Protection against cardiac anoxia — role and limitations of increased glycogen reserves in the isolated rat right ventricular strip

Summary The effects of drugs on rat cardiac glycogen reservesin vivo, and on the subsequentin vitro sensitivity of the right ventricular strip preparation to anoxia have been investigated.Isoproterenol (0.2 mg/kg i.p.) causes immediate cardiac stimulation and reduction of glycogen reserves, coupled with an increased susceptibility to anoxia. Several hours after administration, glycogen levels are found to be greatly (100–200%) increased, by a supercompensation mechanism, and a marked tolerance to anoxia can be simultaneously demonstrated.In contrast, large doses of corticosteroids (dexamethasone, 8 mg/kg i.m.) increase glycogen levels without initial stimulation and glycogen depletion; increased myocardial tolerance to anoxia parallels the increase in glycogen reservesin vivo.We conclude that the myocardial tolerance to anoxia in this model is related to increased glycogen reserves, which increase the rate and/or duration of anaerobic glycolysis during anoxia.Dedicated to Prof. Dr. Grünewald on the occasion of his 60th birthday.     

Gender differences in autonomic modulation of ventricular repolarization in humans

BACKGROUND: Gender differences in the incidence of ventricular arrhythmias have been reported and torsades de pointes associated with long QT syndrome are more common in women than men. Although increased sympathetic tone has an important role in vulnerability to arrhythmia, little is currently known regarding gender differences in the dynamic electrophysiological response to sympathetic stimulation. Therefore, we investigated whether there is a gender difference in humans with respect to the dynamic response of ventricular repolarization to beta-adrenergic stimulation and to autonomic blockade. METHODS: Twelve-lead ECGs were continuously recorded during isoproterenol infusion (protocol 1) and autonomic blockade with propranolol and atropine infusion (protocol 2) in 24 healthy volunteers (12 men, 23 +/- 2 years; 12 women, 23 +/- 5 years). QT (QTc) intervals were measured at the baseline and at a heart rate of 75, 100, and 120 beats/min. RESULTS: (1) The morphology of the T wave dynamically and transiently changed to bifid or biphasic during the acute phase of isoproterenol infusion. The incidence of these morphologic changes was higher in women than men (P < 0.05). (2) The QTc interval was initially prolonged and then shortened in both men and women during isoproterenol administration. However, QTc prolongation was significantly greater in women (0.44 +/- 0.02 to 0.55 +/- 0.03 sec) than men (0.42 +/- 0.03 to 0.51 +/- 0.04 sec; P < 0.05). (3) The QTc interval was significantly prolonged under autonomic blockade and the intrinsic QTc interval was longer in women than men (P < 0.05). CONCLUSION: While sympathetic stimulation and autonomic blockade modulated the dynamics of ventricular repolarization in both sexes, it was more pronounced in women. This gender difference may partially account for the susceptibility of women to arrhythmogenesis.     

Characterisation of somatostatin release from the pancreas

Summary The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 mol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.     

他汀类药物对异丙基肾上腺素致心功能不全大鼠的心肾保护作用

目的 研究他汀类药物对心、肾损害的防治作用,同时探讨心、肾交互影响的病理机制.方法 24只Wistar 大鼠分为3组：空白对照组（n=4）,他汀组（n=10）,异丙肾组（n=10）.空白对照组生理盐水2ml/d灌胃;他汀组瑞舒伐他汀4mg/ （kg·d）灌胃;异丙肾组生理盐水2ml/d灌胃;两周时,空白对照组腹腔注射生理盐水2ml,他汀组与异丙肾组给予异丙肾（85mg/kg）腹腔注射2d.15周后用心脏超声评价大鼠心脏功能,测定肾素-血管紧张素-醛固酮系统、抗氧化系统、炎症因子部分相关生化指标,心、肾组织行病理切片检查脏器损害情况.结果 他汀组大鼠的心功能明显优于异丙肾组[左室射血分数：（73.18±7.89） ％vs（58.58±6.41）％,P＜0.05];他汀组的血管紧张素Ⅱ水平显著低于异丙肾组[（ 928.50± 536.87）vs（1886.80± 718.89） pg/ml,P＜0.05];他汀组的丙二醛[（10.10±0.74） vs（ 12.36±2.11） nmol/ml,P=0.073]及白介素-6[ （44.46±24.57） vs （76.31±20.79） ng/ml,P=0.058]水平与异丙肾组相比下降,但两组间的差异没有统计学意义;他汀组大鼠的心脏、肾脏病理异常改变明显轻于异丙肾组.结论 在异丙基肾上腺素致心功能不全大鼠模型中,瑞舒伐他汀可以改善心脏功能,减轻心脏和肾脏的结构改变.可能通过抑制RAAS系统激活、活性氧损伤和抗炎症的机制削弱心肾之间的不良交互作用.     

Simultaneous Recordings of the Monophasic Action Potential with Silver Chloride- and Ir-Coated Electrodes

Ag AgCI and Ir-coated electrodes allow the recording of the monophasic action potential (MAP) due to their electrical properties like non-polarisability. This study investigates the correlation of MAP recorded with both types of electrodes. In 20 mongrel dogs (18 ± 6 kg) an Ag/AgCI and an Ir-coated catheter (Ir) were placed endo-cardially in the apex of the right ventricle. The effects of isoproterenol and verapamil were investigated during spontaneous rhythm and stimulation simultaneously recorded with both types of electrodes in 10 dogs without AV-node ablation. The correlation at different heart rates were investigated in 10 other dogs with complete AV-block. The morphology and amplitudes of MAP were comparable (AgCl: 15±7 mV; Ir: 13±8 mV). Following an i.v. bolus of 2μg/kg isoproterenol the spontaneous rate increased (175±18 to 245±25 bpm). During stimulation with 250 ms cycle length the duration shortened (MAPd90: AgCl: 160 ± 11 to 130 ± 12 ms; Ir: 154 ± 18 to 128±15 ms). The alterations reversed after 20 mm. An i.v. bolus of 0.2 mg/kg verapamil decreased the spontaneous rate (167±11 to 104 ± 23 bpm) and lengthened the MAPd90 (AgCl: 182 ± 14 to 220±13 ms; Ir: 174 ± 16 to 216, 21 ms) at 300 ms stimulation. The correlation between the MAPd90 of both lead types was r=0.98 during all measurements. Under the effect of beta-agonist and Ca²⁺ -antagonist medication MAP showed a strong correlation recorded with both types of electrodes. Thus, both leads allow the recording of MAP but only the Ir-electrodes with their long-term stability are implantable and allows us to control the effects of drugs with implantable devices.     

强心汤对大鼠实验性左室肥厚及心肌超微结构的影响

目的观察中药强心汤对异丙肾上腺素诱导大鼠实验性心肌肥厚的保护作用。方法连续7d异丙肾上腺素皮下注射建立大鼠心肌肥厚模型。30只大鼠随机分为对照组、模型组和治疗组（造模第2天起强心汤灌胃,连续用药12周）。分别于造模后第2周、6周及12周应用高频超声心动图动态检测心脏结构和功能改变;治疗12周后,测量各组大鼠左心室质量指数,观察心肌超微结构。结果治疗组大鼠的收缩末期室间隔厚度、左室后壁厚度、左室内径、左心室质量指数均较模型组下降（P〈0.05-0.01）,左心功能增强,心肌超微结构损伤程度明显减轻。结论强心汤对异丙肾上腺素引起的大鼠实验性心肌肥厚具有一定的改善作用。     

Head-Up Tilt Testing With and Without Isoproterenol Infusion in Healthy Subjects of Different Ages

Passive head-up tilt testing with or without infusion of isoproterenol is used in the investigation and management of patients with syncope. Twenty-five healthy asymptomatic volunteers prospectively grouped according to age (young [28 ± 1.7 years]: n = 9; middle [51 ± 3.3 years]: n = 11; elderly [81 ± 2.4 years]; n = 5; mean ± SE) were studied during: (1) supine carotid sinus massage: (2) 60° head-up tilt aione; and (3) infusion of isoproterenoJ to raise the heart rate 20% above supine baseline, prior to a 10-minute repeat tilt. Symptoms occurred in three subjects (12%) and only occurred with passive tilting alone. Two young subjects had syncope with sinus pauses greater than 10 seconds, One elderly subject developed atrial flutter. No subject had symptoms or hypotension during tilt plus isoproterenol or a pause greater than 3 seconds with carotid sinus massage. With passive tilt, mean heart rate increased by 16 ± 6 beats/min and 18 ± 7.8 beats/min in the young and middle aged subjects (P < 0.05), but only by 6 ± 5 beats/min in the elderly (P = NS, supine vs 60° in each group). With head-up tilt plus isoproterenol infusion, the mean heart rate elevation in response to tilt was 17 ± 9 beats/ min, 8 ± 3 beats/min, and 12 ± 4 beats/min for the young, middle, and elderly subjects, respectively (P < 0.05, supine vs 60° in each group). Supine serum norepinephrine concentration values were 229 ± 33 pg/mL, 374 ± 107 pg/mL, and 409 ± 41 pg/mL (mean ± SE) in the young, middle aged, and elderly groups, respectively (P = 0.05, young vs elderly). With head-up tilt, these significantly rose in the three groups. With tilt, serum epinephrine tended to rise (P < 0.10) only in the young and middle aged groups. Serum dopamine did not significantly increase in response to tilt in any of the groups. These studies suggest that tilt testing protocols need to be assessed against age and protocol matched controls.     

缺血性损伤对大鼠心肌生物膜的影响及益心康胶囊的保护作用

观察了异丙肾上腺素（ISO）对大鼠心肌生物膜的损伤作用,评价了益心康胶囊对心肌生物膜－线粒体和肌纤维膜的保护作用。     

急性心力衰竭大鼠心肌intermedin受体的变化

目的 观察心肌浆膜上新发现的血管活性肽intermedin（IMD）受体在异丙肾上腺素诱导心肌缺血损伤中的变化及意义.方法 在异丙基肾上腺素（isoproterenol,ISO）诱导的大鼠心肌缺血损伤模型实验组和假手术对照组,采用Western blot方法检测IMD蛋白水平,放射性配基结合技术,测定大鼠心肌浆膜上IMD 受体的结合能力.结果 ISO处理大鼠心脏呈现广泛心内膜下心肌坏死;血浆LDH活性、心肌和血浆MDA含量比对照组明显增加（均P＜0.01）;心功能明显降低,呈现严重心衰表现;IMD蛋白表达降低4倍（P＜0.01）;受体数目（Bmax）上调118% （P＜0.01）,受体与配体解离常数（Kd）比对照组增加（P＜0.05）.结论 心肌缺血性损伤引起心肌浆膜IMD蛋白表达降低、受体增加,其变化可能参与心肌损伤的发病过程.     

Ginsenoside Rg2 alleviates myocardial fibrosis by regulating TGF-β1/Smad signalling pathway

ContextPanax ginseng C.A. Meyer (Araliaceae) has cardioprotective effects. Ginsenosides are responsible for most of the pharmacological activities of ginseng.ObjectiveThis study investigates the effect of ginsenoside Rg2 on myocardial fibrosis in myocardial ischaemia rats.Materials and methodsMale Wistar rats were divided into control, isoproterenol, ginsenoside Rg2 (5, 20 mg/kg) groups (n = 8). The rats were subcutaneously injected with isoproterenol (5 mg/kg) or normal saline (control group) once daily for 7 days. The animals were intragastrically treated with ginsenoside Rg2 or 0.5% CMC-Na (control and isoproterenol groups) daily for 28 days. At day 28, cardiac function, myocardial fibrosis, and TGF-β1/Smad signalling pathway were evaluated.ResultsCompared with myocardial ischaemic rats, ginsenoside Rg2 at doses of 5, 20 mg/kg abated partially the augment of LVEDP (8.9 ± 1.3 vs. 7.5 ± 0.7, 7.2 ± 1.0 mmHg) and the decreases of the LVSP (96.75 ± 13.2 vs. 118.3 ± 19.4, 124.3 ± 21.3 mmHg), the + dp/dt (2142.8 ± 309.3 vs. 2598.6 ± 404.0, 2661.5 ± 445.2 mmHg/s), and the -dp/dt (1996.3 ± 306.3 vs. 2476.6 ± 289.7, 2509.6 ± 353.1 mmHg/s). Ginsenoside Rg2 (9.2 ± 0.9%, 8.5 ± 0.8%) alleviated myocardial fibrosis when compared with the isoproterenol group (10.1 ± 1.0%), which was accompanied by suppressed TGF-β1/Smad signalling in heart tissues.ConclusionsGinsenosides from ginseng possess the property of alleviating myocardial fibrosis, improving cardiac function after myocardial ischaemia. Ginsenosides may be promising agents for improving the outcomes of patients with myocardial ischaemia.