35 results on '"Zapol, W"'
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2. INHALED NITRIC OXIDE DOES NOT ALTER ENDOTOXIN-INDUCED NITRIC OXIDE SYNTHASE ACTIVITY DURING PERFUSION OF THE ISOLATED RAT LUNG
- Author
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Kurrek, M. M., primary, Castillo, L., additional, Bloch, K. D., additional, Tannenbaum, S. R., additional, Hurford, W. E., additional, and Zapol, W. M., additional
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- 1994
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3. A COMPARISON OF INHALED NITRIC OXIDE AND HALOTHANE AS A BRONCHODILATOR IN METHACHOLINE CONSTRICTED GUINEA PIGS
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Kim, K., primary, Dupuy, P. M., additional, Stanek, K., additional, and Zapol, W. M., additional
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- 1992
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4. EFFECTS OF INHALED NITRIC OXIDE AND L-NAME ON INTRAPULMONARY SHUNTING IN AN OVINE LAVAGE ARDS MODEL
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Rovira, I., primary, Chen, T. Y., additional, Greene, E., additional, and Zapol, W. M., additional
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- 1992
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5. INHALED NITRIC OXIDE DILATES HUMAN HYPOXIC PULMONARY VASOCONSTRICTION WITHOUT CAUSING SYSTEMIC VASODILATION
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Frostell, C., primary, Blomqvist, H., additional, Lundberg, J., additional, Hedenstierna, G., additional, and Zapol, W., additional
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- 1991
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6. EFFECT OF THROMBOXANE SYNTHESIS INHIBITION DURING ANAPHYLAXIS IN SHEEP
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Morel, D. R., primary, Skoskiewicz, M., additional, Nguyenduy, T., additional, Melvin, C., additional, Robinson, D. R., additional, Bloch, K. J., additional, Zapol, W. M., additional, and Lowenstein, E., additional
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- 1986
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7. EFFECT OF THEOPHYLLINE ON COSTAL AND CRURAL DIAPHRAGMATIC SHORTENING IN THE AWAKE SHEEP
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Polaner, D., primary, Kimball, W., additional, Fratacci, M., additional, Kacmarek, R., additional, and Zapol, W., additional
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- 1989
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8. VENTRICULAR INTERACTION DURING ACUTE PROGRESSIVE PULMONARY HYPERTENSION IN DOGS
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Hurford, W. E., primary, Barlai-Kovaoh, M., additional, Strauss, H. W., additional, Zapol, W. M., additional, and Lowenstein, E., additional
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- 1985
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9. ACUTE PULMONARY SEQUESTRATION OF WHITE BLOOD CELLS PRODUCED BY IV BOLUS ADMINISTRATION OF PROTAMINE AFTER CPB
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Morel, D. R., primary, Kitain, E., additional, Purcell, M. H., additional, Thomas, S. J., additional, Zapol, W. M., additional, and Lowenstein, E., additional
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- 1984
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10. Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of acute respiratory distress syndrome.
- Author
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Adrie C, Holzmann A, Hirani WM, Zapol WM, and Hurford WE
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- Administration, Inhalation, Analysis of Variance, Animals, Bronchodilator Agents administration & dosage, Dose-Response Relationship, Drug, Drug Synergism, Infusions, Intravenous, Models, Biological, Nitric Oxide administration & dosage, Phosphodiesterase Inhibitors administration & dosage, Purinones administration & dosage, Sheep, Bronchodilator Agents therapeutic use, Hemodynamics drug effects, Nitric Oxide therapeutic use, Phosphodiesterase Inhibitors therapeutic use, Pulmonary Gas Exchange drug effects, Purinones therapeutic use, Respiratory Distress Syndrome drug therapy
- Abstract
Background: Inhaled nitric oxide (No) selectively dilates the pulmonary vasculature and improves gas exchange in acute respiratory distress syndrome. Because of the very short half-life of NO, inhaled NO is administered continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the efficacy and prolongs the duration of action of inhaled NO in models of acute pulmonary hypertension. Its efficacy in lung injury models is uncertain. The authors hypothesized that the use of intravenous Zaprinast would have similar beneficial effects when used in combination with inhaled NO to improve oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung injury., Methods: The authors studied two groups of sheep with lung injury produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO were administered in a random order before and after an intravenous Zaprinast infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group, inhaled NO was administered at the same concentrations before and after an intravenous infusion of Zaprinast solvent (0.05 m NaOH)., Results: After lavage, inhaled NO decreased pulmonary arterial pressure and resistance with no systemic hemodynamic effects, increased arterial oxygen partial pressure, and decreased venous admixture (all P < 0.05). The intravenous administration of Zaprinast alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05). Zaprinast infusion abolished the beneficial ability of inhaled NO to improve pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs. control)., Conclusions: This study suggests that nonselective vasodilation induced by intravenously administered Zaprinast at the dose used in our study not only worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.
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- 2000
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11. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension.
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Weimann J, Ullrich R, Hromi J, Fujino Y, Clark MW, Bloch KD, and Zapol WM
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- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid, 3',5'-Cyclic-GMP Phosphodiesterases, Acute Disease, Animals, Blood Pressure drug effects, Cyclic GMP blood, Cyclic Nucleotide Phosphodiesterases, Type 5, Enzyme Inhibitors pharmacology, Hypertension, Pulmonary chemically induced, Hypertension, Pulmonary physiopathology, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide pharmacology, Nitric Oxide physiology, Nitric Oxide Synthase antagonists & inhibitors, Piperazines antagonists & inhibitors, Pulmonary Artery drug effects, Pulmonary Artery physiopathology, Purines, Purinones pharmacology, Sheep, Sildenafil Citrate, Sulfones, Vascular Resistance drug effects, Vasoconstrictor Agents pharmacology, Vasodilator Agents antagonists & inhibitors, Wakefulness, Hypertension, Pulmonary drug therapy, Phosphodiesterase Inhibitors pharmacology, Phosphoric Diester Hydrolases metabolism, Piperazines pharmacology, Pulmonary Circulation drug effects, Vasodilator Agents pharmacology
- Abstract
Background: Phosphodiesterase type 5 (PDE5) hydrolyzes cyclic guanosine monophosphate in the lung, thereby modulating nitric oxide (NO)/cyclic guanosine monophosphate-mediated pulmonary vasodilation. Inhibitors of PDE5 have been proposed for the treatment of pulmonary hypertension. In this study, we examined the pulmonary and systemic vasodilator properties of sildenafil, a novel selective PDE5 inhibitor, which has been approved for the treatment of erectile dysfunction., Methods: In an awake lamb model of acute pulmonary hypertension induced by an intravenous infusion of the thromboxane analog U46619, we measured the effects of 12.5, 25, and 50 mg sildenafil administered via a nasogastric tube on pulmonary and systemic hemodynamics (n = 5). We also compared the effects of sildenafil (n = 7) and zaprinast (n = 5), a second PDE5 inhibitor, on the pulmonary vasodilator effects of 2.5, 10, and 40 parts per million inhaled NO. Finally, we examined the effect of infusing intravenous l-NAME (an inhibitor of endogenous NO production) on pulmonary vasodilation induced by 50 mg sildenafil (n = 6)., Results: Cumulative doses of sildenafil (12.5, 25, and 50 mg) decreased the pulmonary artery pressure 21%, 28%, and 42%, respectively, and the pulmonary vascular resistance 19%, 23%, and 45%, respectively. Systemic arterial pressure decreased 12% only after the maximum cumulative sildenafil dose. Neither sildenafil nor zaprinast augmented the ability of inhaled NO to dilate the pulmonary vasculature. Zaprinast, but not sildenafil, markedly prolonged the duration of pulmonary vasodilation after NO inhalation was discontinued. Infusion of l-NAME abolished sildenafil-induced pulmonary vasodilation., Conclusions: Sildenafil is a selective pulmonary vasodilator in an ovine model of acute pulmonary hypertension. Sildenafil induces pulmonary vasodilation via a NO-dependent mechanism. In contrast to zaprinast, sildenafil did not prolong the pulmonary vasodilator action of inhaled NO.
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- 2000
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12. Congenital NOS2 deficiency protects mice from LPS-induced hyporesponsiveness to inhaled nitric oxide.
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Weimann J, Bloch KD, Takata M, Steudel W, and Zapol WM
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- Administration, Inhalation, Animals, Body Weight drug effects, Cyclic GMP analogs & derivatives, Cyclic GMP pharmacology, Escherichia coli, In Vitro Techniques, Lung anatomy & histology, Lung blood supply, Lung drug effects, Male, Mice, Mice, Inbred C57BL, Nitric Oxide administration & dosage, Nitric Oxide Synthase genetics, Nitric Oxide Synthase Type II, Organ Size drug effects, Respiration, Artificial, Thionucleotides pharmacology, Endotoxins toxicity, Lipopolysaccharides toxicity, Nitric Oxide pharmacology, Nitric Oxide Synthase deficiency, Vasodilation drug effects
- Abstract
Background: In animal models, endotoxin (lipopolysaccharide) challenge impairs the pulmonary vasodilator response to inhaled nitric oxide (NO). This impairment is prevented by treatment with inhibitors of NO synthase 2 (NOS2), including glucocorticoids and L-arginine analogs. However, because these inhibitors are not specific for NOS2, the role of this enzyme in the impairment of NO responsiveness by lipopolysaccharide remains incompletely defined., Methods: To investigate the role of NOS2 in the development of lipopolysaccharide-induced impairment of NO responsiveness, the authors measured the vasodilator response to inhalation of 0.4, 4, and 40 ppm NO in isolated, perfused, and ventilated lungs obtained from lipopolysaccharide-pretreated (50 mg/kg intraperitoneally 16 h before lung perfusion) and untreated wild-type and NOS2-deficient mice. The authors also evaluated the effects of breathing NO for 16 h on pulmonary vascular responsiveness during subsequent ventilation with NO., Results: In wild-type mice, lipopolysaccharide challenge impaired the pulmonary vasodilator response to 0.4 and 4 ppm NO (reduced 79% and 45%, respectively, P < 0.001), but not to 40 ppm. In contrast, lipopolysaccharide administration did not impair the vasodilator response to inhaled NO in NOS2-deficient mice. Breathing 20 ppm NO for 16 h decreased the vasodilator response to subsequent ventilation with NO in lipopolysaccharide-pretreated NOS2-deficient mice, but not in lipopolysaccharide-pretreated wild-type, untreated NOS2-deficient or untreated wild-type mice., Conclusions: In response to endotoxin challenge, NO, either endogenously produced by NOS2 in wild-type mice or added to the air inhaled by NOS2-deficient mice, is necessary to impair vascular responsiveness to inhaled NO. Prolonged NO breathing, without endotoxin, does not impair vasodilation in response to subsequent NO inhalation. These results suggest that NO, plus other lipopolysaccharide-induced products, are necessary to impair responsiveness to inhaled NO in a murine sepsis model.
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- 1999
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13. Inhaled nitric oxide: basic biology and clinical applications.
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Steudel W, Hurford WE, and Zapol WM
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- Administration, Inhalation, Animals, Bronchodilator Agents chemistry, Clinical Trials as Topic, Drug Interactions, Humans, Hypertension, Pulmonary drug therapy, Nitric Oxide metabolism, Nitric Oxide therapeutic use, Bronchodilator Agents administration & dosage, Nitric Oxide administration & dosage, Nitric Oxide chemistry
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- 1999
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14. Inhibition of nitric oxide synthase prevents hyporesponsiveness to inhaled nitric oxide in lungs from endotoxin-challenged rats.
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Holzmann A, Manktelow C, Taut FJ, Bloch KD, and Zapol WM
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- Administration, Inhalation, Animals, Dexamethasone pharmacology, Guanidines pharmacology, Isoproterenol pharmacology, Nitric Oxide Synthase Type II, Perfusion, Rats, Rats, Sprague-Dawley, Enzyme Inhibitors pharmacology, Lipopolysaccharides toxicity, Lung drug effects, Nitric Oxide administration & dosage, Nitric Oxide Synthase antagonists & inhibitors
- Abstract
Background: Inhalation of nitric oxide (NO) selectively dilates the pulmonary circulation and improves arterial oxygenation in patients with adult respiratory distress syndrome (ARDS). In approximately 60% of patients with septic ARDS, minimal or no response to inhaled NO is observed. Because sepsis is associated with increased NO production by inducible NO synthase (NOS2), the authors investigated whether NOS inhibition alters NO responsiveness in rats exposed to gram-negative lipopolysaccharide (LPS)., Methods: Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli O111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured., Results: Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75+/-0.25, 1.25+/-0.25, 1.75+/-0.25 mmHg) than in lungs of control rats (3+/-0.5, 4.25+/-0.25, 4.5+/-0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75+/-0.25, 4.5+/-0.25, 4.5+/-0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0+/-1.0, 4.0+/-1.0, 4.0+/-0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75+/-0.25, 2.25+/-0.5, 2.75+/-0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness., Conclusion: These observations demonstrate that LPS-mediated increases in pulmonary NOS2 are involved in decreasing responsiveness to inhaled NO.
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- 1999
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15. Selective pulmonary vasodilation induced by aerosolized zaprinast.
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Ichinose F, Adrie C, Hurford WE, Bloch KD, and Zapol WM
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- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid adverse effects, Administration, Inhalation, Aerosols, Animals, Cyclic GMP blood, Dose-Response Relationship, Drug, Drug Combinations, Hemodynamics drug effects, Hypertension, Pulmonary chemically induced, Nitric Oxide administration & dosage, Phosphodiesterase Inhibitors administration & dosage, Pulmonary Circulation drug effects, Purinones administration & dosage, Sheep, Vasoconstrictor Agents adverse effects, Lung drug effects, Nitric Oxide pharmacology, Phosphodiesterase Inhibitors pharmacology, Purinones pharmacology, Vasodilation drug effects
- Abstract
Background: Zaprinast, an inhibitor of guanosine-3',5'-cyclic monophosphate (cGMP)-selective phosphodiesterase, augments smooth muscle relaxation induced by endothelium-dependent vasodilators (including inhaled nitric oxide [NO]). The present study was designed to examine the effects of inhaled nebulized zaprinast, alone, and combined with inhaled NO., Methods: Eight awake lambs with U46619-induced pulmonary hypertension sequentially breathed two concentrations of NO (5 and 20 ppm), followed by inhalation of aerosols generated from solutions containing four concentrations of zaprinast (10, 20, 30, and 50 mg/ml). The delivered doses of nebulized zaprinast at each concentration (mean +/- SD) were 0.23 +/- 0.06, 0.49 +/- 0.14, 0.71 +/- 0.24, and 1.20 +/- 0.98 mg x kg(-1) x min(-1), respectively. Each lamb also breathed NO (5 and 20 ppm) and zaprinast (0.23 +/- 0.06 mg x kg[-1] x min[-1]) in combination after a 2-h recovery period., Results: Inhaled NO selectively dilated the pulmonary vasculature. Inhaled zaprinast selectively dilated the pulmonary circulation and potentiated and prolonged the pulmonary vasodilating effects of inhaled NO. The net transpulmonary release of cGMP was increased by inhalation of NO, zaprinast, or both. The duration of the vasodilation induced by zaprinast inhalation was greater than that induced by NO inhalation., Conclusions: Aerosolization of a cGMP-selective phosphodiesterase inhibitor alone or combined with NO may be a useful noninvasive therapeutic method to treat acute or chronic pulmonary hypertension.
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- 1998
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16. Selective pulmonary vasodilation by intravenous infusion of an ultrashort half-life nucleophile/nitric oxide adduct.
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Adrie C, Hirani WM, Holzmann A, Keefer L, Zapol WM, and Hurford WE
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- 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid pharmacology, Animals, Infusions, Intravenous, Nitric Oxide administration & dosage, Nitrogen Oxides, Nitroprusside pharmacology, Proline administration & dosage, Proline pharmacology, Sheep, Hypertension, Pulmonary drug therapy, Nitric Oxide pharmacology, Proline analogs & derivatives, Vasodilation drug effects
- Abstract
Background: PROLI/NO (C5H7N3O4Na2 x CH3OH) is an ultrashort-acting nucleophile/NO adduct that generates NO (half-life 2 s at 37 degrees C and pH 7.4). Because of its short half-life, the authors hypothesized that intravenous administration of this compound would selectively dilate the pulmonary vasculature but cause little or no systemic hypotension., Methods: In eight awake healthy sheep with pulmonary hypertension induced by 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha, the authors compared PROLI/NO with two reference drugs-inhaled NO, a well-studied selective pulmonary vasodilator, and intravenous sodium nitroprusside (SNP), a nonselective vasodilator. Sheep inhaled 10, 20, 40, and 80 parts per million NO or received intravenous infusions of 0.25, 0.5, 1, 2, and 4 microg x kg-1 x min-1 of SNP or 0.75, 1.5, 3, 6, and 12 microg x kg-1 x min-1 of PROLI/NO. The order of administration of the vasoactive drugs (NO, SNP, PROLI/NO) and their doses were randomized., Results: Inhaled NO selectively dilated the pulmonary vasculature. Intravenous SNP induced nonselective vasodilation of the systemic and pulmonary circulation. Intravenous PROLI/NO selectively vasodilated the pulmonary circulation at doses up to 6 microg x kg-1 x min-1, which decreased pulmonary vascular resistance by 63% (P < 0.01) from pulmonary hypertensive baseline values without changing systemic vascular resistance. At 12 microg x kg-1 x min-1, PROLI/NO decreased systemic and pulmonary vascular resistance and pressure. Exhaled NO concentrations were higher during PROLI/NO infusion than during SNP infusion (P < 0.01 with all data pooled)., Conclusions: The results suggest that PROLI/NO could be a useful intravenous drug to vasodilate the pulmonary circulation selectively.
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- 1998
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17. Effects of targeted neuronal nitric oxide synthase gene disruption and nitroG-L-arginine methylester on the threshold for isoflurane anesthesia.
- Author
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Ichinose F, Huang PL, and Zapol WM
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- Amino Acid Oxidoreductases antagonists & inhibitors, Amino Acid Oxidoreductases genetics, Animals, Arginine pharmacology, Female, Ketamine pharmacology, Male, Mice, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase, Amino Acid Oxidoreductases deficiency, Anesthesia, Arginine analogs & derivatives, Isoflurane pharmacology, Neurons enzymology, Nitric Oxide physiology
- Abstract
Background: Considerable evidence suggests that nitric oxide plays a role in synaptic transmission in the central and peripheral nervous system. Nonselective inhibition of nitric oxide synthase by nitroG-L-arginine methylester (L-NAME) reduces the minimum alveolar concentration of halothane anesthesia. The effects of selective neuronal nitric oxide synthase inhibition on the anesthetic requirements in mice congenitally deficient in neuronal nitric oxide synthase (knockout mice) were examined., Methods: Isoflurane minimum alveolar concentration and righting reflex ED50 (RRED50) were determined in knockout and wild-type mice. Subsequently, the effects of intraperitoneal L-NAME on minimum alveolar concentration and RRED50 of knockout and wild-type mice were examined. In a separate experiment, the effects of week-long administration of L-NAME were examined in wild-type mice. Isoflurane minimum alveolar concentration and RRED50 were measured on the 8th day and were repeated after an acute intraperitoneal dose of L-NAME., Results: Targeted disruption of the neuronal nitric oxide synthase gene did not modify isoflurane minimum alveolar concentration and RRED50 of knockout mice. Acute intraperitoneal L-NAME decreased the minimum alveolar concentration and RRED50 of wild-type but did not alter those values in knockout mice. The wild-type mice, when given L-NAME for a week, showed a minimum alveolar concentration and RRED50 identical to that of untreated wild-type mice., Conclusions: Although acute nonselective inhibition of nitric oxide synthase reduces the anesthetic requirements of wild-type mice, a chronic congenital deficiency of neuronal nitric oxide synthase or a week of L-NAME treatment of wild-type mice does not produce a state of greater sensitivity to the effects of isoflurane anesthesia.
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- 1995
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18. Platelet factor 4 injection produces acute pulmonary hypertension in the awake lamb.
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Kurrek MM, Winkler M, Robinson DR, and Zapol WM
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- Animals, Hemodynamics drug effects, Heparin Antagonists pharmacology, Injections, Intravenous, Platelet Factor 4 administration & dosage, Protamines pharmacology, Sheep, Thromboxane B2 blood, Hypertension, Pulmonary chemically induced, Platelet Factor 4 toxicity
- Abstract
Background: Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morphologic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs., Methods: The authors evaluated the hemodynamic response and plasma release rates of thromboxane during intravenous challenges with heparin-rPF4 (n = 2), rPF-free carrier (n = 5), rPF4 (n = 5), rPF4 after indomethacin (n = 5), protamine (n = 5) and heparin-protamine (n = 5) in 17 awake, hemodynamically monitored lambs. Each lamb underwent up to three random challenges with a 2-h recovery period between each challenge., Results: In two lambs, systemic anticoagulation with heparin followed by reversal of anticoagulation with an intravenous bolus of rPF4 (4 mg/kg) led to acute pulmonary vasoconstriction and hypertension with the release of thromboxane (peak pulmonary artery pressure [Ppa] 40 and 33 mmHg and peak plasma thromboxane B2 50 and 30 ng/ml, respectively). Intravenous administration of rPF4 (1.5 mg/kg) alone increased the Ppa from 17.2 +/- 0.7 mmHg (mean +/- SEM) at baseline to 31.2 +/- 2 mmHg at 1 min (n = 5, P < 0.05). This was associated with an increase of plasma thromboxane B2 from 0.06 +/- 0.02 to 3.96 +/- 1.21 ng/ml. Acute pulmonary vasoconstriction lasted approximately 5 min and was completely prevented by pre-treatment with oral indomethacin (10 mg/kg). Intravenous bolus administration of rPF4 carrier (n = 5) or protamine (2 mg/kg) alone (n = 5) did not induce pulmonary hypertension or the release of thromboxane. In five lambs, intravenous heparin (200 U/kg) followed by protamine (2 mg/kg) consistently produced acute pulmonary vasoconstriction and hypertension., Conclusions: Intravenous injection of human rPF4 into the awake lamb produces acute pulmonary vasoconstriction and hypertension associated with thromboxane release into circulating blood. The effects of rPF4 on the pulmonary vasculature should be evaluated in primates before rPF4 is substituted for protamine in reversing heparin anticoagulation in humans.
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- 1995
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19. Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.
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Bigatello LM, Hurford WE, Kacmarek RM, Roberts JD Jr, and Zapol WM
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- Administration, Inhalation, Adult, Aged, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Middle Aged, Partial Pressure, Respiratory Distress Syndrome physiopathology, Tachyphylaxis physiology, Hypertension, Pulmonary blood, Hypertension, Pulmonary drug therapy, Nitric Oxide administration & dosage, Oxygen blood, Pulmonary Circulation drug effects, Respiratory Distress Syndrome blood, Respiratory Distress Syndrome drug therapy
- Abstract
Background: Nitric oxide (NO) inhalation selectively decreases pulmonary artery hypertension and improves arterial oxygenation in patients with the adult respiratory distress syndrome (ARDS). In this study of patients with severe ARDS, we sought to determine the effect of inhaled NO dose and time on pulmonary artery pressure and oxygen exchange and to determine which patients with ARDS are most likely to show this response., Methods: Thirteen patients with severe ARDS (hospital mortality 67%) inhaled 0-40 parts per million (ppm) NO. Seven of these patients continued to breathe 2-20 ppm NO for 2-27 days., Results: Inhaling 5-40 ppm NO decreased mean pulmonary artery pressure in a dose-related fashion (from 34 +/- 7 to 30 +/- 7 mmHg at 20 ppm NO). Systemic arterial pressure did not change. The ratio of arterial oxygen tension to inspired oxygen fraction increased (from 126 +/- 36 to 149 +/- 38 mmHg) and the venous admixture decreased (from 31.2 +/- 5.5 to 28.2 +/- 5.2%) without a clear dose-response effect. During prolonged NO inhalation, 2-20 ppm NO effectively reduced mean pulmonary artery pressure (38 +/- 7 vs. 31 +/- 6 mmHg) and increased arterial oxygen tension (79 +/- 10 vs. 114 +/- 27 mmHg) without evidence of tachyphylaxis. The decrease of pulmonary vascular resistance during NO inhalation correlated with the level of pulmonary vascular resistance without NO (r = -0.72). The reduction of venous admixture correlated with the level of venous admixture without NO (r = -0.78)., Conclusions: Long-term NO inhalation at low concentrations selectively decreases mean pulmonary artery pressure and improves arterial oxygen tension in patients with ARDS. The selective pulmonary vasodilation effect is most pronounced in ARDS patients with the greatest degree of pulmonary vasoconstriction.
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- 1994
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20. Thoracic epidural anesthesia increases diaphragmatic shortening after thoracotomy in the awake lamb.
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Polaner DM, Kimball WR, Fratacci MD, Wain JC, and Zapol WM
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- Animals, Carbon Dioxide physiology, Diaphragm drug effects, Injections, Epidural, Iopamidol, Lidocaine, Neural Pathways physiology, Neurons, Afferent physiology, Plethysmography, Impedance, Respiratory Mechanics drug effects, Respiratory Mechanics physiology, Sheep, Thorax, Anesthesia, Epidural adverse effects, Diaphragm anatomy & histology, Diaphragm physiology, Thoracotomy adverse effects
- Abstract
Background: Prolonged inhibition of diaphragmatic function occurs after thoracic and upper abdominal surgery. It was hypothesized that thoracic epidural anesthesia on the day after a thoracotomy could block inhibitory neural pathways and increase the shortening of costal and crural diaphragmatic segments., Methods: Pairs of sonomicrometer crystals were implanted into the costal and crural regions of the diaphragm through a right lateral thoracotomy in 14 30-kg, 4-5-month-old lambs. One day after surgery, a thoracic epidural catheter was placed at the T8-T9 level. Regional diaphragmatic shortening normalized to end-expiratory length (%LFRC), was measured by sonomicrometry in these awake lambs. Changes in gastric (delta Pgas), esophageal (delta Pes), and transdiaphragmatic (delta Pdi) pressures were measured with transnasal balloon catheters. End-tidal carbon dioxide (FETCO2), costal and crural electromyogram (Edi), and tidal volume (VT) were measured. Inductance plethysmography was used in four lambs to assess relative contributions of the rib cage and abdomen to VT. Control values were obtained during quiet breathing and while rebreathing at up to 10% FETCO2. To block thoracic dermatomes, 1% or 2% lidocaine was injected through the epidural catheter. Measurements were repeated after each lidocaine injection., Results: There was no change of resting length with 1% lidocaine; costal resting length increased by 22% with 2% lidocaine. After 2% lidocaine, costal %LFRC increased from control both during quiet breathing (8.7 +/- 0.7 to 18.1 +/- 1, mean +/- SEM%) and at FETCO2 10% (22.1 +/- 2 to 33.7 +/- 3%). VT during quiet breathing was unchanged after 1% lidocaine but increased from 235 +/- 16 to 283 +/- 28 ml after 2% lidocaine. At 10% FETCO2, delta Pdi was unchanged after 1% lidocaine and decreased from 36.5 +/- 4.3 to 26.3 +/- 4.9 cmH2O after 2% lidocaine. Regional delta Edi was unchanged with both 1% and 2% lidocaine at rest and during carbon dioxide rebreathing. Plethysmography in three lambs showed a reduction in rib cage contribution to tidal volume with 2% lidocaine during quiet breathing., Conclusions: Improved postoperative tidal volume and diaphragmatic shortening after thoracic epidural blockade may be due to changes of chest wall conformation and resting length and a shift of the workload of breathing from the rib cage to the diaphragm caused by intercostal muscle paralysis.
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- 1993
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21. Diaphragmatic shortening after thoracic surgery in humans. Effects of mechanical ventilation and thoracic epidural anesthesia.
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Fratacci MD, Kimball WR, Wain JC, Kacmarek RM, Polaner DM, and Zapol WM
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- Adenocarcinoma surgery, Aged, Autonomic Nerve Block, Female, Humans, Lidocaine, Lung Neoplasms surgery, Lung Volume Measurements, Male, Middle Aged, Muscle Contraction physiology, Posture physiology, Respiration physiology, Anesthesia, Epidural, Diaphragm anatomy & histology, Diaphragm physiology, Postoperative Complications etiology, Respiration, Artificial, Thoracic Surgery
- Abstract
Background: Diaphragmatic function is believed to be inhibited after thoracic surgery and may be improved by thoracic epidural anesthesia., Methods: Diaphragmatic function after a thoracotomy was monitored by implanting one pair of sonomicrometry crystals and two electromyogram (EMG) electrodes on the costal diaphragm of six patients undergoing an elective pulmonary resection. Crystals and EMG electrodes remained in place for 12-24 h., Results: During mechanical ventilation, costal diaphragmatic length (as a percent of rest length; %LFRC) decreased passively as tidal volume (VT) increased (%LFRC = 2.81 + 1.12 x 10(-2) VT (ml), r = 0.99). During spontaneous ventilation, the costal shortening (2.1 +/- 2.3 %LFRC) was less than during mechanical ventilation (7.9 +/- 3.0 %LFRC, P < 0.05) at the same VT. Comparing spontaneous ventilation before and 30 min after thoracic epidural anesthesia, there were increases of VT (390 +/- 78 to 555 +/- 75 ml), vital capacity (1.37 +/- 0.16 to 1.68 +/- 0.21 l), and esophageal (-8.5 +/- 1.5 to -10.6 +/- 1.7 cmH2O), gastric (-0.7 +/- 0.8 to +0.8 +/- 0.8 cmH2O), and transdiaphragmatic (7.7 +/- 1.5 to 11.5 +/- 1.9 cmH2O) pressures, but diaphragmatic EMG and shortening fraction remained constant. In three of six patients, epidural anesthesia produced paradoxical segment lengthening upon inspiration., Conclusions: Thoracotomy and pulmonary resection produce a marked reduction of active diaphragmatic shortening, which is not reversed by thoracic epidural anesthesia despite improvement of other indices of respiratory function.
- Published
- 1993
- Full Text
- View/download PDF
22. Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation.
- Author
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Frostell CG, Blomqvist H, Hedenstierna G, Lundberg J, and Zapol WM
- Subjects
- Administration, Inhalation, Adult, Blood Pressure drug effects, Carbon Dioxide blood, Endothelins blood, Endothelins metabolism, Female, Humans, Lung drug effects, Lung metabolism, Male, Methemoglobin analysis, Nitric Oxide administration & dosage, Oxygen blood, Pulmonary Artery drug effects, Pulmonary Circulation drug effects, Pulmonary Gas Exchange drug effects, Stroke Volume drug effects, Vascular Resistance drug effects, Vasodilation drug effects, Ventricular Function, Right drug effects, Hypoxia physiopathology, Lung blood supply, Nitric Oxide pharmacology, Vasoconstriction drug effects
- Abstract
Background: Nitric oxide (NO), an endothelium-derived relaxing factor, acts as a local vasodilator. The authors examined the effects of NO on pulmonary and systemic circulation in human volunteers., Methods: Nine healthy adults were studied awake while breathing 1) air, 2) 12% O2 in N2, 3) followed by the same mixture of O2 and N2 containing 40 ppm of NO. Pulmonary artery and radial artery pressures were monitored., Results: The PaO2 decreased from 106 +/- 4 (mean +/- standard error of the mean) while breathing air (21% O2) to 47 +/- 2 mmHg after 6 min of breathing 12% O2. Concomitantly, the pulmonary artery mean pressure (PAP) increased from 14.7 +/- 0.8 mmHg to 19.8 +/- 0.9 mmHg, and the cardiac output (CO) increased from 6.1 +/- 0.4 to 7.7 +/- 0.6 L/min. After adding 40 ppm NO to the inspired gas while maintaining the FIO2 at 0.12, the PAP decreased (P < 0.01, by analysis of variance) to the level when breathing air while the PaO2 and PaCO2 were unchanged. The dilation (or recruitment) of pulmonary vessels produced by inhaling NO during hypoxia was not accompanied by any alteration in the systemic vascular resistance or mean arterial pressure (MAP). The authors also examined the effects of inhaling NO while breathing air. Breathing 40 ppm NO in 21% O2 for 6 min produced no significant changes of PAP, CO, PaO2, MAP, or central venous pressure. Plasma endothelinlike immunoreactivity concentrations did not change either during hypoxia or hypoxia with NO inhalation., Conclusions: Inhalation of 40 ppm NO selectively induced pulmonary vasodilation and reversed hypoxic pulmonary vasoconstriction in healthy humans without causing systemic vasodilation.
- Published
- 1993
- Full Text
- View/download PDF
23. Volotrauma and the intravenous oxygenator in patients with adult respiratory distress syndrome.
- Author
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Zapol WM
- Subjects
- Humans, Lung Injury, Oxygenators, Membrane adverse effects, Respiratory Distress Syndrome therapy
- Published
- 1992
- Full Text
- View/download PDF
24. Effects of aminophylline on regional diaphragmatic shortening after thoracotomy in the awake lamb.
- Author
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Polaner DM, Kimball WR, Fratacci MD, Wain JC, Torres A, Kacmarek RM, and Zapol WM
- Subjects
- Aminophylline administration & dosage, Animals, Diaphragm physiology, Electromyography, Injections, Intravenous, Muscle Contraction physiology, Postoperative Period, Sheep, Stimulation, Chemical, Aminophylline therapeutic use, Diaphragm drug effects, Muscle Contraction drug effects, Thoracotomy
- Abstract
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.
- Published
- 1992
- Full Text
- View/download PDF
25. Inhaled nitric oxide. A selective pulmonary vasodilator of heparin-protamine vasoconstriction in sheep.
- Author
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Fratacci MD, Frostell CG, Chen TY, Wain JC Jr, Robinson DR, and Zapol WM
- Subjects
- Animals, Blood Pressure drug effects, Heparin metabolism, Prostaglandin Endoperoxides, Synthetic antagonists & inhibitors, Prostaglandin Endoperoxides, Synthetic pharmacology, Protamines metabolism, Sheep, Thromboxane B2 blood, Vascular Resistance drug effects, Nitric Oxide pharmacology, Pulmonary Artery physiology, Vasodilation drug effects
- Abstract
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.
- Published
- 1991
- Full Text
- View/download PDF
26. Myocardial perfusion as assessed by thallium-201 scintigraphy during the discontinuation of mechanical ventilation in ventilator-dependent patients.
- Author
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Hurford WE, Lynch KE, Strauss HW, Lowenstein E, and Zapol WM
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Radionuclide Imaging, Respiration Disorders therapy, Coronary Circulation physiology, Heart diagnostic imaging, Respiration Disorders physiopathology, Respiration, Artificial, Thallium Radioisotopes
- Abstract
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)
- Published
- 1991
- Full Text
- View/download PDF
27. Protamine reactions, explosive mediator release, and pulmonary vasoconstriction.
- Author
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Lowenstein E and Zapol WM
- Subjects
- Humans, Heparin Antagonists adverse effects, Lung blood supply, Protamines adverse effects, Thromboxane B2 blood, Vasoconstriction physiology
- Published
- 1990
28. Understanding images: correlation between computerized tomographic scans of lung structure with impaired function in ARDS.
- Author
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Zapol WM
- Subjects
- Humans, Lung pathology, Lung physiopathology, Organ Size, Positive-Pressure Respiration, Respiratory Distress Syndrome diagnostic imaging, Respiratory Distress Syndrome pathology, Lung diagnostic imaging, Respiratory Distress Syndrome physiopathology, Tomography, X-Ray Computed
- Published
- 1988
29. Bedside measurement of pulmonary capillary pressure in patients with acute respiratory failure.
- Author
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Collee GG, Lynch KE, Hill RD, and Zapol WM
- Subjects
- Acute Disease, Adult, Aged, Capillaries physiopathology, Humans, Middle Aged, Norepinephrine pharmacology, Pulmonary Artery physiopathology, Respiratory Distress Syndrome physiopathology, Vascular Resistance, Blood Pressure, Pulmonary Circulation, Respiratory Insufficiency physiopathology
- Abstract
In this report, the authors present the results of 34 estimates of pulmonary capillary pressure (Pcap) in 15 adult patients receiving intensive care for acute respiratory failure (ARF). Within the pulmonary artery pressure profile during transient balloon occlusion, the authors identified two exponential pressure decay components-the slower one representing the discharge of the pulmonary capillary pressure through the pulmonary venous resistance. By extrapolating this exponential to its origin at the moment of pulmonary artery occlusion, a pressure within the pulmonary vascular bed which approximates pulmonary capillary pressure (Pcap) was identified. Pcap, and not the pulmonary artery occlusion pressure (PAOP), is the major driving pressure forcing fluid from the pulmonary microvasculature. The results indicate that a discrete value for pulmonary capillary pressure can be reproducibly measured in paralyzed ventilated patients. The data report that mean pulmonary artery pressure, pulmonary capillary pressure, and total pulmonary vascular resistance (PVR) are increased in acute respiratory failure, but there is considerable variation in the distribution of pulmonary vascular resistance between the arterial and venous beds. The data suggest that there is unequal and variable partitioning of the increased PVR during acute respiratory failure. Bedside pressure profile Pcap measurements will allow optimum reduction of Pcap during ARF by infusing vasoactive agents to modify the distribution of PVR or reducing the PAOP.
- Published
- 1987
- Full Text
- View/download PDF
30. C5a and thromboxane generation associated with pulmonary vaso- and broncho-constriction during protamine reversal of heparin.
- Author
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Morel DR, Zapol WM, Thomas SJ, Kitain EM, Robinson DR, Moss J, Chenoweth DE, and Lowenstein E
- Subjects
- Adult, Aged, Complement C3 analysis, Complement C3a, Complement C4 analysis, Complement C4a, Complement C5a, Hemodynamics drug effects, Histamine blood, Humans, Leukocyte Count, Middle Aged, Platelet Count, Bronchi drug effects, Complement C5 biosynthesis, Protamines adverse effects, Pulmonary Circulation drug effects, Thromboxanes biosynthesis, Vasoconstriction drug effects
- Abstract
The authors conducted a study in humans to determine the mediators associated with acute pulmonary vaso- and broncho-constriction occurring episodically with protamine reversal of heparin anticoagulation. Of 48 adult patients investigated prospectively after termination of cardiopulmonary bypass, two presented a sudden increase of airway pressure, acute pulmonary hypertension, and systemic hypotension 1-3 min after right atrial protamine injection. In these two subjects, plasma levels of C5a increased from 0.7 and 2.2 to 9.8 and 9.9 ng/ml, respectively, and thromboxane B2 increased from 0.26 and 0.34 to 7.5 and 16.2 ng/ml 1 minute after drug injection. A third subject not identified prospectively had an identical reaction and mediator profile (C5a, 10.2 ng/ml; TxB2, 18.6 ng/ml at 1 min). The plasma levels of these mediators were unchanged in the remaining patients (C5a, 0.7 +/- 1.1 [x +/- S.D.] to 0.6 +/- 0.9 ng/ml; TxB2, 0.16 +/- 0.12 to 0.15 +/- 0.07 ng/ml). Plasma histamine was not involved in this type of reaction, but increased from 0.7-10.4 ng/ml in a fourth patient who became hypotensive without acute pulmonary hypertension, bronchoconstriction, or elevation of C5a or TxB2. The authors' data indicate that the generation of high plasma levels of C5a anaphylatoxins and thromboxane is associated with pulmonary vaso- and broncho-constriction induced by protamine reversal of heparin in humans.
- Published
- 1987
- Full Text
- View/download PDF
31. Unplanned intraoperative and postoperative hemodilution: oxygen transport and consumption during severe anemia.
- Author
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Lichtenstein A, Eckhart WF, Swanson KJ, Vacanti CA, and Zapol WM
- Subjects
- Adult, Christianity, Female, Humans, Anemia complications, Hemodilution, Intraoperative Care, Oxygen blood, Postoperative Care
- Published
- 1988
- Full Text
- View/download PDF
32. Extracorporeal membrane oxygenation for acute respiratory failure.
- Author
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Zapol WM, Snider MT, and Schneider RC
- Subjects
- Carbon Dioxide metabolism, Carotid Arteries, Catheterization methods, Embolism, Amniotic Fluid therapy, Female, Femoral Artery, Femoral Vein, Hemodynamics, Humans, Oxygen Consumption, Pregnancy, Pulmonary Circulation, Silicones adverse effects, Oxygenators, Membrane adverse effects, Oxygenators, Membrane methods, Respiratory Insufficiency therapy
- Published
- 1977
- Full Text
- View/download PDF
33. A comparison of pulmonary artery occlusion pressure and left ventricular end-diastolic pressure during mechanical ventilation with PEEP in patients with severe ARDS.
- Author
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Teboul JL, Zapol WM, Brun-Buisson C, Abrouk F, Rauss A, and Lemaire F
- Subjects
- Adult, Aged, Blood Pressure, Female, Humans, Male, Middle Aged, Respiratory Distress Syndrome therapy, Heart Ventricles physiopathology, Positive-Pressure Respiration, Pulmonary Artery physiopathology, Respiratory Distress Syndrome physiopathology
- Abstract
When positive end-expiratory pressure (PEEP) is applied to normal lungs, the pulmonary artery occlusion pressure (PAOP) may reflect alveolar pressure and not left ventricular end-diastolic pressure (LVEDP). The reliability of PAOP measurements has been questioned when PEEP levels greater than 10 cm H2O are applied. To verify whether this disparity occurs in patients with severe lung injury, the authors simultaneously measured both PAOP and LVEDP at 0, 10, and 16-20 cm H2O PEEP in 12 supine patients with severe adult respiratory distress syndrome (ARDS). In all patients, the radiographic location of the PA catheter tip was at or below the level of the posterior border of the left atrium. A close correlation was found between PAOP and LVEDP at each level of PEEP. In only six of 35 simultaneous measurements was the PAOP-LVEDP gradient 2 mmHg or more (2-3 mmHg in four, and 4 mmHg in two). In five patients, the highest PEEP level was 4-9 cm H2O greater than LVEDP; however, no gradient was measured between LVEDP and PAOP. The authors conclude that, in severe ARDS, a close correspondence between PAOP and LVEDP is maintained despite applying PEEP levels up to 20 cm H2O, suggesting that, in ARDS, surrounding pathology prevents transmitted alveolar pressure from collapsing adjacent pulmonary vessels.
- Published
- 1989
- Full Text
- View/download PDF
34. Acute left ventricular dysfunction during unsuccessful weaning from mechanical ventilation.
- Author
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Lemaire F, Teboul JL, Cinotti L, Giotto G, Abrouk F, Steg G, Macquin-Mavier I, and Zapol WM
- Subjects
- Adult, Aged, Cardiac Output, Esophagus physiology, Female, Heart Ventricles, Humans, Lung Diseases, Obstructive physiopathology, Lung Volume Measurements, Male, Middle Aged, Pressure, Prospective Studies, Pulmonary Wedge Pressure, Stroke Volume, Heart physiopathology, Hemodynamics, Lung Diseases, Obstructive therapy, Positive-Pressure Respiration
- Abstract
The authors studied the hemodynamic effects of rapidly weaning from mechanical ventilation (MV) 15 patients with severe chronic obstructive pulmonary disease (COPD) and cardiovascular disease who were recovering from acute cardiopulmonary decompensation. In each patient, 10 min of spontaneous ventilation (SV) with supplemental oxygen resulted in reducing the mean esophageal pressure (X +/- SD, + 5 +/- 3 to -2 +/- 2.5 mmHg, P less than .01) and increasing cardiac index (CI) 3.2 +/- 0.9 to 4.3 +/- 1.3 1/min/M2, P less than .001), systemic blood pressure (BP 77 +/- 12 to 90 +/- 11 mmHg, P less than .001), heart rate (HR 97 +/- 12 to 112 +/- 16 beats/min, P less than .001), and, most importantly, transmural pulmonary artery occlusion pressure markedly increased (PAOPtm 8 +/- 5 to 25 +/- 13 mmHg, P less than .001), mandating a reinstitution of MV. In four patients with left ventricular (LV) catheters, the PAOP correlated with the LV end-diastolic pressure during both MV and SV. Gated blood pool imaging showed SV increased the LV end-diastolic volume index (65 +/- 24 to 83 +/- 32/M2, P less than .002) with LV ejection fraction unchanged. Patients were treated for a mean of 10 days with diuretics, resulting in a reduction of blood volume (4.55 +/- 0.9 1 to 3.56 +/- 0.55 1) and body weight (-5 kg, P less than .001). Subsequently, nine of the 15 patients were weaned successfully from mechanical ventilation with unchanged PAOP.
- Published
- 1988
- Full Text
- View/download PDF
35. Pure oxygen breathing increases sheep lung microvascular permeability.
- Author
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Erdmann AJ 3rd, Hüttemeier PC, Landolt C, and Zapol WM
- Subjects
- Animals, Capillary Permeability drug effects, Lymph analysis, Microcirculation drug effects, Oxygen administration & dosage, Oxygen blood, Proteins analysis, Pulmonary Edema chemically induced, Sheep, Time Factors, Lung blood supply, Oxygen toxicity
- Abstract
Sheep that breathe pure oxygen via a tracheostomy develop progressive respiratory failure and die within four days. The characteristic terminal findings include an increased water content of the lung, a decrease in lung compliance, and severe hypercarbia. To sequentially assess alterations of lung transvascular fluid dynamics during prolonged oxygen breathing the authors measured lung lymph flow (Q lymph), protein transport (Q protein), and pulmonary vascular pressures in five sheep with chronic lung lymph fistulas. No significant changes of lung transvascular fluid dynamics occurred during the first 60 hours of oxygen breathing, although an increasing trend of Q lymph and Q protein was demonstrable. However, after 72 hours of oxygen breathing, Q lymph, Q protein, and extravascular lung water had increased significantly without any change of pulmonary vascular pressures. The authors conclude that the toxic effects of oxygen on the lungs of sheep include a delayed but marked increase of pulmonary microvascular permeability to protein and fluid.
- Published
- 1983
- Full Text
- View/download PDF
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