| Objectives:To investigate the effects ofβ-blocker carvedilol on blood pressure,heart rate,Pmax,P wave interval dispersion(Pd),PR interval,QRS interval(QRSD),QRS interval dispersion(QRSd),QT interval dispersion(QTd) changes at different blood concentrations in 20 young men in good health.To observe wether there are significant correlations between the targets above and the drug blood concentrations. To supply some evidence for mechanisms of carvedilol in clinical antiarrhythmic.Methods:Forty healthy volunteers were all young men.Their average age was 22.95 years(21～25) years.They were randomly allocated to two groups.There are no significant difference in age,height,weight and intex of weight between the two group.The first group,20 cases,with 20 mg carvedilol administrated.They were tested men.The second group,20 cases,with no drugs admimistrated.They were controls.The volunteers body condition history,physical examination and every laboratory test were accomplished 48 hours before the test was initiated.They began to live in the hospital the day before the administration.The rest ECG were done at 6:45 and were respectively done at 0.5,1,2,3,4,6,8,10,24 hour after 7:15 when the test group began to take the 20 mg carvedilol.Food fasting at 22:00 the day before the test.The fast blood sample was drawn at 7:00 on the test day.At 7:15 20mg(2 tablets) carvedilol were administrated by the 20 cases of test group with 200 ml warm water.The symptom,sitting pressure,and heart rate were observed,and 12-head electrocardiographs and blood drug concentrations were checked respectively at 0.5,1,2,3,4,6,8,10,24 hours after 7:15.The Pmax,Pmin,Pd,PR interval,QRS interval,QRSd,QTd at different time point were measured.The data were analysed with SPSS software(12.0).The comparison of the different targets before and after administration was applied with paired T-test.The comparison of the different targets between the test group and control group was applied with independent-samples T test.The same targets were observed at the same time in the group of control to be comparison.Results:(1) Compared with that before administration,the SBp and DBp at every time point after administration were decreased significantly(P＜0.01);Compared with that at -0.5 hour,except the SBP at 4 hour,the SBp of control group at 0.5,1,2,3,6,8,10,24 hour after the time same like the test group didn't change and the DBp of control group at every time point didn't change;Compared with the results of the control group,wether the SBP or the DBP at 0.5,1,2,3,6,8,10,24 hour were all decreased significantly(P＜0.01);(2) Compared with that before administration except at 0.5 and 3 hour(P＜0.01),the heart rate at every time point after administration was decreased(P＜0.01).Though the heart rate at 0.5 and 3 hour was not significantly different(P＞0.05),it also had a dropping tendency.Compared with that at -0.5 hour(except that at 6,8 hour),the heart rate of control group at 0.5,1,2,3,4,10,24 hour didn't change(P＞0.05).Compared with that at -0.5 hour,the heart rate at 6,8 hour was increased(P＜0.01);Compared with the results of the control group,the heart rates of test group at -0.5,4,6,8,10 hour were all decreased significantly(P＜0.01),and at the other time point the heart rates didn't change;(3) Compared with that before administration,the Pmax and Pd at every time point after administration didn't change(P＞0.05);compared with that at -0.5 hour,the Pmax and Pd of control group at every time point didn't change(P＞0.05);compared with the results of the control group,the Pmax,and Pd of test group at every time point didn't change(P＞0.05);(4) Compared with that before administration,the PR interval after administration didn't change(P＞0.05).Compared with that at -0.5 hour (except that at 6 hour),the PR interval of control group at every time point didn't change(P＞0.05).Compared with that at -0.5,the PR interval of control group at 6 hour was short significantly(P＜0.01);compared with the results of the control group, the PR interval of test group at every time point didn't change(P＞0.05); (5)Compared with that before administration,the QRSD,QRSd and QTd at every time point after administration didn't change(P＞0.05).Compared with that at -0.5 hour,the QRSD,QRSd and QTd of control group at every time point didn t change(P＞0.05);compared with the results of the control group,the QRSd and QTd of the test group at every time point didn't change(P＞0.05);but the QRSD of the test group at 1,2,3 hour prolonged significantly;the QRSD of test group at other time point didn't change(P＞0.05);(6) The blood drug concentration gradually went up by the time going,there was a highest point at 1 hour after administration.Then the blood drug concentration grandually went down with the time going;(7)All the targets showed no significant correlation with the blood concentration except QRSD.The change of QRSD showed positive correlation with blood drug concentration(r=0.693, P＜0.05).And wether the control test or the test group,the PR interval showed negative correlation with heart rate.Conclusions:Carvedilol has brilliant blood pressure lowering activity in the healthy young men.They have good tolerance to the drug;Carvedilol has brilliant heart rate lowering activity to the healthy young men.They have good tolerance to the drug;Carvedilol has a lowering tendency for the P wave interval dispersion to the healthy young men,but the change wasn't different significantly;Carvedilol had a prolonging action to the PR interval of the healthy young men,but the significant change was not found;Carvedilol had no significant influence to the QRS interval and the QRS interval dispersion for the healthy young men;Carvedilol had no brilliant influence to the QT interval dispersion for the healthy young men;All the targets had no significant correlation with the blood concentration except QRSD;The change of QRSD had significantly positive correlation with the change of the blood drug concentration. |
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