The protective effect of vagus nerve stimulation on catecholamine-halothane-induced ventricular fibrillation in dogs

Parasympathetic neural activity modulates some ventricular arrhythmias in man. Therefore, a canine model of arrhythmias produced by the interaction of halothane and catecholamines was used to study the effects of vagal stimulation on the induction of ventricular fibrillation. The dose of catecholamine required to induce ventricular fibrillation was determined during a constant heart rate. Vagal stimulation reversibly raised the norepinephrine dose that produced ventricular fibrillation from 16.4 +/- 2.4 to 30.0 +/- 3.8 micrograms (p less than 0.001, n = 10), and the epinephrine dose from 15.5 +/- 2.0 to 22.5 +/- 2.6 micrograms (p less than 0.001, n = 5). Following atropine, vagal stimulation failed to raise the threshold dose of norepinephrine (16.8 +/- 2.4 vs. 18.3 +/- 3.3 micrograms, nonsignificant, n = 6) or epinephrine (15.5 +/- 2.0 vs. 16.0 +/- 2.3 micrograms, nonsignificant, n = 5). Ligation of the cervical vagus nerves did not affect the epinephrine threshold dose (16.3 +/- 3.3 vs. 17.5 +/- 2.7 micrograms, nonsignificant, n = 5). Following elevation of basal vagal tone by morphine premedication, the norepinephrine threshold of 53.0 +/- 9.2 micrograms declined by a nonsignificant amount to 46.5 +/- 11.5 micrograms after vagotomy (nonsignificant, n = 5). Thus resting vagal tone does not prevent catecholamine-halothane-induced ventricular fibrillation, whereas increasing vagal tone by electrical stimulation substantially protects against this arrhythmia. The protection is mediated through a muscarinic cholinergic receptor.     

Effects of acute reduction of temperature on ventricular fibrillation activation patterns

Because of its electrophysiological effects, hypothermia can influence the mechanisms that intervene in the sustaining of ventricular fibrillation. We hypothesized that a rapid and profound reduction of myocardial temperature impedes the maintenance of ventricular fibrillation, leading to termination of the arrhythmia. High-resolution epicardial mapping (series 1; n = 11) and transmural recordings of ventricular activation (series 2; n = 10) were used to analyze ventricular fibrillation modification during rapid myocardial cooling in Langendorff-perfused rabbit hearts. Myocardial cooling was produced by the injection of cold Tyrode into the left ventricle after induction of ventricular fibrillation. Temperature and ventricular fibrillation dominant frequency decay fit an exponential model to arrhythmia termination in all experiments, and both parameters were significantly correlated (r = 0.70, P < 0.0001). Termination of the arrhythmia occurred preferentially in the left ventricle and was associated with a reduction in conduction velocity (-60% in left ventricle and -54% in right ventricle; P < 0.0001) and with activation maps predominantly exhibiting a single wave front, with evidence of wave front extinction. We conclude that a rapid reduction of temperature to <20 degrees C terminates ventricular fibrillation after producing an important depression in myocardial conduction.     

New concepts in pacemaker syndrome

After implantation of a permanent pacemaker, patients may experience severe symptoms of dyspnea, palpitations, malaise, and syncope resulting from pacemaker syndrome. Although pacemaker syndrome is most often ascribed to the loss of atrioventricular (A-V) synchrony, more recent data may also implicate left ventricular dysynchrony caused by right ventricular pacing. Previous studies have not shown reductions in mortality or stroke with rate-modulated dual-chamber (DDDR) pacing as compared to ventricular-based (VVI) pacing. The benefits in A-V sequential pacing with the DDDR mode are likely mitigated by the interventricular (V-V) dysynchrony imposed by the high percentage of ventricular pacing commonly seen in the DDDR mode. Programming DDDR pacemakers to encourage intrinsic A-V conduction and reduce right ventricular pacing will likely decrease heart failure and pacemaker syndrome. Studies are currently ongoing to address these questions.     

Electrocardiographic alterations induced by AGEPC in Wistar rats in relation to its hypotensive and hematologic effects

AGEPC administration into Wistar rats caused no remarkable thrombocytopenia, slight decrease of the percent count of PMNs in whole blood accompanied by anequal leukocytopenia and a transient increase in hematocrit, due to fluid extraversion. Apart from the dramatic fall in blood pressure caused by AGEPC, relatively sinus bradycardia was recorded at doses over 6 micrograms/kg b.w. S-T segment elevation, mainly evident in II, III and AVF leads, was also recorded within the first minutes after AGEPC administration, at doses over 1 microgram/kg b.w. At lethal doses, various degrees of A-V block resulting in complete A-V block with idioventricular rhythm, or injury pattern resulting in ventricular fibrillation or ventricular flutter, were recorded. At sublethal doses no arrhythic manifestations were recorded, while S-T segment elevation upward inversion became gradually normal.     

Mouse heart rate in a human: diagnostic mystery of an extreme tachyarrhythmia

We report telemetry recording of an extreme non-fatal tachyarrhythmia noted in a hospitalized quadriplegic male with history of atrial fibrillation where the average ventricular conduction rate was found to be about 600 beats per minute and was associated with transient syncope. A medical literature review suggests that the fastest human ventricular conduction rate reported to date in a tachyarrhythmia is 480 beats per minute. We therefore report the fastest human heart rate noted in a tachyarrhythmia and the most probable mechanism of this arrhythmia being a rapid atrial fibrillation with 1:1 conduction in the setting of probable co-existing multiple bypass tracts.     

Disordered cardiac electrical stability in beta-adrenergic damage and antioxidant protection]

The electrical threshold of ventricular fibrillation induced by premature single impulses and the ectopic activity and also an abnormal conduction during vagus inhibition of sinus node were estimated 24 hours after the administration of isoproterenol (10 mg/kg, s/c, on time) in rats. In addition the cardiac contractile function of the left ventricle was studied. The study was performed on male Wistar rats, 250-300 body weight, under nembutal anesthesia. Isoproterenol had no effect on the contractile function in the rest and during maximal isometric load, induced by coarctation of ascending aorta. But in the treated animals the threshold of fibrillation fell more than 2-fold and the vagal bradycardia was more 2-fold then in the untreated animals. The AB-block, idioventricular rhythm and extrasystoles appeared during vagal bradycardia in treated animals, while in the untreated ones there were no any disturbances. The preliminary administration of the antioxidant ionol (BMT, 30 mg/kg, per os, in sun oil) prevented the enumerated shifts.     

Changes in cardiac resistance to arrhythmogenic effects during ATP-dependent K+ channel activation

It has been found that pretreatment with ATP-dependent potassium channel (KATP-channel) opener, BMS 180448 (3 mg/kg, intravenously), increases cardiac resistance against arrhythmogenic action of coronary artery occlusion and reperfusion in anaesthetized rats. However, BMS 180448 induced a decrease in ventricular fibrillation threshold in rats postinfarction cardiac fibrosis. This effect was completely abolished by administration of the KATP-channel inhibitor, glibenclamide. By contrast, coadministration of BMS 180448 and selective sarcolemmal KATP-channel inhibitor, HMR 1098, promoted an increase in ventricular fibrillation threshold in rats with postinfarction cardiac fibrosis before normal value. The selective mitochondrial KATP-channel opener, diazoxide, also exacerbated a decrease in ventricular fibrillation threshold induced by postinfarction cardiac sclerosis. But after depletion of endogenous catecholamine storage by pretreatment with guanthidine, diazoxide, on the contrary, elevated the ventricular fibrillation threshold. It has been suggested that stimulation of mitochondrial ATP-sensitive potassium channels promotes an elevation in electrical stability of the heart, whereas opening of sarcolemmal KATP-channel increases a possibility of ventricular arrhythmias.     

Ventricular Pacing on the Prognosis of Patients with Pacemaker Implantation

Excessive right ventricular apex pacing has significant adverse effects on the cardiac function and hence, it is necessary to clinically optimize pacing parameters and advocate suitable physiological pacing to safeguard the cardiac function after pacemaker implant. Minimizing ventricular pacing is an atrioventricular node priority function, to encourage ventricular self conduction and to reduce unnecessary right ventricular pacing. Minimized ventricular pacing reduces ventricular pacing by encouraging self atrioventricular conduction function and extending the AV interval. This study is a prospective cohort study to evaluate the changes of cardiac function in patients and serum amino-terminal natriuretic peptide (NT-proBNP) before and after pacing, and the risk of atrial fibrillation with different CUM% VP. The study has shown that the cardiac function will deteriorate with an increase in pacing rate.     

Iproveratril: Experimental Data on Coronary Dilatation and Antiarrhythmic Action

Various cardiovascular effects of a new synthetic coronary vasodilator, α-isopropyl-α [(N-methyl - N - homoveratryl)-γ-amino-propyl]-3, 4-dimethoxyphenylacetonitrile HCI (D365, Iproveratril or Isoptin) have been studied. In isolated perfused rabbit hearts the drug exerts a potent coronary vasodilator action, but can depress myocardial contractions and A-V conduction. In anesthetized cats it produces varying degrees of hypotension with bradycardia, and antagonizes ST-T changes induced by ouabain. It can also protect against chloroform-adrenaline and ouabain ventricular fibrillation. On isolated papillary muscle preparations it can lead to adrenergic blockade. It is concluded that in addition to its coronary dilator action, the drug exerts `quinidine-like'' antiarrythmic effects, and appears to deserve further study.     

Changes in ventricular fibrillation threshold with stimulation of cardiac sympathetic nerves of the developing dog

The effect of stimulation of the developing cardiac sympathetic nerves on the vulnerability to ventricular fibrillation was investigated in 50 puppies 1 to 6 weeks of age. Ventricular fibrillation thresholds were obtained before and during sympathetic nerve stimulation. Stimulation of either stellate ganglion increased ventricular fibrillation threshold, possibly due to diffuse functional innervation in pups. The effect of the left stellate increased progressively with age, whereas the effect of the right, although initially greater than that of the left, did not increase further with age. In contrast, stimulation of the left ventrolateral cardiac nerve, which is locally distributed, resulted in decreased ventricular fibrillation threshold. This decrease was progressively greater with age. The fact that activation of the left stellate ganglion and the left ventrolateral cardiac nerve affects ventricular fibrillation threshold in opposite directions suggests different sympathetically mediated changes on ventricular vulnerability in early life. The differing temporal patterns of maturation and the localized nature of the major distal branch distributions could provide a mechanism for promotion of arrhythmiogenesis under some conditions in early life.     

The development of the conduction system in the mouse embryo heart: I. The first embryonic A-V conduction pathway

In the 8-, 9-, and 10-day-old mouse embryos, the primitive atria are interconnected with the ventricles via the atrioventricular (A-V) canal. Due to the twisting process of the tubular heart, the wall of the A-V canal establishes continuity not only with the left ventricle but also with the bulbus and truncus arteriosus. At this stage of heart development, the A-V node and bundle have not yet appeared, and, thus, the atrial impulse must be conveyed to the ventricle by the muscle tissue of the wall of the A-V canal, in which two muscle cell layers have been observed. The inner layer extends deep into the left ventricular cavity and is interconnected with both the trabecular system and the ventricular (IV) septum, which begins to develop on the tenth day. In the inner dorsal wall of the A-V canal, the cells are large (～ 20 μm in diameter) and show a strong PAS reaction. It is likely that these large glycogen-rich cells from which the A-V node primordium develops on the eleventh day play the main role in the A-V impulse conduction. The muscle cells at the ventrolateral walls of the canal are small and form a loose spongy myocardium into which the connective tissue cells begin to penetrate on the tenth day, ultimately to form the annulus fibrosus. At the same time, the outer cell layer of the dorsal wall begins to deteriorate; the cells show vacuolar degeneration, myolysis, and shrinkage necrosis. This process appears to represent a programmed cell death, as was described in the bird heart (Pexieder, 1975). On the basis of morphological data, the sequence of atrioventricular activation before the appearance of the A-V node and bundle is discussed.     

Intrinsic changes on automatism, conduction, and refractoriness by exercise in isolated rabbit heart.

We have studied the intrinsic modifications on myocardial automatism, conduction, and refractoriness produced by chronic exercise. Experiments were performed on isolated rabbit hearts. Trained animals were submitted to exercise on a treadmill. The parameters investigated were 1) R-R interval, noncorrected and corrected sinus node recovery time (SNRT) as automatism index; 2) sinoatrial conduction time; 3) Wenckebach cycle length (WCL) and retrograde WCL, as atrioventricular (A-V) and ventriculoatrial conduction index; and 4) effective and functional refractory periods of left ventricle, A-V node, and ventriculoatrial retrograde conduction system. Measurements were also performed on coronary flow, weight of the hearts, and thiobarbituric acid reagent substances and glutathione in myocardium, quadriceps femoris muscle, liver, and kidney, to analyze whether these substances related to oxidative stress were modified by training. The following parameters were larger (P < 0.05) in trained vs. untrained animals: R-R interval (365 +/- 49 vs. 286 +/- 60 ms), WCL (177 +/- 20 vs. 146 +/- 32 ms), and functional refractory period of the left ventricle (172 +/- 27 vs. 141 +/- 5 ms). Corrected SNRT was not different between groups despite the larger noncorrected SNRT obtained in trained animals. Thus training depresses sinus chronotropism, A-V nodal conduction, and increases ventricular refractoriness by intrinsic mechanisms, which do not involve changes in myocardial mass and/or coronary flow.     

Ventricular fibrillation in hibernators and nonhibernators

Previous studies have shown that there are differences between hibernators and nonhibernators in the susceptibility to ventricular fibrillation. In an attempt to clarify these differences ventricular fibrillation was induced in isolated hearts of the hibernator, the woodchuck, Marmota monax by cooling, warming, puncture, and by norepinephrine administration. It was shown that the hearts of the winter animals were completely resistant toward the ventricular fibrillation inducing agents, which was not the case for the hearts from summer, active animals. Further, the hearts of another hibernator, the hedgehog, Erinaceus europaeus, and guinea pig, Cavia porcellus, were studied electrophysiologically in anesthetized animals with open chests and with bipolar electrodes attached to the epicardium. During pacing it was shown that the hedgehog had a higher stimulus threshold and a lower maximal following frequency than the guinea pig. The summer hedgehogs showed resistance toward both ventricular premature beats and ventricular fibrillation. Sixty percent of the summer hedgehogs and 100 percent of the winter hedgehogs and guinea pigs developed ventricular fibrillation. The threshold for ventricular fibrillation was highest for summer hedgehogs. The effective refractory period of papillary muscle of summer hedgehogs was shorter than that of guinea pigs. The force frequency relationship of the isolated papillary muscle showed a greater degree of independence in the hedgehog than in the guinea pig. Consequently, the results show that the heart of the hibernator is more arrhythmia resistant than the heart of the nonhibernator, although there are seasonal differences.     

Developmental changes of ventricular fibrillation threshold and spontaneous defibrillation in young dogs.

This study was conducted to systematically investigate whether induction and maintenance of ventricular fibrillation in the canine heart, change with age during the early postnatal development. Forty-eight mongrel puppies from seven litters, were randomly selected for size and studied at weekly intervals from 1-6 weeks for determination of ventricular fibrillation threshold and incidence of spontaneous defibrillation. Another fourteen mongrel puppies 8-11 weeks old and 10 adult dogs were similarly studied. Ventricular fibrillation threshold increased progressively with age up to the eighth week (VFTmA = 8.38 + 2.67 wk-0.134.wk2, r = 0.995) and thereafter reached a plateau, which was not significantly different from the ventricular fibrillation threshold of adult dogs (26.5 +/- 2.2 mA). In contrast, the high incidence of spontaneous defibrillation at early age decreased rapidly between second and fourth week and became rare thereafter, (%SDF = 281.e-0.60wk, r = 0.94. This rapid drop could not be explained by the increase in mean body weight, which did not change significantly during this early period (BWkg = 0.59.e0.23wk, r = 0.97). Our findings suggest first, that the vulnerability of the neonatal dog heart to electrical induction of ventricular fibrillation decreases progressively during early age. Second, that spontaneous defibrillation decreases precipitously between the second and fourth week of age, a change not sufficiently explained by the modest body weight gain during that time. Thus, it appears that about the third week of age ventricular vulnerability to fibrillation and ability to defibrillation reach a critical point, where lethal arrhythmias may become both inducible and sustainable, to result in death.     

On the mechanisms of coupling in adrenaline-induced bigeminy in sensitized hearts.

The mechanism of coupling in adrenaline-induced ventricular bigeminy in sensitized hearts has been investigated in intact animals, isolated preparations, and single cardiac fibers. The electrophysiological and cardiovascular dynamic changes during the development of fixed interval coupling strongly indicate that the coupled beats result from stretch of subsidiary pacemaker fibers in the specialized ventricular conduction system, induced by the mechanical response to the normally conducted sinus impulse. The resulting intraventricular pressure elicits an extrasystole when a certain critical end systolic pressure for a particular animal is reached. The interval between the normal and premature ventricular beat decreases progressively as the intraventricular pressure rises, as a result of the combined action of adrenaline and postextrasystolic potentiation. The onset of ventricular bigeminy is preceded by a shift in the pacemaker site to the A-V junctional area, due to a differential effect of the anesthetic-adrenaline combination on fibers of the S-A node and those in the junctional area. The degree of prematurity of the coupled beat shows an inverse linear relationship to the intraventricular pressure of the initiating beat at the end of systole. The premature QRS complex occurs after a period of mechano-electrical latency, the duration of which is directly related to this pressure.     

Quantification of concealed conduction in the atrioventricular node

Twenty-eight anaesthetized open-chest mongrel dogs were used. Programmed atrial pacing was used and Hisian electrograms recorded through endocavitary electro-catheters to study and quantify the concealed conduction of non-transmitted atrial impulses in the A-V node. An exponential model was used in three situations to quantify the nodal conduction during incremental atrial pacing: a) during 1:1 conduction, b) during 2:1 nodal block, and c) during pacing, coupling an atrial impulse delivered at fixed intervals and blocked in the A-V node to each transmitted impulse. The relation between intranodal conduction times was analyzed both with and without the presence of blocked impulses, and the quotient between the obtained functions in situations b, c and situation a was determined. In a subgroup of 13 dogs the study was repeated following pharmacological block of the autonomic nervous system. In dogs with autonomic block, this relation always tended to decrease when the atrial pacing rate increased. The variations in the group of dogs with intact autonomic nervous systems were not homogeneous. During pacing with coupled block impulses, the progressive removal of conduction curves obtained for each coupling interval with respect to those obtained during 1:1 transmission, expresses the interval with respect ot those obtained during 1:1 transmission, expresses the lesser influence of the blocked impulses on decreasing their coupling interval.     

基于虚拟心脏的早期后除极导致室颤的仿真研究

为了分析早期后除极(early afterdepolarizations,EADs)诱发室颤的机理,本研究基于精细的浦肯野纤维网络与心室解剖数据,构建了一个三维心室电传导模型.基于该模型,模拟了产生早期后除极的电生理变化,探讨了三种心室细胞的早期后除极的易感性,分析了早期后除极易感细胞对折返波的影响,最后定量比较早期后除极诱发室颤的伪心电图的改变情况.实验结果表明:中间层细胞早期后除极易感性最强,中间层细胞早期后除极的产生能够导致折返波破裂,并且在心电图中表现为紊乱的不规则的颤动心律,这与之前在动物实验观察得到的现象一致,因此中间层细胞可能是一个诱发室颤的重要靶点.     

Non-pharmacological treatment of atrial fibrillation

In selected patients with atrial fibrillation and severe symptoms, non-pharmacological treatment may be an alternative or supplement to drug therapy. Atrioventricular nodal radiofrequency ablation (requires pacemaker implantation), or atrial pacing for sick sinus syndrome, are established treatment modalities. All other non-pharmacological therapies for atrial fibrillation are still experimental. After the Maze operation, atrial depolarization has to follow one specific path determined by surgical scars in the myocardium. This prevents new episodes of atrial fibrillation, but at a cost of perioperative morbidity and mortality. Catheter-based "Maze-like" radiofrequency ablation is technically difficult, and thrombo-embolic complications may occur. Paroxysmal atrial fibrillation sometimes is initiated by spontaneous depolarizations in a pulmonary vein inlet. Radio frequency ablation against such focal activity has been reported with high therapeutic success, but the results await confirmation from several centres. For ventricular rate control, most electrophysiologists presently prefer ablation to induce a complete atrioventricular conduction block (with pacemaker) rather than trying to modify conduction by incomplete block. Atrial or dual chamber pacing may prevent atrial fibrillation induced by bradycardia. It remains to confirm that biatrial or multisite right atrial pacing prevents atrial fibrillation more efficiently than ordinary right atrial pacing. An atrial defibrillator is able to diagnose and convert atrial fibrillation. The equipment is expensive, and therapy without sedation may be unpleasant beyond tolerability.     

Hemodynamic changes before and after short and prolonged periods of hypothermia in dogs

Dogs were cooled to 30 °C and either rewarmed immediately or after being kept at 30 °C for 6 hr. The acid-base balance was determined and hemodynamic data were collected. At the beginning of the rewarming period the arterial blood pressure and the left ventricular work output were increased after short hypothermia, but not after prolonged hypothermia. The survivors of prolonged hypothermia had had a higher arterial blood pressure and left ventricular work output before cooling began than did nonsurvivors. An additional load on the cardiovascular system (A-V shunt) was incompatible with survival. The so-called rewarming shock, therefore, appears to be cardiogenic, and the treatment of the victims of accidents causing hypothermia due to exposure should be directed against cardiogenic shock.     

Effect of atrio-ventricular conduction on the appearance of supraventricular arrhythmia and thrombotic complications in patients with chronic stimulation of cardiac ventricles in sick sinus syndrome]

Two hundred three patients with sick sinus node disease were treated with continuous ventricular stimulation between 1981 and 1985. To 1988, 168 patients aged between 26 and 88 years were followed-up for 5.1 years on the average. All these patients were divided into two groups: I (93 patients) with sinusal bradycardia, and group II (93 patients) with brady-tachycardia. Ventriculo-atrial conduction was seen in 82.61% of patients of group I in whom the implantation of electric stimulator produced the attacks of atrial fibrillation, and in 44.23% of patients without such attacks (p < 0.01); in 80.77% of patients of group II in whom atrial fibrillation became stable with time, and in 50.57% with intermittent atrial fibrillation (p < 0.01) ventriculo-atrial conduction was noted. It may be concluded, that the presence of ventriculo-atrial conduction in patients with prolonged stimulation of the cardiac ventricles favor the occurrence and stabilization of the paroxysmal atrial fibrillation and thrombotic complications.