烟碱及相关药物对大鼠心率影响的初步研究

烟碱受体(nAchRs)是一种由α与β亚基所组成的同源或异源五聚体,已有研究表明心脏内含有nAChRs。为确定何种nAChRs亚基在烟碱(Nicotine)对心脏的影响中起主要调节作用,本试验利用大鼠模型进行药物试验。在给大鼠注射100μmol/L烟碱后,起初引起大鼠短暂的心率降低-7次±2%,随之出现大幅度的心率增加17次±5%,增加的心率在10 min~15 min恢复正常。烟碱引起心率的降低作用能被α7亚基特异性阻断剂α-金环蛇毒素(-αBTX,100 nmol/L)所抵消;相反,心率的增加现象在α-金环蛇毒素存在时得到延续。选择性β4亚基竞争剂金花雀碱(Cytisine)对大鼠进行注射后,结果与烟碱对大鼠心率作用的结果相似,因此在心脏交感神经末梢可能存在nAChRsβ4亚基。试验结果,显示不同的nAChRs亚基在对烟碱对心脏的作用中起不同的调节作用,更多药理试验结果显示,α7亚基在对烟碱引起心率降低的调节中起主要作用,β4亚基则在心率的增加过程中起主要作用。     

盐酸椒苯酮胺对新西兰兔心电图QT间期的影响

旨在观察不同剂量盐酸椒苯酮胺(piperphentonamine hydrochloride,PPTA)对新西兰兔心电图QT间期(从QRS波开始到T波结束时的时限)的影响。将40只新西兰兔随机分为5组,每组8只,分别为溶剂对照组(5%葡萄糖)、PPTA低(2.5mg/kg)、中(10mg/kg)、高(25mg/kg)剂量组以及阳性对照组(9mg/kg索他洛尔),采用体表心电图技术,通过Pclab-530C生物医学信号采集处理系统记录各组新西兰兔注射相应药物后PPTA标准肢体Ⅱ导联心电图变化。结果表明,2.5mg/kg、10mg/kg PPTA在缓慢给药后不引发QT间期延长,25mg/kg PPTA在缓慢给药后15min内引起QT间期轻度延长(P0.05);PPTA对QT间期的影响主要发生在给药后0~15min,45min后基本恢复正常。因此,低、中剂量盐酸椒苯酮胺(PPTA)不引发新西兰兔心电图QT间期延长,安全性较高,高剂量可能有引发QT间期延长风险,提示在临床用药时需要注意药物使用剂量,以防QT间期延长和心律失常的发生。     

氯仿对蟾蜍心电图的影响

观察氯仿对在体蟾蜍心电图的影响。用数字式心电图机记录蟾蜍用氯仿熏前、熏后即刻和恢复正常呼吸后的心电图的变化。结果表明,用氯仿熏后即刻或恢复正常呼吸后蟾蜍心电图与用氯仿前相比,心率减慢,QRS波群增宽,QT间期延长,T波明显,部分心电图出现大U波。氯仿不能导致蟾蜍发生室颤。     

黄芪注射液对犬心脏双向变时作用的初步观察

为了观察黄芪注射液对正常犬和二尖瓣关闭不全病理模型 (MR)犬的变时作用 ,并探讨其机制 ,在异氟烷吸入麻醉下 ,对正常及外科方法制作的犬亚急性二尖瓣关闭不全模型 (术后 5 0天后 )一次性静脉推注含生药 2 g/ m L的黄芪注射液 1 .2 5 m L/ kg,通过体表心电图测定心率和 PQ、QRS、RR、QT,并计算 QTC(QT/ RR)间期。在正常犬 ,开始注射黄芪注射液后 ,心率出现先减少后恢复再持续减少和显著变化。 MR模型犬开始注射液后 ,心率出现先升高后恢复再持续升高的显著变化。 MR模型犬的心率减慢变化与 RR、PQ、QT、QTc呈高度显著负相关 (P<0 .0 1 )。表明黄芪注射液对正常比格犬 ,具有加快心率的正性变时作用。对二尖瓣闭锁不全 (MR)模型犬具有减缓心率的负性变时作用。黄芪注射液的变时作用似与机体的机能状态有关 ,呈现双向调节作用。     

α_2肾上腺素受体在中枢神经系统的药理学

α_2~-肾上腺素受体介导中枢神经和外周组织的各种生理机能。用激动或阻断这些受体的药物,引起各种器官和组织的复杂反应。α_2—肾上腺素受体激动剂在兽医上已广泛用于镇静和镇痛,也能加强麻醉药的作用和减少用量。还能在麻醉和手术中减轻交感神经—肾上腺对有害剌激的反应。最近的研究证明有不同的α_2—肾上腺素受体亚型,出现对受体亚型有选择作用的药物和更特异的治疗作用。     

氟马西尼联合肾上腺素对钩吻中毒的解救作用

旨在研究氟马西尼联合肾上腺素对钩吻中毒大鼠的解救效果,并验证钩吻可能的毒性作用靶点,为钩吻中毒机制探讨及解救钩吻中毒病例提供参考。构建钩吻大鼠中毒模型,将60只大鼠随机分为4组,分别为对照组、氟马西尼解救组、肾上腺素解救组、联合用药(氟马西尼+肾上腺素)解救组,记录各组大鼠中毒及死亡情况,并监测各组大鼠血压、心率,评价各组药物的解救效果。采用分子对接、全细胞膜片钳技术,预测钩吻主要毒性物质钩吻素己与解救药物作用的靶点,阐释其可能的解毒机制。结果显示:钩吻灌胃大鼠的半数致死量(LD₅₀)为0.25 g·kg^-1,氟马西尼联合肾上腺素使用时对钩吻中毒的大鼠有显著的解救效果,存活率由25%提高到92%(P<0.01),且平均中毒症状出现时间由16.56 min延长至25.98 min (P<0.01),平均死亡时间由40.13 min延长至58.05 min (P<0.01),解救效果显著高于氟马西尼和肾上腺素单独解救组。联合用药组还可显著缓解中毒所致的大鼠血压、心率下降的临床表征。分子对接计算机模拟结果显示,氟马西尼与钩吻素己都与GABA_A受体同一活性位点有较好的结合效果,且氟马西尼的结合能-85.47 kJ·mol^-1,强于钩吻素己结合能-77.15 kJ·mol^-1。全细胞膜片钳结果显示,钩吻素己可显著延长GABA_A受体离子通道的开放时间,而氟马西尼可拮抗此作用。综上所述,氟马西尼和肾上腺素联合使用对钩吻中毒大鼠具有明显的解救效果,钩吻神经毒性靶点与氟马西尼作用的GABA_A受体密切相关,肾上腺素对调节中毒所致的血压下降起到关键作用,联合用药可起到标本兼治效果。     

禁止非法使用β-兴奋剂的措施浅析

β-兴奋剂,全称β-肾上腺素能兴奋剂或β-肾腺素能受体激动剂,也有称能量重分配剂。它是一化学结构和生理功能类似肾上腺素的苯乙醇胺类生物,能与动物体内大多数β-肾上腺素能受体结,激发β-肾上腺素能受体兴奋的药物。β-兴奋剂影响营养物质在动物体内的流向和重新分配,有促进肌肉组织生长,降低胴体脂肪含量,提高瘦肉和增加瘦肉产量,因而曾在欧美广泛使用;但另一面,能与细胞表面的β-受体结合产生明显的生理用,如心悸、头疼、目眩、恶心、呕吐、发烧、战粟、神过敏、血管扩张、心率加快、肌肉震颤等,而且β-奋剂残留会聚集在动物可食用组织…     

β2肾上腺素能受体的研究进展及其在兴奋剂残留检测中的应用

β肾上腺素能受体属于G蛋白偶联受体的1种,能够与一系列内源或外源性肾上腺素能物质相互作用,激活受体并引起信号转导从而引发机体的生理化学反应。目前已经研究了β2肾上腺素能受体的结构活性、蛋白表达和检测应用,但是仍然因为7次跨膜结构的蛋白表达量低等特点,造成该受体的发展进程缓慢。本文重点叙述了β2肾上腺素能受体的结构以及活性氨基酸残基,分析目前该受体蛋白在真核和原核细胞表达的现状以及在β兴奋剂药物的残留检测中的应用,总结在β2肾上腺素能受体研究方面存在的问题和发展趋势。     

青海藏獒不同年龄心电图的测定

对60条不同年龄的藏獒在清醒状态下进行了12个导联的心电图测定,建立了心电图基本数据。结果发现,被检健康藏獒皆为正常窦性心律,是生活在青藏高原动物的共同特性,青海藏獒的总体心率为(108±6)次/min,R-R间期时限为(0.558±0.035)s,心电轴皆正常不偏移,青海藏獒不同年龄间心电图差异不显著(P0.05);心率随年龄的增加逐渐变缓,且年龄与P-R间期的时限成正相关,反之则缩短,不同年龄的藏獒QRS波群均无明显差异(P0.05)。     

西藏小型猪心电图分析

通过对西藏小型猪心电图分析,寻求西藏小型猪心电图变化的规律,并与人类和贵州小型猪心电图进行比较,以期为西藏小型猪实验动物化提供心电图基本资料。用ECG-9020K心电图仪,描记完全清醒状态的西藏小型猪45头,选择Ⅰ、Ⅱ、Ⅲ标准导联和aVR、aVL、aVF单极加压肢体导联的心电图。结果显示:①心电图均为窦性心率;②P波在Ⅰ、Ⅱ、aVF导联均为直立,在Ⅲ、aVL导联大部分直立,在aVR导联均倒置;③QRS综合波形在Ⅰ导联以qR为主,Ⅱ导联以qRs、Rs为主,Ⅲ导联以Rs、qRs为主,aVL导联以qRr、sr’和qr为主,aVR导联以rsr’、Qr和Q为主,aVF导联以Rs和qRs为主;④T波在Ⅰ、Ⅱ、Ⅲ、aVF导联中多为直立,在aVL、aVR导联中多为倒置;⑤各波间期时间(ms):P波(68.18±23.54),P-R间期(92.69±20.64),QRS间期(47.76±13.50),Q-T间期(225.93±45.03),Q-Tc间期(225.47±31.23)。西藏小型猪心电图特征与人心电图基本相似,但心率较快,P-R间期、QRS间期、S-T间期和Q-T间期较短及T波方向变化大;西藏小型猪心电图特征与贵州小型猪心电图很相似,但Q-T间期较贵州小型猪短。     

Effect of intermittent administration of sustained release isosorbide dinitrate (sr-ISDN) in rats with pressure-overload heart

Recent studies have demonstrated the benefits of nitric oxide (NO) on myocardial hypertrophy and myocardial fibrosis. It was suggested that NO has a protective effect on myocardial cell through the neurohormonal system. This effect serves to highlight the important role of NO in maintaining the function and form of heart with chronic heart failure. However, there are no known reports about on the effect of prolonged administration of nitrate on pressure over-load heart. This study was conducted to examine the long-term effect of oral nitrate therapy in rats with pressure-overloaded heart. An abdominal aorta constricted (AC) model of pressure-overloaded heart was created in male Wistar rats. Sustained release isosorbide dinitrate (sr-ISDN) (5 mg/kg once a daily) was administered to the rats once a daily for 12 weeks. The animals were euthanized during the study period, and the heart was collected and weighed. Histopathological examination was performed to evaluate the effect of sr-ISDN on myocardial hypertrophy and fibrosis. The ratio of heart to body weight increased significantly in AC rat and this increase was significantly prevented by sr-ISDN treatment. Histopathological examination showed significant increase in fibrotic area of AC rat compared to sham rat, this increase was inhibited by sr-ISDN treatment. Cardiomyocyte transverse diameter was significantly increased in AC rat compared with sham rat, but this increase tended to decrease by sr-ISDN treatment. In conclusion, intermittent administration with sr-ISDN has mild effect in inhibiting cardiac hypertrophy and marked effect in inhibiting fibrosis due to pressure-overload.     

Evaluation of QT interval prolongation in dogs with heart failure

Comparison of the QT interval and corrected QT interval values that were calculated by the methods of Bazett (QTc1) and Fridericia (QTc2) were made between dogs with or without cardiac diseases to determine the influence of the QT interval on canine heart failure. Upon comparison of the measured values on ECG between the cardiac disease and non-cardiac disease groups, it was observed that the heart rate(HR) was significantly higher in the cardiac disease group than in the non-cardiac disease group, although the QT interval was similar in the two groups. The QTc1 and QTc2 were significantly longer in the cardiac disease group than in the non-cardiac disease group. With the progression of the New York Heart Association Class, the HR tended to increase. The QTc1 and QTc2 became significantly prolonged with the progression of heart failure. Nevertheless, because Bazett's correction formula is known to overcorrect when the HR is high, it was considered that the QTc1 was actually overcorrected by high HR with the progression of heart failure. The QTc2, on the other hand, was only slightly influenced by HR, suggesting that the prolongation was due to the progression of heart failure. These results suggest that the prolongation of QTc2 in cardiac disease reflects the substantial prolongation of the QT interval without the influence of HR. It is suggested that the QTc2 could be a useful parameter for assessing the degree of heart failure in dogs with cardiac disease.     

Duration of the QT interval in healthy cats

OBJECTIVE: To develop a clinically useful model for predicting QT interval duration as a function of heart rate in healthy cats. ANIMALS: 20 healthy cats. PROCEDURE: For all cats, results of a physical examination, electrocardiography, and echocardiography were normal. Twenty-four hour heart rate and rhythm data were collected by means of ambulatory electrocardiography. Hourly ECG segments were obtained from the 24-hour recordings. Mean heart rate and the mean of 5 QT interval measurements were calculated for each of 479 usable ECG segments. Analysis of covariance was used to develop models to describe variability in QT interval duration. RESULTS: Prediction equations (R2 = 0.81) including terms for heart rate, (heart rate)2, age group (1 to 4 vs 8 to 14 years old), and their interactions were developed. Sex, individual cat, and time of day were of little value in predicting QT interval duration. A simplified prediction equation without age group (R2 = 0.71) also was developed and had better predictive ability than reported correction formulas for QT interval duration. CONCLUSIONS AND CLINICAL RELEVANCE: Prediction equations with 95% prediction intervals for expected QT interval duration in healthy cats were generated. Abnormal QT interval duration can be associated with cardiac electrical instability, yet QT interval duration is greatly influenced by heart rate. Results of the present study provide reference ranges for expected QT interval duration as a function of heart rate in healthy cats.     

Comparison of the effects of thiopentone and propofol on the electrocardiogram of dogs

Sixty-four dogs were randomly assigned to receive either thiopentone or propofol and their electrocardiograms were recorded immediately before and shortly after they were anaesthetised. Thiopentone caused a marked increase in QT and JT intervals, a flattening of the T-wave and an increase in precordial QT dispersion. Propofol induced a less marked increase in QT and JT intervals, corrected for heart rate. Both agents induced an increase in heart rate and a decrease in heart rate variability, consistent with reduced vagal tone. Shortly after anaesthesia was induced, thiopentone affected ventricular repolarisation to a far greater extent than propofol, changes which suggest that it may be more likely to induce re-entrant ventricular arrhythmogenesis and could be associated with an increase in sympathetic tone. Propofol may therefore be more suitable than thiopentone for dogs with a susceptibility to ventricular arrhythmias or a long QT interval.     

Toxicity of Nicotine by Repeated Intratracheal Instillation to F344 Rats

In vivo, nicotine in cigarette smoke induces various effects not only on the respiratory system but also the central and peripheral nerve systems, circulatory organs and digestive organs, and there is a possibility of promotion of lung tumorigenesis. The present experiment was conducted to examine histopathological changes caused by nicotine in the lung with repeated intratracheal instillation (i.t.). Six-week-old male F344 rats were administered nicotine by i.t. at doses of 0.05, 0.1 and 0.2 mg nicotine/rat every 3 weeks beginning at week 4, for up to a total of 9 times and were then sacrificed at week 30. The total number of administrations, total dose of nicotine and effective number of rats were 9 times, 0.45 mg and 5 rats and 4 times, 0.20 mg and 5 rats for the 0.05 mg nicotine/rat group; 3 times, 0.30 mg and 5 rats and 4 times, 0.40 mg and 3 rats for the 0.1 mg group; and 3 times, 0.60 mg and 3 rats for the 0.2 mg group, respectively. As a control group, 5 rats were administered 0.2 ml saline/rat 9 times. Some rats administered 0.1 and 0.2 mg nicotine suffered convulsions just after administration. Histopathologically, though proliferative changes were not observed, neutrophil infiltration, edema and fibrosis in the lung were induced by nicotine. In conclusion, repeated treatment of nicotine promoted neurologic symptoms in the acute phase, and strong inflammation in the lungs in the chronic phase, even at a low dose. Toxicity of nicotine is suggested to depend not on total dose of nicotine in the experiment but rather on repeated injury with consecutive administration.     

防治奶牛子宫内膜炎复方药物对大鼠血清NO含量及NOS活性影响的研究

本试验应用硝酸还原酶法对大鼠血清NO含量进行测定；应用比色法对大鼠血清NOS活性进行测定。试验结果表明：复方Ⅰ与复方Ⅱ对大鼠血清NO、NOS与cNOS有显著促进作用，但仅是正常范围内的促进，并未超出大鼠血清三种指标的范围；复方Ⅰ与复方Ⅱ对大鼠血清iNOS有显著抑制作用；从而说明复方Ⅰ与复方Ⅱ能通过增强NOS活性而增加NO含量．从而增强子宫平滑肌兴奋性而有利于子宫内恶露排出而对奶牛子宫内膜炎起到一定治疗作用。     

不同比例虫草培养基混合料对SPF级Wistar大鼠主要脏器重量及其系数的影响

为探讨不同比例的虫草培养基混合料对SPF级Wistar大鼠主要脏器重量及脏器系数的影响，用电子天平测定3组动物的体重、心、肝、脾、肺、肾、肾上腺、睾丸、卵巢和胃的重量，并计算其脏器系数。结果表明，不同比例组的同性别Wistar大鼠，其体重之间不存在显著差异；低比例组雄性Wistar大鼠心脏、肺脏和睾丸，雌性Wistar大鼠肺脏的重量显著或极显著高〖JP2〗于对照组、高比例组；低比例组雄性Wistar大鼠心脏、肺脏、肾脏和睾丸，雌性Wistar大鼠心脏、肝脏、肺脏、肾脏和胃的脏器系数显著或极显著高于对照组、高比例组；低、高比例组Wistar雄鼠和高比例组Wistar雌鼠的肾上腺重量及其系数均显著低于对照组。可见，适当比例的虫草培养基可以作为啮齿类试验动物的添加料，但是否适用于饲喂其它动物还有待于进一步的试验研究。     

Effect of equilateral administration of monensin and tiamulin on the peripheral nerve function and the electrocardiogram of broilers

The influence of the simultaneous administration of monensin and tiamulin on the motor nerve conduction velocity and the refractory periods of the N. ischiadicus was studied on 4-week old cockerels. The combined administration of the two substances resulted in significant decrease of the conduction velocities of the peripheral nerve, while the relative and absolute refractory periods were seen to increase significantly as a result of the medications. The observed alteration of the peripheral nerve function in the early phase can already attribute to the development of the serious clinical signs of the toxic interaction. The simultaneous application of monensin and tiamulin caused also changes in the electrocardiogram which was expressed in a prolongation of the RS interval and the ST segment. At the same time the heart rate was reduced.     

Haemodynamic alterations induced by toxic level of sodium taurocholate

Haemodynamic effects of sodium taurocholate (S.T.) were studied on isolated guinea pig's auricles, rabbit's heart, rabbit's aortic strip, guinea pig's tracheal chain as well as the blood pressure and ECG pattern changes in pentobarbital anaesthetized dogs. S.T. induced significant negative inotropic and chronotropic effects on the isolated auricles of guinea pig's especially in higher concentrations. Using isolated rabbit's heart, the negative inotropic and chronotropic effects induced by S.T. were found to be depending on the concentration. Cardio-inhibitory actions of the salt are not due to either cholinergic beta 1-adrenergic blocking effect or nicotine like activity. S.T. in all tested concentrations had no effect on the contractile response of isolated rabbit's aortic strip or guinea pig's tracheal chain and did not prevent the contractile response induced by noradrenaline and histamine. In anaesthetized dogs, i.v. injections of the salt in a dose of 30 mg/kg b. wt. produced a significant decrease in systolic and diastolic pressure, but lower doses induced no significant changes. A dose of 30 mg/kg b. wt. of the salt potentiates the decrease in systolic and diastolic pressure when coadministered with the neuromuscular blocking agent, atracurium besylate. Atropine, propranolol and phentolamine did not alter the hypotensive effect of S.T. (neither cholinergic nor beta 1-adrenergic blocking effect). The electrocardiographic pattern induced by S.T. (20-30 mg/kg b. wt.) in dogs were mainly characterized by decrease in heart rate and prolongation of P-T interval.     

Current concepts in vasodilator therapy for advanced or refractory congestive heart failure

The use of vasodilators to assist in the management of advanced heart failure has gained widespread acceptance in human cardiology. The early experience with these same drugs in the management of heart failure in domestic animals has similarly been encouraging.Vasodilators function to favorably alter preload and afterload in the heart failure setting. Venodilators can resolve pulmonary edema by reducing an elevated left heart preload. Arterial vasodilators can increase stroke volume, reduce an elevated preload, and blunt or abolish the stimulation of the harmful compensatory measures that are induced in the presence of heart failure. Both classes require careful monitoring to ensure that marked hypotension does not occur.Vasodilator therapy can significantly complement other traditional modalities of drug therapy in cases of advanced heart failure.