Preventive and therapeutic effects of penehyclidine hydrochloride on morphine-induced increased bladder pressure, urinary bladder sphincter pressure and histological damage in rabbits

摘要

Background Morphine has become the preferred drug for analgesia.However,analgesic doses of morphine can result in urinary retention,which is an intractable problem in clinical practice.Though bladder catheterization is one available therapeutic option,data supporting the technique's effectiveness are controversial.As a novel anti-cholinergic medicine developed in China,penehyclidine hydrochloride (PHC) exhibits greater selectivity for M3/M1 receptors than M2 receptors.Therefore,this study aimed to determine the efficacy of PHC in treating urinary retention.Methods Thirty-two healthy male New Zealand white rabbits were randomly divided in four groups (n=8 each) as follows:control group (C group),PHC low-dose group (PL group,0.01 mg/kg of PHC intramuscularly),PHC middle-dose group (PM group,0.02 mg/kg of PHC intramuscularly),and PHC high-dose group (PH group,0.05 mg/kg of PHC intramuscularly).All rabbits were injected intravenously with morphine (1 mg/kg) to induce urinary retention and different doses of PHC were injected intramuscularly in the PL,PM and PH groups.In the C group,1 ml saline was administered instead of PHC.The bladder pressure and the bladder sphincter pressure were recorded at different time points.The plasma concentration of PHC was measured at different time points with high performance liquid chromatography.Arterial blood pressure and heart rate (HR) were recorded at different time points.Results Bladder pressure and urinary bladder sphincter pressure rose significantly from 30 minutes after morphine administration until the end of the experiment.PHC markedly attenuated the elevations in pressure induced by morphine.Morphometric analysis also revealed histological damage,erythrocytes and ruptures of the microcirculation in regions of the submucosa and smooth muscle.Morphometric damage was ameliorated with PHC but not with saline.Hemodynamic data (mean arterial pressure (MAP) and HR) did not differ between groups over the observation period.Conclusions This study demonstrated that intravenous morphine significantly increased bladder pressure and urinary bladder sphincter pressure and induced histological damage in the bladder and urinary bladder sphincter.Importantly,preliminary data showed that PHC could decrease the extent of these changes.