Dimethylthiourea attenuates endotoxin-induced acute respiratory failure in pigs

1987 ◽  
Vol 63 (6) ◽  
pp. 2426-2432 ◽  
Author(s):  
N. C. Olson ◽  
D. L. Anderson ◽  
M. K. Grizzle
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Membrane Permeability ◽  
Phase 1 ◽  
Weight Ratio ◽  
Albumin Concentration ◽  
Phase 2 ◽  
Lung Water ◽  
Capillary Membrane ◽  
Alveolar Capillary

We hypothesized that toxic O2 radicals might be important mediators of endotoxin-induced acute respiratory failure in pigs. As a relatively specific scavenger of .OH, we infused dimethylthiourea (DMTU, 1 g/kg) before endotoxemia. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0–2 h) and phase 2 (i.e., 2–4.5 h), endotoxin decreased cardiac index (CI) and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDo2), and hematocrit (Hct). Endotoxemia also caused leukopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet weight-to-dry weight ratio of bloodless lung. Dimethylthiourea did not significantly modify the phase 1 response. However, during phase 2, DMTU attenuated the endotoxin-induced decrease in CI and increases in Ppa, PVR, Hct, AaDo2, lung water, and BALF albumin concentration. In separate groups of endotoxin- and DMTU + endotoxin-treated pigs, lung microvascular hydrostatic pressure was increased to approximately 16 Torr (by fluid overload) to assess alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced increase in alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced induced increase in alveolar-capillary membrane permeability. We conclude that .OH (and possibly H2O2) significantly contributes to endotoxin-induced lung injury in anesthetized pigs.

Dexamethasone and indomethacin modify endotoxin-induced respiratory failure in pigs

1985 ◽  
Vol 58 (1) ◽  
pp. 274-284 ◽  
Author(s):  
N. C. Olson ◽  
T. T. Brown ◽  
D. L. Anderson
Keyword(s):  
Respiratory Failure ◽  
Phase 1 ◽  
Dynamic Compliance ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Arachidonic Acid Metabolism ◽  
Antiinflammatory Drugs ◽  
Lung Water ◽  
Pulmonary Response ◽  
Flunixin Meglumine ◽  
Before And After

We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0–2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2–4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.

scholarly journals Effects of Ischemic Acute Kidney Injury on Lung Water Balance: Nephrogenic Pulmonary Edema?

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Rajit K. Basu ◽  
Derek Wheeler
Keyword(s):  
Acute Kidney Injury ◽  
Pulmonary Edema ◽  
Disease Process ◽  
Kidney Injury ◽  
Fluid Accumulation ◽  
Lung Water ◽  
Edema Formation ◽  
Bulk Fluid ◽  
Capillary Membrane ◽  
Alveolar Capillary

Pulmonary edema worsens the morbidity and increases the mortality of critically ill patients. Mechanistically, edema formation in the lung is a result of net flow across the alveolar capillary membrane, dependent on the relationship of hydrostatic and oncotic pressures. Traditionally, the contribution of acute kidney injury (AKI) to the formation of pulmonary edema has been attributed to bulk fluid accumulation, increasing capillary hydrostatic pressure and the gradient favoring net flow into the alveolar spaces. Recent research has revealed more subtle, and distant, effects of AKI. In this review we discuss the concept of nephrogenic pulmonary edema. Pro-inflammatory gene upregulation, chemokine over-expression, altered biochemical channel function, and apoptotic dysregulation manifest in the lung are now understood as “extra-renal” and pulmonary effects of AKI. AKI should be counted as a disease process that alters the endothelial integrity of the alveolar capillary barrier and has the potential to overpower the ability of the lung to regulate fluid balance. Nephrogenic pulmonary edema, therefore, is the net effect of fluid accumulation in the lung as a result of both the macroscopic and microscopic effects of AKI.

Capsaicin pretreatment attenuates monocrotaline-induced ventilatory dysfunction and pulmonary hypertension

1993 ◽  
Vol 75 (6) ◽  
pp. 2781-2788 ◽  
Author(s):  
K. R. Zhou ◽  
Y. L. Lai
Keyword(s):  
Pulmonary Hypertension ◽  
Substance P ◽  
Tissue Injury ◽  
Phase 1 ◽  
Weight Ratio ◽  
Functional Study ◽  
Control Group ◽  
Neurokinin A ◽  
Phase 2 ◽  
Phase 3

In view of bronchoconstrictor and proliferative effects of tachykinins (TKs; mainly substance P and neurokinin A), as well as increased TK release during tissue injury, we hypothesized that monocrotaline (MCT)-induced ventilatory dysfunction and pulmonary hypertension may be mediated via TKs. In phase 1 of the study (n = 19 rats), we tested and found that elevated lung substance P level and suppressed neutral endopeptidase activity occurred 1–2 wk post-MCT (60 mg/kg sc). Both phase 2 (n = 32) and phase 3 (n = 32) young Sprague-Dawley rats were divided into five groups: control, sham, capsaicin, MCT, and capsaicin + MCT. Rats in the control group received no treatment. Each sham rat received the vehicles. Chronic capsaicin treatment was used to deplete neuropeptides. Each MCT rat received a single injection of MCT 1 wk (phase 2) or 3 wk (phase 3) before the functional study. Each capsaicin + MCT rat received the MCT administration 3 days after the completion of capsaicin pretreatment. In the MCT group, there were significant decreases in dynamic compliance, quasi-static compliance, and the maximal expiratory flow rate at 50% total lung capacity in phase 2, which was accompanied by significant increases in pulmonary arterial pressure, the weight ratio of right ventricle/(left ventricle + septum), and the arterial medial wall thickness in phase 3. In the capsaicin + MCT group, however, all the above MCT-induced changes were significantly attenuated or abolished. All values from the sham and capsaicin groups were not significantly different from those of the control group. These data demonstrate that MCT induces pneumotoxicity, accompanied by elevated levels of substance P in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Sign in / Sign up

Export Citation Format

Share Document