卡维地洛对陈旧性心梗兔代偿区心肌细胞T-钙电流的作用

研究卡维地洛 (Car) 对陈旧性心肌梗死兔代偿区心肌细胞T-钙电流 (I_Ca,T) 的影响及其机制。选择健康兔行冠状动脉前降支结扎术制备陈旧性心梗模型, 分离代偿区心肌细胞, 利用全细胞膜片钳技术记录I_Ca,T。结果显示, HMI组心肌细胞I_Ca,T电流明显增加, 在 −30 mV时, I_Ca,T的电流密度从 (−0.35 ± 0.02) pA/pF增至 (−2.36 ± 0.12) pA/pF。同时, HMI可以使I_Ca,T的稳态激活曲线向超极化方向移动, 延长电流灭活时间常数和缩短失活后恢复时间, 从而增大了电流幅值。1.0 μmol·L⁻¹ 卡维地洛一方面直接抑制I_Ca,T通道的激活过程减少电流密度, 可降至 (−1.38 ± 0.07) pA/pF; 另一方面可以恢复代偿细胞被改变的通道门控参数。结果表明, 卡维地洛可直接降低陈旧性心肌梗死兔代偿区心肌细胞I_Ca,T电流的密度, 改变其门控特性, 这可能有利于减少心梗后心律失常的发生。     

Comparative Dose Titration Responses to the Introduction of Bisoprolol or Carvedilol in Stable Chronic Systolic Heart Failure

Introduction Several beta blocking drugs (BB) reduce mortality in systolic heart failure (LVSD). We have compared the initial response to introduction of carvedilol and bisoprolol during the standard dose titration protocols for each drug. Methods Approximately 31 unselected patients with stable LVSD were randomised to either carvedilol or bisoprolol measuring blood pressure, heart rate responses and both time and frequency domain heart rate variability (HRV). Results One subject died; five withdrew due to intolerable BB related side effects. Carvedilol (n = 13) and bisoprolol (n = 12) attained similar maximal heart rate reduction and induced comparable falls in systolic and diastolic blood pressure. Higher carvedilol doses were associated with lower blood pressure compared to baseline. Individual time domain HRV indices remained unchanged over the initial titration period. Significant increases in triangular Index (TI) were seen with both BB. Carvedilol demonstrated greater (but non-significant) rises in TI compared to Bisoprolol. Conclusions In this study we found similar degrees and rate of onset of HR, HRV and BP response to both carvedilol and bisoprolol in treated LVSD patients. Carvedilol appears to show superior HRV rises compared to bisoprolol during initial titration. Any significant increases in HRV attributable to carvedilol compared to bisoprolol may emerge over a longer treatment interval in LVSD.     

比索洛尔和卡维地洛治疗慢性心力衰竭疗效比较

目的分析比较比索洛尔和卡维地洛治疗慢性心力衰竭的疗效。方法将2007年1月至2008年1月收治的78例慢性心力衰竭患者随机分为比索洛尔组40例和卡维地洛组38例,比索洛尔组在继续常规抗治疗的基础上,给予口服比索洛尔治疗;卡维地洛组在继续常规抗治疗的基础上,给予13服卡维地洛治疗。所有患者治疗前后均行超声心动图检查,测量LVEF和左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）,测量血压和心率。治疗一年后,比较两组患者各项指标。结果索洛尔组和卡维地洛组治疗前后超声心动图指标LVEDV、LVESV、LVEF、血压、收缩压和舒张压均具有显著性差异（P〈0．01）;而治疗后两组组间比较只有LVEF比较有显著性差异（P〈0．05）,其余各项指标均不存在显著性差异（P〉0．05）,差异无统计学意义。结论应用比索洛尔和卡维地洛治疗慢性心力衰竭患者,疗效相似,均能显著改善心力衰竭患者的心功能,临床可以推广应用。     

Effect of poloxamer 188 on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles for bioavailability enhancement

The present work aimed to investigate the effect of different concentrations of poloxamer 188, a surfactant, on lymphatic uptake of carvedilol-loaded solid lipid nanoparticles (SLNs) for oral bioavailability enhancement. Microemulsion technique was employed to prepare the SLN formulations having varying concentrations of poloxamer 188, which were subsequently subjected to various in vitro and in vivo evaluations to study their release pattern. On increasing the percentage concentration of poloxamer 188, the bioavailability decreased from 4.91- to 2.84-fold after intraduodenal administration in the male Wister rat. It could be attributed to the increase in particle size as well as reduction in hydrophobicity of SLNs. As indicated by pharmacokinetic data, the AUC_(0–t) of all three (SLN) formulations (6.27?±?0.24 μgh/mL with FZ-1, 4.13?± 0.11 μgh/mL with FZ-2, and 3.63?±?0.10 μgh/mL with FZ-3) were significantly higher (p?<?0.05) than that of carvedilol suspension (1.27?±?0.23 μgh/mL). These findings augur well with the possibility of enhancement of the oral bioavailability of drug, via the lymphatic system bypassing hepatic first pass metabolism.     

卡维地洛对充血性心衰患者心脏功能的影响

将符合本试验纳入标准的88例充血性心衰患者分成试验组（40例）和对照组（48例），患者均口服地高辛、血管紧张素转换酶抑制剂制剂、血管扩张剂（非钙离子拮抗剂）和利尿剂等基本抗心衰药物，在此基础上试验组加服卡维地洛。随访7个月后，复查心脏彩超心脏射血分数和左室短轴缩短率，与试验初比较两组均有显著的改善，而服药7个月后试验组较对照组有显著的升高（P＜0.05)。表明卡维地洛可使心肌重塑过程得到缓解，还可以更显著地改善心功能。     

卡维地洛对心力衰竭病人血流动力学相关指标影响

①目的　观察卡维地洛对心力衰竭 (心衰 )病人血流动力学状态及心室功能的影响。②方法　选择NYHA分级Ⅱ～Ⅲ级的慢性心力衰竭病人 77例 ,随机分成两组 ,治疗组 4 9例 ,给予卡维地洛治疗 ,剂量由 6 .2 5mg增至 2 5 .0 0mg ,每日 2次 ,持续 8周 ;对照组 2 8例 ,给予常规治疗。两组均应用无创血流动力学检测仪监测治疗开始及终点的血流动力学指标 ,同时作超声心动图检查 ,以评价左室功能。③结果　治疗后对照组病人左心做功指数 (LCWI)、左室排血分数 (LVEF)增高 ,心率 (HR)、体循环阻力指数 (SVRI)、左室舒张末内径降低 ,差异有显著意义 (t=1 .6 5～ 1 .86 ,P <0 .0 5 ) ;治疗组LCWI、LVEF显著增高 ,HR、SVRI、左室舒张末内径显著降低 ,差异有显著意义 (t=2 .0 3～ 2 .38,P <0 .0 5 ) ;以上各指标两组间比较差异亦有显著性 (t=1 .72～ 1 .98,P <0 .0 5 )。④结论　卡维地洛可以降低心脏前、后负荷 ,显著改善左心功能     

Congestive Heart Failure and Genomic Medicine: A Look into the 21st Century

Congestive heart failure (CHF) has emerged as one of the leadingcardiovascular disorders in developed countries, as indicated by theprevalence of the disease; the incidence of hospitalization, morbidity, andmortality; and its global economic burden. Furthermore, it is expected thatheart failure and other cardiovascular disorders will become the majordisease burdens in developing countries by the year 2020. It is wellestablished that pharmacological therapy of CHF, although still notoptimum, improves patient quality of life and reduces morbidity andmortality. However, CHF remains a relentlessly progressive disease. In thisbrief review an attempt is made to explore the contemporary,state-of-the-art pharmacological approach to the treatment of heartfailure, the unmet medical need that still remains, and the potentialimpact of genomic medicine on the treatment of heart failure in the 21stcentury.     

卡维地洛治疗心绞痛临床疗效观察

目的：评价卡维地洛对心绞痛患者的临床疗效。方法：56例冠心病心绞痛患者随机分为2组，治疗组29例，患者服用卡维地洛10-40mg/d。4周为1疗程；对照组27例未服卡维地洛，基础治疗同治疗组，观察2组患者疗效。结果：治疗组用药后心绞痛缓解的总有效率达82.76%。对照组为62.96%。结论：卡维地洛是治疗心绞痛的有效药物。     

卡维地洛对高血压大鼠心脏成纤维细胞胶原合成的抑制作用

目的 :探讨卡维地洛、比索洛尔、哌唑嗪对培养的 SHR和 Wistar大鼠心脏成纤维细胞 （ CFs）胶原合成的影响。方法 :采用胰酶消化法培养 CFs,用3 H-脯氨酸掺入法分别观察卡维地洛、比索洛尔、哌唑嗪干预下两组大鼠 CFs胶原合成的情况。结果 :1各种浓度的卡维地洛 （ 0 .0 1～ 10μmol/ L ）可以浓度依赖的方式抑制 CFs 3 H-脯氨酸掺入量 ,与 Wistar大鼠组相比 ,SHR组 CFs受抑制的效应更强。2同等浓度比索洛尔对两组大鼠 CFs3 H-脯氨酸掺入量表现出轻度抑制。 3同等浓度哌唑嗪对两组大鼠 CFs3 H-脯氨酸掺入量均无明显影响。结论 :卡维地洛呈浓度依赖性抑制 CFs合成胶原 ,其作用机制部分与阻滞β1 受体有关。