Tetrodotoxin potentiation of the antiarrhythmic action of lidocaine in the late stage of experimental myocardial infarct

Lidocaine (4--12 mg/kg) and the specific fast sodium current blocker tetrodotoxin (TTX) (1--6 mg/kg, i. v.) reduced ventricular arrhythmias that occurred 24 h after coronary artery ligation in dogs. Infusion of a mixture of subthreshold doses of lidocaine and TTX decreased ventricular arrhythmias to the same degree as infusion of threshold doses of either agent alone. This finding suggests that the antiarrhythmic action of lidocaine in the late stage of myocardial infarction is due to inhibition of the fast inward, sodium current. The possible mechanisms of rhythm disturbances in the late stage of myocardial infarction are discussed.     

Anti-arrhythmic effect of tetrodotoxin in the late stage of experimental myocardial infarct]

The action of tetrodotoxin (TT), blocking the fast sodium current, on arrhythmias that occurred 24 hours after occlusion of the coronary artery was studied in 10 dogs. TT injected intravenously in doses of 0.5--3.0 micrograms/kg significantly decreased the number of ventricular extrasystoles, and completely restored sinum rhythm in 4 animals. The maximum antiarrhythmic effect was noted 3 to 5 minutes after TT adminstration. It is suggested that arrhythmias and the antiarrhythmic effect of the drugs in the late stage of myocardial infarction are connected with the fast inward sodium current.     

Effect of intravenous infusion of insulin in diabetics with acute myocardial infarction.

Diabetes mellitus is associated with a high mortality after myocardial infarction. To see whether this may be decreased by improved diabetic control the effect of an insulin infusion regimen was studied in patients with acute myocardial infarction. From April 1982 to April 1983, 33 diabetics were admitted with acute myocardial infarction. Those being treated with diet alone or oral hypoglycaemic drugs continued with this unless control was poor, when they were changed to a "sliding scale" regimen of subcutaneous insulin injections thrice daily. Those already receiving insulin were maintained on thrice daily subcutaneous injections. From April 1983 to April 1984, 29 diabetics had acute myocardial infarction. Those receiving treatment with oral hypoglycaemic drugs or insulin were changed to continuous intravenous infusion of insulin, the aim being to maintain the blood glucose concentration at 4-7 mmol/I (72-126 mg/100 ml). Those being treated with diet alone continued with this if blood glucose concentrations were acceptable. Total mortality fell from 42% in the first year to 17% in the second (p less than 0.05). Over the same period mortality among non-diabetic patients with myocardial infarction did not change significantly. There was a significant fall in cardiac arrhythmias (expressed as the percentage of patients in whom arrhythmias were recorded) from 42% to 17% (p less than 0.05). The most significant fall in the incidence of complications occurred in those who had been receiving oral hypoglycaemic drugs on entry to the study (87% to 50%, p less than 0.05).     

Myocardial Infarction and Complete Heart Block

The clinical and electrocardiographic records of 20 patients with complete A-V block due to acute myocardial infarction have been analyzed. This study indicated that patients with an inferior wall myocardial infarction had, most commonly, a block above the bifurcation. The block was transitory, the patients had no Stokes-Adams attacks and the outcome was good. None of our patients required artificial pacing. On the other hand, patients with an anteroseptal myocardial infarction suffered from a bilateral bundle branch block (below the bifurcation). They had severe Stokes-Adams attacks and they all required artificial pacing. The destruction of the conducting system was extensive and the outcome was poor. Five out of seven patients treated with artificial pacing recovered the A-V conduction through the left bundle within a few days. However, in spite of this they all died.From this small series clearly defined clinical and electrocardiographic features can be identified in two different groups of cases.     

Influence of substances produced by lipophilic Corynebacterium CDC G1 ZMF 3P13 on the microorganisms inhabiting human skin

Lipophilic species of Corynebacterium inhabiting skin as residents produces substances that can regulate the composition of natural flora. Research that was carried out concerned an influence of the substances produced by Corynebacterium CDC G1 ZMF 3P13 on the set of 22 bacterial strains (Staphylococcus spp., Corynebacterium spp., Propionibacterium spp.) mutually existing on the skin and the set of 6 Candida spp. isolated from patients. It was found out that the strain gives off into environment a mixture of substances with opposite effects. In the course of research an inhibiting substance (BLIS) was isolated with its evident effect on S. aureus, S. epidermidis, C. diphtheriae i Propionibacterium spp.     

Function of myocardial alpha-adrenoceptors

In addition to beta-adrenoceptors (beta ARs), cardiac myocytes of animals and man possess alpha 1ARs, but not alpha 2ARs. Norepinephrine and epinephrine have a higher affinity for myocardial alpha 1ARs than for beta ARs. Unlike beta AR stimulation, myocardial alpha 1AR stimulation does not increase the slow inward current. The alpha 1AR-mediated positive inotropic effect seen in isolated heart preparations appears to involve increased Ca sensitivity of myofibrils and production of inositol triphosphate (IP3) and diacylglycerol (DAG), but the functions of IP3 and DAG are not clear. Myocardial alpha 1AR stimulation reduces rate of isolated atria and Purkinje fibers and lengthens refractory period and action potential duration. Hypoxia increases alpha 1AR density in cardiomyocytes. alpha 1AR-mediated arrhythmias occur in isolated Purkinje fibers during hypoxia, following infarction, and in the presence of Ba2+ or high Ca2+. In animals, coronary artery occlusion and/or reperfusion increase myocardial alpha 1AR density and responsiveness, and alpha AR blocking drugs attenuate arrhythmias. However, an antiarrhythmic effect of alpha AR blocking drugs mediated by action on coronary vascular alpha ARs cannot be excluded. Presently available drugs do not differentiate between myocardial and vascular alpha ARs and thus affect the coronary and systemic circulations and, indirectly, the heart. Additional myocardial alpha 1AR-mediated effects include production of cardiac hypertrophy, stimulation of glucose uptake and phosphofructokinase and cyclic AMP phosphodiesterase activity, and release of atrial natriuretic peptide.     

Bundle-branch Block in Acute Myocardial Infarction

Bundle-branch block was present in 41 out of 415 patients admitted to a coronary care unit with acute myocardial infarction and was associated with more severe clinical infarction and an overall mortality of 56%. It is probable that permanent bundle-branch block develops soon after infarction and that most of the patients with permanent block have had clinically severe infarction. Bundle-branch block developing during observation is usually transient, and the later it develops the sooner it resolves.Analysis of the arrhythmias and clinical course of the patients suggests that those with bundle-branch block and shock and those in whom bundle-branch block is present on admission may benefit from the use of a demand pacemaker attached to a transvenous pacemaker catheter, though the dividends of pacing may be small and the risks of the procedure significant. Post-mortem examination of 17 hearts showed extensive infarction, usually involving the septum, and severe coronary artery disease.     

Cardiac arrhythmias in myocardial infarction as an extension of lesions to the myocardium and the state of circulatory efficiency

The study involved 55 patients with the acute myocardial infarction aged between 34 and 69 years (mean 53 years) in whom the relation of cardiac arrhythmias incidence to the extension of myocardial involvement and circulatory efficiency was assessed. All patients were examined clinically, a 24-hour ECG with Holter technique (in the first day, 21st day and 6th months after myocardial infarction) and echocardiographic (Echo-2D) tests were registered. Echocardiography was performed during hospital phase and 6 months after myocardial infarction. Cardiac arrhythmias were evaluated with classification into classes described by Lown. Close relation of serious cardiac arrhythmias with extension of myocardial involvement was noted especially in the acute phase of myocardial infarction. High risk arrhythmias--class IVA, IVB and V were noted in nearly 100% of patients in this phase with cardiac aneurysm, extensive akinesis of apex and anterior wall of the heart. Mean value of the ejection fraction was 31% in this group. Incidence of cardiac arrhythmias did not exceed 40%, ejection fraction was 56% in the group of patients with limited lesions to the heart, e.g. akinesis of the lower wall. Incidence of late cardiac arrhythmias (6 months) did not differ significantly in particular groups of patients. The value of ejection fraction remained, however, on the same level as in the hospital phase of the myocardial infarction.     

The antiarrhythmic effect of prostaglandin E2 on catecholamine-induced arrhythmias

The antiarrhythmic effect of PGE2 as compared with the adrenergic beta-receptor blocking substance propranolol and the unspecific antiarrhythmic agent ajmaline was examanined on catecholamine-induced arrhythmias of the guinea-pig after preliminary sensibilisation by means of chloroform. Prophylactic administration of the tested substances resulted in a decrease in severity of arrhythmia by 91% after propranolol, by 37% after PGE2 and by 34% after ajmaline. Onset and duration of the arrhythmia were affected only to a negligible degree. The possible mode of action is still under discussion.     

Natural killer-like function of activated T lymphocytes: differential blocking effects of monoclonal antibodies specific for a 90-kDa clonotypic structure

A monoclonal antibody termed anti-NKTb has been generated following immunization of mice with cloned human cells (JT9) displaying natural killer (NK)-like activity. This antibody has the capacity to block cytotoxicity of the immunizing clone against several targets. In the present study, anti-NKTb was compared with a monoclonal antibody termed anti-NKTa that had previously been generated against JT9 cells and that had also been shown to block the NK-like function of these cells. The expression of a NKTb determinant, like that of NKTa, was found to be restricted to two NK active clones derived from the same individual, JT9 and JT10, both of which have the same mature T-cell phenotype (T3+, T8+, T11+). Comodulation, immunoprecipitation, and competitive binding experiments showed that both antibodies are directed to the same 90-kDa heterodimer associated with the T3 structure on the cell surface. However, cytotoxicity blocking studies suggested that NKTa and NKTb may represent functionally distinct epitopes of this 90-kDa molecule. Anti-NKTa uniformly blocked the cytotoxicity of both JT9 and JT10 cells when tested against 11 randomly selected target cell lines. In contrast, anti-NKTb totally blocked the cytotoxicity of these cloned cells against some targets (i.e., HPB-ALL, Nalm-1) but had very little effect when cytotoxicity was measured against other target cells (i.e., K562, U937, KG-1). This selective blocking effect, therefore, supports the notion that the heterodimer defined by the NKT antibodies is involved in the process of target cell recognition rather than in the cytolytic pathway of the cloned effector cells. Moreover, the unique functional effects of anti-NKTb suggest that additional levels of complexity exist in the specific recognition mechanisms of these clonal populations of NK active mature T lymphocytes.     

Pharmacokinetics of antipyrine, nifedipine and diazepam in experimental myocardial infarct]

It has been shown, that antipyrine, nifedipine, diazepam pharmacokinetics changes in different ways after myocardial infarction. On day 7, 14, and 21 after myocardial ischemia antipyrine T1/2 increased considerably, and antipyrine Cl and Kel decreased. Nifedipine T1/2 increased on day 7 only. There were no diazepam pharmacokinetic changes during restoration period. However, microsomal diazepam metabolism changed significantly. Diazepam hydroxylation increased on day 7 of myocardial infarction, and on day 14 and 21 did not differ from the control. Diazepam metabolites content changed considerably during restoration period. Under myocardial infarction cytochrome P-450 isoenzymes, oxidizing present substances seem to be altered to different extent.     

Optical mapping of late myocardial infarction in rats

Late myocardial infarction (MI) is associated with ventricular arrhythmias and sudden cardiac death. The exact mechanistic relationship between abnormal cellular electrophysiology, conduction abnormalities, and arrhythmogenesis associated with late MI is not completely understood. We report a novel, rapid dye superfusion technique to enable whole heart, high-resolution optical mapping of late MI. Optical mapping of action potentials was performed in normal rats and rats with anterior MI 7 days after left anterior descending artery ligation. Hearts from normal rats exhibited normal action potentials and impulse conduction. With the use of programmed stimulation to assess arrhythmia inducibility, 29% of hearts with late MI had inducible sustained ventricular tachycardia, compared with 0% in normal rats. A causal relationship between the site of infarction, abnormal action potential conduction (i.e., block and slow conduction), and arrhythmogenesis was observed. Optical mapping techniques can be used to measure high-resolution action potentials in a whole heart model of late MI. This experimental model reproduces many of the electrophysiological characteristics (i.e., conduction slowing, block, and ventricular tachycardia) associated with MI in patients. Importantly, the results of this study can enhance our ability to understand the interplay between cellular heterogeneity, conduction abnormalities, and arrhythmogenesis associated with MI.     

Wavelet formation in excitable cardiac tissue: the role of wavefront-obstacle interactions in initiating high-frequency fibrillatory-like arrhythmias.

High-frequency arrhythmias leading to fibrillation are often associated with the presence of inhomogeneities (obstacles) in cardiac tissue and reduced excitability of cardiac cells. Studies of antiarrhythmic drugs in patients surviving myocardial infarction revealed an increased rate of sudden cardiac death compared with untreated patients. These drugs block the cardiac sodium channel, thereby reducing excitability, which may alter wavefront-obstacle interactions. In diseased atrial tissue, excitability is reduced by diminished sodium channel availability secondary to depolarized rest potentials and cellular decoupling secondary to intercellular fibrosis. Excitability can also be reduced by incomplete recovery between successive excitations. In all of these cases, wavefront-obstacle interactions in a poorly excitable medium may reflect an arrhythmogenic process that permits formation of reentrant wavelets leading to flutter, fibrillation, and sudden cardiac death. To probe the relationship between excitability and arrhythmogenesis, we explored conditions for new wavelet formation after collision of a plane wave with an obstacle in an otherwise homogeneous excitable medium. Formulating our approach in terms of the balance between charge available in the wavefront and the excitation charge requirements of adjacent medium, we found analytically the critical medium parameters that defined conditions for wavefront-obstacle separation. Under these conditions, when a parent wavefront collided with a primitive obstacle, the resultant fragments separated from the obstacle boundaries, subsequently curled, and spawned new "daughter" wavelets. We identified spatial arrangements of obstacles such that wavefront-obstacle collisions leading to spawning of new wavelets could produce high-frequency wavelet trains similar to fibrillation-like arrhythmias.     

Clinical Experience with Dextro-Alprenolol

Experience with dextro-alprenolol in nine patients has shown that it is relatively ineffective in treating arrhythmias associated with acute myocardial infarction. Marginal effectiveness in the control of ventricular ectopic beats after myocardial infarction is outweighed by an appreciable hypotensive effect with risk of infarction. The drug was ineffective in the management of supraventricular arrhythmias.     

T波峰-末间期对急性心肌梗死并发室性心律失常的预测价值

目的:探讨T波峰-末间期(Tp-Te间期)和Tp-Te间期离散度(Tp-Ted)对急性心肌梗死并发室性心律失常的预测价值。方法:选择我院2013年5月至2014年5月收治的140例确诊急性ST段抬高型心肌梗死(STEMI)患者,按照心律失常类型分为室性心动过速组,室性早搏组以及无室性心律失常组。分析并比较各组患者心电图Tp-Te间期及Tp-Ted的变化情况。结果:急性期FPG、Tp-Te、Tp-Ted高于恢复期,差异有统计学意义(P0.05);急性期与恢复期之间TG、CHOL、LDL-C、K+、Na+水平差异无统计学意义(P0.05)。无室性心律失常组与室性心动过速组及室性早搏组比较,Tp-Te和Tp-Ted更低,差异有统计学意义(P0.05);室性早搏组和室性心动过速组比较,Tp-Te和Tp-Ted更低,差异有统计学意义(P0.05)。结论:Tp-Te间期和Tp-Ted可用于区分急性心肌梗死患者室性心律失常类型。     

Ventricular tachycardia due to cardiac ischaemia: assessment by exercise electrocardiography

Although ventricular tachycardia is a well-known complication of myocardial ischaemia and may be provoked by exercise, many patients may appreciate only the angina and be unaware of the unduly rapid heart rate that precipitates it. Exercise testing is needed to show this arrhythmia and to enable treatment to be started.Twenty-three patients were found to have chronic ischaemic heart disease complicated by ventricular tachycardia. Six patients with old myocardial infarction had ventricular tachycardia at rest which required conversion to sinus rhythm; 17 patients developed ventricular tachycardia only when they exercised. In 12 of these 17 patients coronary angiography showed disease of the anterior descending branch of the left coronary artery; other vessels were usually also affected. Although beta-adrenergic blocking drugs increased exercise tolerance, ventricular tachycardia still occurred when the heart rate on exercise reached a level similar to that before treatment. In five patients coronary artery bypass surgery was performed because of angina and exercise-induced ventricular tachycardia. Exercise tolerance was increased in all three patients who underwent exercise tests after operation, and in two of these patients, both of whom were known to have patent grafts, ventricular tachycardia was abolished.If part of the beneficial effect of coronary bypass surgery is preventing life-threatening ventricular arrhythmias it is essential to detect these, and ambulatory monitoring and stress testing have a complementary role.     

Anomalous origin of the left coronary artery connected to the pulmonary artery in a 31-year-old woman

Anomalous origin of the left coronary artery connected to the pulmonary artery (ALCAPA) is a rare congenital defect with a high mortality rate in infancy if left untreated. It may cause myocardial ischaemia and can lead to myocardial infarction, mitral dysfunction, cardiac arrhythmias, heart failure and sudden death. Without operation, survival into adulthood is rare. We report clinical findings, diagnostic characteristics and therapy in a 31-year-old woman with ALCAPA and preserved left ventricular function.     

细胞药物的研发现状——细胞药物连载之三

近年来,细胞药物的研究受到了国内外重视。特别是干细胞药物,已成为世界各国竞相研究的热点领域,但各国的干细胞药物绝大多数仍处于研究阶段,全球真正上市的干细胞药物很少。目前正在研发的干细胞药物主要集中在治疗慢性疾病（关节炎、糖尿病和癌症等）和心脏相关疾病（心肌梗死、心脏衰竭等）。一些传统体细胞药物（软骨细胞、心肌细胞、胰岛细胞等）和免疫细胞药物已在临床应用。     

The effect of bretylium tosylate on ventricular arrhythmias in patients with acute myocardial infarction]

Sixty three patients with the acute myocardial infarction, aged between 34 and 85 years, admitted to the Intensive Cardiological Care Unit during the first 12 hours following the infarction were randomly divided into two groups. Patients of group I (20 subjects) were treated with nitroglycerin and additional intravenous infusions of bretylium tosylate in the dose of 5 mg/kg administered every 6 hours for 48-72 hours. Patients of group II (33 subjects) were mainly treated with intravenous nitroglycerin. A type and incidence of the ventricular arrhythmias, conduction disorders in AV node, and hemodynamic complications were analysed during the first 72 hours. It was found that bretylium tosylate reduces the incidence of ventricular arrhythmias accompanying myocardial infarction but after 2-3 hours following its administration (p < 0.05). Therefore, bretylium tosylate should be administrated to patients with the acute myocardial infarction in combination with other rapidly acting anti-arrhythmic drug. Bretylium tosylate increases also the effectiveness of electric defibrillation in patients with ventricular fibrillation or ventricular tachyarrhythmia. No evidence of the effectiveness of bretylium tosylate on atrio-ventricular conduction and hemodynamic complications of myocardial infarction was found.     

Effect of Heparin on Serum Free-fatty-acids,Plasma Catecholamines,and the Incidence of Arrhythmias following Acute Myocardial Infarction

The effect of intravenous heparin in a therapeutic dosage on cardiac arrhythmias in patients with indubitable acute myocardial infarction was investigated. The value of serum free-fatty-acids (F.F.A.s) and plasma catecholamines in the prediction of patients vulnerable to serious arrhythmias was also studied.Heparin produced a significant rise in F.F.A., maximal within 10 minutes of injection, but did not increase the incidence of cardiac arrhythmias.No relationship was found between the incidence of arrhythmias and the initial levels of F.F.A. or adrenaline. No correlation was obtained between F.F.A. and plasma catecholamine levels. Heparin did not have a consistent effect on plasma catecholamines. Initial control plasma noradrenaline concentrations, however, were found to be significantly correlated with the incidence of subsequent arrhythmias. It is suggested that the level of plasma noradrenaline may be a valuable predictive guide to those patients likely to develop significant arrhythmias after acute myocardial infarction.