Biochemical studies on the cardioprotective effect of glutamine on tissue antioxidant defense system in isoprenaline-induced myocardial infarction in rats

Oxidative stress is one of the mechanisms with a central role involved in the pathogenesis of myocardial infarction. The protective effect of glutamine on myocardial antioxidant defense system was investigated during isoprenaline-induced myocardial infarction, an animal model of myocardial infarction of human beings. Levels of diagnostic marker enzymes in plasma, reduced glutathione (GSH) and lipid peroxides and the activities of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase in heart tissue were determined. Injection of isoprenaline caused significant increases in the levels of diagnostic marker enzymes in plasma and lipid peroxidation in heart tissue. A parallel decline in the levels of ATP (Adenosine triphosphate) and GSH and the activities of glutathione-dependent antioxidant enzymes and antiperoxidative enzymes in heart tissue was also observed. Prior oral administration of glutamine significantly prevented isoprenaline-induced adverse effects and maintained myocardial antioxidant status at near normal status. The cardioprotective effect of glutamine is probably related to a strengthening of the myocardial membrane by its membrane stabilizing action, or to a counteraction of free radicals by its antioxidant property, or to its ability to maintain near to normal status the activities of free radical scavenging enzymes and the level of GSH, which protect myocardial membrane against oxidative damage by decreasing lipid peroxidation.     

稳心颗粒对异丙肾上腺素诱发豚鼠心律失常的电生理影响

目的探讨稳心颗粒对异丙肾上腺素(Iso)诱发心律失常的电生理影响。方法用标准微电极细胞内记录技术,观测稳心颗粒对异丙肾上腺素诱发豚鼠心律失常的影响。观测指标:最大舒张电位(maxi mal diastolic potential,MDP)、动作电位幅度(am-plitude of action potential,APA)、0相最大去极速度(maxi mal rate of depolarization,Vmax)、4相自动去极速度(velocity of diastolicdepolarization,VDD)、复极50%和90%时间(50%and90%of duration of action potential,APD50and APD90)以及自发放电频率(rate of pacemaker firing,RPF)。结果用100μmol/LIso灌流后左心室流出道自律细胞出现了心律失常,用Iso+稳心颗粒灌胃组血浆灌流后,与Iso模型组和Iso+生理盐水灌胃血浆比较,RPF和VDD减慢(P0.01),APA和MDP的绝对值显著减小(P0.01),Vmax明显减慢(P0.01),APD80和APD90明显延长(P0.01)。结论稳心颗粒能降低自发放电频率,拮抗异丙肾上腺素诱发的心律失常。     

Vasodilator agents and supracollicular transection fail to inhibit cortical spreading depression in the cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.     

Age and gender differences in basal and isoprenaline protocols for head-up tilt table testing.

AIMS: Syncope is a common occurrence, the prevalence of which increases with age, and among the multiple causes of syncope, neurally mediated syncope is thought to be a frequent cause in the young and in the elderly. Head-up tilt table testing (HUT) has become the diagnostic test of choice for neurally mediated syncope, the response to which varies clearly with age. The purpose of this study is to report the differences among patients suffering syncope referred for HUT, and the influence of age and gender on HUT results (percentage of positive responses and response patterns) in two study protocols (basal and isoprenaline). METHODS AND RESULTS: One thousand, two hundred and nineteen patients with syncope were referred to the authors' Cardiology Department for HUT from September 1990 to April 2000; 1061 undergoing basal HUT (Group A) and 158 undergoing isoprenaline tilt table testing (Group B). Complications were noted in neither protocol. Females were more frequent among young people, and males in the elderly (P<0.05). Head-up tilt table testing was abnormal in 259 (24.4%) patients in Group A and in 85 (53.7%) patients in Group B (P<0.05), and no gender differences were observed. The positive rate of tests in men and women significantly declined with age in Group A (P<0.05), but not in Group B (P=ns). There were no differences in the patterns of haemodynamic collapse in both groups. CONCLUSIONS: In the study of syncope, basal HUT has a high positive rate in young people; a decrease in positive rate with age suggests, however, the need for using another protocol with a similar diagnostic accuracy in the elderly.     

异丙肾上腺素对心肌细胞内钙释放和肌浆网内钙容量的影响

目的 :心肌细胞膜上的 β-肾上腺素受体的激活对兴奋 -收缩耦联 （ECC）过程有重要的调节作用。本课题利用异丙肾上腺素 （ISO,1μmol/ L）激活 β-肾上腺素受体从而研究其对源自心肌细胞肌浆网的胞内钙释放 （ECC的重要环节 ）和肌浆网内钙容量的影响 ,进而分析钙释放与钙容量之间的关系。方法 :局部场刺激作用于成年大鼠心肌细胞 ,促使后者产生动作电位 ,进而诱发胞内钙瞬变 （ACT） ,由 ACT可估测胞内钙释放。肌浆网内钙容量则由咖啡因 （2 0 m mol/ L）诱发的钙瞬变 （CCT）估测。实验结果均由 Zeiss L SM- 5 10激光共聚焦显微镜系统记录。结果 :ISO作用下的 ACT峰值为 10 .2 9± 0 .35 （n=13）比正常情况下的 5 .74± 0 .2 7（n=18）高 （P<0 .0 1）。 ISO作用下的CCT峰值为 11.2 3± 0 .2 9（n=13）比正常情况下的 7.6 2± 0 .2 4 （n=18）高 （P<0 .0 1）。结论 :ISO可明显地提高心肌细胞内钙释放量和肌浆网内的钙容量。不管有无 ISO存在 ,胞内钙释放量总是只占肌浆网内钙容量的一部分。在正常情况下 ,心肌的钙释放量有较大的储备能力 ,且此储备可因β-肾上腺素受体的激活而动员。     

Isoprenaline and inducibility of atrioventricular nodal re-entrant tachycardia

Objectives—To examine the effect of isoprenaline on slow and fast pathway properties and tachycardia initiation.
Design—Consecutive patients, prospective study.
Setting—Referral centre for cardiology, academic hospital.
Patients—24 patients suffering from common type atrioventricular nodal re-entrant tachycardia (AVNRT).
Interventions—Programmed electrical stimulation and radiofrequency catheter ablation of the slow pathway.
Measurements and main results—AVNRT was induced before and after the administration of isoprenaline in nine patients (group 1), before isoprenaline only in five (group 2), and after isoprenaline only in 10 (group 3). The anterograde effective refractory period of the fast pathway was prolonged significantly during isoprenaline administration in group 1 (405 (31) v 335 (34) ms, p < 0.001) and shortened in group 2 (308 (57) v 324 (52) ms, p = 0.005). There was also significant shortening in group 3 (346 (85) v 395 (76) ms, p < 0.001). Isoprenaline administration did not result in a significant change of the anterograde effective refractory period of the slow pathway in groups 1 and 3, but eliminated slow pathway conduction in group 2. Isoprenaline significantly shortened the minimal and maximal atrial to His bundle conduction interval recording in response to each extrastimulus of the slow pathway (210 (24) v 267 (25) ms, p < 0.001 and 275 (25) v 328 (25) ms, p < 0.001, respectively) in group 1 and significantly prolonged these intervals (331 (34) v 274 (34) ms and 407 (33) v 351 (33) ms, respectively) in group 3. In all groups only minimal changes in the refractory period of the atrium occurred after isoprenaline administration. The effect of isoprenaline was also measured on the ventricular effective refractory period and on the minimal and maximal length of the ventriculoatrial (V₂-A₂) interval during ventricular pacing. Isoprenaline did not result in a significant change of the ventricular effective refractory period in groups 1 and 2 nor of the shortest and longest V₂-A₂ interval. In group 3, however, the ventricular effective refractory period and the shortest and longest V₂-A₂ interval shortened significantly after isoprenaline administration.
Conclusions—In group 1 isoprenaline did not affect inducibility of AVNRT because it prolonged the fast pathway refractory period without affecting slow pathway conduction. In group 2 isoprenaline shortened the fast pathway refractory period and appeared to abolish slow pathway conduction. Consequencely, isoprenaline prevented induction of AVNRT. In group 3 isoprenaline facilitated induction of AVNRT. This effect seemed primarily to be the result of shortening of retrograde refractoriness of the fast pathway with prolongation of slow pathway anterograde conduction and refractory period.

Keywords: atrioventricular re-entrant tachycardia;  isoprenaline     

肥厚心肌细胞Na^＋／Ca^2＋交换活性对β—肾上腺素能药物的反应性降低

目的 探讨肥厚心肌细胞Na^ /Ca^2 交换对β-类肾上腺素能药物刺激的反应及发生这种改变的可能机制。方法 采用胶原酶消化的高血压大鼠单个心室肌细胞及全细胞膜片钳技术，记录Na^ /Ca^2 交换电流并观察药物对它的影响。结果 (1)异丙肾上腺患可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，但其对肥厚心室肌细胞Na^ /Ca^2 交换电流的增强作用要弱于正常心室肌细胞(P＜0．05)。(2)cAMP可浓度依赖性地增加正常及肥厚大鼠心室肌细胞的Na^ /Ca^2 交换电流，其对正常及肥厚大鼠心室肌细胞Na^ /Ca^2 交换电流的增强作用无差别(P＞0．05)。结论 高血压大鼠心室肌细胞Na^ /Ca^2 交换对β-类肾上腺患能药物的反应性降低，可随与翘厚心肌细胞的g—受体数目及功能、G蛋白及腺昔酸环化酶的活性改变等环节有关，此种反应可能是肥厚心肌收缩及舒张功能障碍的机制之一。