The Concentration-Dependent Contractile Effect of Methylene Blue in the Human Internal Mammary Artery: A Quantitative Approach to Its Use in the Vasoplegic Syndrome

Objective: To quantitate the contractile effect of methylene blue on isolated human internal mammary artery (IMA) as used in the vasoplegic syndrome. Design: An in vitro experimental study. Setting: Cardiovascular Pharmacology Laboratory, Department of Medical Pharmacology. Participants: IMA segments were used from 24 patients undergoing coronary artery bypass surgery. Interventions: The responses to methylene blue, norepinephrine, and acetylcholine were recorded isometrically by a force-displacement transducer in an isolated organ bath. Measurement and Main Results: Methylene blue (10 nmol/L-100 μmol/L) produced concentration-dependent contraction in the arteries. The maximal contraction to methylene blue was 44.2% ± 3.8% of KCl (68 mmol/L) maximum contraction; the pEC50 (−log10 of 50% effective concentration) value was 5.5 ± 0.1. Methylene blue caused an insignificant leftward shift of the concentration-response curve of norepinephrine. Acetylcholine-induced relaxation in submaximal contracted rings with phenylephrine recovered nearly 6 hours after the methylene blue challenge. Conclusion: Methylene blue caused concentration-dependent contraction in human IMAs. Furthermore, the inhibition of ACh-induced relaxation for 6 hours after the methylene blue challenge points out an additional mechanism (ie, receptor occupation). The concentration-dependent contractile effect of methylene blue justifies its use in the vasoplegic syndrome. The findings also suggest that the time course of contraction is longer than the exposure to methylene blue.