PubMed Health⌕ Search

Biomedical subjects

W M Zapol

Publications and source records attributed to W M Zapol.

At least 73 records · Page 4Linked to original sources
PubMed1994

Hemodynamic effects of inhaled nitric oxide in heart failure.

OBJECTIVES: This study was performed to assess the utility of inhaled nitric oxide as a selective pulmonary vasodilator in patients with severe chronic heart failure and to compare its hemodynamic effects with those of nitroprusside, a nonselective vasodilator. BACKGROUND: Preoperative pulmonary vascular resistance is a predictor of right heart failure after heart transplantation. Non-selective vasodilators administered preoperatively to assess the reversibility of pulmonary vasoconstriction cause systemic hypotension, limiting their utility. METHODS: Systemic and pulmonary hemodynamic measurement were made at baseline, during oxygen inhalation and with the addition of graded doses of inhaled nitric oxide or intravenous nitroprusside in 16 patients with New York Heart Association class III or IV heart failure referred for heart transplantation. RESULTS: Pulmonary vascular resistance decreased to a greater extent with 80 ppm nitric oxide (mean +/- SEM 256 +/- 41 to 139 +/- 14 dynes.s.cm-5) than with the maximally tolerated dose of nitroprusside (264 +/- 49 to 169 +/- 30 dynes.s.cm-5, p < 0.05, nitric oxide vs. nitroprusside). Pulmonary capillary wedge pressure increased with 80 ppm nitric oxide (26 +/- 2 to 32 +/- 2 mm Hg, p < 0.05). Mean arterial pressure did not change with nitric oxide but decreased with nitroprusside. Seven of the 16 patients, including 1 patient who did not have an adequate decrease in pulmonary vascular resistance with nitroprusside but did with nitric oxide, have undergone successful heart transplantation. CONCLUSIONS: Inhaled nitric oxide is a selective pulmonary vasodilator in patients with pulmonary hypertension due to left heart failure and may identify patients with reversible pulmonary vasoconstriction in whom agents such as nitroprusside cause systemic hypotension. Inhaled nitric oxide causes an increase in left ventricular filling pressure by an unknown mechanism.

Administration, Inhalation↗
PubMed1994

Prolonged inhalation of low concentrations of nitric oxide in patients with severe adult respiratory distress syndrome. Effects on pulmonary hemodynamics and oxygenation.

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.

Administration, Inhalation↗
PubMed1994

Effects of inhaled nitric oxide on pulmonary hemodynamics and gas exchange in an ovine model of ARDS.

Inhaling low concentrations of nitric oxide (NO) gas causes selective pulmonary vasodilation of ventilated lung regions. NO activates soluble guanylate cyclase, increasing guanosine 3',5'-cyclic monophosphate (cGMP). Inhibition of NO synthesis enhances hypoxic pulmonary vasoconstriction. Therefore we examined independent and combined effects of NO inhalation and infusion of NG-nitro-L-arginine methyl ester (L-NAME), an NO synthesis inhibitor, on pulmonary vascular pressure-flow relationships, gas exchange, and plasma cGMP levels in anesthetized and mechanically ventilated sheep with acute lung injury induced by bilateral lavage. After lavage, inhaling 60 ppm by volume of NO decreased pulmonary arterial pressure (PAP) and resistance without any systemic hemodynamic effects, increased arterial PO2, and decreased venous admixture (Qva/QT; all P < 0.05) without altering cardiac output (QT), mixed venous PO2, or O2 uptake, major determinants of intrapulmonary shunt. During NO inhalation, PAP-left atrial pressure gradient (PAP-LAP) and Qva/QT were reduced (both P < 0.05) independently of QT, which was varied mechanically. L-NAME infusion produced systemic and pulmonary vasoconstriction and increased PAP-LAP gradient across the entire range of QT, whereas Qva/QT, was not changed. NO inhalation after L-NAME infusion produced pulmonary vasodilation and decreased Qva/QT to the same degree as NO inhalation alone. Five to 10 min after inhalation of 60 ppm NO, before and after L-NAME infusion, arterial plasma cGMP levels were increased by 80% (both P < 0.05). With NO breathing after L-NAME, we measured a consistent transpulmonary cGMP arteriovenous gradient [31 +/- 8 and 33 +/- 7 (SE) pmol/ml at 5 and 10 min, respectively; both P < 0.05]. NO inhalation before or after L-NAME administration in this acute lung injury model reduced Qva/QT, most likely by increasing cGMP concentration in ventilated lung regions and causing selective pulmonary vasodilation.

Administration, Inhalation↗
PubMed1994

Exhaled nitric oxide as a marker for organic nitrate tolerance.

BACKGROUND: This study was designed to demonstrate the development of biochemical tolerance to organic nitrates by measuring levels of exhaled gaseous nitric oxide (NO) in lambs given intravenous (IV) nitroglycerin or sodium nitroprusside. METHODS AND RESULTS: IV injections of nitroglycerin or sodium nitroprusside produced dose-dependent and sustained increases in the exhaled levels of nitric oxide measured by chemiluminescence in awake lambs with tracheostomies. After a 6-hour IV infusion of 25 micrograms.kg-1.min-1 nitroglycerin, peak exhaled NO levels were significantly reduced (-53.6 +/- 4.9%, mean +/- SEM, P < .001) and systemic hypotensive responses were attenuated (-52.6 +/- 5.9%, P < .001) after an IV challenge of nitroglycerin but not sodium nitroprusside. After a subsequent 12-hour nitroglycerin-free period, there was complete recovery of NO excretion in exhaled breath and a return to baseline of systemic hypotensive changes on administration of IV nitroglycerin boluses. For IV sodium nitroprusside challenges, pulmonary NO excretion and systemic hypotensive responses remained constant throughout the study. Challenges with IV nitroglycerin but not sodium nitroprusside during a 12-hour nitroglycerin-free period resulted in delayed biochemical recovery with various exhaled NO levels and systemic hypotensive responses to challenges with IV nitroglycerin. CONCLUSIONS: Measurements of exhaled NO provide in vivo, noninvasive evidence for the development of biochemical tolerance to nitroglycerin. There was reduced NO release into exhaled gas from the pulmonary vasculature concomitant with evidence of tolerance to nitroglycerin vasodilation in the systemic circulation.

Animals↗
PubMed1993

Inhaled nitric oxide for the adult respiratory distress syndrome.

BACKGROUND: The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. METHODS: Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. RESULTS: Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days. CONCLUSIONS: Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome.

Adolescent↗
PubMed1993

Inhaled nitric oxide selectively reverses human hypoxic pulmonary vasoconstriction without causing systemic vasodilation.

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.

Administration, Inhalation↗
PubMed1993

Diaphragmatic shortening after thoracic surgery in humans. Effects of mechanical ventilation and thoracic epidural anesthesia.

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.

Adenocarcinoma↗
PubMed1993

Thoracic epidural anesthesia increases diaphragmatic shortening after thoracotomy in the awake lamb.

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.

Anesthesia, Epidural↗
PubMed1993

cAMP regulates soluble guanylate cyclase beta 1-subunit gene expression in RFL-6 rat fetal lung fibroblasts.

Endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) activates soluble guanylate cyclase, thereby stimulating the synthesis of guanosine 3',5'-cyclic monophosphate (cGMP). To investigate the regulation of this important EDRF/NO receptor, we studied soluble guanylate cyclase gene expression in a rat fetal lung fibroblast cell line (RFL-6). 3-Isobutyl-1-methylxanthine, forskolin, and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP), agents which increase intracellular cAMP, decreased the concentration of mRNA encoding the beta 1-subunit of soluble guanylate cyclase in RFL-6 cells. To investigate whether a decrease in beta 1-subunit mRNA concentration was reflected in diminished capacity to produce cGMP, forskolin-treated RFL-6 cells were exposed to the NO-donor compound sodium nitroprusside. Exposure to forskolin reversibly reduced the ability of RFL-6 cells to increase cGMP in response to NO. These observations suggest that cAMP can modulate the cellular response to EDRF/NO by decreasing the expression of one of the subunits of soluble guanylate cyclase.

1-Methyl-3-isobutylxanthine↗
PubMed1993

Protective effects of anti-O polysaccharide and anti-lipid A monoclonal antibodies on pulmonary hemodynamics.

Monoclonal antibodies (MAbs) directed to endotoxin can protect in some animal models against the pathophysiological effects of endotoxin infusion. When 0.02 microgram/kg of lipopolysaccharide (LPS) derived from Escherichia coli O111:B4 was incubated in vitro for 2 h with the murine immunoglobulin G MAb, 5B10, directed against the O-polysaccharide antigenic domain of E. coli O111:B4 and then the mixture was infused into sheep, we noted significant protection. The second temperature peak was decreased (P < 0.05 vs. LPS control). The acute pulmonary arterial pressure elevation was diminished (mean peak pulmonary arterial pressure 23.2 +/- 2.5 mmHg, P < 0.05 vs. LPS control), and the peak plasma thromboxane B2 level was reduced (mean peak thromboxane B2 level 0.50 +/- 0.15 ng/ml, P < 0.05 vs. LPS control). In contrast, preincubation of the LPS with a human immunoglobulin M MAb, HA-1A, directed against the core glycolipid of the LPS molecule provided no protective effects in this sheep model. This finding is in agreement with recent studies reporting HA-1A may bind to antibiotic-treated bacteria but not to purified smooth LPS.

Animals↗
PubMed1993

Regional diaphragmatic length and EMG activity during inspiratory pressure support and CPAP in awake sheep.

We examined diaphragmatic mechanics in awake sheep during quiet breathing (QB) and the randomized application of 5, 10, and 15 cmH2O continuous positive airway pressure (CPAP), inspiratory pressure support (IPS), and equal combinations of IPS and CPAP (IPS/CPAP). We measured esophageal, gastric, and transdiaphragmatic (Pdi) pressures and regional length, shortening, and electromyogram (EMG) activity of both costal and crural diaphragmatic segments. Segmental resting length normalized to QB decreased during 15 cmH2O CPAP (costal, 19.2 +/- 3.3%; crural, 7.5 +/- 2.1%; P < 0.05) and during 15/15 cmH2O IPS/CPAP (costal 25.3 +/- 4.8%, crural 9.9 +/- 2.6%; P < 0.05). Only during 15 cmH2O IPS did costal shortening fraction increase (67% QB; P < 0.05). Compared with QB, during 15 cmH2O CPAP, end-tidal CO2 increased 6 Torr, regional EMG activity increased threefold, and Pdi increased 58%. During 15 cmH2O IPS these values decreased 3 Torr, threefold, and 44% respectively, but during IPS/CPAP they remained unchanged. Expiratory gastric pressure (Exp-Pga) reached 4.3 +/- 0.4 cmH2O at 15 cmH2O CPAP, but during IPS/CPAP Exp-Pga was less (maximum of 1.7 +/- 0.4 cmH2O) than at comparable CPAP (P < 0.05), despite the shorter diaphragmatic length. We conclude that: 1) IPS alters the actions of the diaphragm during CPAP, 2) Exp-Pga is poorly coupled to diaphragmatic end-expiratory length, and 3) both IPS and the release of Exp-Pga assist active diaphragmatic shortening.

Animals↗
PubMed1993

Protective effects of E5, an antiendotoxin monoclonal antibody, in the ovine pulmonary circulation.

The cross-protective effects of a murine immunoglobulin M monoclonal antilipid A antibody (E5 MAb) were tested by challenging awake sheep with mixtures of in vitro incubated E5 MAb (0.02 mg/kg) with lipopolysaccharide (LPS, 0.02 micrograms/kg) derived from Escherichia coli O111:B4, E. coli O55:B5, or Serratia marcescens. Intravenous infusion of these LPS preparations without antibody into awake sheep produced a similar pattern of fever, leukopenia, plasma thromboxane B2 (TxB2) release, and acute pulmonary vasoconstriction with pulmonary hypertension. The addition of MAb E5 to LPS from E. coli O111:B4 reduced these responses to the LPS in a fashion comparable to that achieved with an MAb specific to the E. coli O111:B4 O-side chain. Incubation of LPS derived from E. coli O55:B5 with the E5 MAb only slightly diminished acute pulmonary hypertension, the delayed temperature increase, and the degree of leukopenia (all P = NS) but reduced the mean peak TxB2 at 60 min (P < 0.05) compared with a control infusion of E. coli O55:B5 LPS. We were unable to demonstrate any protective effects on the pulmonary circulation from incubating E5 with LPS derived from S. marcescens. Preincubation of B55 MAb (a murine immunoglobulin M MAb directed against a human milk fat globulin), the control antibody, with LPS from E. coli 0111:B4 decreased the mean peak TxB2 but had no effect on the other parameters. We conclude that incubating E5 with LPS protects the pulmonary circulation of sheep from challenge with LPS derived from the parent E. coli strain. There were trends toward protection by E5 against LPS from 055:B5 E. coli, but these did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Imaging the ovine heparin-protamine interaction with 111In-protamine.

Protamine reversal of heparin anticoagulation occasionally induces the release of thromboxane into plasma with catastrophic pulmonary hypertension. To examine the site of neutralization, we labeled protamine sulfate with 111In and compared activity scans after administration of labeled protamine in unheparinized and heparin-anticoagulated sheep. Protamine administration in sheep without prior heparinization did not cause thromboxane release, pulmonary hypertension, or significant leukopenia, and 111In-protamine was rapidly cleared from the lungs (half time 0.48 +/- 0.08 min). Neutralization of heparin anticoagulation by labeled protamine produced elevated plasma thromboxane, pulmonary vasoconstriction, leukopenia, and prolonged pulmonary clearance of 111In-protamine (half time 3.32 +/- 0.43 min). In rats, protamine reversal of heparin anticoagulation did not induce either thromboxane synthesis or pulmonary hypertension, and 111In-protamine cleared rapidly from the lungs. Thus the ovine heparin-protamine reaction produces concomitant pulmonary sequestration of heparin-protamine complexes, thromboxane release, and pulmonary vasoconstriction; this did not occur in the rat. The lung specificity of the reaction and interspecies differences suggest that ovine pulmonary intravascular macrophages may be activated by heparin-protamine complexes to release thromboxane and provoke acute pulmonary vasoconstriction.

Animals↗