Vagus nerve stimulation inhibits the increase in Ca2+ transient and left ventricular force caused by sympathetic nerve stimulation but has no direct effects alone #8211; epicardial Ca2+ fluorescence studies using fura-2 AM in the isolated innervated beating rabbit heart (original) (raw)
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Experimental Physiology, 2010
The effects of direct autonomic nerve stimulation on the heart may be quite different to those of perfusion with pharmacological neuromodulating agents. This study was designed to investigate the effect of autonomic nerve stimulation on intracellular calcium fluorescence using fura-2 AM in the isolated Langendorff-perfused rabbit heart preparation with intact dual autonomic innervation. The effects of autonomic nerve stimulation on cardiac force and calcium transients were more obvious during intrinsic sinus rhythm. High-frequency (15 Hz, n = 5) right vagus nerve stimulation (VS) decreased heart rate from 142.7 ± 2.6 to 75.5 ± 10.2 beats min -1 and left ventricular pressure from 36.4 ± 3.2 to 25.9 ± 1.9 mmHg, whilst simultaneously decreasing the diastolic and systolic level of the calcium transient. Direct sympathetic nerve stimulation (7 Hz, n = 8) increased heart rate (from 144.7 ± 10.5 to 213.2 ± 4.9 beats min -1 ) and left ventricular pressure (from 37.5 ± 3.6 to 43.7 ± 2.8 mmHg), whilst simultaneously increasing the diastolic and systolic level of the calcium transient. During constant ventricular pacing, the highfrequency right vagus nerve stimulation did not have any direct effect on ventricular force or the calcium transient (n = 8), but was effective in reducing the effect of direct sympathetic nerve stimulation.
Experimental Physiology, 2004
The interaction between the effects of vagus nerve stimulation (VS) and sympathetic stimulation (SS) on intrinsic heart rate was studied in the novel innervated isolated rabbit heart preparation. The effects of background VS, at different frequencies -2 Hz (low), 5 Hz (medium), 7 Hz (high) -on the chronotropic effects of different frequencies of SS -2 Hz (low), 5 Hz (medium), 10 Hz (high) -were studied. The experiments were repeated in the reverse direction studying the effects of different levels of background SS on the chronotropic effects of different levels of VS. Background VS reduced the overall positive chronotropic effect of SS at steady state in a frequency dependent manner and the rate of increase in heart rate during low and medium SS (but not high SS) was slowed in the presence of background VS. These results suggest that pre-and postjunctional mechanisms may be involved in the sympatho-vagal interaction on heart rate. On the other hand, the chronotropic effect of VS was enhanced in the presence of background SS. Vagal stimulation appears to play a dominant role over sympathetic stimulation in chronotropic effects on the isolated heart. The innervated isolated heart preparation is a valuable model to study the complex mechanisms underlying the interaction between sympathetic and parasympathetic stimulation on cardiac function.
Electrophysiological effects of right and left vagal nerve stimulation on the ventricular myocardium
Vagal nerve stimulation (VNS) has been proposed as a cardioprotective intervention. However, regional ventricular electrophysiological effects of VNS are not well characterized. The purpose of this study was to evaluate effects of right and left VNS on electrophysiological properties of the ventricles and hemodynamic parameters. In Yorkshire pigs, a 56-electrode sock was used for epicardial (n ϭ 12) activation recovery interval (ARI) recordings and a 64-electrode catheter for endocardial (n ϭ 9) ARI recordings at baseline and during VNS. Hemodynamic recordings were obtained using a conductance catheter. Right and left VNS decreased heart rate (84 Ϯ 5 to 71 Ϯ 5 beats/min and 84 Ϯ 4 to 73 Ϯ 5 beats/min), left ventricular pressure (89 Ϯ 9 to 77 Ϯ 9 mmHg and 91 Ϯ 9 to 83 Ϯ 9 mmHg), and dP/dt max (1,660 Ϯ 154 to 1,490 Ϯ 160 mmHg/s and 1,595 Ϯ 155 to 1,416 Ϯ 134 mmHg/s) and prolonged ARI (327 Ϯ 18 to 350 Ϯ 23 ms and 327 Ϯ 16 to 347 Ϯ 21 ms, P Ͻ 0.05 vs. baseline for all parameters and P ϭ not significant for right VNS vs. left VNS). No anteriorposterior-lateral regional differences in the prolongation of ARI during right or left VNS were found. However, endocardial ARI prolonged more than epicardial ARI, and apical ARI prolonged more than basal ARI during both right and left VNS. Changes in dP/dt max showed the strongest correlation with ventricular ARI effects (R 2 ϭ 0.81, P Ͻ 0.0001) than either heart rate (R 2 ϭ 0.58, P Ͻ 0.01) or left ventricular pressure (R 2 ϭ 0.52, P Ͻ 0.05). Therefore, right and left VNS have similar effects on ventricular ARI, in contrast to sympathetic stimulation, which shows regional differences. The decrease in inotropy correlates best with ventricular electrophysiological effects.
Experimental Physiology, 2001
A novel isolated Langendorff perfused rabbit heart preparation with intact dual autonomic innervation is described. This preparation allows the study of the effects of direct sympathetic and vagus nerve stimulation on the physiology of the whole heart. These hearts (n = 10) had baseline heart rates of 146 ± 2 beats min _1 which could be increased to 240 ±11 beats min _1 by sympathetic stimulation (15 Hz) and decreased to 74 ± 11 beats min _1 by stimulation of the vagus nerve (right vagus, 7 Hz). This model has the advantage of isolated preparations, with the absence of influence from circulating hormones and haemodynamic reflexes, and also that of in vivo preparations where direct nerve stimulation is possible without the need to use pharmacological agents. Data are presented characterising the preparation with respect to the effects of autonomic nerve stimulation on intrinsic heart rate and atrioventricular conduction at different stimulation frequencies. We show that stimulation of the right and left vagus nerve have differential effects on heart rate and atrioventricular conduction. Experimental Physiology (2001) 86.3, 319-329. 2146
Bradycardia Induced by Intravascular Versus Direct Stimulation of the Vagus Nerve
The Annals of Thoracic Surgery, 1998
Electrical stimulation of the parasympathetic nervous system results in slowing of the heart. We sought to determine whether cardiac vagal efferent axons can be stimulated adequately to induce bradycardia without disturbing the integrity of the thorax. Cardiodepressor effects elicited by direct stimulation of a vagus nerve in anesthetized dogs and pigs were compared with those generated when the same nerve was stimulated indirectly through bipolar electrodes placed in the adjacent superior vena cava. The heart rate of dogs decreased by about 80% when electrical stimuli were delivered to the right thoracic vagus at the level of the thoracic outlet through bipolar electrodes placed either in the adjacent superior vena cava (intravascular method) or directly on the nerve (direct method). Maximal responses were achieved with 10-V, 5-ms, and 20-Hz stimuli. In anesthetized pigs, similar bradycardia occurred when the right cervical vagus or the right cranial thoracic vagus was stimulated either directly or indirectly through the intravascular method. Atrial dysrhythmias occurred when the stimulating electrodes were placed by either method within 1 cm of the right atrium in both animal models. Controlled bradycardia can be induced during operation without the risk of generating cardiac dysrhythmias using electrical stimuli (10 V, 5 ms, and 10 to 20 Hz) delivered to the right cervical vagus nerve or the right cranial thoracic vagus nerve through adjacent intravascular electrodes.
Autonomic Neuroscience, 2006
The relative contribution of the chronotropic effects of stimulating sympathetic and vagus nerves on cardiac inotropic changes in the isolated Langendorff perfused rabbit heart with intact dual autonomic nerves was studied. The force -frequency relationship was investigated, in addition to sympathetic nerve stimulation (SS) at 2 Hz (low), 5 Hz (med) and 10 Hz (high), and left and right vagus nerve stimulation (VS) studied at 2 Hz (low), 5 Hz (med) and 7 Hz (high) with and without right ventricular pacing. It was shown that a biphasic force -frequency relationship is present with a positive relationship at low heart rates and a negative force -frequency relationship at higher heart rates. There was a trend for left-and right-VS to decrease left ventricular pressure with a decrease in heart rate, whilst SS had the opposing effects in a frequency-dependent manner. When heart rate was kept constant, there was no effect from left-or right-VS, while SS increased left ventricular pressure in a frequency-dependent manner. Together these results suggest that SS, left-and right-VS alter left ventricular force by two different mechanisms. Left-and right-VS decrease left ventricular pressure predominantly via chronotropic effects whilst SS increases force predominantly by direct changes in contractility. D
AJP: Heart and Circulatory Physiology, 2004
Complex sympathovagal interactions govern heart rate (HR). Activation of the postjunctional -adrenergic receptors on the sinus nodal cells augments the HR response to vagal stimulation, whereas exogenous activation of the presynaptic ␣-adrenergic receptors on the vagal nerve terminals attenuates vagal control of HR. Whether the ␣-adrenergic mechanism associated with cardiac postganglionic sympathetic nerve activation plays a significant role in modulation of the dynamic vagal control of HR remains unknown. The right vagal nerve was stimulated in seven anesthetized rabbits that had undergone sinoaortic denervation and vagotomy according to a binary white-noise signal (0-10 Hz) for 10 min; subsequently, the transfer function from vagal stimulation to HR was estimated. The effects of -adrenergic blockade with propranolol (1 mg/kg iv) and the combined effects of -adrenergic blockade and tonic cardiac sympathetic nerve stimulation at 5 Hz were examined. The transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with pure delay. -Adrenergic blockade decreased the dynamic gain from 6.0 Ϯ 0.4 to 3.7 Ϯ 0.6 beats ⅐ min Ϫ1 ⅐ Hz Ϫ1 (P Ͻ 0.01) with no alteration of the corner frequency or pure delay. Under -adrenergic blockade conditions, tonic sympathetic stimulation did not further change the dynamic gain (3.8 Ϯ 0.5 beats ⅐ min Ϫ1 ⅐ Hz Ϫ1). In conclusion, cardiac postganglionic sympathetic nerve stimulation did not affect the dynamic HR response to vagal stimulation via the ␣-adrenergic mechanism. systems analysis; transfer function; -adrenergic blockade; rabbits; sympathovagal interaction COMPLEX SYMPATHOVAGAL INTERACTIONS are known to occur in the regulation of heart rate (HR). These interactions involve neural interactions within and between cardiac ganglia (2, 3), at the end terminals for their cardiac projections (18), and via second-messenger systems in the innervated myocytes (29). An increase in background sympathetic tone augments the HR response to vagal nerve activity (19, 20). Levy (19) referred to this phenomenon as an accentuated antagonism of HR control.
PloS one
Although the therapeutic effects of Vagus Nerve Stimulation (VNS) have been recognized in pre-clinical and pilot clinical studies, the effect of different stimulation configurations on the cardiovascular response is still an open question, especially in the case of VNS delivered synchronously with cardiac activity. In this paper, we propose a formal mathematical methodology to analyze the acute cardiac response to different VNS configurations, jointly considering the chronotropic, dromotropic and inotropic cardiac effects. A latin hypercube sampling method was chosen to design a uniform experimental plan, composed of 75 different VNS configurations, with different values for the main parameters (current amplitude, number of delivered pulses, pulse width, interpulse period and the delay between the detected cardiac event and VNS onset). These VNS configurations were applied to 6 healthy, anesthetized sheep, while acquiring the associated cardiovascular response. Unobserved VNS config...