山莨菪碱治疗冠状动脉微循环障碍的实验观察

目的 通过建立新西兰大白兔冠状动脉微血栓模型,观察山莨菪碱对冠状动脉微循环障碍的治疗效果并探讨其作用机制.方法 新西兰大白兔24只,随机分为对照组、模型组和治疗组,每组8只.开胸后阻断升主动脉10 s,模型组经主动脉根部注入月桂酸钠1.5 mg/kg(40 mg/mL) 建立冠状动脉微血栓模型;治疗组于注射月桂酸钠后即刻肌肉注射山莨菪碱10 mg;对照组不予任何处理.模型组和治疗组于术前和术后3 h经耳动脉采血2 mL(对照组随机时间点采血,相隔3 h),测定各组血清中一氧化氮(NO)、内皮素-1(ET-1)、血管内皮生长因子(VEGF)和肌钙蛋白Ⅰ(cTnⅠ)水平.血液样本采集完成后处死所有动物,取心脏制作病理切片,HE染色观察各组微血栓的形成情况并计算微血栓形成率.结果 模型组注射月桂酸钠后3 h,血清NO浓度较术前降低,而ET-1、VEGF和cTnⅠ质量浓度均较术前升高;治疗组各项指标变化趋势与模型组一致,但程度较轻;两组间各指标手术前后差值比较,差异均有统计学意义(P<0.01).冠状动脉内注入月桂酸钠后3 h,治疗组NO/ET-1比值高于模型组(P<0.05).各组冠状动脉大动脉中均无血栓形成.对照组微动脉中无血栓形成;模型组和治疗组微动脉中均可见血栓形成,治疗组微血栓形成率低于模型组(P<0.05).结论 山莨菪碱能有效改善冠状动脉微循环.其机制可能与扩张微血管、减轻内皮受损程度、纠正NO/ET-1的失平衡状态而减少月桂酸钠诱发的血栓形成有关.     

山莨菪碱改善大鼠冠状动脉微循环及其机制的研究

目的观察山莨菪碱对大鼠冠状动脉微循环的影响,并探讨其可能的作用机制.方法通过在SD大鼠冠状动脉内注射42μm微粒子的方法构建冠状动脉微栓塞模型,将模型大鼠随机分为正常对照组(n＝6)、治疗组(山莨菪碱10mg*kg-1*d-1,腹腔注射,1次*d-1,n＝15)和微栓塞组(生理盐水代替,n＝15),用非放射性彩色微粒子(15μm)观察术后24h心肌局部血流量的变化,采用超声心动图评价大鼠术后第1、3、7天的心功能变化,同时观察治疗组和微栓塞组间氧化应激[指标为超氧化物歧化酶(SOD)活力及丙二醛(MDA)水平]的差异.结果术后3h治疗组大鼠心肌内微栓塞数量明显少于微栓塞组(P<0.05),氧化应激减轻(SOD活力比较,P<0.05;MDA水平比较,P<0.001);术后24h心肌局部血流明显增加(P<0.001);第1、3、7天大鼠的左心室射血分数分别较对照组高13%、33%、27%.结论山莨菪碱可明显减少大鼠心肌微梗死的面积,增加局部心肌血流量,改善心功能,其机制可能与减轻氧化应激有关.     

氢溴酸山莨菪碱改善微循环障碍的机制研究进展

氢溴酸山莨菪碱是从我国特产植物唐古特山莨菪中提取的一种天然生物碱,于1965年率先应用于临床,代号为654-1.临床上常使用其人工合成替代品消旋山莨菪碱(654-2),改善微循环治疗感染性休克、平滑肌痉挛、有机磷农药中毒等.近年来,氢溴酸山莨菪碱的来源得到了有效保障,为了帮助氢溴酸山莨菪碱的临床应用开发及作用机制研究,本文对氢溴酸山莨菪碱在稳定细胞质膜、抗脂质过氧化、拮抗胆碱能受体、抗凝血与促纤溶、保护血管内皮糖萼和细胞间连接等方面的作用及其机制进行综述.     

氢溴酸山莨菪碱改善微循环障碍的机制研究进展

氢溴酸山莨菪碱是从我国特产植物唐古特山莨菪中提取的一种天然生物碱,于1965年率先应用于临床,代号为654-1.临床上常使用其人工合成替代品消旋山莨菪碱(654-2),改善微循环治疗感染性休克、平滑肌痉挛、有机磷农药中毒等.近年来,氢溴酸山莨菪碱的来源得到了有效保障,为了帮助氢溴酸山莨菪碱的临床应用开发及作用机制研究,本文对氢溴酸山莨菪碱在稳定细胞质膜、抗脂质过氧化、拮抗胆碱能受体、抗凝血与促纤溶、保护血管内皮糖萼和细胞间连接等方面的作用及其机制进行综述.     

山莨菪碱活跃兔耳窗微循环的实验研究

应用兔耳开窗技术观察山莨菪碱活跃兔耳窗微循环的作用。可以观察到耳缘静脉推注山莨菪碱２０ｍｇ后２０ｓ开始出现微血管扩张，血流速度增快，自律运动振幅增大；４０ｓ达到高峰，以后持续维持此种活跃状态。停止静推后４０ｓ，可见微血管开始缩退，自律运动振幅减少，９０ｓ时已恢复到静推前的水平。     

山莨菪碱活跃兔耳窗微循环的实验研究

应用兔耳开窗技术观察山莨菪碱活跃兔耳窗微循环的作用。可以观察到耳缘静脉推注山莨菪碱20mg后20s开始出现微血管扩张,血流速度增快,自律运动振幅增大；40s达到高峰,以后持续维持此种活跃状态。停止静推后40s,可见微血管开始缩退,自律运动振幅减少,90s时已恢复到静推前的水平。     

冠状动脉微循环障碍概述及研究进展

冠状动脉(冠脉)微循环对多种心血管疾病的发生、发展、预后具有重要意义。近年来,随着心血管影像技术的快速发展,冠脉微循环障碍的检测水平也明显提高,相信在不久的未来,冠脉微循环会成为心血管病基础和临床最重要的研究课题之一。本文就冠脉微循环障碍及其研究进展作一综述。     

山莨菪碱治疗感染性休克的临床观察和动物实验

通过对37例感染性休克患者和实验性休克狗、家兔及小鼠的观察,证实山莨菪碱有改善微循环,保护组织细胞功能的作用。可使心肌收缩功能增强,冠状动脉(冠脉)流量改善,肾血管阻力降低,肾血流量增加及肾功能改善。     

月桂酸钠诱导建立三种冠状动脉微循环障碍大鼠模型的比较

目的 比较利用月桂酸钠诱导建立的3种SD大鼠冠状动脉微循环障碍模型,评价出较优方案。方法 50只6～8周龄雄性SD大鼠使用随机数字表法分为空白组、假手术组和模型组1～3,每组10只。空白组未行任何干预;模型组1采用扩张肋间后挤出心脏+心尖注入月桂酸钠（1 mg/kg）1次,模型组2采用扩张肋间后挤出心脏+心尖注入月桂酸钠（1 mg/kg）2次,模型组3采用扩张肋间后挤出心脏+夹闭主动脉根部+心尖注入月桂酸钠（1 mg/kg）1次;假手术组操作同模型组2,注入等量生理盐水。造模后持续饲养并于72 h后采用超声心动图评价心功能,HE、Heidenhain和Carstairs染色观察心肌组织病理变化。结果 手术大鼠死亡率为17.5%(7/40)。假手术组与空白组左室射血分数（LVEF）比较,差异无统计学意义（P> 0.05）。与假手术组比较,模型组1～3 LVEF均降低（P <0.05）;与模型组2比较,模型组1、3 LVEF升高（P <0.05）。HE染色显示,模型组1～3均出现心肌细胞溶解、断裂及炎症细胞浸润,可见不同程度的冠状动脉微血管内血栓形成。Heidenhain...     

Safety and efficacy of anisodamine on prevention of contrast induced nephropathy in patients with acute coronary syndrome

Background  Previous studies have proved the renal protective effects of anisodamine in patients with septic shock. The aim of this study was to investigate anisodamine for the prevention of contrast induced nephropathy (CIN) in patients with acute coronary syndrome (ACS).

Methods  Consecutive ACS patients undergoing elective percutaneous coronary intervention (PCI) were randomly assigned to one of two groups: patients in the anisodamine group (ANI group) were assigned to receive intravenous infusions of anisodamine by an adjusted-dose (0.1–0.2 μg∙kg^-1∙min^-1) from the PCI procedure to 24 hours after PCI, and the control group (CON group) received 0.9% isotonic saline of the same volume. All patients were hydrated for 6 to 12 hours before and 12 hours after PCI. Blood samples were taken on the day of PCI and at 24, 48 and 72 hours after PCI to measure the serum creatinine (SCr).

Results  A total of 177 patients were involved in the study, 88 in the ANI group and 89 in the CON group. In both groups, the SCr concentrations significantly increased after PCI, with the peak value occurring at 48 hours. At 72 hours, the SCr concentration in the ANI group retuned to the baseline level (P >0.05), but the SCr concentration in CON group was still higher than baseline level (P <0.01). The SCr concentrations at 48 and 72 hours after PCI were much lower in the ANI group than those in the CON group (both P <0.01). The estimated glomerular filtration rate (eGFR) significantly decreased after PCI, the lowest value occurred at 48 hours. In the ANI group, the eGFR at 72 hours was similar to the baseline level. In the CON group, the eGFR failed to return to baseline at 72 hours (P <0.01). The eGFR at 24, 48 and 72 hours after PCI were higher in the ANI group (all P <0.05). The incidence of CIN in the ANI group was lower than that in the CON group within 72 hours after PCI (P <0.05). The results of multiple Logistic regression proved that both diabetes and left ventricular ejection fraction (LVEF) were independent predictors of CIN, and treatment with anisodamine was an independent preventive factor of CIN (OR 0.369 and 95% CI 0.171 to 0.794, P＝0.011). No serious side effects were found in the ANI group.

Conclusion  Intravenous infusion of anisodamine during and after elective PCI may safely prevent the occurrence of CIN in ACS patients.

     

多支冠脉病变并心功能不全患者PCI的临床观察

目的:观察多支冠脉病变并心功能不全患者经皮冠脉介入术(PCI)后部分血运重建的安全性和有效性。方法:56例多支血管病变的冠心病患者,男41例,女15例,平均年龄67±10岁,心功能Ⅱ~Ⅲ级,依自愿原则随机分为两组,介入治疗(PCI)组和单纯药物治疗(MT)组。两组常规应用抗心绞痛及抗心衰药物治疗。于治疗1个月、6个月、12个月分别行超声心动图检查评价心功能。结果:PCI组和MT组1年生存率分别为98%和89%,未发生Q波心梗者分别占96%和87%,两组间未再发作明显心绞痛者分别占82%和49%,与术前比,PCI组在术后1个月左室射血分数有所增加(P<0.05),同时高于药物治疗组(P<0.05)。在6个月时进一步改善,1年与6个月无显著差异。而药物治疗组仅在治疗6个月后,左室射血分数方有改善。结论:该结果显示:PCI组与MT组相比,不完全血运重建对于冠脉多支病变伴心功能不全患者仍不失为积极有效的治疗手段,可以改善心功能,提高生存率,改善生活质量。     

尿激酶配合氢溴酸山莨菪碱股动脉溶栓对糖尿病足的疗效观察

观察股动脉溶栓治疗糖尿病足的临床疗效。方法 将40例糖尿病足患者随机分为治疗组和对照组,每组20例,治疗组患侧股动脉穿刺并滴注尿激酶（2.5×105 U）配合氢溴酸山莨菪碱（10 mg）溶栓,对照组静脉滴注前列腺素E1注射液（10 μg）。结果 治疗组糖尿病足的有效率95%,对照组的有效率80%,两组比较差异有显著性（P＜0.05）。足背动脉多普勒检查显示,治疗组治疗后血流速度改善显著优于对照组（P＜0.05）。结论 动脉内溶栓治疗糖尿病足具有操作简便、治疗时间短、见效快以及治疗费用低的特点,容易被老年患者接受,可以在老年病医院推广。     

蝮蛇毒蛋白C激活物对大鼠心肌微血栓形成的抑制作用

目的:观察蝮蛇毒蛋白C激活物(PCA)对大鼠心肌微血栓形成的影响,并进一步探讨其抗凝机制。方法:取健康雄性SD大鼠48只,随机分为假手术(SH)组、微血栓(MI)组、MI+PCA组和PCA组,其中MI+PCA组又分为1mg/kg、3mg/kg、6mg/kg三个剂量组,每组8只。以月桂酸钠复制大鼠心肌微血栓模型,测定并比较各组血浆中PAF、ET-1、vWF、MDA的含量及SOD的活性;心肌石蜡切片,常规HE染色,光镜观察;观察心肌梗死范围。结果:MI+PCA(3mg/kg)组及MI+PCA(6mg/kg)组大鼠血浆中PAF、ET-1、vWF、MDA的含量较MI组显著降低(P<0.05);病理亦显示MI+PCA(3mg/kg)组及MI+PCA(6mg/kg)组心肌无微血管血栓形成、无梗死;PCA组与SH组各指标无明显差异。结论:PCA可有效抑制微血栓形成,其除了可通过激活蛋白C系统抗凝外,保护血管内皮亦可能是其另一抗凝途径。     

Effect of intracoronary administration of anisodamine on slow reflow phenomenon following primary percutaneous coronary intervention in patients with acute myocardial infarction

Background Many basic and clinical studies have proved that anisodamine can produce significant effect on relieving microvascular spasm, improving and dredging the coronary microcirculation. It may be beneficial to the improvement of slow-reflow phenomenon (SRP) following percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). So we investigated the effect of intracoronary administration of anisodamine on SRP of infarct related artery (IRA) following primary PCI in patients with ST segment elevated acute myocardial infarction (STEAMI). Methods Twenty-one patients with SRP from a total of 148 STEAMI patients accepted primary PCI were enrolled into this study from September 2004 to December 2005. When SRP happened, nitroglycerin (200 &micro;g) was “bolus” injected firstly into IRA to exclude the spasm of epicardial artery and identify SRP as well as a baseline and self-control agent following PCI. Ten minutes later, 1000 &micro;g of anisodamine was injected into IRA with SRP at 200 &micro;g/s, while the coronary angiography (CAG) was taken before and at 1st, 3rd and 10th minute after administration of nitroglycerin or anisodamine, respectively. The corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and the diameter of IRA were calculated and analyzed by Gibson’s TIMI frame count method using quantitative computer angiography (QCA) system to evaluate the influence of anisodamine on coronary flow and vessel lumen. In the meantime the invasive hemodynamic parameters of intracoronary and systemic artery (systolic, diastolic and mean pressure) and electrocardiogram (ECG) were measured and monitored. The changes of ventricular performance parameters and the adverse reaction were evaluated and followed-up at 1 month post-PCI. Results No significant changes in cTFCs and TMPGs were found at 1st, 3rd and 10th minute after intracoronary administration of nitroglycerin as compared with the baseline control (P＞0.05). cTFCs were decreased by 58.3%, 56.2%, and 54.6%, respectively (P&lt;0.001), and TMPGs were increased from 1.13±0.21 grade to 2.03±0.32, 2.65±0.45 and 2.51±0.57 grades (P&lt;0.05) at 1st, 3rd and 10th minute after intracoronary administration of anisodamine as compared with those after intracoronary administration of nitroglycerine, respectively. The average coronary blood flow of TIMI grade was improved from 1.76±0.43 to 2.71±0.46 (P&lt;0.05) while the diameter of middle segment in re-patented coronary artery was slightly increased from (3.20±0.40) mm to (3.40±0.50) mm at the 3rd minute after intracoronary administration of anisodamine (P＞0.05) as compared with those of nitroglycerine control. The systolic, diastolic and mean pressures of intracoronary artery after intracoronary administration of anisodamine increased from 115 to 123, 75 to 84, 88 to 95 mmHg (P&lt;0.05), respectively, along with the rise of heart rate from 68 to 84 beats per minute (P&lt;0.05). There were no significant changes in intervals of PR, QT and QRS (P＞0.05) and no any severe fast arrhythmia after intracoronary administration of anisodamine. The ventricular performance parameters were significantly improved and no major adverse cardiovascular events (MACE) were found during follow-up at 1 month post-PCI. Conclusions Intracoronary administration of 1000 &micro;g anisodamine is effictive in reversing SRP following PCI in STEAMI patients, especially it is suitable for SRP patients with bradycardia or hypotension.     

山莨菪碱预处理对兔肺缺血再灌注损伤的实验研究

目的 探讨山莨菪碱预处理对兔肺缺血再灌注损伤的保护作用及其作用机制.方法 建立兔肺缺血再灌注动物模型,健康家兔24只,随机分为3组,每组8只.假手术组不行缺血再灌注处理,对照组进行左肺缺血再灌注处理,山莨菪碱组静脉给予山莨菪碱预处理后行左肺缺血再灌注处理.各组不同时间点采血,测血浆丙二醛(MDA)和一氧化氮(NO)含量;术后取左肺组织进行形态学观察和还原型谷胱甘肽过氧化物酶(GSHpx)含量测定;最后通过静脉注射伊文思兰的方法比较3组肺血管通透性差异.结果 缺血再灌注处理后,对照组血浆MDA和NO含量明显高于假手术组(P均<0.01),GSHpx含量明显低于假手术组(P<0.01),组织病理损伤严重,肺血管通透性高,山莨菪碱组上述指标水平改善(P均<0.05),组织损伤减轻,肺血管通透性低.结论 应用山莨菪碱预处理可以显著减轻肺缺血再灌注损伤的程度.     

山茛菪碱对绞窄缺血肠段肠系膜微循环作用的实验观察

本实验用兔制成绞窄性肠梗阻的动物模型,用微循环显微镜观察肠系膜微循环的变化。解除梗阻后缺血肠段肠系膜微循环在一段时间内存在明显障碍,并伴有肠粘膜缺血性损伤。肠系膜根部加静脉应用山茛菪碱,能明显扩张细动脉,加快血流,改善肠系膜微循环,促进肠管生机恢复。以减少术后肠穿孔的发生。     

大鼠冠状动脉微血栓模型

目的　建立大鼠冠状动脉微血栓模型。　方法　大鼠分为对照组和冠脉微血栓组 (模型组 ) ,每组各12只。钳夹升主动脉后自主动脉根部注入生理盐水或月桂酸钠 1.0 mg/ kg,1h后取标本。苏木精 -伊红染色观察冠脉微循环改变 ,Nagar- Olsen染色观察早期心肌低氧程度。　结果　 (1)模型组出现微动脉血管内皮损伤及微动脉血栓形成 ,对照组无此情况 (P <0 .0 1) ;模型组微动脉内皮损伤率为 10 .17%± 2 .33% ,血栓形成率 9.4 2 %±2 .0 2 %。 (2 ) Nagar- Olsen染色模型组心肌缺血区域占所观察心肌横截面面积的 7.2 0 %± 2 .4 3% ,对照组无心肌缺血 (P<0 .0 1)。　结论　月桂酸钠可稳定地诱发冠脉微血栓形成 ,该模型可用于冠脉微血栓及微栓塞研究的平台