The effect of direct autonomic nerve stimulation on left ventricular force in the isolated innervated Langendorff perfused rabbit heart (original) (raw)
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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
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.
Exp Physiol, 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.
Autonomic Neuroscience, 2012
The heart receives both a left and right sympathetic innervation. Currently there is no description of an in vitro whole heart preparation for comparing the influence of each sympathetic supply on cardiac function. The aim was to establish the viability of using an in vitro model to investigate the effects of left and right sympathetic chain stimulation (LSS/RSS). For this purpose the upper sympathetic chain on each side was isolated and bipolar stimulating electrodes were attached between T2-T3 and electrically insulated from surrounding tissue in a Langendorff innervated rabbit heart preparation (n= 8). Heart rate (HR) was investigated during sinus rhythm, whilst dromotropic, inotropic and ventricular electrophysiological effects were measured during constant pacing (250 bpm). All responses exhibited linear increases with increases in stimulation frequency (2-10 Hz). The change in HR was larger during RSS than LSS (Pb 0.01), increasing by 78± 9 bpm and 49± 8 bpm respectively (10 Hz, baseline; 145 ± 7 bpm). Left ventricular pressure was increased from a baseline of 50± 4 mm Hg, by 22± 5 mm Hg (LSS, 10 Hz) and 4 ± 1 mm Hg (RSS, 10 Hz) respectively (Pb 0.001). LSS, but not RSS, caused a shortening of basal and apical monophasic action potential duration (MAPD90). We demonstrate that RSS exerts a greater effect at the sinoatrial node and LSS at the left ventricle. The study confirms previous experiments on dogs and cats, provides quantitative data on the comparative influence of right and left sympathetic nerves and demonstrates the feasibility of isolating and stimulating the ipsilateral cardiac sympathetic supply in an in vitro innervated rabbit heart preparation.
The Japanese Journal of Physiology, 2001
Regulation of heart rate (HR) and cardiac contractility by the sympathetic efferent nervous system is vital for maintaining a stable hemodynamic state under various stresses. The sympathetic regulation of ventricular contractility includes a direct inotropic effect through the innervation on the myocardium and an indirect inotropic effect through changes in HR (forcefrequency mechanism). Although previous studies investigated sympathetic regulation of left ventricular function and HR [1-4], the load dependency of the indexes of ventricular contractility used in these studies, such as dP/dt (the first derivative of pressure waveform), ejection fraction, and stroke volume, makes it difficult to quantitatively compare the relative contribution of the direct and indirect inotropic effects. On the other hand, left ventricular end-systolic elastance (E es), which is the slope of the end-systolic pressurevolume relationship, has been shown to be a load-insensitive index of ventricular contractility [5-9]. Although the precise estimation of E es can be achieved in an isolated cross-circulated canine heart preparation, because the heart was denervated during the isolation procedure makes this preparation inappropriate for investigating its autonomic regulation. To overcome this problem, we recently developed a new preparation wherein we isolated the canine heart with functional autonomic nerves [10]. In this preparation, the heart is decentralized, but the sympathetic efferent nerves are preserved for electrical stimulation. The purpose of this study was to evaluate the relative contribution of the direct and indirect inotropic effects on E es in response to right or left sympathetic stimulation by using the isolated cross-circulated canine heart with the functional sympathetic nerves. The results of the investigation indicated that the right sympathetic nerve regulated left ventricular contractility via both the direct inotropic effect and the indirect HR-dependent inotropic effect. In contrast, the left
Autonomic Nerve Stimulation Reverses Ventricular Repolarization Sequence in Rabbit Hearts
Circulation Research, 2007
Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. Rabbit hearts were perfused in a Langendorff apparatus with full sympathetic and parasympathetic innervation and were optically mapped to measure action potential durations and DOR (apex-base) over the left ventricles. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 mol/L) infusion. In sinus rhythm, repolarization started at the apex and systematically progressed toward the base. SNS (10 to 15 Hz) increased DOR by 29% (from ⌬action potential durationϭ17Ϯ0.7 to Ϫ22Ϯ1.6 ms, nϭ6) and reversed DOR as the direction of repolarization from apex3base in sinus rhythm shifted to base3apex in 5 to 15 seconds after SNS. DOR flipped back to its sinus rhythm DOR pattern 115Ϯ15 seconds after the interruption of SNS. During right or left vagus nerve stimulation, there was no change in the direction of DOR, but bilateral vagus nerve stimulation increased and reversed DOR to base3apex direction. Infusion of isoproterenol or acetylcholine increased DOR but did not alter the direction of repolarization sequences. These findings demonstrate that bilateral autonomic activity (SNS or vagus nerve stimulation) cause reversible shifts of apex-base DOR and that the spatial heterogeneities of autonomic effects on the ventricles are most likely attributable to a greater innervation at the base than the apex of the heart. (Circ Res. 2007;100:e72-e80.) Key Words: autonomic nerve stimulation Ⅲ sympathetic nerve stimulation Ⅲ vagus nerve stimulation Ⅲ dispersion of repolarization Ⅲ action potential durations Ⅲ optical mapping Original
Sympathetic influences on electrical and mechanical alternans in the canine heart
Cardiovascular Research, 1996
Objective: The aim was to investigate the influence of the sympathetic nervous system on the induction of mechanical and electrical altemans in the intact canine heart Methods: Experiments were. performed on 8 open-chest dogs anesthetized with sodium pentobarbital. A micromanometer-tipped catheter was used to measure left ventricular pressure, dp/dt and the time constant of isovolumic relaxation.
Augmentation of Left Ventricular Contractility by Cardiac Sympathetic Neural Stimulation
Circulation, 2010
stimulation of mediastinal sympathetic cardiac nerves increases cardiac contractility but is not selective for the left ventricle because it elicits sinus tachycardia and enhanced atrioventricular conduction. The aim of this study was to identify sympathetic neural structures inside the heart that selectively control left ventricular inotropy and can be accessed by transvenous catheter stimulation. Methods and Results-In 20 sheep, high-frequency stimulation (200 Hz) during the myocardial refractory period with electrode catheters inside the coronary sinus evoked a systolic left ventricular pressure increase from 97Ϯ20 to 138Ϯ32 mm Hg (PϽ0.001) without changes in sinus rate or PR time. Likewise, the rate of systolic pressure development (1143Ϯ334 versus 1725Ϯ632 mm Hg/s; Pϭ0.004) and rate of diastolic relaxation (531Ϯ128 versus 888Ϯ331 mm Hg/s; Pϭ0.001) increased. The slope of the end-systolic pressure-volume relationship increased (2.3Ϯ0.8 versus 3.1Ϯ0.6 mm Hg/mL; Pϭ0.04), as did cardiac output (3.5Ϯ0.8 versus 4.4Ϯ0.8 L/min; PϽ0.001). Systemic vascular resistance and right ventricular pressure remained unchanged. There was a sigmoid dose-response curve. Ultrasound analysis revealed an increase in circumferential and radial strain in all left ventricular segments that was significant for the posterior, lateral, and anterior segments. Pressure effects were maintained for at least 4 hours of continued high-frequency stimulation and abolished by 1-receptor blockade. Histology showed distinct adrenergic nerve bundles at the high-frequency stimulation site. Conclusions-Cardiac nerve fibers that innervate the left ventricle are amenable to transvenous electric catheter stimulation. This may permit direct interference with and modulation of the sympathetic tone of the left ventricle. (Circulation. 2010;121: 1286-1294.)