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Updated: Oct 3, 2026
A Reproducible Intensive Care Unit-Oriented Endotoxin Model in Rats
Published on: February 20, 2021
Continuously infused methylene blue modulates the early cardiopulmonary response to endotoxin in awake sheep
O V Evgenov1, B Sveinbjørnsson, L J Bjertnaes
1Department of Anesthesiology, Faculty of Medicine, University of Tromsø, Tromsø, Norway.
Background:
In endotoxemia and septic shock, enhanced generation of endogenous nitric oxide (NO) contributes to myocardial depression, hypotension, and derangement of gas exchange. We hypothesized that continuous infusion of methylene blue (MB), an inhibitor of the NO pathway, would counteract these effects in endotoxemic sheep.
Methods:
Twenty-one sheep were anesthetized and instrumented for a chronic study with vascular catheters. On the day of the experiment, 18 conscious animals randomly received either an intravenous injection of MB 10 mg x kg(-1) or isotonic saline. Thirty minutes later, sheep received a 20-min intravenous infusion of Escherichia coli endotoxin 1 microg x kg(-1) and either an intravenous infusion of MB 2.5 mg x kg(-1) x h(-1) or isotonic saline, respectively, for 5 h. In addition, 3 animals were exposed to the same dose of MB alone.
Results:
MB reduced the early endotoxin-induced declines in stroke volume, left ventricular stroke work and cardiac indices, and prevented mean arterial pressure from falling. Moreover, MB ameliorated the increases in pulmonary arterial pressure and pulmonary vascular resistance index. In addition, MB reduced the increments in venous admixture and AaPO2, decreased the falls in PaO2, SaO2, and oxygen delivery, and maintained oxygen consumption. MB also prevented the rises in body temperature and plasma nitrites and nitrates, and delayed the elevation of plasma lactate. When given alone to healthy sheep, MB transiently reduced plasma lactate and PaO2, and increased AaPO2.
Conclusion:
In ovine endotoxemia, continuously infused MB counteracts the early myocardial dysfunction and derangement of hemodynamics and gas exchange.
Insights
Methylene blue (MB) infusion counteracts myocardial depression and hypotension in endotoxemia by inhibiting nitric oxide (NO) pathways. This study shows MB improves hemodynamics and gas exchange in endotoxemic sheep.
Area of Science:
- Cardiovascular Physiology
- Sepsis Pathophysiology
- Pharmacology
Background:
- Endotoxemia and septic shock involve increased nitric oxide (NO) production, leading to myocardial depression, hypotension, and impaired gas exchange.
- Methylene blue (MB) is an inhibitor of the NO pathway.
Purpose of the Study:
- To investigate the hypothesis that continuous infusion of MB would counteract the detrimental effects of NO in endotoxemic sheep.
Main Methods:
- Twenty-one instrumented sheep received either MB or saline intravenously, followed by Escherichia coli endotoxin infusion.
- MB was administered as an initial bolus and continuous infusion during endotoxemia.
- Control groups received saline or MB alone.
Main Results:
- MB prevented endotoxin-induced decreases in stroke volume, cardiac indices, and mean arterial pressure.
- MB ameliorated pulmonary hypertension and improved oxygenation and delivery.
- MB prevented hyperthermia, reduced plasma nitrites/nitrates, and delayed lactate elevation.
Conclusions:
- Continuous MB infusion effectively counteracts early myocardial dysfunction, hemodynamic derangement, and gas exchange abnormalities in ovine endotoxemia.
- MB demonstrates therapeutic potential in managing sepsis-induced cardiovascular and respiratory compromise.
