The effects of sympathetic denervation on spontaneous ventricular defibrillation in the rat.

Ventricular tachycardia or ventricular fibrillation was electrically induced in 38 normal rats (group 1) and 24 sympathetically denervated rats (6-hydroxydopamine) (group 2). The time for spontaneous reversion to sinus rhythm was measured during (1) control, (2) isoproterenol, and (3) the combination of isoproterenol and phenylephrine. The time for spontaneous reversion was the same in both groups in the three states. The reversion time was prolonged threefold by isoproterenol, and restored to control values when phenylephrine was added to the infusion of isoproterenol. The tachycardia duration and the refractory period were inversely related: log10 (tachycardia duration) = 3.466-0.091 (refractory period). Ventricular tachycardia/fibrillation induction was examined as follows: (i) Ventricular tachycardia/fibrillation was induced in 100% of normal rats (group 1), but only 42% of the denervated rats (group 2, p less than 0.001); (ii) during isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of rats of both groups; and (iii) when phenylephrine was added to isoproterenol, ventricular tachycardia/fibrillation was induced in 100% of group 1 rats versus 82% of group 2 rats, (p = NS). These observations suggest (1) the induction of ventricular tachycardia/fibrillation is highly dependent on intact sympathetic innervation, and (2) exogenous adrenergic agonists modulate the duration of ventricular fibrillation through their effects on ventricular refractory period, independent of sympathetic innervation.     

Differentiation and innervation of the atrioventricular bundle and ventricular Purkinje system in sheep heart

The development of the atrioventricular bundle (AVB) and ventricular Purkinje system and their innervation have been studied in fetal sheep from 27 to 140 days gestation (term is 147 days). The AVB initially consisted of a primordium, which lacked innervation and was composed of small, relatively undifferentiated myocytes. Differentiation of Purkinje-like cells within the AVB began near its distal end and extended towards the atrioventricular node (AVN). Differentiation of the ventricular Purkinje system extended distally from the region of bifurcation of the AVB from cells that were indistinguishable from the working myocardium and continuous with the AVB primordium. Differentiation of Purkinje-like AVB cells was complete by 46 days gestation but Purkinje fibres were still differentiating within the ventricular wall at 60 days gestation. The main morphological changes included a large increase in cell size and organization into strands, development of characteristic glycogen-filled regions containing many intermediate filaments and early development of myofibrillar M lines compared to the working myocardium. The differentiation of AVB cells and the ventricular Purkinje system preceded their innervation. The AVB became innervated earlier than ventricular Purkinje fibres, intimate contacts between proximal AVB cells and nerve axons being present at 60 days gestation. Nerve fibres were present in the septomarginal band at this time, however, en passant associations with ventricular Purkinje fibres were rarely observed until 140 days gestation and intimate contacts were not present at any stage. Although the AVB and ventricular Purkinje system of adult sheep are composed of morphologically similar cells, the present study demonstrates that they differ in origin and their mode of differentiation as well as timing and intimacy of innervation. Innervation is not part of the developmental mechanism leading to the differentiation of Purkinje fibres. No primordium of the ventricular Purkinje system could be identified, suggesting that the mechanism of differentiation of ventricular Purkinje fibres involves recruitment from early working myocardium.     

The effect of lidocaine compared with verapamil on the enhanced ventricular rhythm in the infarcted canine heart

Myocardial ischemia was produced in dogs by the occlusion of the left anterior descending (LAD) coronary artery for 24 or 48 h. After complete atrioventricular block was produced, enhanced ventricular rhythm was observed in all animals. The enhanced ventricular rhythm showed multiple QRS configurations and had spontaneous cycle lengths (SCL) of 397 +/- 18 ms (n = 20) after 24 h of LAD occlusion and 446 +/- 23 ms (n = 20) after 48 h of LAD occlusion. Overdrive pacing did not result in the termination of the enhanced ventricular rhythm in any experiment. Propranolol, as a cumulative dose of 1.5-2.0 mg/kg i.v., also did not abolish the enhanced ventricular rhythm. In 24-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 1 of 11 experiments. In the remaining 10 experiments, the ventricular SCL was increased from 401 +/- 22 to 491 +/- 26 ms after a cumulative dose of 8.8 +/- 0.7 mg/kg of lidocaine. In the presence of verapamil, given as a cumulative dose of 0.60 +/- 0.11 mg/kg, the ventricular SCL was increased from 401 +/- 33 to 482 +/- 64 ms (n = 9). In 48-h infarcted hearts, lidocaine abolished the enhanced ventricular rhythm in 5 of 11 experiments. Both lidocaine and verapamil increased the SCL of hearts in which the enhanced ventricular rhythm persisted. Analysis of variance showed that only the increase in SCL by lidocaine in 48-h infarcted hearts was statistically significant. The atrial and idioventricular rhythms in noninfarcted hearts responded differently to lidocaine and verapamil. The results suggest that some electrophysiological effects of antiarrhythmic drugs in the normal heart may not be applicable to those in the diseased situation.     

Left ventricular myocardal activation under ventricular paced beats in chickens Gallus gallus domesticus

The aim of the study was to advance our knowledge regarding the activation process of the ventricular myocardium in birds in which Purkinje fibres penetrate into the ventricular wall to reach the epicardium. A depolarization pattern of the left ventricular free wall was studied in chickens (Gallus gallus) during ventricular paced beats. Duration of the activation process of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular free wall myocardium in chicken are expressed in a considerably less degree during ventricular paced beats in comparison with sinus rhythm. During ventricular paced beats, excitation of the left ventricular free wall is mostly due to the successive spreading of the depolarization wave from pacing sites.     

The cardiac innervation of Eledone cirrhosa (Lamarck) (Mollusca: Cephalopoda)

The innervation to the cardiac organs and vessels of the octopods Eledone cirrhosa, E. moschata and Octopus vulgaris is described from vitally stained fresh material and wax-embedded sections. This innervation arises from the paired visceral nerves and includes two main peripheral ganglia (fusiform and cardiac) on each side. Several new details of the innervation are reported. Nerves supplying the lateral venae cavae arise from the ventricular nerves at the level of the ventricle. Nerve fibres run to the efferent branchial vessels from the cardiac ganglia. A small ganglion, lying on the auriculo-ventricular nerve, is described for some specimens of both species of Eledone, and is named the auricular ganglion. Commissural strands linking the right and left ventricular nerves of either side are found in Eledone, comparable to those previously described from Octopus. The detailed branching pattern of the innervation shows considerable individual variation and consistent interspecific differences. In E. cirrhosa the fine fibres innervating the inner and outer muscle layers of the auricle show distinct differences in their configuration. Innervation at the surface of the ventricular lumen and around the coronary arterial vessels shows evidence of specialization. The muscle of the branchial heart, particularly the valve leaflets at the junction of the heart and the lateral vena cava, is abundantly innervated. The observations are discussed in relation to other cephalopods and to their probable physiological significance. It is suggested that they provide evidence for a greater degree of neural influence in the control of the cardiac organs than is usually supposed and that they support the idea that the lateral venae cavae have a significant role in the generation of circulatory pressures.     

Ventricular pump function under ectopic excitation of the frog heart

The ventricular pump function under ectopic excitation of the heart was studied in decapitated and pithed adult frogs Rana temporaria (n = 21) at 18-19 degrees C. The intraventricular pressure was recorded with a catheter via ventricular wall. During pacing of the ventricular base and apex, the systolic pressure decreased (6.1 +/- 4.5 mm Hg and 8.9 +/- 5.0 mm Hg, respectively) as compared to the supraventricular rhythm (8.9 +/- 5.0 mm Hg, p < 0.05). The end-diastolic pressure decreased insignificantly both under basal and apical pacing. The systolic rate of pressure rise during dP/dtmax decreased under ventricular pacing, especially during pacing of the ventricular apex, as compared to the supraventricular rhythm (14.4 +/- 6/9 mm Hg/s and 22.1 +/- 11.2 mm Hg/s, respectively, p < 0.003). The isovolumetric relaxation (dP/dtmin) slowed during apical pacing as compared to the supraventricular rhythm (-25.1 +/- 13.6 and -35.6 +/- 18.3 mm Hg/s, respectively, p < 0.03). Ectopic excitation of the ventricular base and apex resulted in increase of the QRS duration (93 +/- 33 ms and 81 +/- 30 ms, respectively) as compared to the supraventricular rhythm (63 +/- 13 ms, p < 0.05). Thus, pacing of different ventricular areas ventricular myocardium with the ventricular pump function being reduced more obviously during the apical pacing compared to the pacing of ventricular base.     

Increased choline acetyltransferase activity in pressure-overloaded right ventricles of guinea pigs

Choline acetyltransferase activity, a biochemical indication of parasympathetic innervation, is increased in the hypertrophied right ventricle of guinea pigs after pulmonary artery constriction (PAC). The increase appears to be dependent on the severity and the duration of hypertrophy. This change in choline acetyltransferase activity suggests compensatory changes occur in the parasympathetic innervation of PAC guinea pigs which allows the right ventricle to maintain its level of parasympathetic innervation despite marked hypertrophy. Unlike the right ventricle, the SA node of PAC guinea pigs does not have detectable changes in choline acetyltransferase activity. This model of right ventricular hypertrophy also does not have detectable changes in baroreflex control of heart rate.     

The distribution of acetylcholine and choline in guinea pig heart

The regional distributions of acetylcholine (ACh) and choline (Ch) in the guinea pig heart were investigated with a pyrolysis-mass fragmentography technique. Using ACh as a marker for cholinergic neurons, we have described a pattern of parasympathetic innervation in the guinea pig heart. This distribution is very similar to that suggested by studies using several different cholinergic indicators in various species. Atrial areas receive richer parasympathetic innervation than ventricular areas, with the right portions receiving more than the left. The nodal areas were the most abundantly innervated regions examined. Ch content is not a good indicator for cholinergic innervation as the regional distribution of ACh and Ch throughout the guinea pig heart are not strongly associated.     

Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart rate and respiration in ontogenesis

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneos motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations--secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart beating rhythm within the limits of 10% of bradicardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.     

Adrenal splanchnic innervation contributes to the diurnal rhythm of plasma corticosterone in rats by modulating adrenal sensitivity to ACTH

Activity of the hypothalamic-pituitary-adrenal axis is characterized by a diurnal rhythm with an AM nadir and PM peak. Splanchnic nerve transection disrupts the diurnal rhythm in plasma corticosterone; however, there is a controversy as to whether the nerve-mediated effect is 1) via inhibition in the AM vs. excitation in the PM, or 2) involves changes in adrenal sensitivity to ACTH. The present studies were designed to address these issues. Adult male rats were anesthetized and underwent bilateral transection of the thoracic splanchnic nerve or sham transection. One week after surgery, rats were killed in the AM or PM with collection of nonstress plasma for measurement of corticosterone and ACTH. Plasma corticosterone was increased in the PM relative to the AM; however, plasma corticosterone in the PM was attenuated by splanchnic nerve transection, without affecting plasma ACTH. This decrease in PM plasma corticosterone after nerve-transection was 1) associated with decreased adrenal responsivity to ACTH, 2) associated with decreased adrenal cAMP content, 3) prevented by adrenal demedullation, and 4) not affected by removal of adrenal capsaicin-sensitive afferent fibers. Repeated serial blood sampling from individual rats confirmed the excitatory effect of splanchnic innervation in the PM. These results support the hypothesis that the adrenal splanchnic innervation modulates the diurnal rhythm in plasma corticosterone by increasing adrenal responsivity to ACTH and augmenting steroidogenesis in the PM and suggest that alterations in adrenal corticosterone secretion obscured by pulsatile secretion are more clearly revealed with repeated serial blood sampling.     

Hemodynamic effects of pacing-induced tachycardia in valvular aortic stenosis.

The hemodynamic effects of tachycardia were studied in 13 patients with valvular aortic stenosis. Observations were made during sinus rhythm (average heart rate 80 beats/min) and two periods (P1 and P2) when atrial pacing increased the heart rate to 109 and 131 beats/min respectively. The cardiac index did not change, but the left ventricular stroke work index fell from 61.8 to 39.5 g X m/m2 (p less than 0.001) as the heart rate increased. The left ventricular end-diastolic pressure averaged 18 mm Hg during sinus rhythm and fell to about 11.5 mm Hg at P1 and P2 (p less than 0.001). The brachial arterial systolic pressure did not change during pacing, but the left ventricular systolic pressure fell from 208 mm Hg to 201 mm Hg during P1 (p less than 0.05) and 193 mm Hg during P2 (p less than 0.001). The mean systolic aortic valve gradient averaged 64 mm Hg during sinus rhythm and fell to 51 mm Hg during P2 (p less than 0.001), and the peak aortic valve gradient fell from 82 to 69 mm Hg during P2 (p less than 0.001). The left ventricular ejection time fraction increased from 26.9% during sinus rhythm to 31.9% during P1 (p less than 0.05) and 34.7% during P2 (p less than 0.005). Because of the prolonged left ventricular ejection time fraction and smaller stroke volume, a smaller pressure gradient developed across the stenosed valve at higher heart rates. The pacing test was of little value in assessing left ventricular function and thus is not useful during invasive investigations of valvular aortic stenosis.     

Constant amplitude of postsynaptic responses for single presynaptic action potentials but not bursting input during growth of an identified neuromuscular junction in the lobster, Homarus americanus

As lobsters grow from early juveniles to adults their body size increases more than 20-fold, raising the question of how function is maintained during these ongoing changes in size. To address this question we studied the pyloric 1 (p1) muscle of the stomach of the lobster, Homarus americanus. The p1 muscle receives multiterminal innervation from one motor neuron, the lateral pyloric neuron of the stomatogastric ganglion. Staining with antibodies raised against synaptotagmin showed that as the muscle fibers increased in length, the spacing between the terminal innervation increased proportionally, so the number of synaptic contact regions/muscle fiber did not change. Muscle fibers were electrically coupled in both juveniles and adults. The amplitude of single intracellularly recorded excitatory junctional potentials evoked by motor nerve stimulation was the same in both juveniles and adults. Nonetheless, the peak depolarizations reached in response to ongoing pyloric rhythm activity or in response to high-frequency trains of stimuli similar to those produced during the pyloric rhythm were approximately twofold larger in juveniles than in adults. This suggests that homeostatic regulation of synaptic connections may operate at the level of the amplitude of the single synaptic potential rather than on the summed depolarization evoked during strong rhythmic activity.     

Ganglionic Plexus Ablation During Pulmonary Vein Isolation - Predisposing to Ventricular Arrhythmias?

Catheter ablation is increasingly used to treat patients with atrial fibrillation (AF). Ablation of ganglionic plexi is often performed to reduce vagal innervation and has been shown to confer a better long-term outcome in terms of AF recurrence. We report a case of a patient having AF ablation with a profound vagal response, suggesting ganglionic plexus ablation, who subsequently developed ventricular fibrillation after programmed ventricular stimulation. Reduced vagal modulation is known to predispose to ventricular arrhythmias and vagal denervation following AF ablation may predispose to ventricular arrhythmias and requires further study.     

The melatonin rhythm generating system: developmental aspects

Development of the melatonin rhythm generating system, including the suprachiasmatic nucleus, sympathetic innervation, and biochemistry of the pineal gland is reviewed. This system offers investigators an interesting opportunity to study the effects of drugs, hormones, and other factors on the developmental appearance of specific structures and biochemical parameters, and to determine the role, if any, each has in the development of an integrated neural system.     

经颈静脉途径制备Beagle犬心脏记忆模型

目的经颈静脉途径应用心室起搏的方法制备心脏记忆犬模型。方法 8只普通级成年健康Beagle犬经腹腔麻醉后,Seldinger’s法穿刺颈外静脉成功后送入心内膜起搏电极,将电极头端固定于右室心尖部,近端连接于脉冲发生器。起搏频率设置较犬窦性心律时的基础心率快15%,保证起搏器连续起搏。结果连续起搏1周后所有动物均成功制备为心脏记忆模型。建模后犬的心率、呼吸、体重与建模前比较,无明显改变;所有模型组犬起搏前心电图均为窦性心律,起搏1周后出现心脏T波记忆,在下壁导联以及胸前导联均出现T波倒置,停止起搏后,心脏T波记忆逐渐消失;模型组犬与正常组犬心肌病理相比,无明显改变。结论经颈静脉途径应用心室起搏法建立心脏记忆犬模型的方法,具有手术简单,创伤小,诱发方式与临床相似等优点,为深入展开心脏记忆的机制研究奠定基础。     

Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart beatings and respiration in ontogenesis

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneous motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations—secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart contraction rhythm within the limits of 10% of bradycardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.     

Demonstration of choline acetyltransferase of a peripheral type in the rat heart.

Cholinergic innervation of the heart has been analyzed using cholinergic markers including acetylcholinesterase, choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). In the present study we demonstrate putative cholinergic nerves in the rat heart using an antibody to ChAT of a peripheral type (pChAT), which is the product of a splice variant of ChAT mRNA and preferentially localized to peripheral cholinergic nerves. Expression of mRNAs for pChAT and the conventional form of ChAT (cChAT) were verified in the rat atrium by RT-PCR. Localization of both protein products in the atrium was confirmed by Western blotting. Virtually all neurons and small intensely fluorescent cells in the intrinsic cardiac ganglia were stained immunohistochemically for pChAT. The density of pChAT-positive fibers was very high in the conducting system, high in both atria, the right atrium in particular, and low in the ventricular walls. pChAT and VAChT immunoreactivities were closely associated in some fibers and fiber bundles in the ventricular walls. These results indicate that intrinsic cardiac neurons homogeneously express both pChAT and cChAT. Furthermore, innervation of the ventricular walls by pChAT- and VAChT-positive fibers provides morphological evidence for a significant role of cholinergic mechanisms in ventricular functions.     

Biorhythms and pineal gland

Endocrine biorhythms are classified according to the period time, as one of the most characteristic properties of biorhythms. Each endocrine organ has parallel more than one biorhythms with different period time (e. g. circadian and circannual rhythms). The time of acrophase of the biorhythms at the different endocrine organs is fairly variant. This review summarizes the rhythmic function of the THS-thyroid, gonadotrophic-gonadal and ACTH-adrenocortical systems. Pineal gland plays an integrative role in the regulation of rhythmic function of the endocrine system. The melatonin secretion of this gland also reveals conspicuous circadian and circannual rhythms both in mammals and in birds. Mammalian pineal is functional only if its peripheral sympathetic innervation from the superior cervical ganglion is intact. In contrast, melatonin secretion and its circadian rhythm is also maintained in birds under isolated conditions (explanted into an in vitro superfusion system). The 24 hours period time of melatonin circadian rhythm can not be changed by light impulses. The phases of the circadian rhythm, however, can be turned by changing the time of environmental light-dark phases. The wavelength of the artificial light used for reversal of circadian rhythm is an important factor. The development of the entrainment and synchronization of the circadian melatonin rhythm in birds is independent of the rhythmic day-night changes in environmental lighting condition. The differences in the main elements of the biological clock between mammals and birds are discussed.     

Defining the substrate for ventricular tachycardia ablation: The impact of rhythm at the time of mapping

BackgroundVoltage mapping is critical to define substrate during ablation. In ventricular tachycardia, abnormal potentials may be targets. However, wavefront of activation could impact local signal characteristics. This may be particularly true when comparing sinus rhythm versus paced rhythms. We sought to determine how activation wavefront impacts electrogram characteristics.MethodsPatients with ischemic cardiomyopathy, ventricular tachycardia, and without fascicular or bundle branch block were included. Point by point mapping was done and at each point, one was obtained during an atrial paced rhythm and one during a right ventricular paced rhythm. Signals were adjudicated after ablation to define late potentials, fractionated potentials, and quantify local voltage. Areas of abnormal voltage (defined as <1.5 mV) were also determined.Results9 patients were included (age 61.3 ± 9.2 years, 56% male, mean LVEF 34.9 ± 8.6%). LV endocardium was mapped with an average 375 ± 53 points/rhythm. Late potentials were more frequent during right ventricular pacing (51 ± 21 versus 32 ± 15, p < 0.01) while overall scar area was higher during atrial pacing (22 ± 11% vs 13 ± 7%, p < 0.05). In 1/9 patients, abnormal potentials were seen during a right ventricular paced rhythm that were not apparent in an atrial paced rhythm, ablation of which resulted in non-inducibility.ConclusionRhythm in which mapping is performed has an impact on electrogram characteristics. Whether one rhythm is preferable to map in remains to be determined. However, it is possible defining local signals during normal conduction as well as variable paced rhythms may impart a greater likelihood of elucidating arrhythmogenic substrate.     

Relationship between cardiac arrhythmia and elevated concentrations of free fatty acids in plasma after an acute myocardial ischemia in dogs]

The influence, on the heart rhythm, of an acute myocardial ischemia produced by a coronary occlusion, is studied in ten opened chest dogs. After elevation of plasmatic free fatty acids, the consequence of a second occlusion on the cardiac rhythm is analysed. There is no significant correlation between the appearance of severe ventricular arrhythmias and high plasmatic levels of free fatty acids.