Biomedical subjects
S A Lang
Publications and source records attributed to S A Lang.
Changes in PETCO2 and pulmonary blood flow after bronchial occlusion in dogs.
The use of PETCO2 in detecting accidental bronchial intubation was investigated. The PETCO2 was measured in six mongrel dogs after occluding the left mainstem bronchus in three conditions; pentobarbital anaesthesia, 0.8% halothane insufflation together with pentobarbital anaesthesia, and simultaneous left pulmonary artery and bronchial airway occlusion with intravenous pentobarbital anaesthesia. An external flow probe measured left pulmonary artery blood flow. The PETCO2 decreased after bronchial occlusion during pentobarbital (35 +/- 3 vs 30 +/- 5 mmHg) and halothane-pentobarbital (30 +/- 6 vs 25 +/- 6 mmHg) conditions (P less than 0.05). However, within three minutes of bronchial occlusion, the values of PETCO2 had returned to their pre-occlusion values. After five minutes of bronchial occlusion pulmonary artery blood flow in the non-ventilated lung decreased (P less than 0.05) during pentobarbital (770 +/- 533 ml.min-1 vs 575 +/- 306 ml.min-1) and halothane-pentobarbital (495 +/- 127 ml.min-1 vs 387 +/- 178 ml.min-1) conditions. Simultaneous bronchial and pulmonary artery occlusion prevented any changes in PETCO2. It was concluded that accidental one-lung ventilation results in small and transient decreases in PETCO2. A redistribution of blood flow from the non-ventilated to ventilated lung occurs which restores PETCO2 to the original values observed with two-lung ventilation.
Castable glass ceramics for veneer restorations.
Porcelain veneer restorations are the usual technique chosen for the placement of esthetic veneer restorations. Cast glass ceramic veneers exhibit properties that make them extremely useful for this dental application. They have a hardness, abrasion resistance, coefficient of thermal expansion, and translucency similar to that of enamel. The use of the lost wax casting technique to provide precise anatomic form and margins allows for increased accuracy during veneer fabrication. Chairside time requirements may be decreased as a result of the improved accuracy inherent in the lost wax casting technique. The dentist's ability to maximize esthetics and decrease chairside time make this a technique likely to see increased use in the future.
Effect of extreme elevations in venous pressure on reflection coefficient in the lung.
We determined whether the solvent drag reflection coefficient (sigma f) for total proteins of a canine perfused left lower lung lobe (LLL) preparation decreases at elevated venous pressures (Pv). We found that sigma f (estimated using the hematocrit-protein technique) remained constant at all Pv's (30-95 mm Hg) evaluated. These results were unanticipated, since previous studies reported increases in protein permeability at Pv's within this range. We conducted two additional studies to better understand the basis for these observations. In the first, we evaluated the effect of high Pv (85 mm Hg) on sigma f of a canine perfused forelimb preparation and found sigma f to be reduced. This difference in response suggests that the normal sigma f's observed in the LLL were not due to high Pv per se, but rather that there is some intrinsic difference between the pulmonary and the systemic circulations that accounts for the difference. The second study was designed to determine whether the normal sigma f's observed in the LLL at high Pv's provide meaningful information about pulmonary vascular endothelial permeability. We damaged LLL's with alloxan, oleic acid, or HCl and obtained near normal estimates of sigma f at high Pv. These results indicated that it is not possible to easily distinguish between a normal and a damaged pulmonary vasculature when sigma f is measured at high Pv. We suggest that the normal estimates of sigma f obtained at high Pv in the LLL results from an increased fraction of the transvascular flow occurring through pathways that exclude macromolecules.
Comparisons of anti-human immunodeficiency virus activities, cellular transport, and plasma and intracellular pharmacokinetics of 3'-fluoro-3'-deoxythymidine and 3'-azido-3'-deoxythymidine.
3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady-state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration-time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels.
Circulating neuropeptide Y does not produce pulmonary hypertension during massive sympathetic activation.
We tested the possibility that neuropeptide Y (NPY) may contribute to the pulmonary hypertension that occurs after massive sympathetic activation produced by intracisternal veratrine administration in the chloralose-anesthetized dog. In six dogs, veratrine caused arterial NPY-like immunoreactivity (NPY-LI) to rise from 873 +/- 150 (SE) pg/ml to peak values of 3,780 +/- 666 pg/ml by 60-120 min. (In 3 animals, adrenalectomy significantly reduced the increases in NPY-LI.) In five additional dogs, we infused porcine NPY for 30 min in doses that increased arterial NPY-LI to 8,354 +/- 1,514 pg/ml and observed only minor changes in pulmonary hemodynamics. In three isolated perfused canine left lower lung lobe (LLL) preparations, increasing doses of NPY were administered, producing levels of plasma NPY-LI, at the highest dose, that exceeded those observed after veratrine administration by three orders of magnitude. No changes in LLL arterial or double-occlusion capillary pressures were observed at any dose. Similarly, no changes in LLL hemodynamics were observed in three additional lobes when NPY was administered while norepinephrine was being infused. We conclude that it is unlikely that NPY plays a role as a circulating vasoactive agent in producing the pulmonary hypertension and edema that occur in this model.
Surgery for mediastinal masses.
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Hemodynamic basis for cocaine-induced pulmonary edema in dogs.
We tested the hypothesis that cocaine-induced impairment of left ventricular function results in cardiogenic pulmonary edema. Mongrel dogs, anesthetized with alpha-chloralose, were injected with two doses of cocaine (5 mg/kg iv) 27 min apart. Cocaine produced transient decreases in aortic and left ventricular systolic pressures that were followed by increases exceeding control. As aortic pressure recovered, left ventricular end-diastolic, left atrial (Pla), pulmonary arterial (Ppa), and central venous pressures rose. Cardiac output and stroke volume were reduced when measured 4-5 min after cocaine administration. Peak Ppa and Pla were 31 +/- 5 (SE) mmHg (range 17-51 mmHg) and 26 +/- 5 mmHg (range 12-47 mmHg), respectively. Increases in extravascular lung water content (4.10 to 6.24 g H2O/g dry lung wt) developed in four animals in which Pla exceeded 30 mmHg. Analysis of left ventricular function curves revealed that cocaine depressed the inotropic state of the left ventricle. Cocaine-induced changes in hemodynamics spontaneously recovered and could be elicited again by the second dose of the drug. Our results show that cocaine-induced pulmonary hypertension, associated with decreased left ventricular function, produces pulmonary edema if pulmonary vascular pressures rise sufficiently.
Pulmonary oedema associated with airway obstruction.
The purpose of this review is to describe the pathogenesis of pulmonary oedema associated with upper airway obstruction, summarize what is known of its clinical presentation, and reflect upon its implications for the clinical management of airway obstruction. The pathogenesis of pulmonary oedema associated with upper airway obstruction is multifactorial. However, as the phrase "negative pressure pulmonary oedema" suggests, markedly negative intrapleural pressure is the dominant pathophysiological mechanism involved in the genesis of pulmonary oedema associated with upper airway obstruction. The frequency of the event is impossible to ascertain from the literature but paediatric cases requiring airway intervention for croup or epiglottitis and adults requiring airway intervention for emergence laryngospasm or upper airway tumours account for over 50 per cent of the documented cases in each age group, respectively. Individuals at risk should be observed closely while they remain at risk. The majority of cases present within minutes either of the development of acute severe upper airway obstruction or of relief of the obstruction. Resolution is typically rapid, over a period of a few hours. Rarely is anything more required for management than the maintenance of a patent airway, supplemental oxygen, and, in approximately 50 per cent of cases, mechanical ventilation and positive end-expiratory pressure.
Role of hemodynamics and vagus nerves in development of fibrin-induced pulmonary edema.
The rapid development of pulmonary edema that may occur in the rabbit after the intracisternal injection of a mixture of fibrinogen and thrombin has classically been considered to result from a vagally mediated increase in vascular permeability (G. R. Cameron and S. N. De, J. Pathol. Bacteriol 61: 375, 1949) and to not be dependent on hemodynamic mechanisms. We tested this hypothesis by evaluating the relationship between the degree of pulmonary hypertension and postmortem extravascular lung water content (EVLW) in both nonvagotomized (n = 10) and vagotomized (n = 7) rabbits administered thrombin (0.1 ml, 500 U/ml) and fibrinogen (1 ml, 27 mg/ml) intracisternally. No increase in EVLW was observed in either group unless pulmonary arterial pressure (Ppa) exceeded 25 Torr, and large increases in EVLW were only observed at higher Ppa's. These results thus indicate that some degree of pulmonary hypertension is required for the development of this form of edema. Because the vascular pressure required to produce edema in this model approaches that required to increase pulmonary vascular permeability in the rabbit, a pressure-dependent increase in permeability may be a common characteristic of neurogenic pulmonary edema in this species. Vagotomy had no protective effect but instead appeared to increase the amount of edema development for a given degree of pulmonary hypertension.
Insignificant bilateral convergence of preganglionic vagal fibers on postganglionic neurons to the canine heart.
We determined the extent of convergence of preganglionic fibers from the right and left vagus nerves on postganglionic neurons that supply the sinoatrial node in chloralose-anesthetized dogs. We administered hemicholinium-3 and stimulated the right vagus nerve at a high frequency to deplete acetylcholine from the postganglionic parasympathetic neurons supplied by that nerve. We compared the effects of this "depletion regimen" with the responses in two control groups: a stimulation control group, which was subjected to high-frequency right vagus stimulation only, and a drug control group, which received a hemicholinium-3 infusion only. The effects of right vagus stimulation did not differ from those of left vagus stimulation in either of the control groups. In the animals subjected to the depletion regimen, the responses to right vagus stimulation were almost abolished. However, the left vagus nerve retained its ability to prolong cardiac cycle length in these animals. Thus, our experiments indicate that left vagus preganglionic fibers do not converge with right vagus preganglionic fibers on a substantial pool of postganglionic neurons that innervate the canine sinoatrial node.
Endobronchial intubation in dogs.
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Synthesis and in vitro antibacterial activity of some 1-(difluoromethoxyphenyl)quinolone-3-carboxylic acids.
We report on the synthesis of N-1-phenylquinolones in which the difluoromethoxy moiety is utilized as a halogen replacement. The antibacterial activity is discussed with reference to N-1-halophenylquinolones.
Water-soluble third generation antitumor platinum complexes, [2,2-bis (aminomethyl)-1,3-propanediol-N,N']-[1,1-cyclobutanedicarboxylato (2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylato(2-)-O,O'] [tetrahydro-4H-pyran-4,4-dimethanamine-N,N']platinum(II).
The synthesis, stability, and antitumor activity of a series of water-soluble third generation platinum(II) complexes have been described. Among these complexes, [2,2-bis(aminomethyl)-1,3- propanediol-N,N'] [1,1-cyclobutanedicarboxylato(2-)-O,O']platinum(II) and [1,1-cyclobutanedicarboxylate(2-)-O,O'](tetrahydro-4H-pyran-4,4- dimethanamine-N,N'-)platinum(II) have shown the greatest promise for further investigation and are currently under clinical evaluation.
A new family of water-soluble, third generation antitumor platinum complexes.
[1,1-Cyclobutanedicarboxylato(2)-O,O'](1,3-dioxane-5,5-dimethan amine- N,N')platinum(II), 3a, a third generation, very water-soluble platinum complex, has been synthesized along with several of its analogues. All members of the new family contain a 1,3-dioxane or 1,3-dioxolane-1,3-diamine as their basic ligand, a moiety which contributes to their increased water solubility, and a bidentate acid ligand, which is responsible for their good stability. They were all easily crystallized and characterized by 1H NMR and elemental analysis, and the parent complex 3a was further characterized by 13C NMR. Their very desirable physical properties combined with their broad spectrum of antitumor activity and reduced toxicity make them good candidates of further development.
Oxygen consumption after massive sympathetic nervous system discharge.
We evaluated the possibility that massive, sympathetic nervous system (SNS) activation [as may precede the development of neurogenic pulmonary edema (NPE)] increases O2 demand. O2 consumption (VO2) and plasma concentrations of the calorigenic agents, epinephrine (EPI) and norepinephrine (NE) were measured in alpha-chloralose-anesthetized dogs under control conditions and for 3 h after the administration of either 1) intracisternal (ic) veratrine to activate the SNS, 2) intravenous (iv) veratrine, 3) ic saline, or 4) ic veratrine, after clamping the adrenal blood vessels. VO2 increased 31.7 +/- 3.6% (SE), and EPI and NE increased to, respectively, 30,853 +/- 8,347 and 8,176 +/- 2,104 pg/ml in the ic veratrine group. No increases in VO2 and EPI and attenuated increases in NE were observed in the ic veratrine animals with clamped adrenals. No significant increases in VO2 or catecholamine concentrations were observed after ic saline or iv veratrine administration. These data suggest that the elevated VO2 may have been mediated by adrenal catecholamines and that an increased metabolic rate may complicate the ability of patients with severe NPE to balance O2 supply with demand.
Effects of vagus nerve on heart rate and ventricular contractility in chicken.
We determined the effects of vagus nerve stimulation on cardiac cycle length and on ventricular contraction and relaxation in 18 chickens anesthetized with pentobarbital. Right vagus stimulation at a constant frequency of 35 Hz prolonged cycle length by 190%, whereas left vagus stimulation at the same frequency increased cycle length by 136%. When one burst of stimuli was delivered to the right vagus nerve each cardiac cycle, but the timing of the stimuli was changed within the cardiac cycle, the response of the avian pacemaker cells varied substantially with the timing of the stimuli. Right and left vagus stimulation at a constant frequency of 20 Hz depressed ventricular contraction by 62 +/- 6 and 52 +/- 6%, respectively, and depressed ventricular relaxation by 56 +/- 7 and 53 +/- 7%, respectively. These results indicate that in the chicken the chronotropic effects of right vagus stimulation are greater than those of left vagus stimulation, whereas right and left vagus stimulation are approximately equipotent on ventricular contraction and relaxation.