairs gas exchange in a canine model of acute lung injury.

UNLABELLED: The effectiveness of surfactant (SURF) treatment in acute lung injury in the adult is controversial. In this study, we tested the effectiveness of early surfactant treatment in a commonly used animal model of acute lung injury, phorbol-myristate acetate (PMA), to see if it would attenuate the progression of lung injury. We measured the effect on lung compliance and whether positive end-expiratory pressure (PEEP) (10 cm H2O) during SURF administration had a synergistic effect. METHODS: Four groups of anesthetized dogs were studied: a) normals; b) PMA injury only; c) PMA injury + SURF; and d) PMA + SURF + PEEP. Lung injury was induced with 25-30 microg/kg of PMA. Responses were measured over 7 hrs. Surfactant was administered in the form of Survanta, 4 x 25 mg/kg doses via tracheal instillation 2.5 hrs after PMA. For the group receiving PEEP, 10 cm H2O PEEP was begun 1.5 hrs after PMA, 1 hr before SURF. Postmortem, the left lung was excised and inflated three times to total lung capacity (volume at 30 cm H2O) and expiratory compliance was measured with 25-100 mL volume increments. The trachea was then clamped and trapped volume was determined by water displacement. RESULTS: PMA-induced lung injury significantly reduced expiratory compliance and total lung capacity (p < .05 from normal). Wet/dry lung weights did not differ between groups. SURF without PEEP further decreased lung compliance as compared with PMA only. CONCLUSIONS: SURF administration after PMA injury causes marked reductions in lung compliance when no PEEP is coadministered. However, the loss of static expiratory lung compliance appears partly ameliorated by application of PEEP + SURF. Given that tracheal instillation of SURF is known to acutely elevate lung impedance in the first few hours after administration, coadministration of PEEP appears to be critically important in counteracting these early effects of surfactant instillation on the lung.

Acute Disease↗

PubMed2000

Cyanide increases reduction but decreases sequestration of methylene blue by endothelial cells.

The mechanisms of endothelial cell transplasma membrane electron transport (TMET) have not been completely identified. Redox probes such as methylene blue (MB) can be useful tools, but the complexity of their disposition upon exposure to the cells can hinder interpretation. For example, MB is reduced on the cell surface by TMET, but after entering the cell in reduced form, it is reoxidized and sequestered within the cell. We developed a method to separately quantify the reduction and reoxidation rates such that it can be determined whether a metabolic inhibitor such as cyanide affects the reduction or oxidation process. MB was introduced at the inlet to a column filled with endothelial cell covered beads either as a short 12 s injection (bolus) or a long 45 min infusion (pulse), and its effluent concentration was measured as a function of time. The cells extracted 56% of the MB from the bolus, but only 41% during the pulse steady state. In the presence of cyanide, these extractions increased to 70% and decreased to 4%, respectively. Mathematical model results support the interpretation that these paradoxical effects on bolus and pulse extractions reflect the differential effects of cyanide on extracellular reduction and intracellular oxidation, i.e., cyanide increased the reduction rate from 7.3 to 13.0 cm s-1 X 10(-5) and decreased the oxidation rate from 1.09 to 0.02 cm s-1 X 10(-3). Cyanide also increased intracellular NADH by almost eight times, suggesting that TMET is sensitive to the cell redox status, i.e., NADH is a direct or indirect electron source. The cyanide-induced decrease in sequestration indicates a cyanide-sensitive intracellular oxidation mechanism. The results also demonstrate the potential utility of this approach for further evaluation of these endothelial redox mechanisms.

Animals↗

PubMed2000

Toluidine blue O and methylene blue as endothelial redox probes in the intact lung.

There is increasing evidence that the redox activities of the pulmonary endothelial surface may have important implications for the function of both lungs and blood. Because of the inherent complexity of intact organs, it can be difficult to study these activities in situ. Given the availability of appropriate indicator probes, the multiple-indicator dilution (MID) method is one approach for dealing with some aspects of this complexity. Therefore, the objectives of the present study were to 1) evaluate the potential utility of two thiazine redox indicators, methylene blue (MB) and toluidine blue O (TBO), as MID electron acceptor probes for in situ pulmonary endothelium and 2) develop a mathematical model of the pulmonary disposition of these indicators as a tool for quantifying their reduction on passage through the lungs. Experiments were carried out using isolated rabbit lungs perfused with physiological salt solution with or without plasma albumin over a range of flow rates. A large fraction of the injected TBO disappeared from the perfusate on passage through the lungs. The reduction of its oxidized, strongly polar, relatively hydrophilic blue form to its colorless, highly lipophilic reduced form was revealed by the presence of the reduced form in the venous effluent when plasma albumin was included in the perfusate. MB was also lost from the perfusate, but the fraction was considerably smaller than for TBO. A distributed-in-space-and-time model was developed to estimate the reduction rate parameter, which was approximately 29 and 1.0 ml/s for TBO and MB, respectively, and almost flow rate independent for both indicators. The results suggest the utility particularly of TBO as an electron acceptor probe for MID studies of in situ pulmonary endothelium and of the model for quantitative evaluation of the data.

Animals↗

PubMed1998

Ascorbate-mediated transplasma membrane electron transport in pulmonary arterial endothelial cells.

Pulmonary endothelial cells are capable of reducing certain electron acceptors at the luminal plasma membrane surface. Motivation for studying this phenomenon comes in part from the expectation that it may be important both as an endothelial antioxidant defense mechanism and in redox cycling of toxic free radicals. Pulmonary arterial endothelial cells in culture reduce the oxidized forms of thiazine compounds that have been used as electron acceptor probes for studying the mechanisms of transplasma membrane electron transport. However, they reduce another commonly studied electron acceptor, ferricyanide, only very slowly by comparison. In the present study, we examined the influence of ascorbate [ascorbic acid (AA)] and dehydroascorbate [dehydroascorbic acid (DHAA)] on the ferricyanide and thiazine reductase activities of the bovine pulmonary arterial endothelial cell surface. The endothelial cells were grown on microcarrier beads so that the reduction of ferricyanide and methylene blue could be studied colorimetrically in spectrophotometer cuvettes and in flow-through cell columns. The ferricyanide reductase activity could be increased 80-fold by adding DHAA to the medium, with virtually no effect on methylene blue reduction. The DHAA effect persisted after the DHAA was removed from the medium. AA also stimulated the ferricyanide reductase activity but was less potent, and the relative potencies of AA and DHAA correlated with their relative rates of uptake by the cells. The results are consistent with the hypothesis that AA is an intracellular electron donor for an endothelial plasma membrane ferricyanide reductase and that the stimulatory effect of DHAA is the result of increasing intracellular AA. Adding sufficient DHAA to markedly increase extracellular ferricyanide reduction had little effect on the plasma membrane methylene blue reductase activity, suggesting that pulmonary arterial endothelial cells have at least two separate transplasma membrane electron transport systems.

Animals↗

PubMed1997

Coronary stent and over-the-wire catheter exchange using standard length guidewires: Jet exchange (JEX) practice and theory.

The practice and theoretical principles of hydraulic exchange of over-the-wire (OTW) stent and PTCA catheters are described. Seventy-eight Palmaz-Schatz coronary stent delivery systems (PS-SDS), 8 Cook Flex-stents, and 247 assorted OTW catheters were delivered and extracted over standard length coronary guidewires using Jet Exchange (JEX). JEX was performed by pressurizing the wire lumen of coronary stent catheters to 18-20 atm and PTCA catheters to 15 atm. Extraction and insertion times were measured in the last 10 PS-SDS and PTCA procedures. Mechanical analysis of JEX was performed for PS-SDS and a representative OTW PTCA catheter by solving the Navier Stokes equation for annular flow with changing geometry. The force/mass relationship, extraction time, average velocity, net force on the guidewire, and drag force on the guidewire were determined for varying pressures, catheter masses, and extraction wire lumen fluids. JEX was successful in 75/78 (96%) of coronary stents and in 243/247 (98%) of the PTCA catheter exchanges. After catheter removal, reinsertion of another OTW catheter was successful in 324/325 (99%) attempts. The mean force on the guidewire at 15 and 20 atm ranged from 16,000 to 22,000 dynes. Extraction velocity was approximately equal to 250% greater when saline was used compared to the more viscous 50/50 contrast-saline solution. Timed JEX extractions for the PS-SDS and standard PTCA catheters were 8.9 +/- 2.3 sec and 5.3 +/- 1.4 sec and compared favorably to theoretical calculations of extraction times, 9.8 and 3.8 sec respectively. JEX is a simple, reliable, and cost effective means of rapidly exchanging OTW stent delivery and PTCA catheters without using exchange wires, extension, or wire trapping devices. Analysis of the principles of conservation of momentum provides a basis for understanding the physical laws that permit safe and expedient JEX in a clinically setting.

Catheterization↗

PubMed1995

Heart-lung interactions determined by electron beam X-ray CT in laterally recumbent rabbits.

Electron beam X-ray computed tomography (CT) was used to measure lung air content and its distribution within the lung as well as lung shape and heart position in rabbits in right and left lateral recumbency. Sham-operated control (S) rabbits and left-pneumonectomized rabbits with wax plombage were studied at functional residual capacity (FRC) and total lung capacity. Results were obtained for both lungs and for the right lung only of S rabbits. FRC of both lungs and the right lung only of the S rabbits and of the remaining right lung of the pneumonectomized rabbits was smaller in rabbits in right lateral recumbency than in those in left lateral recumbency. The reduction in right lung volume at FRC was accompanied by an overall reduction in lung size, although the lung shape remained similar, and was accompanied by movement of the heart centroid toward the dependent chest and spine. Application of a positive tracheal pressure of 25 cmH2O increased lung volume and reduced the dependency of lung volume and shape on posture. Lung inflation in the right lateral position was accompanied by movement of the heart centroid away from the dependent chest and spine. Gravitational gradients in regional air content did not differ between the cranial half of the lung, which was in contact with the heart, and the caudal half of the right lung, which was not in contact with the heart. Likewise, the cephalocaudal gradient in regional air content was similar when the right lung was dependent and nondependent. The location of the heart in the cranial half of the thorax does not appear to induce differences in regional air content between the cranial and caudal lung halves.

Animals↗

PubMed1994

Lung volumes and distribution of regional air content determined by cine X-ray CT of pneumonectomized rabbits.

Lung volume, gradients in lung air content, and maximum in vivo lung dimensions were determined in rabbits in the prone, supine, and right and left lateral positions with a high-speed electron beam X-ray computed tomography scanner (Imatron C-100). Measurements were made at lung volumes corresponding to tracheal pressures of 0, 10, and 25 cmH2O. Three groups of rabbits were studied > or = 8 wk after surgery: sham-operated controls, left pneumonectomized, and left pneumonectomized with wax plombage. The magnitudes of the gradients in each direction (lung, length, width, and height) depended on lung volume and body position. The vertical gradient in air content was the largest in each group in each posture. In general, pneumonectomy did not influence the effects of the prone and supine positions on lung volume and volume distribution but did influence the effects of the right and left lateral positions on those variables. These results may be attributed to the variable effects of the mediastinal and abdominal contents on regional distending pressures.

Animals↗

PubMed1993

Pleural pressure measured with a rib capsule in anesthetized pneumonectomized rabbits.

Pleural pressure was measured at end expiration in anesthetized rabbits using a rib capsule placed in the right fifth rib. Three groups of rabbits were studied in right and left lateral recumbency at least 8 weeks after surgery; rabbits that had undergone left pneumonectomy (Px, n = 8), rabbits that had undergone left pneumonectomy with wax plombage (Px + W, n = 7), and sham-operated control rabbits (S, n = 6). In S, Px, and Px + W rabbits in the left lateral position (lung and capsule nondependent), pleural pressure was -2.11 +/- 0.88 (mean +/- SD), -2.65 +/- 0.23, and -1.96 +/- 0.55 cmH2O respectively. In S, Px and Px + W rabbits in the right lateral position (lung and capsule dependent), pleural pressure was 0.64 +/- 0.22, 0.85 +/- 1.42, and 0.48 +/- 1.77 cmH2O respectively. In each position, pleural pressure did not differ among groups. This suggests that the compensatory increase in lung volume and reduced lung compliance following pneumonectomy in rabbits (Olson, J. Appl. Physiol. 74: 415-422, 1993) was not simply due to hyperinflation of the remaining lung.

Anesthesia↗

PubMed1993

Effect of posture on static lung volumes and pulmonary mechanics in pneumonectomized rabbits.

Static lung volumes, lung (CL) and respiratory system compliance (Crs), and the slope of phase III of the single-breath O2 test (slope III) were measured in rabbits in the prone, supine, and right and left lateral positions. Control rabbits, rabbits that had the left lung removed (Px), and rabbits that had the left lung removed and replaced with wax (Px + W) were studied. Surgeries were performed > or = 7 wk before study. Lung volumes, Crs, and slope III were not different among groups. Total lung capacity, vital capacity, residual volume, Crs, and slope III were smallest in all rabbits in the prone position. Functional residual capacity and expiratory reserve volume were unaffected by posture in control rabbits but were larger in Px and Px + W rabbits in the left lateral position. CL was unaffected by posture but was smaller in Px and Px + W rabbits than in control rabbits. Pneumonectomy-induced changes in lung shape altered the effect of posture on functional residual capacity but not on regional lung function, as assessed by the single-breath O2 test.

Airway Resistance↗

PubMed1993

Effect of isoproterenol on peripheral airway pressure-diameter behavior.

I radiographically evaluated the pressure-diameter relationships of peripheral airways (average diameter approximately 2 mm at total lung capacity) in a collaterally ventilating lung segment in 22 caudal dog lung lobes. Eleven lobes were studied when freshly excised, and 11 lobes were studied after being rinsed with 0.5% isoproterenol. Airways within the segment (intrasegmental) and a control region of similarly sized airways external to the segment were studied. Radiographs were taken when airway opening pressure (Pao) equaled pressure in the segment (Ps) (homogeneous case) and when Pao was 5, 10, or 15 cmH2O greater than Ps (nonhomogeneous case). Airway diameter was calculated as a fraction of the diameter at Pao = Ps = 25 cmH2O. The response of intrasegmental airways to increases in pressure in the homogeneous case (Ps = Pao) and nonhomogeneous case (Ps > Pao) differed between freshly excised and isoproterenol-rinsed lobes. I conclude that dilating peripheral airways by decreasing bronchomotor tone limits the extent to which they can respond to a regional increase in alveolar pressure.

Air Pressure↗

PubMed1992

Mechanical properties of small airways in excised pony lungs.

We evaluated the pressure-flow relationships in collaterally ventilating segments of excised pony lungs by infusing N2, He, Ne, or SF6 at known flows (V) through a catheter wedged in a peripheral airway. Measurements were made at segment- (Ps) to-airway opening (Pao) pressure differentials of 3-15 cmH2O when the lungs were held at transpulmonary pressures of 5, 10, and 15 cmH2O. The data were analyzed both by calculating collateral resistance (Ps-Pao/V) and by constructing Moody-type plots of normalized pressure drop [(Ps-Pao)/(1/2 rho U2, where rho is density and U is velocity)] against Reynolds number to assess the pattern of flow through the segment and the change in dimension of the flow channels as Ps and Pao were changed. The interpretations from these analyses were compared with radiographic measurements of the diameters of small airways within the collaterally ventilating lung segment at similar pressures. Collateral resistance increased as Ps-Pao increased at high Reynolds numbers, i.e., high flows or dense gas (SF6). Analysis of the Moody-type plots revealed that flow was density dependent at Reynolds number greater than 100, which frequently occurred when N2 was the inflow gas. The radiographic data revealed that small airway diameter increased as Ps-Pao increased at all lung volumes. In addition, at 5 cmH2O Pao, small-airway diameter was smaller for a given Ps in the nonhomogeneous case (Ps greater than Pao) than small-airway diameter for the same Ps in the homogeneous case (Ps = Pao). We interpret these data to suggest that the surrounding lung prevented the segment from expanding in the nonhomogeneous case.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pressure↗

PubMed1992

Effect of a regional increase in alveolar pressure on pulmonary blood flow.

We examined whether wedging a catheter (0.5 cm OD) into a subsegmental airway in dog (n = 6) or pig lungs (n = 5) and increasing pressure in the distal lung segment affected pulmonary blood flow. Dogs and pigs were anesthetized and studied in the prone position. Pulmonary blood flow was measured by injecting radiolabeled microspheres (15 microns diam) into the right atrium when airway pressure (Pao) was 0 cmH2O and pressure in the segment distal to the wedged catheter (Ps) was 0, 5, or 15 cmH2O and when Pao = Ps = 15 cmH2O. The lungs were excised, air-dried, and sectioned. Blood flow per gram dry weight normalized to cardiac output to the right or left lung, as appropriate, was calculated for the test segment, a control segment in the opposite lung corresponding anatomically to the test segment, the remainder of the lung containing the test segment (test lung), and the remainder of the lung containing the control segment (control lung). The presence of the catheter reduced blood flow in the test segment compared with that in the control segment and in the test lung. Blood flow was not affected by increasing pressure in the test segment. We conclude that, in studies designed to measure collateral ventilation in dog lungs, the presence of the wedged catheter is likely to have a greater effect on blood flow than the increase in pressure associated with measuring collateral airway resistance.

Animals↗

PubMed1991

Regional compliance and bronchial pressure-diameter relationships in excised pig lungs.

We estimated the magnitude of parenchymal interdependence in excised pig lungs by measuring small airway diameter during homogeneous and nonhomogeneous lung inflation, by comparing the ratio of the specific compliance of the lung (Cl) to the specific compliance of a single lung region (Cs) and by using a continuum mechanics analysis to estimate the pressure at the interface between a single lung region and the surrounding lung. We found that the diameter of airways in a single lung region increased when the lung was held at a transpulmonary pressure (Ptp) of 5, 10 or 15 cmH2O and pressure in the region was increased by up to Ptp + 15 cmH2O, indicating that the surrounding lung offered little resistance to expansion of the lung region. The ratio of Cl to Cs averaged 1.22 (n = 5 lungs), indicating that the parenchyma surrounding the lung region caused a small reduction in its distensibility. When the lung was held at a Ptp of 5 cmH2O, pressure at the interface was estimated to be 1.1, 0.8 and -1.9 cmH2O when pressure in the single lung region was 15, 10 and O cmH2O, respectively. The relatively small change in boundary pressure from pleural pressure as the region was inflated or deflated indicated that the mechanical interaction between adjacent lung regions was small. Taken together, these results confirm the prediction of a small interdependence effect as determined by measurements of the distensibility and distortability of the pulmonary parenchyma.

Animals↗

PubMed1991

Surface area-independent assessment of lung microvascular permeability with an amphipathic tracer.

A combination of an amphipathic-indicator-dilution (ID) diffusing tracer 1,4[14C]butanediol (B) and a hydrophilic tracer ([14C]urea) (U) was hypothesized to provide a capillary surface area- (S) independent assessment of lung microvascular permeability (P). We performed ID studies on isolated perfused dog lungs and administered randomly two interventions, increasing P by alloxan infusion and reduction in S by lobar ligation. The ratio of PS product of U (PSU) to that for butanediol (PSB) was sensitive to changes in P yet insensitive to changes in S. We performed ID studies in which the dependence of PSU and PSB on flow, hematocrit, and plasma protein binding were examined. Measurements of PSU and PSB after flow and hematocrit were changed suggested that these factors have no significant independent effects. From ID and in vitro studies we also found that no significant binding of B to plasma proteins (albumin) occurred. We concluded that ID techniques using B and U provide a consistent measure of P, despite changes in S, hematocrit, plasma protein concentration, and recruitment.

Animals↗

PubMed1990

Pleural pressure as a function of body position in rabbits.

Pleural pressure was measured at end expiration in spontaneously breathing anesthetized rabbits. A liquid-filled capsule was implanted into a rib to measure pleural liquid pressure with minimal distortion of the pleural space. Capsule position relative to lung height was measured from thoracic radiographs. Measurements were made when the rabbits were in the prone, supine, right lateral, and left lateral positions. Average lung heights in the prone and supine positions were 4.21 +/- 0.58 and 4.42 +/- 0.51 (SD) cm, respectively (n = 7). Pleural pressure was -2.60 +/- 1.87 (SD) cmH2O at 50.2 +/- 7.75% lung height in the prone position and -3.10 +/- 1.22 cmH2O at 51.4 +/- 6.75% lung height in the supine position. There was no difference between the values recorded in the prone and supine positions. Placement of the capsule into the right or left chest had no effect on the magnitude of the pleural pressure recorded in rabbits in right and left lateral recumbency (n = 12). Measurements over the nondependent lung were repeatable when rabbits were turned between the right and left lateral positions. Lung height in laterally recumbent rabbits averaged 4.55 +/- 0.52 (SD) cm.

Animals↗

PubMed1989

Isoproterenol- and salbutamol-induced relaxation of acetylcholine- and histamine-induced contraction of equine trachealis muscle in vitro.

Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When the tissues were contracted with acetylcholine (3.1 x 10(-6) M) or histamine (10(-4) M), the decrease in active isometric tension was concentration dependent when isoproterenol (10(-9) to 10(-4) M) or salbutamol (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. There was no difference between the response to isoproterenol and salbutamol when tissues from the same horses were compared whether the tissues were contracted in response to acetylcholine (3.1 x 10(-6) M) or histamine (10(-4) M). Relaxation was antagonized by 10(-6) M propranolol. The degree of relaxation obtained in these muscle strips was considerably less than that reported from other species' tracheal muscle strips that had the epithelium and mucosa intact. We concluded that equine tracheal smooth muscle contains beta-adrenoceptors that can be stimulated by either a mixed beta-1, beta-2 agonist or a selective beta-2 agonist.

Acetylcholine↗