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L D Wood

Publications and source records attributed to L D Wood.

At least 37 records · Page 2Linked to original sources
PubMed1993

ANF decreases active sodium transport and increases alveolar epithelial permeability in rats.

Previous studies reported that atrial natriuretic factor (ANF) decreased lung edema in guinea pigs. To determine whether ANF protects against lung edema by increasing active Na+ transport and lung edema clearance, ANF (10(-7) M) was instilled into the air spaces (n = 5) or perfused through the pulmonary circulation (n = 5) of isolated perfused liquid-filled rat lungs. These animals were compared with five control rats and four rats having amiloride (10(-5) M) instilled into the air space. Amiloride reduced lung edema clearance by 65%, perfused ANF reduced lung edema clearance by 32%, and instilled ANF did not change edema clearance compared with responses in control rats after 70 min of experimental protocol. Passive Na+ movement increased by 91% with perfused ANF and by 52% with instilled ANF compared with that in control rats. Albumin flux from the perfusate into the air space increased in ANF-perfused lungs compared with control lungs (P < 0.05) but not when ANF or amiloride was instilled into the air spaces. These results suggest that ANF instilled into rat air spaces or perfused through the pulmonary circulation increases lung epithelial permeability and that ANF perfused through the pulmonary circulation decreases lung edema clearance due to impaired active Na+ transport. Conceivably, the previously observed protective effect of ANF was due to reduced pressures across the pulmonary circulation, which resulted in less edema formation.

Amiloride↗
PubMed1993

The effect of respiratory and lactic acidosis on diaphragm function.

The relative effects of respiratory and metabolic acidosis on diaphragm function are not known. To determine these effects, we compared the effects of respiratory and lactic acidosis on the contractile properties of the diaphragm. We estimated diaphragmatic performance from the change in transdiaphragmatic pressure after supramaximal stimulation of the phrenic nerves in an open-chested, casted-abdomen dog. Similarly, we stimulated the gastrocnemius motor nerve and examined force production and relaxation rate to determine if there was a difference in the response of this skeletal muscle. There was a fall in diaphragm performance with respiratory acidosis (77.1 +/- 16.9 cm H2O versus 93.8 +/- 15.0 cm H2O baseline), but not with lactic acidosis (96.7 +/- 15.7 cm H2O versus 93.8 +/- 15.0 cm H2O baseline); and the gastrocnemius was unaffected by either acidosis. The changes with respiratory acidosis were similar to those seen with diaphragmatic fatigue and had similar relaxation rate changes, suggesting that intracellular pH may play a mechanistic role in respiratory muscle fatigue. In addition, the absence of a respiratory acidosis effect on a non-diaphragmatic skeletal muscle's function represents another physiologic difference between the diaphragm and other skeletal muscles.

Acidosis, Lactic↗
PubMed1993

Metered-dose inhaler versus nebulized albuterol in mechanically ventilated patients.

In nonintubated patients, beta 2-agonist bronchodilators are equally effective when delivered by metered-dose inhalers (MDI) or nebulizers (NEB). The delivery of these drugs by MDI to intubated, mechanically ventilated patients has become a widespread practice. To compare the efficacy of the two delivery systems and establish optimal dosing, we prospectively randomized 10 mechanically ventilated patients, with increased airways resistance, to receive albuterol by either MDI or nebulizer in incrementally higher doses. After a 4-hr washout, patients were crossed-over to receive the drug by the alternative route of administration. Albuterol delivered by NEB to a total dose of 2.5 mg reduced the inspiratory flow-resistive pressure (peak-pause airway pressures) from 21.5 +/- 5.7 to 17.6 +/- 5.4 cm H2O (p < 0.01). Nebulized albuterol at cumulative doses of 7.5 mg led to further reductions in 8 of 10 patients (p < 0.1), but led to toxic side effects in 4 of them; in the remaining 6 patients toxicity occurred at a cumulative dose of 15.0 mg. By contrast, albuterol in cumulative doses reaching 100 puffs (9 mg) from an MDI administered into an endotracheal tube adapter did not significantly reduce resistive pressures, and produced no toxicity. We conclude that nebulized albuterol provides objective physiologic improvement, while albuterol administered by MDI through an endotracheal tube adapter has no effect in mechanically ventilated patients with airflow obstruction. Nebulizer treatments can and should be titrated to higher-than-conventional doses, using toxic side-effects and physiologic response to guide therapy.

Adult↗
PubMed1992

Negative regulation of gene expression by TGF-beta.

Stromelysin gene expression is transcriptionally activated by a number of growth factors (e.g., EGF and PDGF), tumor promoters (e.g., TPA), and oncogenes (e.g., ras, src) through an AP-1-dependent mechanism. TGF-beta repression of stromelysin induction is mediated at the level of transcription by an element located at position -709 in the rat stromelysin promoter referred to as the TGF-beta inhibitory element (TIE). A TIE-binding protein complex is induced by treatment of rat fibroblasts with TGF-beta. This protein complex contains the protooncogene c-fos, and induction of c-fos by TGF-beta is required for the repressive effects of TGF-beta on stromelysin gene expression. Interestingly, c-fos induction is also required for stimulation of stromelysin expression by EGF in rat fibroblasts. Preliminary studies suggest that differential regulation of members of the jun family of early-response genes may explain this apparent paradox and determine whether stromelysin is induced or repressed by growth factors. TGF-beta stimulation therefore initiates a cascade of events that results in a specific pattern of gene expression: the direct stimulation of early-response genes can lead to subsequent induction or repression of other genes. Growth factor regulation of matrix metalloproteinases appears to play a role in embryonic development in the morphogenesis of the murine lung. Treatment of embryonic lungs in organ culture with the growth factors EGF or TGF-alpha results in stimulation of growth and inhibition of branching morphogenesis. A similar inhibition of branching was observed when these lung rudiments were treated with the matrix metalloproteinase collagenase. Most interestingly, the effects of EGF and TGF-alpha can be completely reversed by the tissue inhibitor of metalloproteinases, TIMP. TGF-beta has the opposite effect on growth of murine lung rudiments--growth is inhibited in a dose-dependent manner. This example illustrates a potential role for growth factor regulation of matrix-degrading metalloproteinases in complex developmental processes.

Animals↗
PubMed1992

Noninvasive measurement of blood pressure in conscious cynomolgus monkeys.

Systolic (SP), diastolic (DP), and mean arterial blood pressures (MAP) and pulse rate (PR) were recorded on treated and untreated conscious cynomolgus monkeys by the oscillometric method (Dinamap 1846SX/P). Each monkey was placed in a restraining tube with the cuff placed on the base on the shaved tail. Measurements were taken on untreated animals once or twice a day for 4 weeks. The mean and standard deviations for SP, DP, MAP, and PR were approximately 121 +/- 17, 60 +/- 14, and 84 +/- 17 mm Hg and 193 +/- 18 pulses/min, respectively. One male and one female cynomolgus monkey were treated with isoproterenol, norepinephrine, and nitroprusside. Blood pressure was measured indirectly with the cuff on the tail and directly with an indwelling catheter in the descending thoracic aorta. Although the oscillometric method was not as sensitive as the catheter, the oscillometric method detected a change in the same direction of SP, DP, MAP, and PR compared with the direct method for all drugs administered. The monitor was reliable and sufficiently accurate to conclude that it may be useful in toxicology studies for evaluation of blood pressure parameters in conscious cynomolgus monkeys.

Animals↗
PubMed1992

PEEP is necessary for exogenous surfactant to reduce pulmonary edema in canine aspiration pneumonitis.

Alveolar edema inactivates surfactant, and surfactant depletion causes edema by reducing lung interstitial pressure (Pis). We reasoned that surfactant repletion might reduce edema by raising Pis after acute lung injury and that positive end-expiratory pressure (PEEP) might facilitate this effect. One hour after tracheal administration of hydrochloric acid in 18 anesthetized dogs with transmural pulmonary capillary wedge pressure of 8 Torr, the animals were randomized into three groups: in the SURF + PEEP group, 50 mg/kg of calf lung surfactant extract (CLSE) was instilled into each main stem bronchus with 8 cmH2O of PEEP; in the SAL + PEEP group, PEEP was followed by an equal volume of saline (SAL); in the SURF group, CLSE was given without PEEP. After 5 h, edema in excised lungs (wet-to-dry weight ratios) was significantly less in the SURF + PEEP group (9.1 +/- 1.0) than in the other groups (11.3 +/- 1.8 and 11.3 +/- 1.8, respectively). In the SURF + PEEP group, pulmonary venous admixture fell by 6%; this change was different from the 7% increase in the SAL + PEEP group and 40% increase in the SURF group (P less than 0.05). Airway secretions obtained in the SURF + PEEP group had normal minimum surface tensions of 4 +/- 2 mN/m, a value much lower than in SAL + PEEP and SURF groups (32 +/- 4 and 22 +/- 7 mN/m, respectively). We conclude that surfactant normalizes surface tension and decreases transcapillary hydrostatic forces in this lung injury model, thereby reducing edema formation and improving gas exchange. These benefits occur only if surfactant is given with PEEP, allowing surfactant access to the alveoli and/or minimizing its inhibition by edema proteins.

Animals↗
PubMed1991

Effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium.

The separate effects of hypoxia and hypercapnia on the force-velocity relation of rabbit myocardium were compared in 10 papillary or trabecular muscles superfused using control (95% O2-5% CO2), hypoxic (18% O2), and hypercapnic (20% CO2) physiological salt solutions. This level of hypoxia did not irreversibly damage the muscles and reduced peak isometric force by 53 +/- 11%. The level of hypercapnia was chosen to match the force depression (50 +/- 12%) produced by hypoxia. Multiple force-velocity points were measured by applying critically damped isotonic force steps at 90% of the time to peak isometric force and at the time to 50% peak isometric force. These points defined the force-velocity relation and maximum velocity of shortening, the extrapolated isometric force, and the maximum power of nonpotentiated and postextrasytolic potentiated contractions. Hypoxia and hypercapnia reduced maximum force and maximum power nearly equally. Maximum velocity of shortening decreased more during hypoxia (21 +/- 12%) than during hypercapnia (12 +/- 9%) (p less than 0.01). Postextrasystolic potentiation completely reversed the reduction of maximum velocity of shortening during hypercapnia but not during hypoxia. A 6% internal load could account for the reduction in maximum velocity of shortening during hypercapnia and all but 9% of the reduction in maximum velocity of shortening during hypoxia. The relative time course of the force-velocity relation was not altered by either hypoxia or hypercapnia. We conclude that hypercapnia reduces the effect of activation because increased activation (by postextrasystolic potentiation) restored the force-velocity relation and maximum velocity of shortening to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Management of the critically ill asthmatic patient.

Status asthmaticus is a life-threatening condition characterized by rapid or inexorable progression of airflow obstruction that may lead to respiratory failure. It must be distinguished from other causes of dyspnea with signs of airflow limitation, and therapy must then be directed at relief of bronchospasm and airway inflammation, with use of multiple pharmacologic agents. Patients require moment-to-moment assessment until airway disease reverses. During this early portion of their course, intubation and mechanical ventilation may be required. Successful management on the ventilator requires an understanding of underlying abnormalities of lung mechanics and the interaction of the lungs and circulation.

Asthma↗
PubMed1990

Effect of lactic acidosis on canine hemodynamics and left ventricular function.

Hypoperfusion states cause lactic acidosis, and the acidemia further reduces the inadequate cardiac output. Conceivably, the adverse effect of lactic acidemia on cardiac output is due to depressed contractility demonstrated in isolated myocardium. Alternatively, factors governing venous return cause a relative hypovolemic state and/or acidemic pulmonary vasoconstriction-induced right ventricular dysfunction. We reasoned that examination of left ventricular pressure-volume relationships at end systole and end diastole would determine which of these potential mechanisms accounted for reduced cardiac output during progressive lactic acidosis in anesthetized, mechanically ventilated dogs. Left ventricular (LV) volume was estimated from two pairs of epicardial ultrasonic crystals placed in the anterior-posterior and longitudinal planes, and LV pressure was obtained rom a catheter-tipped transducer. During progressive acidemia induced by a continuous intravenous infusion of 0.5 N lactic acid, cardiac output, stroke volume, and mean systemic arterial pressure fell significantly while mean pulmonary artery pressure and right atrial pressure increased significantly. These variables did not change with time in control (no-acid infusion) dogs. Lactic acidemia caused a 40% reduction in stroke volume, which could be attributed to depressed LV contractility, characterized by a decrease in maximum dP/dt as well as a fall in slope (Emax) with no change in volume intercept (Vo) of the left ventricular pressure-volume relationship at end systole. Neither the measured left ventricular end-diastolic pressure nor the estimated left ventricular end-diastolic volume (LVEDV) decreased with acidemia, suggesting that the reduced venous return did not result from relative hypovolemia. However, acidemic pulmonary hypertension may have interfered with the expected response to myocardial depression, which is an increase in LVEDV.

Acidosis, Lactic↗
PubMed1990

Distribution of pulmonary vascular resistance during lactic acid infusion in dogs.

We sought to determine the longitudinal distribution of pulmonary vascular resistance (PVR) in acute lactic acidosis utilizing pulmonary artery and vein balloon occlusion techniques (Holloway et al. J. Appl. Physiol. 54: 840-851, 1983). In anesthetized dogs, both a systemic vein (I-V) infusion and systemic artery (I-A) infusion of L-lactic acid were studied to control for potential effects of factors other than pH on PVR. During progressive I-A infusion (n = 9) to a pH of 6.94 +/- 0.06 there was no significant change in PVR or its distribution. In contrast, I-V infusion (n = 9) to a pH of 7.08 +/- 0.09 increased median PVR from 3.6 to 21.7 mmHg.1(-1).min (P less than 0.001), due to an increase in middle segment resistance (0.0-15.4 mmHg.1(-1).min, P less than 0.02). Examination by light and electron microscopy demonstrated pulmonary capillary obstruction with hemolyzed erythrocyte (RBC) membranes with I-V infusion, but representative I-A animals did not demonstrate these findings. Conceivably, the systemic vascular bed filtered the fragmented RBC membranes in the I-A model, but this microvascular obstruction with altered RBCs and RBC fragments caused the pulmonary hypertension observed in the I-V infusion. We conclude that lactic acidosis does not increase pulmonary vascular tone in dogs, a finding compatible with most previous studies in which observed increases in PVR may be attributed to other effects from I-V acid infusion on circulating blood elements.

Acidosis, Lactic↗
PubMed1990

Pathogenesis of pulmonary edema associated with intracisternal endotoxin in dogs.

To examine the role of central nervous system injury in the pathogenesis of pulmonary edema, we injected Escherichia coli endotoxin (5 mg/kg) into the cisterna magna of six dogs (group E) and compared, over 4 h, both the pulmonary edema and cerebrospinal fluid (CSF) abnormalities with those in six control dogs (group C). In group E, intracisternal endotoxin raised intracranial pressure from 21 +/- 6 to 38 +/- 8 cmH2O (P less than 0.001), CSF total protein from 18 +/- 6 to 54 +/- 19 mg/dl (P less than 0.001), and CSF malondialdehyde from 0.12 +/- 0.11 to 0.61 +/- 0.35 nmol/ml (P less than 0.05); all were unchanged in group C. When the pulmonary wedge pressure was maintained at 10 mmHg by fluid infusion, extravascular thermal volume in group E increased from 7.2 +/- 1.2 to 12.0 +/- 2.7 ml/kg (P less than 0.005) at 4 h when the excised lungs weighed 13.6 +/- 1.5 g/kg; in group C, extravascular thermal volume did not increase, and the excised lungs weighed less (10.8 +/- 1.3 g/kg, P less than 0.05) than those in group E. The dry weights of the lungs were not different between groups, and the alveolar lining fluid-to-plasma albumin ratio in both groups remained low, 0.1-0.2. Fluid infusion in group E (9.2 +/- 2.9 liters) caused colloid oncotic pressure to decrease 4.5 +/- 2.8 mmHg; colloid oncotic pressure fell less (0.8 +/- 1.9 mmHg, P less than 0.001) in group C as less fluid (2.2 +/- 1.5 liters, P less than 0.001) was required to maintain pulmonary wedge pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Acute respiratory acidosis decreases left ventricular contractility but increases cardiac output in dogs.

To understand the cardiovascular response to respiratory acidosis, we measured hemodynamics, left ventricular pressure, and left ventricular volume (three ultrasonic crystal pairs) during eucapnia and respiratory acidosis in 10 fentanyl-anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope (Emax) and intercept (V0) of the left ventricular end-systolic pressure-volume relation determined by combining end-systolic points from a vena caval occlusion and from brief aortic cross-clamping. Respiratory acidosis (pH 7.09, Pco2 92 mm Hg) reduced contractility by a decrease in Emax (11.4 to 9.2 mm Hg/ml, p less than 0.01) with no change in V0. Despite this, cardiac output increased (1.7 to 2.1 l/min, p less than 0.01), and heart rate increased (96 to 121 beats/min, p less than 0.05), with no change in blood pressure. Systemic vascular resistance fell by 26% (p less than 0.01). During eucapnia, propranolol reduced Emax (11.4 to 4.6 mm Hg/ml, p less than 0.01) with no change in V0. After propranolol treatment, respiratory acidosis further reduced Emax (4.6 to 3.6 mm Hg/ml, p less than 0.05) and increased end-systolic volume more than before propranolol (p less than 0.001). Now cardiac output did not increase even though heart rate increased (81 to 106 beats/min, p less than 0.001) and systemic vascular resistance fell by 20% (p less than 0.01). We conclude that the effect of respiratory acidosis on the circulation is to increase venous return (equals cardiac output) in the face of decreased left ventricular contractility. The beta-adrenergic response to respiratory acidosis substantially ameliorated the increase in end-systolic volume and supported the increase in venous return but did not alter the associated tachycardia or vasodilation. Respiratory acidosis, like propranolol treatment, decreases contractility by decreasing Emax.

Acidosis, Respiratory↗
PubMed1990

The mechanism of respiratory arrest in inspiratory loading and hypoxemia.

Respiratory arrests occur in the clinical setting of respiratory failure, but the mechanism is unclear. We used a dog model with increased inspiratory resistance and hypoxemia to explore the cause. We hypothesized that respiratory muscle fatigue (RMF) played a role in these respiratory arrests, and that the combination of hypoxia and resistive loading would produce respiratory arrest by the mechanism of RMF. Our preparation had transdiaphragmatic pressures that were 40% of maximum (Pdimax = 46.3 +/- 10.0 cm H2O) and progressive hypoxia resulting in a final arterial PO2 of 38 +/- 9 mm Hg and a phrenic vein O2 content of 1.8 +/- 1.1 mg/dl. Instead of failure associated with carbon dioxide retention and RMF, we saw a rapid decrease in tidal volume and respiratory rate, leading to apnea over 30 to 60 s while the diaphragm still responded with significant pressure generation when externally stimulated. These results suggest that respiratory muscle fatigue may not be a major factor in respiratory arrests associated with inspiratory loading and hypoxia, but that suppression of central drive, induced by the combination of inspiratory loading and hypoxemia, may be important.

Acid-Base Equilibrium↗
PubMed1990

Adverse effects of large tidal volume and low PEEP in canine acid aspiration.

When normal lungs are ventilated with large tidal volumes (VT) and end-inspired pressures (Pei), surfactant is depleted and pulmonary edema develops. Both effects are diminished by positive end-expiratory pressure (PEEP). We reasoned that ventilatory with large VT-low PEEP would similarly increase edema following acute lung injury. To test this hypothesis, we ventilated dogs 1 h after hydrochloric acid (HCl) induced pulmonary edema with a large VT (30 ml/kg) and low PEEP (3 cm H2O) (large VT-low PEEP) and compared their results with dogs ventilated with a smaller VT (15 ml/kg) and 12 cm H2O PEEP (small VT-high PEEP). The small VT was the smallest that maintained eucapnia in our preparation; the large VT was chosen to match Pei and end-inspired lung volume. Pulmonary capillary wedge transmural pressure (Ppwtm) was kept at 8 mm Hg in both groups. Five hours after injury, the median lung wet weight to body weight ratio (WW/BW) was 25 g/kg higher in the large VT-low PEEP group than in the small VT-high PEEP group (p less than 0.05). Venous admixture (Qva/Qt) was similarly greater in the large VT-low PEEP group (49.8 versus 23.5%) (p less than 0.05). We conclude that small VT-high PEEP is a better mode of ventilating acute lung injury than large VT-low PEEP because edema accumulation is less and venous admixture is less. These advantages did not result from differences in Pei, end-inspiratory lung volume, or preload (Ppwtm).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The effect of hypopnea on low-pressure pulmonary edema.

The effects of the mechanical factors involved in ventilation on pulmonary edema are only partially understood. To clarify the effect of ventilation on the adult respiratory distress syndrome (ARDS), we examined the effect of reducing rate and tidal volume on oleic acid-induced low-pressure pulmonary edema in dogs, hypothesizing that hypopnea would reduce lung edema. We placed the experimental animals on venous-venous extracorporeal membrane oxygenation (ECMO) for CO2 clearance and oxygenation 1 h after the injury. This allowed reduction of the ventilatory rate from 17.2 +/- 4.8 to 3.3 +/- 0.8 breaths/min and tidal volume from 20 to 16 ml/kg, effectively resting the injured lung. After 5 h of hypopnea there was no reduction in edema by gravimetric or extravascular thermal volume measurements. The ECMO-facilitated hypopnea reduced airway pressure and pulmonary artery pressure while improving arterial oxygen saturation but increased venous admixture. These results suggest that there may be a supportive role for ECMO-assisted hypopnea, but there was no direct beneficial effect of hypopnea on edema.

Animals↗
PubMed1989

Measurement of hydrogen peroxide in plasma and blood.

Measurement of the oxygen metabolite hydrogen peroxide (H2O2) in biological fluids such as plasma could be of interest because it might indicate participation of toxic oxygen species in tissue injury. Recently several reports claimed to measure H2O2 using spectrophotometric and high pressure liquid chromatographic (HPLC) techniques that utilize oxidation of a substrate to a product by a peroxidase. In such a system it is crucial to perform two control experiments to verify whether the measured substance is H2O2. The specificity of the assay for H2O2 should be checked with catalase, and the degradation of H2O2 or inhibition of the assay system by the sample should be checked by determining the recovery of exogenously added H2O2. We performed both types of controls for HPLC and spectrophotometric determinations of H2O2 in plasma and blood. Our results indicate that contrary to previous reports in the literature the measured substance(s) in plasma or blood is not H2O2. Moreover, quantitative measurements of H2O2 in plasma or blood by HPLC was unreliable due to the irreversible binding of H2O2 to the column surface.

Animals↗