Corneal lesions related to an anesthetic mixture of medetomidine, midazolam, and butorphanol treatment in rats

Abstract

An anesthetic mixture of medetomidine, midazolam and butorphanol (MMB) has been recently used in laboratory animals. We observed corneal opacity in nephrectomized rats that had undergone two operations under MMB anesthesia at 4 and 5 weeks of age. To evaluate the features of this corneal opacity, ophthalmic examinations were conducted in 83 nephrectomized rats, and 8 representative animals with corneal opacity were evaluated histopathologically 4 weeks after operation. The ophthalmic examinations revealed that 66/83 animals had corneal opacity, which was characterized histopathologically by mineralization with or without inflammation in the corneal stroma. In addition, to examine the possible causes of this corneal opacity, we investigated whether similar corneal changes were induced by the MMB anesthetic treatment in normal rats. The MMB anesthetic was administered twice to 4-and 5-weekold normal SD rats (5 animals/age) in the same manner as for the nephrectomized rats. Ophthalmic examinations were conducted in all the animals once a week, and the animals were necropsied 4 weeks after the first administration. In normal rats, similar corneal opacity was observed after the first administration, and increases in the severity and size of the corneal opacity were noted after the second administration.In conclusion, this study revealed the features of corneal opacity in rats undergoing nephrectomy under MMB anesthesia and the occurrence of similar corneal opacity in normal rats treated with MMB anesthetic. To the best of our knowledge, this is the first report of corneal opacity related to MMB anesthetic treatment in rats.

Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole

“…The combination between medetomidine, midazolam, and butorphanol (MMB) anesthetic is recently used in experimental animal studies as a substitute for ketamine or pentobarbital sodium ( 21 ). The anesthetic duration of MMB is longer than those of ketamine or pentobarbital sodium and is often associated with depression of respiration and circulation, and reduction of general motor activity and neuronal activity ( 21 ). These side effects may limit the usability of MMB in MI model induction.…”

“…More specifically, medetomidine causes significant cardio-respiratory depression ( 22 ). Atipamezole, a synthetic α2-adrenergic antagonist, can antagonize medetomidine-induced respiratory depression and results in rapid recovery from MMB anesthesia ( 21 ). Atipamezole is also effective for reducing the maintenance concentration of isoflurane which leads to the amelioration of cardio-respiratory depression induced by isoflurane ( 17 ).…”