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Pain is a common and crucial problem in clinical practice, because it has a profound influence on patients in perioperative period. Butorphanol, among plenty of analgesics, is widely used in clinical trials for its various advantages and better analgesic effects. As a typical agonist-antagonist opioid analgesic agent, butorphanol, however, shows different clinical manifestations with different affinity for opioid receptors 25∶4∶1 (κ∶μ∶δ). Besides, butorphanol provides remarkable analgesic and sedative effect in preemptive analgesia, induction and recovery period in general anesthesia, and postoperative analgesia And it could be as a adjuvant to local anaesthesia either. Compared with other opioid drugs, butorphanol is less likely to have side effect on respiratory depression. In addition, its physical dependence is extremely low.
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By reviewing the literature regarding the development mechanism of myocardial stunning, effects of acupuncture on myocardial ischemic injury, and correlation between acupuncture and κ-opioid receptor, it was suggested that acupuncture was highly likely to act on κ-opioid receptor in myocardial cells, and directly treated myocardial malfunction induced by myocardial stunning through κ-opioid receptor and its signaling pathway. In addition, acupuncture could inhabit the signaling pathway of adrenoceptor β1, one of the main functional receptors, to indirectly improve myocardial ischemic injury. From κ-opioid receptor signaling pathway, the action mechanism of acupuncture for prevention and treatment of myocardial stunning was discussed in this paper, hoping to provide new ideas for possible mechanism of acupuncture for myocardial ischemic injury.
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Objective To explore the effect and mechanism of intrathecal injecting κ-opioid receptor agonist U50, 488H on the rats with myocardial ischemia/reperfusion injury.Methods 50 Sprague–Dawley rats were randomly divided into five groups (n=10): sham group (Sham), ischemia/reperfusion group (IR), high-dose intravenous injection group (IV1), low-dose intravenous injection group (IV2), and intrathecal injection group (IT).In sham group the rats were followed by the modeling step without ligation of the left coronary and no drug injection by intravenous or intrathecal; in IR group the rats were underwent 30 minutes of myocardial ischemia followed by 120 minutes of reperfusion, and were not treated with any drug.All the rats in IV1, IV2 and IT groups were intravenous injected with U50, 488H at 1 hour before they were underwent myocardial ischemia/reperfusion as in IR group.IV1 and IV2 groups were intravenous injected with U50, 488H respectively at the dose of 0.1 mg/kg and 0.01 mg/kg, while the IT group was intrathecal injected with U50, 488H at the dose of 0.01mg/kg.All the rats from 5 groups were observed with cardiac ultrasound, myocardial sirius staining, serum CGRP and ET level.Results Compared to IR group(EF%=35.4 ±1.1,FS% =21.1 ±1.1), the rats in IT group (EF%=49.1 ±1.2,FS%=27.1 ±1.0) and IV1 group (EF%=46.3 ±2.2,FS%=26.6 ±0.6) showed better myocardial contraction (P<0.05) and reduced myocardial fibrosis (P<0.05).IT group and IV1 group also showed reduced ET but increased CGRP in the serum (P<0.05).There were no difference between IV2 group and IR group in both observation.Conclusion Pretreatment with intrathecal injection of opium κ-receptor stimulant U50, 488H not only protected the myocardial function from myocardial ischemia/reperfusion injury, but also repressed myocardial fibrosis.The protection may result from modulation of CGRP and ET.
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Background: Opioid analgesics, which are classifi ed as μ-opioid receptor agonists, are known to induce spasms or contraction of the sphincter of Oddi (SO), thereby inducing or exacerbating biliary diseases such as biliary obstruction, gallbladder dysfunction, cholelithiasis, pancreatitis, biliary dyskinesia, cholangitis, and cholecystitis. However, effects of κ-opioid receptor agonists on SO contraction have not been clarifi ed. In the present study, we investigated the effect of nalfurafi ne hydrochloride (nalfurafi ne), (E)-N-[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3- (furan-3-yl)-N-methylprop-2-enamide monohydrochloride, a selective κ-opioid receptor agonist, on spontaneous contraction of rabbit SO. Methods: SO contraction was measured using manometry in anesthetized rabbits. Rabbits were anesthetized with intravenous administration of 25 mg/kg sodium pentobarbital. An open tip catheter was inserted into the common bile duct toward the SO ampullae. Saline was perfused through the lumen of the open tip catheter at a constant rate of 6 ml/hr using a syringe pump. Nalfurafi ne, morphine, and pentazocine were intravenously (i.v.) administered and perfusion pressure was recorded. Results: Morphine (0.3 mg/kg, i.v.) and pentazocine (3 mg/kg, i.v.) were found to increase SO perfusion pressure, suggesting that these opioid analgesics may cause SO contraction. In contrast, nalfurafi ne (0.2 μg/kg, i.v.) decreased the perfusion pressure, indicating that this κ-opioid receptor agonist suppresses SO contraction. Conclusions: These fi ndings suggest that nalfurafi ne is unlikely to induce or exacerbate biliary diseases and may be safely used in patients with these disorders.
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Aim To investigate the effect of U50488H(a selective κ-opioid receptor agonist)and isoproterenol(ISO,a β-adrenergic receptor agonist)on ventricular arrhythmias and Cx43 during myocardial ischemia and reperfusion in rats.Methods 60 rats were randomly divided into five groups,ie,normal control group,I/R group,ISO+I/R group,U50488H+ISO+I/R group,Nor-BNI+U50488H+ISO+I/R group.The incidence of ventricular arrhythmias and arrhythmia score were determined. The expression of Cx43mRNA was tested by RT-PCR.The expression of Cx43 protein in myocardial cell was tested by an immunohistochemical approach with a quantitative imaging system.Results ① Compared with the I/R group,arrhythmia score was increased with administration of ISO(P<0.05).U50488H intravenously injected before ISO significantly decreased the arrhythmia score(P<0.05).② Compared with the normal control group,the expression of Cx43 mRNA was decreased in the I/R group(P<0.05).With administration of ISO,the amount of Cx43 mRNA was not significantly increased.③ Compared with normal control group,total and phosphorylated Cx43 proteins were significantly decreased in the I/R group(P<0.05),and the phosphorylated Cx43 was also decreased with administration of ISO.Compared with ISO+I/R group,phosphorylated Cx43 was increased with administration of U50488H (P<0.05).Conclusion κ-opioid receptor agonist U50488 H antagonizes the arrhythmias through the regulation of Cx43 during myocardial ischemia and reperfusion via inhibiting β-adrenergic receptor pathway.