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Methylene blue reduces pulmonary oedema and cyclo-oxygenase products in endotoxaemic sheep

¹ Dept of Anaesthesiology and ² Dept of Internal Medicine, Faculty of Medicine, University of Tromsø, Tromsø, and ³ Dept of Immunology and Transfusion Medicine, Nordland Central Hospital and University of Tromsø, Bodø, Norway

CORRESPONDENCE: O.V. Evgenov, Dept of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114, USA. Fax: 1 6177263032. E-mail: oleg_evgenov@hotmail.com

Keywords: endotoxin, extravascular lung water, methylene blue, pulmonary circulation, 6-keto-prostaglandin F₁, thromboxane B₂

Received: June 27, 2001
Accepted May 31, 2002

This study was supported in part by the Research Council of Norway (grant 120473/730), the Laerdal Foundation for Acute Medicine, and departmental funds.

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·kg^–1 or isotonic saline. Thirty minutes later, all sheep received an intravenous infusion of Escherichia coli endotoxin 1 µg·kg^–1 for 20 min and either an intravenous infusion of MB 2.5 mg·kg^–1·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 F₁, 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.

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