BiPAP呼吸机联合坎地沙坦酯对肺心病急性期合并呼吸衰竭老年患者心肺功能及血清内皮素-1、Clara细胞蛋白和Copeptin水平的影响

目的分析BiPAP呼吸机联合坎地沙坦酯对肺心病急性期合并呼吸衰竭老年患者心肺功能及血清内皮素(ET)-1、Clara细胞蛋白(CC)16、和肽素(Copeptin)水平的影响。方法96例肺心病急性期合并呼吸衰竭老年患者随机分为两组各48例,对照组接受BiPAP无创呼吸机治疗,观察组接受BiPAP无创呼吸机联合坎地沙坦酯治疗。比较两组治疗2 w后的疗效、心肺功能指标及血清ET-1、CC16和Copeptin水平,并统计不良反应发生情况。结果观察组总有效率较对照组显著高(P<0.05)。治疗2个疗程后观察组肺动脉压(PASP)显著低于对照组,而每搏输出量(SV)、射血分数(EF)、舒张早期峰值速度与舒张晚期峰值速度比值(E/A)、1 s用力呼气容积(FEV1)/用力肺活量(FVC)、FEV1%、呼吸流量峰值(PEF)指标水平显著高于对照组(P<0.05)。两组治疗后血清ET-1、CC16和Copeptin水平均显著下降,且观察组降低较多(P<0.05)。主要不良反应为低血压、头痛、恶心、发热等,两组发生率无统计学差异(P=0.726)。结论BiPAP呼吸机联合坎地沙坦酯对老年患者肺心病急性期合并呼吸衰竭疗效显著。     

卡维地洛联合坎地沙坦对心力衰竭患者血浆N末端B型利钠肽原浓度的影响

目的：观察卡维地洛联合坎地沙坦对心力衰竭（CHF）患者血浆N末端B型利钠肽原（NT-proBNP）浓度的影响。方法：将175例CHF患者随机分为对照组（常规治疗）和治疗组（卡维地洛联合坎地沙坦治疗）。分别于用药前及用药3个月后测定血浆NT-proBNP浓度、左心室射血分数（LVEF）、左室短轴缩短率（FS）及心脏指数（CI）。结果：治疗组总有效率为87.5%,对照组总有效率为70.1%,治疗组较对照组明显提高（P〈0.01）,两组治疗后的LVEF、FS、CI、血浆NT-proBNP浓度明显改善（治疗组t=23.167、14.041、6.602、60.735,均P〈0.01;对照组t=4.943、4.698、3.73、48.673,均P〈0.05）;治疗后治疗组LVEF、FS、CI较对照组改善显著（t=15.948、6.822、5.88,均P〈0.01）,血浆NT-proB-NP浓度明显降低（t=14.794,P〈0.01）。结论：卡维地洛联合坎地沙坦可改善CHF患者心功能,降低血浆NT-proBNP浓度,对治疗心力衰竭安全有效。     

缬沙坦对慢性心力衰竭患者血浆脑钠素水平及左室收缩功能疗效的研究

目的 探讨慢性心力衰竭(CHF)患者在常规治疗基础上加用缬沙坦治疗12周后脑钠素(BNP)水平的变化及心功能的疗效.方法 应用化学发光法测定52例CHF患者治疗前、后和18例对照组血浆BNP浓度:用多普勒超声心动图测定CHF组左室舒张末期内径(LVEDD)及左室射血分数(LVEF).结果 CHF患者血浆BNP水平(456±253)Pg/mL较对照组(28±6)pg/mL明显增高(P＜0.01);不同心功能患者血浆BNP水平差异亦有显著意义,依次为Ⅳ级＞Ⅲ级＞Ⅱ级(P＜0.01),CHF组BNP水平升高与心力衰竭程度呈正相关(r=0.672,P＜0.01).缬沙坦治疗后血浆BNP水平明显下降,与治疗前比较差异有非常显著性(P＜0.01).LVEF有所提高,LVEDD明显缩小与治疗前比较均差异有显著性(P＜0.05).结论 血浆BNP水平可以反映心力衰竭严重程度、作为治疗心力衰竭的一个可靠观察指标.缬沙坦能显著降低脑钠素水平,改善心功能.在心力衰竭的治疗中起着重要作用.     

A Nonpeptide,Piperidine Renin Inhibitor Provides Renal and Cardiac Protection in Double-Transgenic Mice Expressing Human Renin and Angiotensinogen Genes

Introduction  Controlling hypertension by angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB), mechanisms that inhibit later pathway steps in the renin–angiotensin system (RAS), have clinically afforded protection against cardiac and renal disease. Materials and methods  In order to determine if blocking the RAS rate-limiting step of angiotensin II generation via renin inhibition could afford similar end organ protection in a human-relevant preclinical model, this study investigated the cardiac and renal effects of a nonpeptide, piperidine renin inhibitor (RI; 100 mg/kg/day PO) in double transgenic mice (dTGM) which express both human renin and angiotensinogen genes. RI was compared to the ARB, candesartan (3 mg/kg/day PO), and to the ACEI, enalapril (60 mg/kg/day PO) in a 4-week dosing paradigm. These doses of RI, ACEI and ARB were previously found to normalize mean blood pressure (MBP) to 110 + 3, 109 + 7 and 107 + 6 mmHg, respectively, after 1 day of treatment. Results and discussion  In the dTGM, PRA, plasma aldosterone, GFR, microalbuminuria and left ventricular free wall thickness (LVH) were higher than in the wild type C57BL/6 mice. Microalbuminuria and LVH were significantly reduced by 93% and 9% for the RI, 83% and 13% for enalapril and 73% and 6% for candesartan, respectively. PRA and aldosterone were reduced by the RI 56% and 23%, respectively. These results suggest that the RI provides protection against cardiac and renal disease, similar to ARB and ACEI.     

国产坎地沙坦酯治疗轻中度原发性高血压的随机双盲临床试验

目的:评价国产坎地沙坦酯治疗轻、中度高血压的疗效和安全性。方法:采用随机对照双盲临床试验设计,对58例高血压病患者随机分为试验组给予坎地沙坦酯片(=29,8mg/d)或对照组给予厄贝沙坦片(=29,150mg/d);2w后血压未正常者加药1片,疗程4w。结果:试验组和对照组的治疗2w时降压有效率分别为75.86%和37.93%,两组间比较差异有显著性(P<0.05);4w后试验组和对照组的降压有效率分别为89.66%和79.33%,两组比较无差异。治疗4w后试验组坐位、立位收缩压的降压幅度分别为27.52±11.90mmHg、24.59±11.87mmHg与对照组20.72±9.27mmHg、15.90±16.22mmHg相比有差异,P<0.01;P<0.05。两组不良反应发生率相似。结论:国产坎地沙坦酯与厄贝沙坦均有明显的降压效果,不良反应发生少,耐受性好。国产坎地沙坦酯对收缩压控制较好。     

Effects of Candesartan in the Acute Phase of Intracerebral Hemorrhage

Background and Purpose: Uncertainty persists over the effects of blood pressure-lowering treatment in acute intracerebral hemorrhage (ICH). We assessed the effects of treatment with candesartan in acute ICH and according to different types of hematoma. Methods: Post-hoc analysis of the Scandinavian Candesartan Acute Stroke Trial, a randomized- and placebo-controlled, double-masked trial of candesartan in patients with any stroke within the acute phase (<30 hours) and high systolic blood pressure (≥140 mm Hg). We collected baseline computed tomography scans of participants with ICH, and characterized hematoma volume (planimetric approach), location (deep versus lobar or infratentorial), hemisphere side, and presence of intraventricular hemorrhage. The trial's 2 coprimary effect variables were the composite endpoint of vascular death, stroke or myocardial infarction, and functional outcome at 6 months according to the modified Rankin scale. We used Cox, ordinal, and binary logistic regression for analysis and adjusted for key, predefined prognostic variables. Results: Of 274 participants with ICH, computed tomography scans were available in 205 patients (74.8%). There were no significant differences between the candesartan and placebo groups with respect to hematoma volume (median 15.6 mL versus 13.5 mL, P = .96), deep location (77% versus 72%, P = .64), right hemisphere (49% versus 51%, P = .46), and presence of intraventricular hemorrhage (18% versus 11%, P = .22). Candesartan was associated with a significant increase in poor functional outcome in patients with deep hematoma (adjusted common odds ratio 2.27, 95% confidence interval 1.23-4.18, P = .009, P for interaction .015), but there was no differential effect on functional outcome or vascular events in any of the other imaging subgroups. Conclusions: Candesartan was not associated with any beneficial effect when initiated in the acute phase of ICH, a possible adverse effect on functional outcome in patients with deep hematomas cannot be ruled out by this study alone.     

CoQ10 augments candesartan protective effect against tourniquet-induced hind limb ischemia-reperfusion: Involvement of non-classical RAS and ROS pathways

Tourniquet is a well-established model of hind limb ischemia–reperfusion (HLI/R) in rats. Nevertheless, measures should be taken to alleviate the expected injury from ischemia/ reperfusion (I/R). In the present study, 30 adult male Sprague-Dawley rats were randomly divided into 5 groups (n = 6): control, HLI/R, HLI/R given candesartan (1 mg/kg, P.O); HLI/R given Coenzyme Q10 (CoQ10) (10 mg/kg, P.O); HLI/R given candesartan (0.5 mg/kg) and CoQ10 (5 mg/kg). The drugs were administered for 7 days starting one hour after reperfusion. Candesartan and CoQ10 as well as their combination suppressed gastrocnemius content of angiotensin II while they raised angiotensin-converting enzyme 2 (ACE2) activity, angiotensin (1–7) expression, and Mas receptor mRNA level. Consequently, candesartan and/or CoQ10 reversed the oxidative stress and inflammatory changes that occurred following HLI/R as demonstrated by the rise of SOD activity and the decline of MDA, TNF-α, and IL-6 skeletal muscle content. Additionally, candesartan and/or CoQ10 diminished gastrocnemius active caspase-3 level and phospho-p38 MAPK protein expression. Our study proved that CoQ10 enhanced the beneficial effect of candesartan in a model of tourniquet-induced HLI/R by affecting classical and non-classical renin-angiotensin system (RAS) pathway. To our knowledge, this is the first study showing the impact of CoQ10 on skeletal muscle RAS in rats.     

坎地沙坦对缺血-再灌注心脏搏出液心肌酶谱以及组织形态学的影响

目的观察坎地沙坦对离体家兔心脏缺血-再灌注后心肌酶指标的影响,评价其对心肌的保护作用。方法制作全心缺血-再灌注模型,观察坎地沙坦3个剂量组对心肌细胞酶学的影响,同时观察其对缺血再灌注后心肌细胞结构的影响。结果坎地沙坦100nmol·L-1剂量组能明显降低家兔缺血再灌注时LDH;坎地沙坦10和100nmol·L-1剂量组能明显降低家兔缺血再灌注时GOP的升高;100nmol·L-1剂量组对家兔缺血再灌注时CK和CKMB的升高无统计学意义。结论通过降低家兔离体心脏缺血-再灌注后心肌酶学水平的升高,是坎地沙坦保护心肌的作用途径之一。     

坎地沙坦对不稳定型心绞痛患者相关炎性因子及预后的影响分析

目的探讨坎地沙坦对不稳定型心绞痛患者相关炎性因子及预后的影响。方法选择不稳定型心绞痛患者80例,随机分为观察组和对照组。对照组采用常规治疗,观察组在对照组基础上应用坎地沙坦。结果观察组治疗后干扰素γ、白细胞介素2水平与对照组治疗后比较,差异有统计学意义(P<0.05);观察组主要心脏不良事件发生率显著低于对照组,差异有统计学意义(P<0.05)。结论坎地沙坦能显著降低不稳定型心绞痛患者不良心脏事件发生率,改善预后,可能与其抑制炎性反应有关。