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B E Marshall

Publications and source records attributed to B E Marshall.

At least 19 recordsLinked to original sources
PubMed1992

Hypoxic pulmonary vasoconstriction is not endothelium dependent.

Feline intrapulmonary arteries (mean diameter, 0.9 mm) were equilibrated in Earle's solution at constant tension in a chamber bubbled with an hyperoxic gas mixture (30% oxygen, 5% carbon dioxide, balance nitrogen). The endothelium was removed from half the vessels by gentle rubbing. The isometric response to the addition of acetylcholine (1*10(-6) M) was dilator in the vessels with endothelium and constrictor in those without endothelium. Intermittent exposure to a hypoxic gas mixture (0% oxygen, 5% carbon dioxide, balance nitrogen) for 20 min with five repetitions demonstrated sustained constrictor responses in the presence or absence of endothelium. Endothelial cells are, therefore, not required for the mediation of hypoxic pulmonary vasoconstriction.

Animals↗
PubMed1991

Unilateral hypoxic pulmonary vasoconstriction in the dog, pony and miniature swine.

The hypoxic pulmonary vasoconstrictor response to unilateral hypoxia was analyzed in pentobarbital anesthetized dogs (n = 5), miniature swine (n = 5), and ponies (n = 5). The left and right lungs (LL, RL) were separately ventilated with the LL exposed to inspired oxygen concentrations (CIO2) of 100%, 12%, 8% or 4%, while the RL always received a CIO2 = 100%. Pulmonary blood flow distribution was measured using 15 microns radioactive microspheres. LL PAO2, and percent pulmonary blood flow diversion (%FD) were calculated at each CIO2. At CIO2 of 4% there were significant differences (P greater than or equal to 0.05) between the %FD responses of each species (mean +/- S.E.): the %FDswine (95.1 +/- 1.3) greater than %FDpony (76.0 +/- 4.6) greater than %FDdog (50.1 +/- 9.4). For all species, the %FD was inversely related to the level of regional hypoxia, but there were marked species differences in the magnitude and sensitivity of hypoxic pulmonary vasoconstriction with the swine being the strongest responder, the pony intermediate, and the dog the weakest responder.

Animals↗
PubMed1991

Closed-loop infusion of atracurium with four different anesthetic techniques.

A new proportional-integral-derivative (PID) controller for the automated closed-loop delivery of atracurium was tested in 32 patients. Groups of 8 patients received halothane, enflurane, isoflurane, or N2O/morphine anesthesia. After induction of anesthesia with sodium thiopental 3-5 mg.kg-1, a bolus of atracurium 0.2 mg.kg-1 was delivered by the controller; this was followed by an infusion calculated by the controller to maintain the electromyogram (EMG) at a setpoint of 90% neuromuscular blockade. The average overshoot for the controller was 10.1% and the mean steady-state error 3.0%. The mean infusion rates for atracurium to maintain 90% blockade were calculated for each anesthetic group, with the inhalation anesthetics at 1 MAC. Infusion rates for N2O/morphine, halothane 0.8%, enflurane 1.7%, and isoflurane 1.4% at 90% blockade were 5.7 +/- 0.6, 4.9 +/- 0.3, 3.5 +/- 0.3, and 4.1 +/- 0.5 micrograms.kg-1.min-1, respectively (mean +/- SE). The infusion rate for atracurium at 90% blockade under N2O/morphine anesthesia was in general agreement with published values. The other infusion rates at 90% blockade have not been reported previously, but correspond to the known potencies of these inhalation anesthetics for augmentation of neuromuscular blockade. This controller performed well in comparison to previously developed controllers, and in addition was used as a research tool for rapid estimation of infusion rates.

Adult↗
PubMed1991

Influence of bronchial arterial PO2 on pulmonary vascular resistance.

In six anesthetized and mechanically ventilated adult sheep, the bronchial artery was perfused with blood from an oxygenator-pump circuit. When the lungs were ventilated with 100% O2 and the bronchial O2 tension (PbrO2) was approximately 600 Torr, the mean of the pulmonary vascular resistances (PVR) measured at the beginning (3.32 +/- 0.29 units) and end (3.17 +/- 0.13 units) of the experiment was 3.24 +/- 0.20 units. When the PbrO2 was changed to 58 +/- 1 Torr, the PVR (2.99 +/- 0.14 units) did not change significantly. However, when the lungs were ventilated with air as PbrO2 was decreased to 91 +/- 4, 77 +/- 3, 56 +/- 2, and 42 +/- 1 Torr, the PVR increased to 3.67 +/- 0.18, 4.03 +/- 0.16, 4.79 +/- 0.19, and 4.71 +/- 0.35 units, respectively. However, when the PbrO2 was decreased further to 26 +/- 1 and 13 +/- 1 Torr, the PVR decreased to 3.77 +/- 0.28 and 3.91 +/- 0.30 units, respectively. In contrast, the bronchial vascular resistance decreased monotonically as PbrO2 decreased. The bronchial circulation supplies vasa vasorum to the walls of all but the smallest pulmonary arteries, and it is therefore suggested that the PO2 of the bronchial circulation is responsible for the bimodal response of the pulmonary vasculature, with stimulation of hypoxic pulmonary vasoconstriction at moderate hypoxemia and of hypoxic pulmonary vasodilation at profound hypoxemia. The physiological and pathophysiological significance of the influence of systemic PO2 on pulmonary vascular tone is discussed.

Animals↗
PubMed1991

The final curtain?

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Fees, Dental↗
PubMed1990

Contraction of vascular smooth muscle in cell culture.

The use of cultured vascular smooth muscle cells for the study of events related to excitation and contraction of smooth muscle has been limited by the inability to reliably induce contractile responses after subculturing of the cells. This limitation has been overcome by the cell culture preparation described herein. We demonstrate that appropriate responses to both smooth muscle agonists and vasodilators were preserved in cells that were serially subcultured. Fetal bovine pulmonary artery and aortic cell cultures were established following enzymatic dispersion of the medial portion of freshly harvested vessels. At various times after isolation, cells were transferred to microscope coverslips coated with a polymerized silicone preparation (polydimethyl siloxane). Tension forces generated by the cells were manifested as wrinkles and distortions of this flexible growth surface. Visual evidence of cell contraction in the form of increased wrinkling was documented for cells exposed to angiotensin II, carbachol, and KCl. Decreases in cell tension occurred following treatment with isoproterenol, and those relaxing effects were overcome by subsequent treatment with the agonist carbachol. The contractile responses did not diminish with prolonged maintenance in culture or repeated subculturing. Phosphorylation of the light chains on the contractile protein myosin was also measured as a biochemical index of agonist-induced contraction. Cells depolarized with KCl or exposed to carbachol showed increased myosin phosphorylation when analyzed by 2-dimensional gel electrophoresis. The responses remained intact through 7 passages and 9 weeks in culture. These results show that cultured vascular smooth muscle cells do not necessarily undergo a phenotypic modulation with loss of contractility under prolonged maintenance in culture.

Angiotensin II↗
PubMed1990

The role of lung perfusate PO2 in the control of the pulmonary vascular resistance of exteriorized fetal lambs.

The isolated perfused lower left lung lobe of the exteriorized fetal lamb was used to define quantitatively the relationship between pulmonary perfusate oxygen tension and pulmonary vascular resistance (PVR) in the fetus at multiple oxygen tensions over the range from 8.3 to 433 mm Hg. This allowed variation of the perfusate PO2 over the range of partial pressures from less than 10 mm Hg to over 400 mm Hg while constant values of PCO2, temperature and perfusate flow were maintained. In all animals, calculated pulmonary vascular resistance varied in an inverse manner with the perfusate PO2. The relationship between PVR and perfusate oxygen tension is described by the equation: PVR = 7.67 - 1.54 (log PO2) R2 = 0.70. While others have shown that a single, large increase in blood oxygen tension will decrease the PVR in fetal lambs, these data present the first quantitative description of the role of oxygen tension in the modulation of fetal pulmonary vascular resistance as determined at multiple perfusate oxygen tensions over a fifty-fold range.

Animals↗
PubMed1990

Endothelium-derived relaxing factor is not responsible for inhibition of hypoxic pulmonary vasoconstriction by inhalational anesthetics.

Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV). One mechanism suggested for this action is stimulation of release of endothelium-derived relaxing factor. The present study has tested this hypothesis. These studies were performed in 66 ventilated and perfused isolated rat lungs. There were three study protocols. Study 1 examined the effect of HPV of the inhibition of soluble guanylate cyclase by methylene blue (MB). In the presence or absence of MB, the lungs constricted to hypoxia with pulmonary artery pressure increases of 8.6 +/- 0.2 cmH2O and 11.5 +/- 0.4 cmH2O, respectively, and halothane, enflurane, and isoflurane caused a reversible 50% decrease in the pulmonary pressor response, but acetylcholine (ACh) was vasodilatory in the saline group and vasoconstrictor in the MB group. In Study II a dose-response curve was established for the potent stimulator (Sin 1) of the enzyme guanylate cyclase. In the presence of MB the dose-response curve for Sin 1 was shifted to the right with an increase in the ED50 for Sin 1 from 44 microM for the control to 85 microM for the MB group. In Study III, baseline pulmonary artery pressure was increased with U46619, and the hypoxic pressor response was increased (28.9 +/- 2.5 cmH2O), but halothane again caused a 50% decrease (11.0 +/- 1.8 cmH2O) in the response to hypoxia. In summary, when soluble guanylate cyclase activity is inhibited by MB, the inhibition of hypoxic pulmonary vasoconstriction by halothane, isoflurane, or enflurane was unaltered, and release of endothelium-derived relaxing factor (EDRF) is therefore not an essential mechanism underlying this action.

Animals↗
PubMed1990

Hypoxic contraction of cultured pulmonary vascular smooth muscle cells.

The cellular events involved in generating the hypoxic pulmonary vasoconstriction response are not clearly understood, in part because of the multitude of factors that alter pulmonary vascular tone. The goal of the present studies was to determine if a cell culture preparation containing vascular smooth muscle (VSM) cells could be made to contract when exposed to a hypoxic atmosphere. Cultures containing only fetal bovine pulmonary artery VSM cells were assessed for contractile responses to hypoxic stimuli by two methods. In the first, tension forces generated by cells grown on a flexible growth surface (polymerized polydimethyl siloxane) were manifested as wrinkles and distortions of the surface under the cells. Wrinkling of the surface was noted to progressively increase with time as the culture medium bathing the cells was made hypoxic (PO2 approximately 25 mmHg). The changes were sometimes reversible upon return to normoxic conditions and appeared to be enhanced in cells already exhibiting evidence of some baseline tone. Repeated passage in culture did not diminish the hypoxic response. Evidence for contractile responses to hypoxia was also obtained from measurements of myosin light chain (MLC) phosphorylation. Conversion of MLC to the phosphorylated species is an early step in the activation of smooth muscle contraction. Lowering the PO2 in the culture medium to 59 mmHg caused a 45% increase in the proportion of MLC in the phosphorylated form as determined by two-dimensional gel electrophoresis. Similarly, cultures preincubated for 4 h with 32P and then exposed to normoxia or hypoxia for a 5-min experimental period showed more than twice as much of the label in MLCs of the hypoxic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Low-dose almitrine bismesylate enhances hypoxic pulmonary vasoconstriction in closed-chest dogs.

The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor response was studied in six closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2; the left lung was ventilated either with 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal oxygen tension = 60.3 +/- 0.6 mm Hg). On two consecutive days, each dog received either almitrine (Vectarion, Servier Lab) or malic acid. Consecutive almitrine doses of 0.003, 0.03, 0.3, and 3.0 micrograms.kg-1.min-1, or the equivalent volumes of malic acid without almitrine, were administered intravenously as a constant peripheral infusion for 15 min. Percent blood flow to each lung was calculated based on a variation of the traditional shunt equation. The change in percent left lung blood flow (delta %QL-VA) increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. The change in arterial oxygen tension (delta PaO2) also increased significantly between the hypoxia-no drug and the hypoxia-almitrine (3.0 micrograms.kg-1.min-1) phase. No significant changes occurred during the other almitrine doses or the respective malic acid control phases. It is concluded that in dogs low-dose almitrine enhances hypoxic pulmonary vasoconstriction and that this enhancement is dose-related.

Almitrine↗
PubMed1989

Mechanical factors do not influence blood flow distribution in atelectasis.

The contribution of mechanical factors to the vascular resistance of the atelectatic lung has been studied in vivo in the anesthetized open-chest dog. When the left lung was ventilated with an hypoxic gas mixture (while the right lung was ventilated with 100% O2), left lung blood flow decreased from 0.99 +/- 0.11 1.min-1 to 0.40 +/- 0.08 1.min-1 due to hypoxic pulmonary vasoconstriction (hypoxic stimulus PSO2 = 36.1 +/- 0.8 mmHg). When the left lung was made atelectatic, blood flow decreased to 0.65 +/- 0.11 1.min-1, consistent with a weaker hypoxic stimulus (PSO2 = 54.0 +/- 3.2 mmHg). With the addition of sodium nitroprusside infused intravenously, left lung blood flow increased to 1.05 +/- 0.14 1.min-1 during atelectasis, and to 0.61 +/- 0.09 1.min-1 during hypoxic ventilation, while flow remained at 0.94 +/- 0.18 1.min-1 during hyperoxic ventilation. When the results were plotted on pressure-flow diagrams, the hyperoxic, hypoxic, and atelectatic lung points fell on the same pressure-flow line in the presence of nitroprusside. It is concluded that hypoxic pulmonary vasoconstriction is the major (but not necessarily only) determinant of increased vascular resistance in the atelectatic lung, and that passive mechanical factors do not measurably affect blood flow distribution during open-chest atelectasis.

Animals↗
PubMed1988

Reduced availability of energy initiates pulmonary vasoconstriction.

The mechanism responsible for initiating hypoxic pulmonary vasoconstriction (HPV) remains controversial. In this study, reversible constriction of the pulmonary artery was produced when the ratio of carbon monoxide to oxygen was increased, demonstrating that HPV could be imitated even in the presence of a constant oxygen tension. Isolated rat lungs from 14 adult rats were perfused with a 5% albumin-physiological salt solution and ventilated with 21% O2, 5% CO2, balance N2. At the end of a 30-min stabilization period, the lungs were injected with a bolus of angiotensin II (0.2 micrograms). They were then challenged three times for 5 min with an hypoxic gas mixture alternating with 5 min of normoxia. The ventilatory circuit was then changed to one in which 10% O2, 5% CO2 and varying concentrations of CO (balance N2) could be administered. The concentration ratios of CO:O2 were 0.5:1, 1:1, 2:1, 4:1, and 8:1. These were randomly administered for 6 min interspersed with 6 min of normoxia; a final angiotensin II challenge was given. The results show a slight but significant vasodilation with CO:O2 of 0.5:1, 1:1 with mean depressor responses of 0.7 +/- 0.1, -0.7 +/- 0.1 cm H2O and progressive vasoconstriction with CO:O2 of 2:1, 4:1, 8.5:1 with mean pressor responses of 0.11 +/- 0.3, 4.0 +/- 0.4 and 6.2 +/- 0.5 cm H2O. The pressor response to angiotensin II remained unchanged from beginning to end (9.5 +/- 0.5, 8.1 +/- 0.7 cm H2O. The pressor responses, therefore, are consistent with reduced function of the cytochromes of the electron transport chain. These results suggest that HPV may be initiated by a reduction of energy state of the vascular smooth muscle and that postulation of a specific oxygen receptor is not necessary.

Animals↗
PubMed1987

The actions of halothane, ibuprofen and BW755C on hypoxic pulmonary vasoconstriction.

The effect of halothane on the pressor responses to hypoxia (3% O2, 5% CO2, balance N2) and to Angiotensin II (Ang II) (0.2 microgram) has been compared in an in vitro perfused and ventilated rat lung preparation in the presence and absence of agents known to block the lipoxygenase (BW755C) and/or the cyclooxygenase (ibuprofen) pathways for arachidonic acid metabolism. Preliminary studies established the stability of the preparation (experiment 1) during two hours of observation and allowed estimation of (experiment 2) the concentration of BW755C that inhibited the HPV response by 50% (ED50 = 125 microM). In experiment 3, the rat lungs were subdivided into four groups: A, B, C, and D. Group A received the drug solvent, and B received 17 microM ibuprofen. Groups C and D received ibuprofen and, in addition, an ED50 dose of BW755C. The lungs were then tested for their response to hypoxia. In addition, groups C and D were tested for their response to 0.2 microgram Ang II. 0.5 MAC halothane was introduced into the ventilatory circuit of A, B, and D. Group C received no halothane. Responses to hypoxia and Ang II (groups C and D) were measured. Halothane was terminated and a further hypoxic response was tested in groups A and B. The results show, in group A, that the addition of halothane reduced the response to hypoxia from (mean +/- SE cm H2O) 13.4 +/- 1.56 to 6.5 +/- 1.28, a 50% reduction. The addition of ibuprofen in group B caused a 33% increase in the response, and the addition of halothane now caused only a 30% decrease.(ABSTRACT TRUNCATED AT 250 WORDS)

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1987

High-dose almitrine bismesylate inhibits hypoxic pulmonary vasoconstriction in closed-chest dogs.

The effect of almitrine bismesylate on the hypoxic pulmonary vasoconstrictor (HPV) response was studied in seven closed-chest dogs anesthetized with pentobarbital and paralyzed with pancuronium. The right lung was ventilated continuously with 100% O2, while the left lung was ventilated with either 100% O2 ("hyperoxia") or with an hypoxic gas mixture ("hypoxia": end-tidal PO2 = 50.1 +/- 0.1 mmHg). Cardiac output (CO) was altered from a "normal" value of 3.10 +/- 0.18 l . min-1 to a "high" value of 3.92 +/- 0.16 l . min-1 by opening arteriovenous fistulae which allowed measurements of two points along a pressure-flow line. These four phases of left lung hypoxia or hyperoxia with normal and high cardiac output were repeated in the presence and absence of almitrine. Almitrine bismesylate was administered as a constant infusion of 14.3 micrograms . kg-1 . min-1 for a mean plasma concentration of 219.5 +/- 26.4 ng . ml-1. Relative blood flow to each lung was measured with a differential CO2 excretion (VCO2) method corrected for the Haldane effect. With both lungs hyperoxic, the percent left lung blood flow (%QL-VCO2) was 44 +/- 1%. When the left lung was exposed to hypoxia, the %QL-VCO2 decreased significantly to 22 +/- 1%. However, with the administration of almitrine, the %QL-VCO2 during left lung hypoxia increased significantly to 36 +/- 2%. The arterial oxygen tension decreased significantly between hyperoxia (PaO2 = 633 +/- 6 mmHg) and hypoxia (271 +/- 31 mmHg). With the addition of almitrine, there was no change during hyperoxia; however, during hypoxia, the PaO2 decreased significantly to 124 +/- 15 mmHg. Cardiac output did not influence these findings. The pulmonary vascular conductance (G) is the slope of the pressure-flow line.(ABSTRACT TRUNCATED AT 250 WORDS)

Almitrine↗
PubMed1979

The hypotensive response to rapid intravenous administration of hypertonic solutions in man and in the rabbit.

Transient hypotension has been observed in patients after rapid intravenous administration of mannitol, 25 per cent, in clinical doses. These studies were conducted to determine the mechanism for the hypotension, to determine dose and rate of injection response curves in rabbits, and to determine which vascular beds were most reactive. Studies in six patients showed mean decreases in blood pressure of 23 +/- 6.0 per cent (+/-SE) and in total peripheral resistance of 38 +/- 7 per cent after infusion of mannitol. Studies in 18 patients during cardiopulmonary bypass with mechanically fixed cardiac output demonstrated decreases in mean blood pressure of 30 +/- 5 to 40 +/- 3 per cent, depending on dose and rate of administration of mannitol. Patients not on bypass compensated for large decreases in total peripheral resistance by increases in cardiac output (3.6 +/- .4 at baseline to 4.4 +/- .4 l/min) during mannitol-induced hypotension with no change in heart rate. Serum osmolality increased as blood pressure decreased. Significant but clinically unimportant decreases in sodium and potassium ions, hemoglobin, pH, and base excess values were observed. Studies in 18 rabbits showed that the greater the dose or rate of injection of mannitol the greater the decrease in blood pressure. Injection of radiolabeled microspheres in rabbits demonstrated a near doubling of blood flow to skeletal muscle tissue during the hypotension. This occurred with both equiosmotic hypertonic glucose (17 +/- 3 to 32 +/- 7 per cent) and mannitol (17 +/- 1 to 31 +/- 5 per cent), but not after isotonic saline solution. Changes in blood flow to other organ beds were variable and unimportant. The results suggest that hypotension following the intravenous administration of hyperosmotic solutions is due primarily to vasodilation in skeletal muscle.

Acid-Base Equilibrium↗