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Biomedical subjects

W M Zapol

Publications and source records attributed to W M Zapol.

At least 19 recordsLinked to original sources
PubMed1992

Inhaled nitric oxide in persistent pulmonary hypertension of the newborn.

Nitric oxide (NO) has vasodilatory effects on the pulmonary vasculature in adults and animals. We examined the effects on systemic oxygenation and blood pressure of inhaling up to 80 parts per million by volume of NO at FiO2 0.9 for up to 30 minutes by 6 infants with persistent pulmonary hypertension of the newborn (PPHN). In all infants this treatment rapidly and significantly increased preductal oxygen saturation (SpO2); in 5 infants postductal SpO2 and oxygen tensions also increased. Inhalation of NO did not cause systemic hypotension or raise methaemoglobin. These data suggest that low levels of inhaled NO have an important role in the reversal of hypoxaemia due to PPHN.

Administration, Inhalation↗
PubMed1992

Pulmonary vascular lesions in the adult respiratory distress syndrome caused by inhalation of zinc chloride smoke: a morphometric study.

Two soldiers were fatally injured by accidental inhalation of zinc chloride (ZnCl2) from a smoke bomb. Although exposed to a relatively short but high smoke concentration, acute injury was minor and for 10 days the patients were clinically satisfactory. Unexpectedly, both then rapidly developed features typical of severe adult respiratory distress syndrome with pulmonary hypertension. Intubation and mechanical ventilation were instigated on day 15 (patient no. 1) and day 12 (patient no. 2) after the inhalation, but death followed at days 25 and 32, respectively. Lung vascular injury was assessed by angiography and morphometric techniques. The lungs showed extensive interstitial and intra-alveolar space fibrosis. Vessels showed a significant lumen reduction by contracture (that is, reduction in vessel external diameter) affecting preacinar and intraacinar arterial and venous segments, the extent of injury suggesting that hexite causes more severe venous injury than seen in other types of adult respiratory distress syndrome. In microvessels there was obliteration and widespread occlusion by endothelial cell proliferation and clot. No evidence of infection was identified during life or at autopsy. It is unclear whether the long lag time was due to the fact that the infection was not a complicating event or because steroids, administered prophylactically, had sufficed to delay, but not to prevent, the amplification of injury that seems responsible for the adult respiratory distress syndrome.

Adult↗
PubMed1992

Effects of aminophylline on regional diaphragmatic shortening after thoracotomy in the awake lamb.

Aminophylline has been reported to augment diaphragmatic contraction, although this remains a controversial finding. We studied the effect of aminophylline on regional diaphragmatic shortening, changes in transdiaphragmatic pressure (delta Pdi), and integrated regional electromyographic (EMG) activity of the diaphragm (Edi) after a right thoracotomy in nine lambs using sonomicrometry, esophageal and gastric balloons, and EMG. Sonomicrometer crystals and EMG leads were implanted into the costal and crural regions of the diaphragm through a right thoracotomy, and a tracheostomy was performed. The animals were studied while awake within 4 days after surgery. Fractional costal and crural diaphragmatic shortening was measured using the sonomicrometer; delta Pdi was calculated from esophageal and gastric pressures. Respiratory variables were measured through the tracheostomy. Data were collected during quiet breathing and during CO2 rebreathing. After control measurements, aminophylline (10 mg/kg) was administered intravenously, producing a serum concentration of 17.7 +/- 1.5 micrograms/ml. Aminophylline did not augment shortening, increase delta Pdi, or overcome postoperative diaphragmatic inhibition acutely in the awake sheep after a right lateral thoracotomy. A small decrease of end-tidal CO2, from 5.2% to 4.9%, was measured at rest during aminophylline infusion, but Edi was unchanged. Although during CO2 rebreathing diaphragmatic shortening increased, the addition of aminophylline did not further augment shortening. Our data in awake lambs suggest that aminophylline does not improve diaphragmatic contraction in the acute postoperative period.

Aminophylline↗
PubMed1992

Binding and neutralization of endotoxin by Limulus antilipopolysaccharide factor.

In order to examine the ability of Limulus antilipopolysaccharide factor (LALF) to bind lipopolysaccharide (LPS), we purified LALF to homogeneity from Limulus amoebocyte lysate and coupled it covalently to agarose beads. LALF-coupled beads captured more tritiated LPS from rough and smooth strains of gram-negative bacteria than did control human serum albumin-coupled beads. Unlabeled homologous and heterologous LPS competed for the binding of 3H-LPS to LALF-coupled beads. LALF bound LPS in a dose-dependent manner as assessed by the precipitation of LPS-LALF complexes with 50% saturated ammonium sulfate. We also studied the ability of LALF to neutralize LPS. LPS preincubated with LALF was less mitogenic for murine splenocytes, was less pyrogenic in the rabbit fever assay, was less lethal in mice which had been sensitized to LPS with actinomycin D, and induced less fever, neutropenia, and pulmonary hypertension when infused into sheep. Our findings extend prior studies which suggested that LALF binds to and neutralizes LPS from multiple strains of gram-negative bacteria.

Animals↗
PubMed1992

Nitrogen tensions in brachial vein blood of Korean ama divers.

Intravascular bubble formation and symptoms of decompression sickness have been reported during repetitive deep breath-hold diving. Therefore we examined the pattern of blood N2 kinetics during and after repetitive breath-hold diving. To study muscle N2 uptake and release, we measured brachial venous N2 partial pressure (PN2) in nine professional Korean breath-hold divers (ama) during a 3-h diving shift at approximately 4 m seawater depth and up to 4 h after diving. PN2 was determined with the manometric Van Slyke method. Diving time and depth were recorded using a backpack computer-assisted dive longer that allowed calculating the surface-to-depth time ratio to derive the effective depth. With the assumption that forearm muscle N2 kinetics follow the general Haldanian principles of compression and decompression, i.e., forearm muscle is a single compartment with a uniform tissue PN2 equal to venous PN2, PN2 data were fitted to monoexponential functions of time. In the early phase of the diving shift, PN2 rapidly increased to 640 Torr (half time = 6 min) and then slowly declined to baseline levels (half time = 36 min) after the work shift. Peak PN2 levels approximated the alveolar PN2 derived from the effective depth. We conclude that forearm muscle N2 kinetics are well described by a Haldanian single-compartment model. Decompression sickness is theoretically possible in the ama; it did not occur because the absolute PN2 remained low due to the shallow working depth of the ama we studied.

Diving↗
PubMed1992

Role of platelet-activating factor in the ovine heparin-protamine reaction.

Platelet-activating factor (PAF) infusion into sheep, as well as protamine reversal of heparin anticoagulation, causes thromboxane release into plasma, pulmonary hypertension, hypoxemia, and leukopenia. We investigated the possible role of PAF in the heparin-protamine reaction. Intravenous protamine was administered to neutralize heparin anticoagulation in five awake sheep and caused an increase of mean pulmonary arterial pressure from 16.6 +/- 1 (SE) mmHg at base-line to 47 +/- 9 mmHg at 1 min after protamine injection (P < 0.01) because of a 4.5-fold increase of pulmonary vascular resistance. This neutralization reaction induced a 25% reduction of circulating leukocyte count and arterial PO2. Undetectable blood levels of PAF were measured by bioassay and high-performance liquid chromatography during these heparin-protamine reactions. Infusion of BN 52021 (20 mg/kg), a PAF receptor antagonist, before rechallenging the same sheep with heparin and then protamine did not reduce the level of peak pulmonary hypertension or the degree of hypoxemia and leukopenia. We conclude that the leukopenia and thromboxane-mediated pulmonary vasoconstriction occurring after rapid intravascular formation of heparin-protamine complexes in sheep are not due to the release of PAF.

Animals↗
PubMed1992

Bronchodilator action of inhaled nitric oxide in guinea pigs.

The effects of inhaling nitric oxide (NO) on airway mechanics were studied in anesthetized and mechanically ventilated guinea pigs. In animals without induced bronchoconstriction, breathing 300 ppm NO decreased baseline pulmonary resistance (RL) from 0.138 +/- 0.004 (mean +/- SE) to 0.125 +/- 0.002 cmH2O/ml.s (P less than 0.05). When an intravenous infusion of methacholine (3.5-12 micrograms/kg.min) was used to increase RL from 0.143 +/- 0.008 to 0.474 +/- 0.041 cmH2O/ml.s (P less than 0.05), inhalation of 5-300 ppm NO-containing gas mixtures produced a dose-related, rapid, consistent, and reversible reduction of RL and an increase of dynamic lung compliance. The onset of bronchodilation was rapid, beginning within 30 s after commencing inhalation. An inhaled NO concentration of 15.0 +/- 2.1 ppm was required to reduce RL by 50% of the induced bronchoconstriction. Inhalation of 100 ppm NO for 1 h did not produce tolerance to its bronchodilator effect nor did it induce substantial methemoglobinemia (less than 2%). The bronchodilating effects of NO were additive with the effects of inhaled terbutaline, irrespective of the sequence of NO and terbutaline administration. Inhaling aerosol generated from S-nitroso-N-acetylpenicillamine also induced a rapid and profound decrease of RL from 0.453 +/- 0.022 to 0.287 +/- 0.022 cmH2O/ml.s, which lasted for over 15 min in guinea pigs broncho-constricted with methacholine. Our results indicate that low levels of inhaled gaseous NO, or an aerosolized NO-releasing compound are potent bronchodilators in guinea pigs.

Aerosols↗
PubMed1991

Myocardial perfusion as assessed by thallium-201 scintigraphy during the discontinuation of mechanical ventilation in ventilator-dependent patients.

Patients who cannot be separated from mechanical ventilation (MV) after an episode of acute respiratory failure often have coexisting coronary artery disease. The authors hypothesized that increased left ventricular (LV) wall stress during periods of spontaneous ventilation (SV) could alter myocardial perfusion in these patients. Using thallium-201 (201TI) myocardial scintigraphy, the authors studied the occurrence of myocardial perfusion abnormalities during periods of SV in 15 MV-dependent patients (nine women, six men; aged 71 +/- 7 yr, mean +/- SD). Fourteen of these patients were studied once with 201TI myocardial scintigraphy during intermittent mechanical ventilation (IMV) and again on another day, after at least 10 min of SV through a T-piece. One patient was studied during SV only. Thirteen of 14 of the patients (93%) studied during MV had abnormal patterns of initial myocardial 201TI uptake, but only 1 patient demonstrated redistribution of 201TI on delayed images. The remainder of the abnormalities observed during MV were fixed defects. SV produced significant alterations of myocardial 201TI distribution or transient LV dilation, or both, in 7 of the 15 patients (47%). Four patients demonstrated new regional decreases of LV myocardial thallium concentration with redistribution of the isotope on delayed images. The patient studied only during SV also had myocardial 201TI defects with redistribution. Five patients (3 also having areas of 201TI redistribution) had transient LV dilation during SV.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep.

Nitric oxide (NO) has recently been discovered to be an important endothelium-derived relaxing factor and produces profound relaxation of vascular smooth muscle. To learn if NO could be a potent and selective pulmonary vasodilator, NO was inhaled by 16 awake lambs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by either the infusion of an exogenous pulmonary vasoconstrictor (the thromboxane analog U46619) or the endogenous release of thromboxane that occurs during the neutralization of heparin anticoagulation by protamine sulfate. Inhaling greater than or equal to 40 ppm of NO during a continuous U46619 infusion returned the PAP to a normal value, without affecting systemic blood pressure or vascular resistance. Pretreatment with the cyclooxygenase inhibitor indomethacin before infusing U46619 did not reduce the pulmonary vasodilatory effect of inhaled NO, and we conclude that the dilatory effect of NO on the lung's circulation is independent of cyclooxygenase products such as prostacyclin. Continuously inhaling NO at 180 ppm did not significantly reduce the mean peak thromboxane B2 concentration at 1 min after protamine injection; however, the mean values of pulmonary hypertension and vasoconstriction at 1 min were markedly reduced below the levels in untreated heparin-protamine reactions. Breathing NO at lower concentrations (40-80 ppm) did not decrease the mean peak PAP and PVR at 1 min after protamine but decreased the PAP and PVR values at 2, 3, and 5 min below those of control heparin-protamine reactions. Intravenous infusion of nitroprusside completely prevented the transient increase of PAP and PVR during the heparin-protamine reaction; however, marked concomitant systemic vasodilation occurred. Inhaled NO is a selective pulmonary vasodilator that can prevent thromboxane-induced pulmonary hypertension during the heparin-protamine reaction in lambs and can do so without causing systemic vasodilation.

Animals↗
PubMed1991

Leukotrienes, thromboxane A2, and prostaglandins during systemic anaphylaxis in sheep.

We investigated the roles of eicosanoid mediators in acute systemic anaphylaxis in anesthetized sheep. Sheep were sensitized with dinitrophenylated Ascaris suum extract and were challenged with an intravenous injection of dinitrophenylated bovine serum albumin. During anaphylaxis, cyclooxygenase inhibitors eliminated the elevation of arterial plasma levels of thromboxane B2 and 6-ketoprostaglandin F 1 alpha but markedly elevated the levels of leukotriene E4 in lung lymph without significantly eliminating elevation of plasma levels of histamine. Most of the measured physiological abnormalities accompanying anaphylaxis were aggravated by cyclooxygenase blockade. Enhancement of this anaphylactic mediator response was associated with an accentuated and prolonged increase of airway pressure (P less than 0.05, compared with sensitized, antigen-challenged but otherwise untreated sheep), a more intense hypoxemia (P less than 0.0001), and leukopenia (P less than 0.001), changes that were largely eliminated by pretreating with the sulfidopeptide leukotriene (SPLT) antagonist FPL 55712, suggesting that the SPLTs were important mediators of these responses. In contrast, the prolonged, but less severe, systemic vascular collapse and the reduced pulmonary hypertension induced by cyclooxygenase inhibitors were not influenced by the SPLT antagonist. These results demonstrate that in sheep cyclooxygenase metabolites are mainly involved in the acute, but transient, systemic and pulmonary vascular response of systemic anaphylaxis, whereas SPLTs are primarily implicated in the airway and secondary cardiovascular response. SPLT may act either directly or by potentiating the release of and reactivity to histamine and other mediators. Our data therefore suggest that a combination of cyclooxygenase and lipoxygenase inhibition will be necessary to more effectively protect against the consequences of an anaphylactic reaction.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction.

Background. The gas nitric oxide (NO) is an important endothelium-derived relaxing factor, inactivated by rapid combination with heme in hemoglobin. Methods and Results. Awake spontaneously breathing lambs inhaled 5-80 ppm NO with an acutely constricted pulmonary circulation due to either infusion of the stable thromboxane endoperoxide analogue U46619 or breathing a hypoxic gas mixture. Within 3 minutes after adding 40 ppm NO or more to inspired gas, pulmonary hypertension was reversed. Systemic vasodilation did not occur. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. During U46619 infusion pulmonary vasodilation was maintained up to 1 hour without tolerance. In the normal lamb, NO inhalation produced no hemodynamic changes. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels nor modify lung histology compared with control lambs. Conclusions. Low dose inhaled NO (5-80 ppm) is a selective pulmonary vasodilator reversing both hypoxia- and thromboxane-induced pulmonary hypertension in the awake lamb [corrected].

Administration, Inhalation↗
PubMed1990

Recombinant gene expression in pulmonary vascular endothelial cells: polarized secretion in vivo.

A unique, spontaneously immortalized rat pulmonary endothelial cell line was transfected with a human growth hormone (hGH) fusion gene generating a line of stably transfected cells that expresses high levels of hGH (Ec/XGH-1). These cells produced significant serum levels of hGH when implanted intraperitoneally, subcutaneously, or intravenously into nude mice. Implantation of Ec/XGH-1 cells under the renal capsule resulted in the formation of large cysts that contained concentrations of hGH that were several thousand times greater than those in serum assayed simultaneously from the same animals. This study presents a new technique for in vivo gene expression using a convenient line of pulmonary vascular endothelial cells as gene carriers. In addition, this system demonstrates the special physiological features of transfected endothelial cells in forming large cysts.

Animals↗
PubMed1990

Splenic contraction during breath-hold diving in the Korean ama.

Major increases of hemoglobin concentration and hematocrit, possibly secondary to splenic contraction, have been noted during diving in the Weddell seal. We sought to learn whether this component of the diving response could be present in professional human breath-hold divers. Splenic size was measured ultrasonically before and after repetitive breath-hold dives to approximately 6-m depth in ten Korean ama (diving women) and in three Japanese male divers who did not routinely practice breath-hold diving. Venous hemoglobin concentration and hematocrit were measured in nine of the ama and all Japanese divers. In the ama, splenic length and width were reduced after diving (P = 0.0007 and 0.0005, respectively) and calculated splenic volume decreased 19.5 +/- 8.7% (mean +/- SD, P = 0.0002). Hemoglobin concentration and hematocrit increased 9.5 +/- 5.9% (P = 0.0009) and 10.5 +/- 4% (P = 0.0001), respectively. In Japanese male divers, splenic size and hematocrit were unaffected by repetitive breath-hold diving and hemoglobin concentration increased only slightly over baseline (3.0 +/- 0.6%, P = 0.0198). Splenic contraction and increased hematocrit occur during breath-hold diving in the Korean ama.

Adult↗
PubMed1990

Neutralization of low molecular weight heparin by polybrene prevents thromboxane release and severe pulmonary hypertension in awake sheep.

Protamine reversal of heparin anticoagulation in patients is occasionally associated with life-threatening acute pulmonary hypertension. In a sheep model, we evaluated the effect on this adverse cardiopulmonary reaction of modifying the type of heparin (low molecular weight heparin compared with unfractionated heparin) and the type of heparin antagonist (polybrene compared with protamine). Protamine reversal of low molecular weight heparin (LMWH) and polybrene reversal of unfractionated heparin induced more than a 10-fold increase of plasma thromboxane B2 levels, a threefold increase of pulmonary vascular resistance and pulmonary artery pressure, and a 25% decrease of PaO2. A similar adverse reaction followed protamine reversal of conventional unfractionated heparin. However, with polybrene (1 mg/kg) reversal of LMWH (1 mg/kg), we measured neither pulmonary hypertension (pulmonary artery pressure was 22.6 +/- 3.6 mm Hg at 1 minute after polybrene reversal of LMWH compared with 47.9 +/- 4.2 mm Hg after protamine reversal of unfractionated heparin, p less than 0.005 groups differ), hypoxemia (PaO2 was unchanged 2 minutes after polybrene compared with a decrease of 26 mm Hg 2 minutes after protamine, p less than 0.05), nor acute release of thromboxane into arterial plasma (thromboxane B2 was 0.2 +/- 0.1 at 1 minute after polybrene compared with 3.7 +/- 1.7 ng/ml at 1 minute after protamine, p less than 0.005). The hemodynamic effects and mediator release were also benign after neutralization of larger doses of LMWH (3 mg/kg) by polybrene (3 mg/kg). The increases of activated clotting time and activated partial thromboplastin time due to both types of heparin were completely reversed with polybrene. Anti-Xa activity increased to more than 3 IU/ml 4 minutes after LMWH anticoagulation (p less than 0.01) but was only partially neutralized by polybrene. Various polyanion-polycation complexes that are formed when heparin anticoagulation is reversed induce thromboxane release and acute pulmonary vasoconstriction in awake sheep. Reversal of LMWH anticoagulation with polybrene does not elicit this adverse reaction.

Animals↗
PubMed1990

Thromboxane receptor blockade prevents pulmonary hypertension induced by heparin-protamine reactions in awake sheep.

We used competitive thromboxane A2-prostaglandin endoperoxide receptor blockade (SQ 30,741) as a probe to evaluate the role of thromboxane in ovine pulmonary vasoconstriction associated with protamine reversal of heparin anticoagulation. Control heparin-protamine reactions induced rapid release of thromboxane into arterial plasma (more than 1 ng/ml plasma), a 2.5-fold increase of pulmonary artery pressure, a 20% decrease of PaO2, and a 30% reduction in arterial white blood cell concentration. After giving SQ 30,741 despite similar thromboxane release into arterial plasma after heparin-protamine challenge, acute pulmonary hypertension was significantly reduced when 94% of pulmonary vascular smooth muscle thromboxane receptors were occupied with SQ 30,741 (p less than 0.01 at 1 minute after protamine versus control heparin-protamine reaction) and was completely abolished by a 10 mg/kg i.v. bolus (p less than 0.0001 at 1 minute after protamine versus control). Peripheral leukopenia was not affected by SQ 30,741 prophylaxis, but hypoxemia was prevented. We conclude that thromboxane causes pulmonary vasoconstriction in ovine heparin-protamine-induced pulmonary hypertension. Pulmonary vasoconstriction and hypoxemia can be completely prevented by thromboxane receptor blockade.

Animals↗