肝动脉灌注维拉帕米对犬生命体征及组织和血药浓度变化的影响

Observation of canine vital signs and concentration alteration of verapamil hydrochloride in hepatic tissue and blood by perfusing verapamil hydrochloride through hepatic artery

目的 :经犬肝动脉灌注维拉帕米 ,了解犬肝组织药物浓度与血液药物浓度及犬的生命体征变化。方法 :应用色谱仪及其分析软件 ,检测经犬肝动脉一次性灌注 0 7mg/kg维拉帕米后肝组织、血液药物浓度。观察犬股动脉血压、呼吸、常规Ⅱ导联心电图变化。结果 :按 0 7mg/kg维拉帕米一次性经犬肝动脉灌注后 5、10、15、2 0、2 5、3 0min血液药物浓度分别为 9 70± 1 0 5、5 78± 0 3 2、3 0 1± 0 5 1、1 5 0± 0 11、0 61± 0 10、0 2 1± 0 0 1μg/mL ;5、15、3 0min犬肝组织药物浓度分别为10 5 2 0± 5 0 1、67 60± 7 0 6、18 97±1 67μg/ g。犬的心电图、动脉血压、呼吸未见明显变化。结论 :按 0 7mg/kg维拉帕米经犬动脉一次性灌注后 ,肝组织维拉帕米浓度超过了逆转肿瘤多药耐药有效浓度 。

OBJECTIVE:To observe canine vital signs and concentration alteration of verapamil hydrochloride in hepatic tissue and blood by perfusing verapamil hydrochloride through hepatic artery.METHODS:Verapamil hydrochloride concentration in canine hepatic tissue and blood were tested after perfuing 0.1×7 mg/kg verapamil one time through hepatic artery,by using chromatogram sepctrophotometer and Dalian chromatographic software.The alteration of canine femoral artery blood pressure,respiration and regular lead Ⅱ electrocardiogram were also observed. RESULTS:After 0.1×7 mg/kg verapamil was perfused one time through canine hepatic artery,the verapmil concentrations in blood were 9.70±1.05,5.78±0.32,3.01±0.51,1.50±0.11,0.61±0.10 and 0.21±0.01 μg/mL at the 5th,10th,15th,20th,25th and 30th minute,respectively.The verapmil concentrations in hepatic tissue were 105.20±5.01,67.60±7.06 and 18.97±1.67 μg/g at the 5th,15th and 30th minute respectively.No distinct alteration was observed in canine electrocardiogram,artery blood pressure and respiration.CONCLUSIONS:No distinct alteration was observed in canine vital signs after 0.1×7 mg/kg verapmil is perfused one time through hepatic artery,and the concentrations in hepatic tissue are extremely higher than those which can effectively reverse tumor multidrug resistance.