The effect of chlorpromazine on the mechanogram, electrocardiogram and membranopotential of the frog heart]

The action of chloropromazine in concentrations between 10(-6) and 10(-3) M was studied with regard to its effect on contractility, ECG, and membrane potential of the isolated frog heart. In concentrations above 10(-6) a depressive influence on the amplitude of contraction was observed; the speed of contraction was reduced. The heart rate showed negatively chronotropic changes. In the ECG there was a striking expansion of the PQ interval. The membrane potential was reduced under the effect of chloropromazine depending on the concentration used. The negative influence on mechanical and bioelectrical parameters of the myocardium is interpreted to be due to membrane-related factors. A vagus-like effect is discussed, particular importance being attached to the mechanisms of the "slow-channel" system.     

Characterization of embryonic cardiac pacemaker and atrioventricular conduction physiology in Xenopus laevis using noninvasive imaging

Congenital heart defects often include altered conduction as well as morphological changes. Model organisms, like the frog Xenopus laevis, offer practical advantages for the study of congenital heart disease. X. laevis embryos are easily obtained free living, and the developing heart is readily visualized. Functional and morphological evidence for a conduction system is available for adult frog hearts, but information on the normal properties of embryonic heart contraction is lacking, especially in intact animals. With the use of fine glass microelectrodes, we were able to obtain cardiac recordings and make standard electrophysiological measurements in 1-wk-old embryos (stage 46). In addition, a system using digital analysis of video images was adapted for measurement of the standard cardiac intervals and compared with invasive measurements. Video images were obtained of the heart in live, pharmacologically paralyzed, stage 46 X. laevis embryos. Normal values for the timing of the cardiac cycle were established. Intervals determined by video analysis (n = 53), including the atrial and ventricular cycle lengths (473 +/- 10 ms and 464 +/- 19 ms, respectively) and the atrioventricular interval (169 +/- 5 ms) were not statistically different from those determined by intrathoracic cardiac recordings. We also present the data obtained from embryos treated with standard medications that affect the human conduction system. We conclude that the physiology of embryonic X. laevis cardiac conduction can be noninvasively studied by using digital video imaging. Additionally, we show the response of X. laevis embryonic hearts to chronotropic agents is similar but not identical to the response of the human heart.     

Developmental changes in dopamine modulation of the heart in the isopod crustacean Ligia exotica: reversal of chronotropic effect

Developmental changes in dopamine modulation of the heart were examined in the isopod crustacean Ligia exotica. The Ligia cardiac pacemaker is transferred from the myocardium to the cardiac ganglion during juvenile development and the heartbeat changes from myogenic to neurogenic. In the myogenic heart of early juveniles, dopamine affected the myocardium and caused a decrease in the frequency and an increase in the duration of the myocardial action potential, resulting in negative chronotropic (decrease in beat frequency) and positive inotropic (increase in contractile force) effects on the heart. Contrastingly, in the heart of immature adults just after juvenile development, dopamine caused effects of adult type, positive chronotropic and positive inotropic effects on the heart affecting the cardiac ganglion and myocardium. During the middle and late juvenile stages, dopamine caused individually a negative or a positive chronotropic effect on the heart. These results suggest that the chronotropic effect of dopamine on the Ligia heart is reversed from negative to positive in association with the cardiac pacemaker transfer from the myocardium to the cardiac ganglion during juvenile development.     

Postnatal development of postganglionic parasympathetic neurones in the heart of the albino rat.

Electrical stimulation of the sinoatrial node region of isolated atria in medium containing physostigmine (0.1 micrograms/ml) produces a negative chronotropic effect whose intensity and duration depend mainly on the amount of acetylcholine released from postganglionic parasympathetic fibres endings. This technique was used to study functional maturation of the given neurones during postnatal development of albino rats. Preparations from animals of different ages were stimulated with 2-second bursts of rectangular pulses (frequency 50 Hz, pulse duration 0.02 ms, voltage 22.5--27.5 V) and frequency changes of the preparation were registered by recording extracellular action potentials. At 10 days the negative chronotropic effect is very weak and at 15 days it is only slightly stronger, but at 18 days it is almost the same as in adult animals. At 24 and 34 days the reaction is somewhat stronger than in adulthood. It can be concluded from these observations that functional maturation of the postganglionic parasympathetic neurones innervating the sinoatrial node in albino rats occurs between the 10th and 20th day of postnatal life.     

Dynamics of the vagus effect on the cardiac rhythm during blockade of various subtypes of M-cholinoreceptors in cats

While single vagus bursts were used in cats with an incremental time delay following P-wave of the ECG, two zones were identified within the cardiac cycle differing from each other by their chronotropic responses. At the initial (approximately 120-130 ms) part of the cardiac cycle, an increase in the P-stimulus interval evoked a "moderate" (+8-16%) increment of the chronotropic response up to its maximal amplitude. Further increase of that interval provoked an "abrupt" (-80-90%) decrease of the vagus response. Block of M1-(pirenzepine), M2-(metoctramine and gallamine) or M3-(DAMP) cholinoreceptors diminished vagally-induced minimal and maximal prolongation of the ECG P-P interval and decreased the amplitude of its alterations associated with varying the position of vagus stimulus within the cardiac cycle. The coefficient delineating magnitude of the vagus effect over a zone with "moderate" changes of the chronotropic response was decreased after blocking the M1- and M2-cholinoreceptors, whereas duration of that zone was shortened following blockade of the M1- and M3-receptors. Velocity of the original vagus response and the rate of its subsequent decline decreased following blockade of the M1- and M2-subtypes of cholinoreceptors.     

Bioelectrical analysis of the regulatory interaction of sympathetic and parasympathetic nervous influences on the heart rhythm]

The changes of chronotropic effect on the isolated sinus node of the frog heart were studied during the separate and simultaneous stimulation of the sympathetic and intracardiac reflex parasympathetic pathways. Intracellular activity of the pacemaker cells was recorded. The separate stimulation of the intracardiac reflex system resulted in bradycardia (in winter) or tachycardia (in summer). Stimulation of sympathetic chain supervening the activation of the intracardiac pathways induced an intensification of both the parasympathetic bradycardia and tachycardia; these effects were cholinergic in nature. The recording of the intracellular pacemaker activity showed the existence of the complicated interaction between the sympathetic and parasympathetic pulse-mediator actions on the heart pacemaker both on the prepulase process and on the membrane polarization and other action potential parameters. Possible mechanisms of this interaction are discussed.     

Action of pilocarpine on the normal frog heart and in pathology

Experiments on frogs were performed to examine the effect of the M-cholinomimetic pilocarpine on the heart. It was discovered that at concentrations of 10(-15)--10(-5) g/ml pilocarpine exerted only an adverse chronotropic effect on the perfused heart. When applied at a concentration of 10(-4) g/ml the drug produced a negative as well as a positive chronotropic effect. The latter occurred spasmodically (without progressive rise in the heart rate) in association with a slow heart rate. In some experiments such effects were preceded by a certain deceleration of the heart. In experiments with positive chronotropic effects, arrhythmias and sinoatrial dissociation were observed sometimes. Experiments with recording of the electrograms of the sinuses and lower parts showed that such effects were caused not by pacemaker acceleration but by the removal of the blockade of conduction, between the pacemaker and the atria. As far as the pacemaker is concerned, pilocarpine exerted only a negative chronotropic effect.     

The spectrogram of heart rate in cats following burst stimulation of the vagus nerve

Denervation of the heart (bilateral vagotomy and propranolol) in artificially ventilated cats didn't remove respiratory peaks on the spectrogram of heart rate, while burst stimulation of vagus nerve increased or decreased them several times by synchronization of the heart and vagus rhythms, which in its turn was observed under the bradycardia only. At the same time, the desynchronization of rhythms provoked severe sinus arrhythmia which had a distinct periodic character. Under these conditions, there were high non-respiratory peaks appearing at the spectrogram of the heart rate that indicated existence of two vagus chronotropic effects: a well known tonic one and special intracycle synchronizing effect correcting duration of every cardiac cycle.     

Effects of adenosine perfusion on the metabolism and contractile activity of Rana ridibunda heart

The effects of adenosine were examined on the isolated perfused heart of the frog Rana ridibunda. Adenosine produced negative chronotropic and inotropic effects on frog ventricle in a concentration-dependent manner. The effects of adenosine on cardiac metabolism were also investigated by measuring the tissue content of adenine nucleotides, lactate, pyruvate, adenosine and inorganic phosphate, during adenosine perfusion. Adenosine had no effect on the tissue content of metabolites. No net synthesis of adenine nucleotides was observed during perfusion with increasing concentrations of adenosine. Lactate output from the heart decreased significantly with adenosine perfusion. Correlation of adenosine effects on cardiac muscle with the effects of hypoxia are discussed.     

The structural dynamics of vagus influence on the heart rhythm in exposures directed at altering the acting acetylcholine concentration]

In 29 experiments on anaesthetized cats burst stimulation of peripheral cut end of right vagus nerve leads to synchronization of heart and vagus rhythm. Influence of proserine, pilocarpine and prolonged vagus stimulation upon extent of vagus chronotropic effect and its components--tonic and synchronizing--was investigated. In all cases changes of vagus chronotropic effect during this actions were caused by unidirectional shifts of tonic component. Extent of synchronizing vagus chronotropic influences did not depend on the changes of acetylcholine concentration.     

Dual effects of dopamine on the adult heart of the isopod crustacean Ligia exotica

In the adult heart of the isopod crustacean Ligia exotica, the cardiac ganglion acts as the primary pacemaker with the myocardium having a latent pacemaker property. We show several lines of evidence that dopamine modulates the heartbeat of adult L. exotica affecting both pacemaker sites in the heart. Dopamine caused positive chronotropic (frequency increase) and inotropic (amplitude increase) effects on the heartbeat in a concentration dependent manner. The time courses of these effects were considerably different and the inotropic effect appeared later and lasted longer than the chronotropic effect. Dopamine rapidly increased the frequency of the bursting activity in the cardiac ganglion neurons and each impulse burst of the cardiac ganglion was always followed by a heartbeat. Moreover, dopamine slowly increased the amplitude and duration of the action potential plateau (plateau potential) of the myocardium. When the myocardial pacemaker activity was induced by application of tetrodotoxin, which suppresses cardiac ganglion activity, dopamine slowly increased the amplitude and duration of the myocardial plateau potential while decreasing its frequency. These results suggest that dopamine modulates the heartbeat in adult L. exotica producing a dual effect on the two pacemaker sites in the heart, the cardiac ganglion and myocardium.     

Cardiovascular effects of bPTH-(1-34) and isoproterenol in the frog, Rana tigrina.

1. The cardiovascular effects of bovine parathyroid hormone fragment [bPTH-(1-34)] and isoproterenol (ISO) on frog (Rana tigrina) isolated atria and helical strips of blood vessels were examined since PTH produces a beta-adrenergic-like effect in the mammal. 2. Data showed that both bPTH-(1-34) and ISO were vasorelaxant in KCl and arginine vasoctocin (AVT) preconstricted dorsal aorta, iliac and femoral arteries. 3. They both relaxed extracellular calcium-dependent contrations. 4. There was no additive nor synergistic effect between them in AVT preconstricted strips. 5. Both bPTH-(1-34) and ISO were positively inotropic but differed in their chronotropic effects, being negative and positive. 6. In the tiger frog, bPTH-(1-34) shows beta-adrenergic like contractile responses in both the cardiac and vascular smooth muscle as in the mammal, but not in the heart rate.     

The action of ADP ribose on the mechanical and bioelectrical activity of the frog heart]

In the frog isolated heart, cyclic perfusion of ADP-ribose induced a dose-dependent decrease in the heart rate and the contraction force, a decrease in the AP duration as well as in the rate of rise in the sinus node. It also shortened the atrial AP and exerted no significant effect upon multicellular ventricular preparations. In conditions of systemic administration in unanesthetised frogs, the ADP-ribose induced a reversible increase in the heart rate due, probably, to a sympathetic effect.     

Electrophysiological effects of the aqueous extract of Averrhoa carambola L. leaves on the guinea pig heart

This work aims to describe some electrophysiological changes promoted by the aqueous extract (AEx) from Averrhoa carambola leaves in guinea pig heart. The experiments were carried out on isolated heart or on right atrium-ventricle preparations. In 6 hearts, the extract induced many kinds of atrioventricular blocks (1st, 2nd, and 3rd degrees); increased the QT interval from 229+/-23 to 264+/-19 ms; increased the QRS complex duration from 27+/-3.1 to 59+/-11 ms, and depressed the cardiac rate from 136+/-17 to 89+/-14b pm. Furthermore, it decreased the conduction velocity of atrial impulse (17+/-3%); reduced the intraventricular pressure (86+/-6%), and increased the conduction time between the right atrium and the His bundle (27+/-6.5%). The conduction time from the His bundle to the right ventricle was not altered. Atropine sulfate did not change either the electrocardiographic parameters or the intraventricular pressure effects promoted by the A. carambola AEx. Based on these results, the popular use of such extracts should be avoided because it can promote electrical and mechanical changes in the normal heart.     

高钙对兔窦房结的负性变时作用

本文采用常规微电极技术在离体兔心窦房结标本上研究了细胞外钙离子浓度([Ca~(2 )]_0)对窦房结的变时性作用。结果显示,[Ca~(2 )]_0的递增(1.1—5.5mM),对窦性周期(CL)大于400ms 的标本引起双相变时作用,但对CL小于400ms的标本却引起负性变时作用。阿托品(0.5mg/l)和心得安(0.2mg/l)对[Ca~(2 )]_0 的变时作用无明显影响。随着[Ca~(2 )]_0的递增,窦房结优势起搏细胞的动作电位幅度、最大舒张期电位和0期最大除极速度均降低,舒张期自动除极化斜率增加,起始电位上移,动作电位时程(APD)延长。高[Ca~(2 )]_0时窦房结起搏细胞的有效不应期(ERP)延长、ERP/APD增大,ERP点的阈值提高(P<0.01)。 上述结果表明,高[Ca~(2 )]_0引起窦房结的负性变时效应,这种作用不是通过交感和副交感神经的传递,而可能是 Ca~(2 )直接作用于窦房结起搏细胞引起其电活动改变的结果。     

Negative chronotropic effect of endothelin-1 (ET-1) in the cardiac pacemaker tissue.

The aim of this study was to asses the direct effect of ET-1 on spontaneous discharge rate of the pacemaker tissue in the presence of isoproterenol. The experiments were performed on pacemaker tissue of the isolated right auricle of the right heart atrium of a two-day-old rat. The spontaneous discharge rate of the pacemaker tissue was recorded on the ECG apparatus and analyzed by the computer. ET-1 alone did not significantly affect the discharge rate of the pacemaker tissue. Isoproterenol rapidly increased the discharge rate of the pacemaker tissue. ET-1 had negative chronotropic effect in the presence of isoproterenol. JKC-301, a blocker of ET(A) receptors, significantly reduced the negative chronotropic effect of ET-1 in the presence of isoproterenol, whereas IRL-1038, a blocker of ET(B) receptors, did not significantly affect the negative chronotropic effect of ET-1 in the presence of isoproterenol. In conlusion, the negative chronotropic effect of ET-1 in the presence of beta-adrenergic stimulation the pacemaker tissue of the right auricle of the right heart atrium of the two-day-old rat is mediated by ET(A) receptors.     

Alpha- and gamma-endorphin suppression of the chronotropic effects of exogenous acetylcholine

On the isolated frog heart alpha- and gamma-endorphins depressed the chronotropic effects of exogenous acetylcholine. Naloxone partially blocked the atropine-like action of alpha-, gamma-endorphins. The latent period of the reaction to the endorphin injection was about 20 min, the endorphin effect retained more than 1 h. The obtained data show that some opioids may act as "endogenous atropine".     

Mechanical control of the time-course of contraction of the frog heart

Changes in load during most phases of an isotonic contraction of the frog and turtle heart increased or decreased the duration of the twitch. It was abbreviated by a maintained increase or by a brief decrease in load. The relaxing effect of these procedures developed with a delay lasting more than a second under some conditions and will be called lengthening deactivation. The reverse procedures, a maintained diminution or a brief increase in load, increased the duration of the twitch. This effect will be called shortening activation. Although the termination of relaxation may be delayed or advanced by the mechanical interventions mentioned, the normal time- course of isotonic relaxation was always resumed later, regardless of the starting level of the load, making it possible to measure accurately changes in the duration of the twitch. The responses to changes in load produce positive feedback during the isotonic contraction and explain, at least in part, the difference in the time- course of isotonic and isometric contraction. The effects of changes in load were much smaller and briefer in the atrium than the ventricle.     

Ca2+ protection from the negative inotropic effect of contraction frequency on teleost hearts

Summary Isometric tension development by ventricular strips of 9 species of teleosts, a frog and a turtle was assessed at varying contraction frequencies and Ca_o (external calcium concentration). With teleost hearts an increase in contraction frequency at constant Ca_o was always associated with a decrease in tension development; however, under comparable conditions a positive staircase was exhibited by the frog and turtle heart preparations. The reaction of the teleost heart was thus very different from the well established response of the hearts of higher vertebrates. Elevations in Ca_o always resulted in an increase in tension development such that the positive inotropic effect of Ca_o could compensate for the negative effect of a high contraction frequency. Perfused isolated cod hearts exhibited an increase in cardiac output and pressure development as a result of increases in Ca_o. At 30 contractions min⁻¹ a transition from 1–2 mM Ca_o led to a 68% increase in performance defined as the product of cardiac output times pressure development. The response was in excess of that of ventricular strips. At low Ca_o increases in rate from in situ resting levels to the high end of the physiological range resulted in a decrease in performance. Increases in Ca_o were able to ameliorate the detrimental effect of high imposed contraction frequency. In conclusion, both ventricular strip and perfused heart experiments show that a positive inotropic effect of increased Ca_o can compensate for or even surpass the negative effect of high contraction frequency when both variables are at physiological levels. This finding could have relevance to the maintenance of cardiac performance during/or following intense swimming when both heart rate and plasma calcium may be elevated.