乌拉地尔、硝酸甘油用于高血压急症院前急救的临床分析

目的观察乌拉地尔、硝酸甘油注射液对高血压急症的临床疗效,并分析其对心率的影响。方法将80例高血压急症患者随机分为乌拉地尔组与硝酸甘油组各40例。乌拉地尔组给予乌拉地尔注射液25mg用0．9％氯化钠注射液20mL稀释,5min内静脉推注,随后用乌拉地尔50mg加入0．9％氯化钠注射液250mL中静脉滴注,初始速度为0．5mL／min（100μg／min）;硝酸甘油组给予硝酸甘油注射液5mg加入0．9％氯化钠注射液250mL中静脉滴注,初始速度为0．5mL／min（10μg／min）。比较两组给药前后血压、心率变化。结果乌拉地尔组、硝酸甘油组均可明显降低高血压急症患者血压．达到治疗目标．两组间疗效比较无明显差异,硝酸甘油组治疗后心率明显增快,不良反应较多。结论乌拉地尔作用迅速、降压平稳．不良反应轻微．是高血压急症院前急救的理想药物。     

不同浓度硝酸甘油对大鼠离体心脏缺血再灌注损伤的影响

目的 探讨不同浓度硝酸甘油对大鼠离体心脏缺血再灌注损伤的影响.方法 健康成年雌性SD大鼠,体重220～330 g,周龄7周,建立Langendorff离体心脏灌注模型,取模型制备成功的心脏30个,随机分为3组(n=10):缺血再灌注组(IR组)K-H液灌注15 min,停灌20 min,再灌注60 min;低浓度硝酸甘油组(LN组)采用含有2.5 μg/L硝酸甘油的K-H液灌注15 min,停灌20 min,再灌注60 min;高浓度硝酸甘油组(HN组)采用含有25μg/L硝酸甘油的K-H液灌注15 min,停灌20 min,再灌注60 min.于再灌注10、20、30、40、50、60 min时记录心率(HR)、冠状动脉流量(CF)、左心室舒张末压(LVEDP)、左心室发展压(LVDP)、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dt_(max)).于平衡灌注末、再灌注5、30和60 min时收集冠状动脉流出液1.5 ml,测定乳酸脱氢酶(LDH)和肌酸激酶(CK)的活性;于再灌注60 min时取心脏,测定心肌梗死面积,计数心肌凋亡细胞.结果 与IR组比较,LN组HR、CF、LVDP,+dp/dt_(max)和-dp/dt_(max)升高,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率降低(P<0.05),HN组HR、CF、LVDP、+dp/dt_(max)和-dp/dt_(max)降低,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率升高(P<0.05).与LN组比较,HN组HR、CF、LVDP、+dp/dt_(max)和-dp/dt_(max)降低,LVEDP、CK活性、LDH活性、心肌梗死面积和细胞凋亡率升高(P<0.05).结论 低浓度硝酸甘油(2.5μg/L)可减轻大鼠离体心脏缺血再灌注损伤,而高浓度硝酸甘油(25 μg/L)则可加重心脏缺血再灌注损伤.     

l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus

Systemic administration of the nitric oxide (NO) donor nitroglycerin (NTG) triggers a delayed attack without aura in many migraineurs, but not in healthy volunteers. In rats, 4 h after the systemic administration of NTG (10 mg/kg bw, s.c.), the neurons of the caudal trigeminal nucleus (TNC) are activated and the expression of neuronal NO synthase (nNOS) in the same area is increased suggesting a self-amplifying process in the trigeminal system, which seems to be crucial in migraine pathogenesis. Kynurenic acid (KYNA) and its analogues may exert modulatory effects in many neuropathological conditions, probably via N-methyl-d-aspartate (NMDA) antagonism. Since NMDA receptors play a crucial role in trigeminal pain processing, the aim of our experiments was to compare the effects of l-kynurenine (l-KYN) combined with probenecid (PROB) or with 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride alone, a newly synthetized KYNA derivative, on the NTG-induced nNOS expression in the rat TNC. Pretreatment with l-KYN (300 mg/kg bw, i.p.) together with PROB (200 mg/kg bw, i.p.) and KYNA derivative (300 mg/kg bw, i.p.) attenuated the NTG-induced nNOS expression in the rat TNC. Our data suggest that the stimulating effect of NTG, and thus of NO, on the expression of nNOS might be modulated by increasing the KYNA level in the brain, probably through the NMDA receptors. These data could help promote a better understanding of the pathogenesis of headaches and the action of antimigraine drugs.     

Intragastric Nitroglycerin at a Vasodilatory Dose Attenuates Acidified Aspirin-Induced Gastric Mucosal Injury

Clinical studies reveal that aspirin intake to prevent myocardial and cerebral ischemia is associated with a significant increase in upper gastrointestinal hemorrhage requiring hospitalization and that nitroglycerin or long-acting nitrates significantly lower this risk. Nitroglycerin can increase gastric blood flow and slow gastric emptying. We hypothesized that both features contribute to its gastroprotective property. Fasted anesthetized rats (Study 1) and conscious mice (Studies 2 to 4) received intragastric nitroglycerin or vehicle. The effects of these two treatments on various parameters were assessed in Study 1, on blood pressure and gastric blood flow; Study 2, on acidified aspirin-induced gastric mucosal lesions; and Study 3, on the weight of gastric content. In Study 4, the effect of nitroglycerin, vehicle, or vehicle plus saline, on acidified aspirin-induced gastric mucosal lesion was assessed. Compared with vehicle, nitroglycerin decreased blood pressure and produced a mild but significant increase in gastric vascular conductance, blood flow, and volume of gastric content. The number and length of gastric mucosal lesions induced by acidified aspirin were significantly attenuated by intragastric nitroglycerin in a vasodilatory dose. Exogenous saline in a volume equivalent to the increase produced by nitroglycerin, however, did not attenuate the lesions. These experimental data are consistent with the clinical observation that nitrates lower the risk of aspirin-induced gastrointestinal complications. Confirmation of the efficacy of nitroglycerin and nitrates in preventing such aspirin-induced complications in controlled trials is worthy of consideration by clinical investigators.     

乙醛脱氢酶2基因多态与硝酸甘油疗效相关性研究

目的探讨冠心病患者乙醛脱氢酶（ALDH）2基因单核苷酸多态性与硝酸甘油疗效以及ALDH2对饮酒面红的影响。方法选择经冠状动脉（冠脉）造影主要冠脉分支狭窄〉50％患者142例,依据饮酒是否面红分为无面红组88例,面红组54例。检测ALDH2基因单核苷酸多态性,依心绞痛缓解程度和时间判断患者硝酸甘油疗效。比较两组ALDH2基因型分布及硝酸甘油疗效差异和关系,最终评价三者之间的相关性。结果饮酒无面红组患者ALDH2＊1分布、硝酸甘油有效率及迅速起效率均显著高于面红组（P〈0．01）,ALDH2＊1患者硝酸甘油有效率及迅速起效率显著高于ALDH2＊2患者（P〈0．01）。结论ALDH2基因单核苷酸多态性与饮酒是否面红及硝酸甘油治疗心绞痛疗效相关,饮酒无面红的冠心病患者硝酸甘油有效率较高,可能与ALDH2＊1酶活性高有关。     

Atorvastatin attenuates NF-κB activation in trigeminal nucleus caudalis in a rat model of migraine

Nitroglycerin-induced NF-κB activation in trigeminal nucleus caudalis is believed to be partly involved in the pathogenesis of migraine. Atorvastatin, an inhibitor of HMG-CoA reductase, is thought to have pleiotropic effects in various neurologic diseases. Moreover, there are several lines of evidences that atorvastatin inhibits NF-κB activation in peripheral blood mononuclear cells. Thus, this study aims to explore whether atorvastatin attenuates NF-κB activation in trigeminal nucleus caudalis in a nitroglycerin-induced migraine model. A significant increase in nuclear content of p65, an indicator of NF-κB activation, was detected in trigeminal nucleus caudalis in rats following injection with nitroglycerin. However, the nitroglycerin-induced NF-κB activation in trigeminal nucleus caudalis was attenuated by pretreatment with atorvastatin in a dose-dependent fashion. These results suggest that atorvastatin may be a novel and promising candidate for future treatment or prophylaxis of migraine via attenuating activation of NF-κB in trigeminal nucleus caudalis.     

穴位按压与药物急救对冠心病心绞痛效应差异观察

目的:观察穴位按压、硝酸甘油、速效救心丸在急救心绞痛方面的疗效差异.方法:将168例冠心病心绞痛患者随机分为穴位按压组(58例)、硝酸甘油组(56例)和速效救心丸组(54例),分别采用穴位按压膻中5～10 min、舌下含服硝酸甘油片、舌下含服速效救心丸治疗.观察各组症状、心电图改善情况、起效时间和不良反应情况.结果:穴位按压组、硝酸甘油组、速效救心丸组3组患者临床症状总有效率分别为93.1%(54/58)、92.9%(52/56)、87.0%(47/54),差异元统计学意义(P＞0.05);平均起效时间分别为(1.67±2.45)min、(2.89±2.64)min、(3.75±2.99)min,穴位按压组较其他两组起效快(P＜0.05,P＜0.001);心电图疗效总有效率分别为86.2%(50/58)、85.7%(48/56)、75.9%(41/54),3组疗效相当(P＞0.05);治疗过程中,穴位按压组无不良反应发生,硝酸甘油组19例、速效救心丸组12例出现不良反应,纽间比较差异有统计学意义(P＜0.05).结论:穴位按压、硝酸甘油片、速效救心丸3种治疗方法用于心绞痛急救疗效无差异,但穴位按压疗法起效更快,无不良反应.     

清醒家兔心绞痛模型的建立

目的：制备清醒家兔心绞痛模型,以便更好的进行抗心绞痛药物研究。方法：家兔在固定盒中适应性训练一段时间后,右前肢及双后肢电极放置区去毛,贴附带泡沫垫的 Ag/AgCl 电极,连接多导生理记录仪测定 Ⅱ 导联心电图。耳缘 iv 血管加压素 0.05 IU/kg 诱发心绞痛。并观察硝苯地平、硝酸甘油对该模型的影响。结果：清醒家兔 iv 加压素 0.05 IU/kg,可导致心电图 T 波电压升高。给予硝苯地平、硝酸甘油可减弱加压素引起的 T 波抬高。结论：该模型结果可靠,有利于抗心绞痛药物的研究。     

硝酸甘油缓解性胸痛对冠心病诊断的意义

目的 探讨胸痛可被舌下含服硝酸甘油缓解在冠心病诊断中的价值.方法 以2006年8月～2008年4月期间由于胸痛到第四军医大学西京医院就诊入院的患者689例进行前瞻性研究,将其冠状动脉造影结果与胸痛可被硝酸甘油缓解的结果进行对比分析.结果 689例患者中,共有282例(41%)患者的胸痛可被硝酸甘油缓解.在确诊为冠心病的患者364例中有39%患者(142例)的胸痛可被硝酸甘油缓解,而在非冠心病病因引起胸痛的患者325例中有43%患者(140例)的胸痛可被硝酸甘油缓解,两者无显著性差异(P>0.5).结论 胸痛可被舌下含服硝酸甘油缓解并不有助于诊断冠心病.     

硝酸甘油静脉滴注治疗高血压急症的疗效观察

目的探讨硝酸甘油静脉滴注治疗高血压急症的临床疗效及安全性。方法选择符合高血压急症的患者68例,按入院的先后顺序,随机分为观察组与对照组,每组34例。观察组用硝酸甘油10～20mg加入5%葡萄糖溶液250ml中,静脉滴注,10～20μg/min。对照组用硝普钠25～50mg加入5%葡萄糖溶液500ml中,避光,缓慢静滴,10～25μg/min。分别记录用药前后血压、心率及临床表现的变化。结果观察组有效率97.1%;对照组有效率94.4%,组间差异有统计学意义(p<0.05)。结论硝酸甘油静脉滴注治疗高血压急症具有起效快、操作方便、副作用少的特点,值得临床推广应用。