Purpose Levobupivacaine was developed as an alternative long-acting local anesthetic with a clinical profile similar to that of bupivacaine but with lower potential to induce systemic toxicity. Levobupivacaine has biphasic vasoactivities, namely, vasoconstriction at a low concentration and vasodilatation at a high concentration. The purpose of this study was to investigate the mechanisms underlying the vasoconstriction induced by levobupivacaine. Methods Functional examinations were performed in Krebs solution using isolated thoracic aortic rings from male Wistar rats. Changes in ring tension induced by levobupivacaine were measured on intact or endothelium-denuded rings. Changes in tension induced by levobupivacaine were also measured in the presence of EGTA in Ca^2＋-free solution or in the presence of L-type Ca^2＋-channel blocker(nifedipine). In addition, functional examinations were performed in the presence of various inhibitors: 2-APB(IP3 receptor inhibitor), ML-7(MLCK inhibitor), staurosporine(PKC inhibitor), H1152(ROK inhibitor), PD98059(ERK inhibitor) and phentolamine(α1-inhibitor). Results Levobupivacaine induced vasoconstriction in intact aortic rings as strongly as that in endothelium-denuded aortic rings. In Ca^2＋-free Krebs solution with EGTA, levobupivacaine could not induce contraction at all. High-concentration levobupivacaine induced limited contraction in the presence of nifedipine. 2-APB and ML-7 inhibited levobupivacaine-induced vasoconstriction. Staurosporine, H1152 and PD98059 inhibited both phenylephrine- and levobupivacaine-induced vasoconstriction to the same degree. The inhibitory effect of phentolamine on levobupivacaine-induced vasoconstriction was limited. Conclusion Levobupivacaine-induced vasoconstriction was independent of the endothelium. Both Ca^2＋-dependent pathway, that is, extracellular Ca^2＋＋influx and sarcoplasmic reticulum Ca^2＋ efflux including IP3 and MLCK pathway, and Ca^2＋-independent pathway(PKC, ROK, and ERK pathway), which increases myofilament Ca^2＋ sensitivity, participated in the contraction induced by levobupivacaine.

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Distigmine bromide, a cholinesterase inhibitor widely used for the treatment of underactive neurogenic bladder, can occasionally precipitate cholinergic crisis. We report a 67-year-old woman with neurogenic bladder who had been taking 5mg distigmine bromide orally daily for two years, but developed severe bradycardia when she became dehydrated as a result of diarrhea. She was admitted to the emergency department of our hospital with severe diarrhoea and respiratory failure, and subsequently suffered severe bradycardia. She was soon resuscitated with intravenous injections of atropine and adrenalin, accompanied by insertion of a temporary pacemaker. She was diagnosed with cholinergic crisis induced by distigmine bromide, with myosis and excess salivation. This case suggests that even a small dose of distigmine bromide can induce cholinergic crisis during dehydration caused by severe diarrhoea.

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