Management of adult respiratory distress syndrome.
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Hemodynamics↗
Biomedical subjects
T W Evans
Publications and source records attributed to T W Evans.
Transpulmonary gradient of type III procollagen peptides: acute effects of cardio-pulmonary bypass.
Type III procollagen N-peptides (PIIINPs) are believed to be released in stoichiometric amounts as type III collagen molecules are secreted from cells. We hypothesized that if the human lung actively produces type III collagen a detectable transpulmonary gradient in PIIINPs would exist in normal individuals that might be altered following a pulmonary insult. PIIINPs were therefore measured by radioimmunoassay in serum taken simultaneously from the pulmonary artery (PA) and left ventricle/aorta (LV) in 11 patients undergoing routine cardiac catheterisation. Mean PIIINP levels +/- SEM in LV were 66.8 +/- 5.4 micrograms.ml-1 and 59.9 +/- 4.1 micrograms.ml-1 in PA (p less than 0.04). In 6 patients, repeat measurements taken 4 h after cardiopulmonary bypass revealed a significant fall in PA values to 43.8 +/- 2.6 micrograms.ml-1 (p less than 0.001) and abolition of the transpulmonary gradient. These results suggest the adult human lung actively synthesis type III collagen and that, in the short term, cardiopulmonary bypass inhibits this process.
Cardiac Catheterization↗
Oxygen transport in the critically ill.
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Biomarkers↗
Bleomycin-induced lung injury in rats selectively abolishes hypoxic pulmonary vasoconstriction: evidence against a role for platelet-activating factor.
1. The role of platelet-activating factor in the attenuated hypoxic pulmonary vasoconstriction associated with lung injury was evaluated using specific platelet-activating factor antagonists and an isolated perfused lung preparation. 2. Intratracheal bleomycin was administered to rats to produce acute lung injury. Animals received intratracheal saline (control), intratracheal bleomycin or the platelet-activating factor antagonists BN 52021, WEB 2170 or WEB 2086 before and after bleomycin treatment. Forty-eight hours after intratracheal administration of bleomycin or saline the animals were killed. 3. The increases in pulmonary artery pressure during two periods of hypoxic ventilation and in response to 0.2 microgram of angiotensin II were measured. Acetylcholine-induced vasodilatation after pre-constriction with prostaglandin F2 alpha was also measured. To quantify lung injury, the wet/dry ratio of lung weight was determined. 4. Bleomycin treatment attenuated the first and second hypoxic pressor responses by 93% and 77%, respectively, but not the pressor response to angiotensin II nor the vasodilator response to acetylcholine. BN 52021 plus bleomycin augmented the first hypoxic pressor response compared with bleomycin treatment alone, but the structurally unrelated platelet-activating factor antagonists WEB 2170 and WEB 2086 had no significant effect on the bleomycin-induced attenuation of hypoxic pulmonary vasoconstriction. None of the platelet-activating factor antagonists blocked the increase in the wet/dry lung weight ratio induced by bleomycin. 5. Bleomycin-induced lung injury selectively attenuates hypoxic pulmonary vasoconstriction, an effect that does not appear to be mediated by platelet-activating factor. The mechanism remains to be elucidated, but may involve destruction of the hypoxic 'sensor' within the respiratory tract.
Acetylcholine↗
Plasma exudation and oedema in asthma.
Gross pathology, histological and ultrastructural observations and analysis of sputum and lavage fluid indicate that plasma exudation from the bronchial microvasculature and the formation of tissue oedema are characteristic features of asthma. Appropriate mediators for the induction of plasma exudation are generated in the blood and airways of asthmatic patients and when administered experimentally will cause plasma leakage and oedema. Plasma exudate may not only contribute directly to the thickened bronchial walls and mucus plugs in the airways of asthmatics, but may also play a role in epithelial shedding, thickening of the basement membrane, hypertrophy of the smooth muscle, inducing mucus secretion and in thickening the secreted mucus. The beneficial effect of corticosteroids in asthma may be due to an anti-leakage action. Development of drugs with a broad spectrum of action against mediator release may have therapeutic advantage over specific receptor antagonist drugs.
Asthma↗
Bleomycin-induced acute lung injury in the rat does not influence pulmonary vascular responsiveness in vitro.
OBJECTIVE: To investigate the effects of the intratracheal and iv administration of bleomycin on the contraction and endothelially dependent vasodilation of rat pulmonary arteries in vitro. DESIGN: Prospective pharmacologic study. SETTING: National Heart and Lung Institute, London, UK. INTERVENTIONS: Intratracheal saline, intratracheal and iv bleomycin. MEASUREMENTS AND MAIN RESULTS: Rats treated with intratracheal bleomycin developed a significant increase in mean lung wet/dry weight ratio (5.6 +/- 0.4 [SEM] vs. 3.9 +/- 0.1, p less than .05) when compared with saline-treated control animals, confirming the development of pulmonary edema. However, these rats displayed normal relaxant responses to the endothelially dependent vasodilator acetylcholine and a normal contractile response to phenylephrine in vitro. Intravenous bleomycin had no effect on either wet/dry weight ratio or the response to either drug. CONCLUSIONS: Despite evidence for the loss of endothelial integrity that characterizes lung injury after intratracheal bleomycin, isolated pulmonary artery rings in vitro showed no loss of endothelial cell function. The role of the endothelium in modulating pulmonary ventilation/perfusion matching after lung injury is unclear.
Animals↗
Chronic adult respiratory distress syndrome--a role for corticosteroids?
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Adrenal Cortex Hormones↗
Changes in lung function and pulmonary capillary permeability after cardiopulmonary bypass.
OBJECTIVE: To assess the possibility that changes in lung function following cardiopulmonary bypass are associated with increased pulmonary capillary permeability. DESIGN: A prospective, descriptive study. SETTING: Adult cardiothoracic ICU in a post-graduate teaching hospital. PATIENTS: Ten sequential patients undergoing cardiac surgery requiring cardiopulmonary bypass. MEASUREMENTS: Arterial blood gas tensions, helium dilution end-expiratory lung volume, and carbon monoxide transfer were measured by a rebreathing technique preoperatively and 2 hrs postoperatively. Lung extravascular protein accumulation index was measured by a double-isotope technique 2 hrs postoperatively and in a group of normal controls. RESULTS: Mean +/- SEM alveolar-arterial PO2 gradient increased from 77 +/- 14 torr (10.3 +/- 1.8 kPa) to 138 +/- 24 torr (18.5 +/- 3.2 kPa) (p less than .01). Functional residual capacity decreased by 20.2 +/- 5.6% (p less than .01). Carbon monoxide transfer decreased by 26.7 +/- 5.3% (p less than .01) for the lung as a whole and by 17.9 +/- 3.2% (p less than .01) per liter of accessible gas volume. Protein accumulation index ranged from 0.03 to 3.2 x 10(-3) (median 0.6) postoperatively (median for normal subjects 0.4; p less than .05), although only one patient had a value indicative of clinically important endothelial injury. CONCLUSIONS: Cardiac surgery involving cardiopulmonary bypass results in a deterioration in lung function characterized by a loss of lung volume, a reduction in carbon monoxide transfer, and an increase in the alveolar-arterial PO2 gradient. These changes do not appear to be mediated by an increase in pulmonary endothelial permeability.
Aged↗
Adult respiratory distress syndrome following cardiopulmonary bypass: incidence and prediction.
The outcome of adult respiratory distress syndrome complicating cardiopulmonary bypass has changed little in recent years. A retrospective, case-controlled study was designed to assess the incidence of the adult respiratory distress syndrome in these circumstances and the extent to which it could be linked with pre and peri-operative predictive factors. Eleven patients who developed the syndrome out of 840 who underwent cardiopulmonary bypass over a 9 month period were compared with 53 controls matched for sex, operation and surgeon. The incidence of adult respiratory distress syndrome and its mortality were 1.3% and 53% respectively. Significant predictors were a high intra and postoperative intervention score, the total volume of blood pumped during bypass (greater than 300 l) and age (greater than 60 years). These risk factors should alert the clinician to the possibility of severe postoperative pulmonary complications.
Adult↗
Role of nitric oxide and guanosine 3',5'-cyclic monophosphate in mediating nonadrenergic, noncholinergic relaxation in guinea-pig pulmonary arteries.
1. Nonadrenergic, noncholinergic (NANC) nerves mediate vasodilatation in guinea-pig pulmonary artery (PA) by both endothelium-dependent and endothelium-independent mechanisms. The transmitter(s) involved in the endothelium-independent pathway have not yet been identified. We have therefore investigated the possibility that nitric oxide (NO) and guanosine 3',5'-cyclic monophosphate (cyclic GMP) may mediate this neural vasodilator response in guinea-pig branch PA rings denuded of endothelium. 2. Electric field stimulation (EFS, 50 V, 0.2 ms) induced a frequency-dependent (1-24 Hz), tetrodotoxin-sensitive relaxation of the U44069-precontracted PA rings in the presence of adrenergic and cholinergic blockade. 3. The NO synthase inhibitors NG-monomethyl L-arginine (L-NMMA, 100 microM) and NG-nitro L-arginine methyl ester (L-NAME, 30 microM), and the guanylyl cyclase inhibitor methylene blue (5 microM) inhibited the EFS (16 Hz)-induced relaxation by 53 +/- 5, 74 +/- 9 and 82 +/- 9% respectively (n = 5-7, P < 0.01, compared with control rings). 4. Excess concentrations of L-, but not D-arginine (300 microM) completely reversed the inhibitory effect of L-NMMA. 5. The EFS-elicited relaxation (4 Hz) was potentiated by 1 microM zaprinast, a type V phosphodiesterase inhibitor which inhibits guanosine 3':5'-cyclic monophosphate (cyclic GMP) degradation, but was unaffected by 0.1 microM zardaverine, a type III/IV phosphodiesterase inhibitor which inhibits cyclic AMP degradation. 6. EFS (50 V, 0.2 ms, 16 Hz) induced a 3 fold increase in tissue cyclic GMP content, an action which was inhibited by L-NMMA (100 microM). 7. Pyrogallol (100microM), a superoxide anion generator, also inhibited the EFS-induced relaxation by 53 +/- 9%, and this effect was prevented by superoxide dismutase.8. Chemical sympathetic denervation with 6-hydroxydopamine had no effect on the relaxant response to EFS in the endothelium-denuded PA rings.9. In endothelium-denuded branch PA rings at resting tone, L-NMMA (100 microM) significantly augmented the adrenergic contractile response, an effect which was completely reversed by L-arginine,but not by D-arginine. In the same groups of vessel rings, L-NMMA had no significant effect on the matched contractile response to exogenous noradrenaline.10. These results suggest that NO may be released from intramural nerve endings other than adrenergic nerves (probably NANC nerves), and this leads to vasodilatation via activation of guanylyl cyclase.
3',5'-Cyclic-GMP Phosphodiesterases↗
Chronic hypoxia impairs soluble guanylyl cyclase-mediated pulmonary arterial relaxation in the rat.
We have examined the effects of exposing rats to hypoxia (10% fractional inspired O2 concentration) for 2 and 7 days on endothelium-dependent and -independent vasodilation and also on the ability of guanosine 3',5'-cyclic monophosphate (cGMP) to activate cGMP-dependent protein kinase (G-kinase) in rat conduit pulmonary arteries (PA). The ability of acetylcholine (ACh) and sodium nitroprusside (SNP) to both relax PA rings and elevate tissue cGMP levels was significantly attenuated in PA from hypoxic animals. The ability of atrial natriuretic peptide to relax and generate cGMP in PA rings was unchanged by hypoxia. Relaxation and elevation of cGMP levels induced by SNP in aortic rings was unaltered by hypoxia. Similarly, hypoxia did not alter the concentration-dependent activation by exogenous cGMP of G-kinase. We conclude that chronic exposure of rats to hypoxia results in a selective impairment of soluble guanylyl cyclase in rat PA, leading to an attenuation of ACh- and SNP-induced cGMP accumulation and relaxation.
Animals↗
Effect of tumor necrosis factor on hypoxic pulmonary vasoconstriction.
The effects of tumor necrosis factor (TNF) on hypoxic pulmonary vasoconstriction (HPV) and endothelium-dependent relaxation were examined in a blood-perfused rat lung preparation. Lungs from TNF-treated rats (0.26 mg/kg iv 12 h before experimentation) had a significantly greater HPV and a reduced vasorelaxant response to the endothelium-dependent vasodilator acetylcholine (ACh) but a similar vasorelaxant response to the endothelium-independent vasodilator nitroprusside compared with lungs from control rats (pretreated with 0.1 ml saline iv). Pentoxifylline (20 mg/kg iv and ip 20 min before administration of TNF) had no detectable effect on either HPV or ACh-induced relaxation but completely negated the augmentation on HPV and the inhibiting action on ACh-induced relaxation caused by TNF. The TNF effect on ACh relaxation was unaffected by pretreatment with L-arginine. These results indicate that TNF induces endothelial dysfunction and enhances HPV, effects that are inhibited by pentoxifylline.
Acetylcholine↗
Endothelin-3 is a potent pulmonary vasodilator in the rat.
The properties of endothelin-3 (ET-3) were investigated in isolated pulmonary artery rings and isolated blood-perfused lungs of the rat. ET-3 elicited a concentration-dependent relaxation of pulmonary artery rings, and effect inhibited by the nitric oxide synthesis inhibitor L-NG-monomethyl-L-arginine. At 0.1 microM, the response to ET-3 was biphasic, resulting in a sustained contraction. In the isolated lung, ET-3 caused a dose-dependent increase in pulmonary arterial pressure. In lungs ventilated with 3% oxygen, 10 nM ET-3 completely reversed the resultant hypoxic vasoconstriction (HPV) by 100 +/- 8%, an effect unchanged by either indomethacin (1 microM) or glibenclamide (10 microM). L-NG-monomethyl-L-arginine attenuated both the ET-3 dilation in prostaglandin F2 alpha-constricted lungs and the dose-dependent vasodilation of HPV by acetylcholine. ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged. These results demonstrate that ET-3 has both vasodilator and constrictor actions in the rat lung and that, like acetylcholine, the former is mediated in part via the release of nitric oxide. ET-3 also has the ability to modulate HPV.
Animals↗
Pulmonary endothelial permeability following lung transplantation.
During lung transplantation, a number of factors may cause endothelial injury to the donor organ, including ischemia, inadequate preservation, cardiopulmonary bypass, high potassium concentrations, and reperfusion. In this study, protein accumulation index (PAI) was used to assess pulmonary endothelial permeability (PEP) in ten patients immediately after lung transplantation. Six were studied sequentially every other day for ten days postoperatively. The PAI was also measured using the same technique in a group of 11 normal volunteers. Mean PAI x 10(-3)/min +/- (SEM) for ten patients measured within 36 h of transplantation was 1.27 (0.56) compared with 0.45 (0.08) for the normal group (p = 0.09). No correlation was found between preservation time and PAI following reperfusion. Three episodes of lung rejection were observed in two patients during the first ten postoperative days, during which PAI rose to 2.26 (0.26) compared with 0.73 (0.11) for all other studies in the group (p less than 0.01). We conclude that no increase in PEP could be demonstrated after graft reperfusion following lung transplantation as assessed by PAI in this small group of patients. However, further studies may show the technique to be useful in the detection of subsequent episodes of graft rejection.
Cell Membrane Permeability↗
Serial assessment of pulmonary microvascular permeability in a patient developing the adult respiratory distress syndrome.
Serial measurements of lung extravascular accumulation of 113mIndium-transferrin were made in a patient with acute respiratory failure during the development of the adult respiratory distress syndrome (ARDS). Abnormality of this index of pulmonary microvascular permeability antedated radiological change and appeared to predict the onset of frank ARDS.
Capillary Permeability↗
Endothelium-dependent nonadrenergic, noncholinergic neural relaxation in guinea pig pulmonary artery.
The presence and the possible mechanism of action of the inhibitory nonadrenergic, noncholinergic nerve system (i-NANC) were investigated in guinea pig pulmonary artery (PA) precontracted with U44069 (a thromboxane analog). In the presence of alpha adrenergic blockage, electrical field stimulation induced a frequency-dependent, tetrodotoxin-sensitive relaxation. This relaxation was reduced by 9.1 +/- 1.9 and 19.4 +/- 2.8% by atropine (1 microM) and combined atropine and propranolol (both 1 microM), indicating that the main component is mediated by i-NANC neural mechanisms. In the branch PA rings, this i-NANC relaxation was unaffected by pretreatment with a cyclooxygenase inhibitor (indomethacin, 10 microM), 5-lipoxygenase inhibitor (A63162, 1 microM) or substance P desensitization, but was inhibited markedly by the P2y-purinoceptor antagonist reactive blue 2 (30 microM) and slightly potentiated by the peptidase alpha-chymotrypsin (2 U/ml). L-NG-monomethyl-arginine(L-NMMA), a nitric oxide synthesis inhibitor, caused a concentration-dependent inhibition of the i-NANC relaxation (53.9 +/- 4.1% at 100 microM), but had no effect on equivalent nitroprusside-induced relaxation. The inhibitory effect of L-NMMA was reversed completely by L-arginine (300 microM), but not by D-arginine (300 microM). Removal of vascular endothelium greatly reduced the i-NANC relaxation in the branch PA rings, but had no effect on i-NANC relaxation in main PA rings. Both in vivo capsaicinization and in vitro desensitization with capsaicin (1 microM) caused a significant reduction of the i-NANC relaxation in main PA, but had no significant effect in the branch PA.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetamides↗
Blood lactate and mixed venous-arterial PCO2 gradient as indices of poor peripheral perfusion following cardiopulmonary bypass surgery.
Conventional indices of tissue perfusion after surgery involving cardiopulmonary bypass (CPB) may not accurately reflect disordered cell metabolism. Venous hypercarbia leading to an increased veno-arterial difference in CO2 tensions (V-aCO2 gradient) has been shown to reflect critical reductions in systemic and pulmonary blood flow that occur during cardiorespiratory arrest and septic shock. We therefore measured plasma lactate levels and V-aCO2 gradients in 10 patients (mean age 57.2 years) following CPB and compared them with conventional indices of tissue perfusion. Plasma lactate levels, cardiac index (CI) and oxygen uptake (VO2) all increased significantly (p less than 0.05 vs baseline levels) up to 3 h following surgery. Oxygen delivery (DO2) did not change. Plasma lactate levels correlated significantly with CI (r = 0.47, p less than 0.01). V-aCO2 fell significantly with time (p less than 0.01 vs baseline). There was an inverse relationship between V-aCO2 and cardiac index and V-aCO2 and lactate (r = -0.37, p less than 0.05; r = -0.3, p less than 0.05 respectively). We conclude that blood lactate, CI and VO2 increase progressively following CPB. An increase in lactate was associated with a decrease in V-aCO2. An increase in V-aCO2 was not therefore associated with evidence of inadequate tissue perfusion as indicated by an increased blood lactate concentration.
Acidosis, Lactic↗
Heart-lung transplantation for adult respiratory distress syndrome.
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Adult↗