Related Experiment Video
Updated: Sep 28, 2026
Visualizing Lung Cellular Adaptations during Combined Ozone and LPS Induced Murine Acute Lung Injury
Published on: March 21, 2021
Methylene blue reduces pulmonary oedema and cyclo-oxygenase products in endotoxaemic sheep
O V Evgenov1, N V Evgenov, T E Mollnes
1Dept of Anaesthesiology, Faculty of Medicine, University of Tromsø, Norway. oleg_evgenov@hotmail.com
Abstract:
The authors recently demonstrated that methylene blue (MB), an inhibitor of the nitric oxide (NO) pathway, reduces the increments in pulmonary capillary pressure, lung lymph flow and protein clearance in endotoxaemic sheep. In the present study, the authors examined whether MB influences pulmonary haemodynamics and accumulation of extravascular lung water (EVLW) by mechanisms other than the NO pathway. Sixteen awake, chronically-instrumented sheep randomly received either an intravenous injection of MB 10 mg x kg(-1) or isotonic saline. Thirty minutes later, all sheep received an intravenous infusion of Escherichia coli endotoxin 1 microg x kg(-1) for 20 min and either an intravenous infusion of MB 2.5 mg x kg(-1) x h(-1) or isotonic saline for 6 h. MB markedly attenuated the endotoxin-induced pulmonary hypertension and right ventricular failure, and reduced the accumulation of EVLW. Moreover, MB reduced the increments in plasma thromboxane B2 and 6-keto-prostaglandin F1alpha, and abolished the febrile response. However, MB had no effect on the changes in circulating neutrophils, serum hyaluronan, and total haemolytic activity of the alternative complement pathway. The authors conclude that in sheep, methylene blue attenuates the endotoxin-induced pulmonary hypertension and oedema, at least in part, by inhibiting the cyclo-oxygenase products of arachidonic acid. This is a novel effect of methylene blue in vivo.
Insights
Methylene blue (MB) reduces endotoxin-induced lung injury in sheep by inhibiting cyclo-oxygenase products, not solely the nitric oxide (NO) pathway. This study reveals a novel in vivo mechanism for MB in managing pulmonary hypertension and edema.
Area of Science:
- Cardiovascular Physiology
- Pulmonary Medicine
- Pharmacology
Background:
- Endotoxemia causes pulmonary hypertension and lung edema.
- Methylene blue (MB) previously inhibited the nitric oxide (NO) pathway, reducing endotoxin-induced lung injury.
- Further investigation is needed to explore MB's effects beyond the NO pathway.
Purpose of the Study:
- To investigate if methylene blue (MB) influences pulmonary hemodynamics and extravascular lung water (EVLW) via mechanisms independent of the nitric oxide (NO) pathway.
- To elucidate the role of cyclo-oxygenase (COX) products in MB's protective effects against endotoxemia.
Main Methods:
- Awake, chronically-instrumented sheep received either MB or saline intravenously.
- Escherichia coli endotoxin was infused, followed by continuous infusion of MB or saline.
- Pulmonary capillary pressure, lung lymph flow, EVLW, plasma thromboxane B2, 6-keto-prostaglandin F1alpha, neutrophils, hyaluronan, and complement activity were measured.
Main Results:
- Methylene blue (MB) significantly attenuated endotoxin-induced pulmonary hypertension, right ventricular failure, and reduced extravascular lung water (EVLW) accumulation.
- MB decreased plasma levels of thromboxane B2 and 6-keto-prostaglandin F1alpha, and abolished fever.
- MB did not affect circulating neutrophils, serum hyaluronan, or alternative complement pathway activity.
Conclusions:
- Methylene blue (MB) mitigates endotoxin-induced pulmonary hypertension and edema in sheep.
- These protective effects are, at least partly, mediated by the inhibition of cyclo-oxygenase products of arachidonic acid.
- This study demonstrates a novel in vivo mechanism of action for methylene blue in endotoxemia, independent of the nitric oxide (NO) pathway.