三七总皂苷与卡维地洛改善心肌梗死后大鼠心功能的作用

目的用不同浓度三七总皂苷（panaxnotoginsengsaponin,PNS）和卡维地洛干预急性心肌梗死（acutemyocardialinfarction,AMI）大鼠,评价其改善心功能作用的疗效。方法建立大鼠AMI模型84只,随机分为心肌梗死对照组（AMI组）,PNS治疗低（PNS．L,20mg·kg-1·d-1）、中（PNS．M,40mg·kg-1·d-1）、高（PNS—H,80mg·kg-1·d-1）3组,卡维地洛治疗低（CARV．L,2．5mg·kg-1·d-1）、中（CARV—M,5mg·kg-1·d-1）、高（CARV—H,10mg·kg-1·d-1）3组,另设假结扎组（sham组）,每组12只。灌胃给药4周后,用小动物超声心动图仪检测心功能,检测血浆心力衰竭标志物N-末端脑钠肽前体（N—terminalpro—brainnatriureticpeptide,NT—pro．BNP）浓度,并行心肌组织的苏木素-伊红染色分析。结果同sham组比较,AMI组左心室射血分数和左心室收缩百分率、左心室前壁舒张期厚度、左心室前壁收缩期厚度均明显降低,差异有统计学意义（P〈0．01）;左心室舒张末期内径、左心室收缩末期内径及血浆NT—pro—BNP浓度显著增高,差异有统计学意义（P〈0．01）。同AMI组比较,PNS和卡维地洛治疗的中、高剂量组左心室射血分数、左心室收缩百分率、左心室前壁舒张期厚度、左心室前壁收缩期厚度均明显增加,而左心室舒张末期内径和左心室收缩末期内径及血浆NT—pro．BNP浓度明显降低,差异有统计学意义（P〈0．01）。而且,各治疗组的心肌组织细胞均得到较好的保护。结论用PNS和卡维地洛治疗AMI大鼠4周均能有效保护心肌组织和改善心功能,减缓心力衰竭的发生、发展,且PNS效果略优。     

卡维地洛对大鼠颈动脉损伤后MMP-9和TIMP-1表达的影响

目的：观察卡维地洛（CAR）对大鼠颈动脉损伤血管组织MMP-9、TIMP-1表达的影响,探讨卡维地洛防治再狭窄的机制。方法：雄性Wistar大鼠90只,随机分为假手术组、损伤组和CAR组,后两组行颈动脉球囊损伤术。三组均于术后1 d、3 d、7 d、14 d、28 d处死大鼠。光镜下观察血管损伤后内膜增生情况,用免疫组化和RT-PCR法检测MMP-9、TIMP-1在各组术后不同时间点的表达情况。结果：与损伤组比较,术后14 d CAR组内膜面积、内膜与中膜面积比值显著减少,管腔面积显著扩大（P〈0.05）;与损伤组比较,CAR组术后3-14d MMP-9表达显著减少（P〈0.05）,而TIMP-1表达无显著变化。结论：卡维地洛有效抑制大鼠颈动脉损伤后MMP-9表达,抑制了VSMCs迁移、增殖,改善了细胞外基质的合成与降解平衡,从而减轻再狭窄。     

卡维地络对原发性高血压病人的降压疗效和左室功能的影响

目的:研究卡维地络对原发性高血压病人降压疗效,左室重量指数和左室功能的影响.方法:80例高血压病患者口服卡维地络10～40 mg 8周,观察血压,心率,副作用,血液生化,左室重量指数,左室功能等改变.结果:服药后1周收缩压和舒张压明显下降,8周有效率90%.收缩压和舒张压谷/峰比值分别为71.73%和63.48%.左室重量指数降低,二尖瓣E/A比值和平均E峰下降速度升高(P＜0.05).射血分数和心输出指数升高(P＞0.05).对肝肾功能,离子,血糖,血脂无影响.不良反应有轻度头晕,干咯,嗜睡,多尿等.结论:卡维地络具有明显降压作用,副作用低.长期用药降低左室重量指数,改善心室舒张功能.     

卡维地洛羟丙基-β-环糊精包合物的制备与评价

目的 制备卡维地洛羟丙基-β-环糊精包合物,对包合物进行物性研究。方法 采用超声法制备包合物,通过相溶解度研究包合类型,以差示扫描热分析法(DSC)和X-射线衍射法验证卡维地洛羟丙基-β-环糊精包合物的形成,并测定包合物的溶解度和溶出度。结果 相溶解度曲线呈AL型,表明卡维地洛能够与羟丙基-β-环糊精形成1∶1的包合物。DSC和X-射线衍射结果显示药物峰消失,证明包合物的形成。包合物的溶解度比原药提高5倍,溶出速度明显加快。结论 超声法制备的卡维地洛羟丙基-β-环糊精包合物能显著提高原药的溶解度和溶出速度。     

卡维地洛对重症充血性心力衰竭患者的临床疗效评价

目的：评价第三代β受体阻滞剂卡维地洛对重症充血性心力衰竭患者的临床疗效。方法：将33例重症充血性心力衰竭患者随机分为2组,卡维地洛组17例,应用卡维地洛及心衰常规治疗,卡维地洛起始剂量为2．5－5mg,Bid,如患者能耐受,在2－4周内逐渐将剂量增加至20mg,Bid,维持治疗3个月。对照组16例,用心衰常规治疗。结果：卡维地洛组能显著改善重症充血性心力衰竭患者的左、右室心功能,使心率、心搏量、左室射血分数、肺动脉收缩压（右室后负荷）与组内治疗前比较差异有显著意义;心搏量、心排血量、左室射血分数与对照组治疗后比较差异有显著意义。卡维地洛组未见明显不良反应。结论：卡维地洛治疗重症充血性心力衰竭是安全、有效的药物。     

卡维地洛、美托洛尔对心衰大鼠心功能及体液因子的影响

目的探讨β受体阻滞剂卡维地洛、美托洛尔对心衰大鼠体液因子及心功能的影响。方法建立心衰大鼠模型,随机分为三组,B组为安慰剂组;C组给予卡维地洛,D组给予美托洛尔;同时设假手术组(A组)。观察6周后行心脏超声、血流动力学检查,以及血清尿钠素(ANP)、血管紧张素(Ang)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)及去甲基肾上腺素(NE)测定。结果β受体阻滞剂能显著降低心衰大鼠的左室舒张末压,增加左室短轴缩短率、左室压力最大上升及下降速率,以及ANP、TNF-α、IL-6、NE(均P<0.05),减小室间隔厚度及左室质量指数(LVWI)(P<0.05);其中卡维地洛降低Ang、减小左室舒张末期直径、降低LVWI的作用明显优于美托洛尔(P<0.05)。结论β受体阻滞剂能较全面地降低神经内分泌、细胞因子,这可能是其改善心脏功能,抑制左室重塑的机制之一。卡维地洛降低神经内分泌、细胞因子,减轻心肌重塑的作用优于美托洛尔。     

Use of beta blockers is associated with hearing loss

Objective: This study was conducted to investigate the hypothesis that patients using β-blockers will develop hearing loss. Design: A cross-sectional study. Study sample: A total of 125 patients completed the study. A total of 63 patients were on β-blockers and 62 were not on β-blockers. Results: Carvedilol was significantly associated with hearing loss. Other beta-blockers including metoprolol and atenolol showed no association with hearing loss. Linear multiple regression analysis was run including variables of gender, age, ischaemic heart disease, cardiac failure/dilated cardiomyopathy, frusemide and carvedilol use as predictors for total hearing loss severity at all frequencies. Age and gender, as well as carvedilol, were found to be the only statistically significant predictors for hearing loss severity. Conclusion: Chronic use of carvedilol was associated with significant hearing loss. This may need to be taken into account when prescribing the drug. Further randomised controlled studies with baseline audiometric hearing tests before starting treatment, and periodic follow-up tests, would provide a better assessment of the effect of carvedilol on hearing.     

Hemodynamic effects of one week of carvedilol administration on cirrhotic rats

Background Carvedilol is a nonselective β-blocker with α₁-adrenergic blocking activity. It has been shown to decrease portal pressure in cirrhotic patients. The current study was undertaken to evaluate the possible mechanism of carvedilol on hemodynamics in cirrhotic rats with portal hypertension produced by common bile duct ligation. Methods Male Sprague-Dawley rats received either a sham operation or common bile duct ligation. Three weeks after surgery, both sham-operated and cirrhotic rats were randomly assigned to receive vehicle or carvedilol 5 mg · kg⁻¹ · 12 h⁻¹ by gastric gavage for 1 week. Hemodynamic measurements, serum biochemistry, serum nitrate/nitrite and 6-keto-PGF_1α levels, and aortic mRNA expression of eNOS and COX-1 were performed on the eighth day after drug administration. Results Carvedilol treatment did not affect serum biochemistry in either sham-operated or cirrhotic rats. In sham-operated rats, administration of carvedilol significantly decreased the heart rate without affecting other hemodynamic values. In contrast, in cirrhotic rats, administration of carvedilol significantly decreased the cardiac index, portal pressure, heart rate, and portal territory blood flow, and it significantly increased systemic and portal territory vascular resistances. The hepatocollateral resistance was significantly decreased, but the hepatic arterial blood showed no significant changes. In sham-operated rats treated with carvedilol, serum nitrate/nitrite and 6-keto-PGF_1α levels were not affected. In contrast, cirrhotic rats receiving carvedilol showed a significant decrease in serum nitrate/nitrite and 6-keto-PGF_1α levels, associated with a decrease in aortic mRNA expression of eNOS and COX-1 compared with those receiving vehicle. Conclusions Carvedilol decreased portal pressure through a reduction of splanchnic blood flow associated with a decrease in hepatocollateral resistance. Additionally, administration of carvedilol decreased endothelial-related vasodilatory activities.     

卡维地洛对那格列奈在大鼠体内药物动力学的影响

目的研究卡维地洛对那格列奈在大鼠体内药物动力学的影响。方法 10只健康雄性Wistar大鼠随机分成2组(单独给药组和联合给药组),用HPLC-MS/MS法测定血浆中那格列奈的浓度。结果单独用药与联合用药组Cmax分别为(1 868±226.3)和(992.8±246.0)μg.L-1,AUC0-t分别为(1 532.1±526.5)和(822.5±298.0)μg.h.L-1,AUC0-∞分别为(1 546.2±530.7)和(845.1±312.0)μg.h.L-1,均具有显著性差异(P<0.05),其他药动学参数无显著性差异(P>0.05)。结论联合用药后卡维地洛抑制了那格列奈的吸收。     

卡维地洛治疗心力衰竭对大鼠心肌细胞凋亡和Bcl-2、Bax蛋白表达水平的影响

目的 从细胞凋亡角度探讨卡维地洛治疗心力衰竭的机制。方法 采用结扎冠状动脉复制慢性心功能不全模型，观察卡维地洛治疗心力衰竭，对心肌细胞凋亡率、bcl-2、Bax蛋白表达水平的影响。结果 卡维地洛干预心功能不合可以剂量依赖地使心肌细胞凋亡率和Bax蛋白表达水平降低，使bcl-2蛋白表达水平增加。特拉唑嗪对心肌细胞凋亡和Bax、bcl-2的蛋白表达水平无影响。结论 抑制Bax蛋白表达水平，同时增加bcl-2蛋白表达水平，从而抑制心肌细胞凋亡，是卡维地洛治疗心力衰竭的重要机制之一。卡维地洛抑制心肌细胞凋亡的效应与α1－受体阻滞作用无关。