Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, ...Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.展开更多
Objective:To observe the effects of electroacupuncture(EA)of different frequencies on transmission function,electromyography,nitric oxide synthase(NOS)content and interstitial cells of Cajal(ICC)expression of colon in...Objective:To observe the effects of electroacupuncture(EA)of different frequencies on transmission function,electromyography,nitric oxide synthase(NOS)content and interstitial cells of Cajal(ICC)expression of colon in rat models with slow transit constipation(STC).Methods:Of the 50 healthy male Wistar rats,10 were randomly selected as a normal group and fed with ordinary diet,and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw)each day for continuous 120 d.The 40 successfully established STC rat models were randomly divided into a model group,a low-frequency EA group(2 Hz),a high-frequency EA group(100 Hz),and a variable-frequency EA group(2 Hz/100 Hz),with 10 rats in each group.Rats in the normal and the model groups were not given any treatment;the low-frequency EA and the high-frequency EA groups were given EA at Tianshu(ST 25),Zusanli(ST 36)and Zhigou(TE 6)with continuous wave at the designated frequency,and the variable-frequency EA group received sparse-dense wave(2 Hz/100 Hz)EA at the same acupoints,once a day for a total of 15 d.After treatment,the colonic transmission function,electromyography,NOS content and ICC expression(calculated by the difference in the area of the C-kit positive cells)of the rats in each group were measured.Results:For the colonic transmission function,compared with the normal group,the first black stool excretion durations of rats in the other groups were significantly prolonged(all P<0.05);compared with the model group,the first black stool excretion durations of rats in the three EA groups were significantly shortened(all P<0.05),which was significantly shorter in the variable-frequency EA group than in the low-frequency EA and high-frequency EA groups(both P<0.05).For the colonic electromyography,compared with the normal group,the amplitude was significantly increased and the frequency was accelerated in rats of the other groups(all P<0.05);compared with the model group,the amplitude was significantly reduced and the frequency was slowed down in the three EA groups(both P<0.05);compared with the low-frequency EA and the high-frequency EA groups,the amplitude was reduced and the frequency was significantly reduced in rats of the variable-frequency EA group(both P<0.05).Compared with the normal group,the colonic NOS contents were significantly increased in the other groups(all P<0.05);compared with the model group,the NOS contents were significantly reduced in the three EA groups(all P<0.05);compared with the low-frequency EA and the high-frequency EA groups,the content was significantly reduced in the variable-frequency EA group(all P<0.05).For the area of rat colonic C-kit-positive cells,compared with the normal group,the areas were significantly reduced in rats of other groups(all P<0.05);compared with the model group,the areas were increased significantly in the three EA groups(all P<0.05);compared with the low-frequency EA group,the area was increased significantly in the variable-frequency EA group(P<0.05).Conclusion:EA,especially EA at the 2 Hz/100 Hz variable-frequency,has a positive treatment effect on the STC model rats.It may improve rats'colonic function by regulating the electromyography,NOS content and ICC expression of colon.展开更多
基金This study was supported by a grant from Education Government Foundation of Shanxi Province, China(No. 2003105).
文摘Promethazine, a first generation antihistamine,has an antiarrhythmic effect on ischemia-reperfusion inducing arrhythmias^1 and experimental arrhythmias.^2 However, terfenadine as a second generation of antihistamine, has been reported to elicit hypotension, bradycardia, prolongation of the QTc interval and torsades de pointes （TdP） like ventricular arrhythmia.^3 This may be due to the blockage on rectifier postassium current （Ik） of terfenadine, resulting in the prolongation of the action potential duration （APD） and dispersion of the repolarization duration, which might provoke a specific form of polymorphic ventricular tachydysrhythmia, i.e. TdP.^4 In clinical practice,however, the class Ⅲ antiarrhythmic agents, which target on the lk and prolong the action potential duration and QTc interval, rarely lead to arrhythmias.Other actions must be considered to underlie the arrhythmogenic tendency of terfenadine besides its inhibition on Ik. Though both promethazine and terfenadine block the H1 receptor, there must be a different pharmacology profile between the two compounds on ion channels of cardiac myocytes.Whole-cell patch clamp technique was used to investigate the effects of these two antagonists of the H1 receptor on the main ion currents in cardiac electrical activities.
文摘Objective:To observe the effects of electroacupuncture(EA)of different frequencies on transmission function,electromyography,nitric oxide synthase(NOS)content and interstitial cells of Cajal(ICC)expression of colon in rat models with slow transit constipation(STC).Methods:Of the 50 healthy male Wistar rats,10 were randomly selected as a normal group and fed with ordinary diet,and the remaining 40 rats were fed with the diet added with the compound diphenoxylate at a dose of 8 mg/(kg·bw)each day for continuous 120 d.The 40 successfully established STC rat models were randomly divided into a model group,a low-frequency EA group(2 Hz),a high-frequency EA group(100 Hz),and a variable-frequency EA group(2 Hz/100 Hz),with 10 rats in each group.Rats in the normal and the model groups were not given any treatment;the low-frequency EA and the high-frequency EA groups were given EA at Tianshu(ST 25),Zusanli(ST 36)and Zhigou(TE 6)with continuous wave at the designated frequency,and the variable-frequency EA group received sparse-dense wave(2 Hz/100 Hz)EA at the same acupoints,once a day for a total of 15 d.After treatment,the colonic transmission function,electromyography,NOS content and ICC expression(calculated by the difference in the area of the C-kit positive cells)of the rats in each group were measured.Results:For the colonic transmission function,compared with the normal group,the first black stool excretion durations of rats in the other groups were significantly prolonged(all P<0.05);compared with the model group,the first black stool excretion durations of rats in the three EA groups were significantly shortened(all P<0.05),which was significantly shorter in the variable-frequency EA group than in the low-frequency EA and high-frequency EA groups(both P<0.05).For the colonic electromyography,compared with the normal group,the amplitude was significantly increased and the frequency was accelerated in rats of the other groups(all P<0.05);compared with the model group,the amplitude was significantly reduced and the frequency was slowed down in the three EA groups(both P<0.05);compared with the low-frequency EA and the high-frequency EA groups,the amplitude was reduced and the frequency was significantly reduced in rats of the variable-frequency EA group(both P<0.05).Compared with the normal group,the colonic NOS contents were significantly increased in the other groups(all P<0.05);compared with the model group,the NOS contents were significantly reduced in the three EA groups(all P<0.05);compared with the low-frequency EA and the high-frequency EA groups,the content was significantly reduced in the variable-frequency EA group(all P<0.05).For the area of rat colonic C-kit-positive cells,compared with the normal group,the areas were significantly reduced in rats of other groups(all P<0.05);compared with the model group,the areas were increased significantly in the three EA groups(all P<0.05);compared with the low-frequency EA group,the area was increased significantly in the variable-frequency EA group(P<0.05).Conclusion:EA,especially EA at the 2 Hz/100 Hz variable-frequency,has a positive treatment effect on the STC model rats.It may improve rats'colonic function by regulating the electromyography,NOS content and ICC expression of colon.
