Left Sympathetic Stimulation Research Articles

Functional selectivity of cardiac preganglionic sympathetic neurones in the rabbit heart

BackgroundStudies have shown regional and functional selectivity of cardiac postganglionic neurones indicating there might exist a similar heterogeneity in spinal segmental preganglionic neurones, which requires further investigation. MethodsRight and left sympathetic chains were electrically stimulated from T6 to T1 in the innervated isolated rabbit heart preparation (n = 18). Sinus rate, left ventricular pressure, retrograde ventriculo-atrial conduction, monophasic action potential duration, effective refractory period, ventricular fibrillation threshold and electrical restitution were measured. ResultsRight sympathetic stimulation had a greater influence on heart rate (T1-T2: right; 59.9 ± 6.0%, left; 41.1 ± 5.6% P < 0.001) and left stimulation had greater effects on left ventricular pressure (T1-T2: right; 20.7 ± 3.2%, left; 40.3 ± 5.4%, P < 0.01) and ventriculo-atrial conduction (T1-T2: right; −6.8 ± 1.1%, left; −15.5 ± 0.2%) at all levels, with greater effects at rostral levels (T1-T3). Left sympathetic stimulation caused shorter monophasic action potentials at the base (T4-T5: right; 119.3 ± 2.7 ms, left; 114.7 ± 2.5 ms. P < 0.05) and apex (T4-T5: right; 118.8 ± 1.2 ms, left; 114.6 ± 2.6 ms. P < 0.05), greater shortening of effective refractory period (T4-T5: right; −3.6 ± 1.3%, left; −7.7 ± 1.8%. P < 0.05), a steeper maximum slope of restitution (T4-T5 base: right; 1.3 ± 0.2, left; 1.8 ± 0.2. P < 0.01. T4-T5 apex: right; 1.0 ± 0.2, left; 1.6 ± 0.3. P < 0.05) and a greater decrease in ventricular fibrillation threshold (T4-T5: right; −22.3 ± 6.8%, left;-39.0 ± 1.7%), with dominant effects at caudal levels (T4-T6). ConclusionsThe preganglionic sympathetic efferent axons show functionally distinct pathways to the heart. The caudal segments (T4-T6) of the left sympathetic chain had a greater potential for arrhythmia generation and hence could pose a target for more focused clinical treatments for impairments in cardiac function.

Laterality in direct and indirect inotropic effects of sympathetic stimulation in isolated canine heart.

Although sympathetic nerve stimulation is known to increase ventricular contractility, concomitant increases in heart rate (HR) make it difficult to separate its direct inotropic effect from indirect inotropic effect through a force-frequency mechanism. We stimulated the stellate ganglia in 8 isolated canine hearts with functional sympathetic nerves. Right sympathetic stimulation at 10 Hz increased ventricular end-systolic elastance (E(es)) by 95.7 +/- 7.5% (p < 0.001) and HR by 32.5 +/- 4.2% (p < 0.05). In contrast, left sympathetic stimulation at 10 Hz increased E(es) by 70.7 +/- 6.5% (p < 0.001) without significant changes in HR. Preventing the chronotropic response by fixed-rate pacing attenuated the E(es) response to right sympathetic stimulation at 5 Hz (52.0 +/- 5.1 vs. 22.8 +/- 2.8%, p < 0.001), but not to left sympathetic stimulation at 5 Hz (54.5 +/- 3.4 vs. 53.3 +/- 2.2%, NS). In the isolated canine heart, the right sympathetic nerve affected E(es) by both the direct inotropic effect and the indirect HR-dependent inotropic effect. In contrast, the left sympathetic nerve regulated E(es) primarily by its direct inotropic effect.

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

Release of vasoactive intestinal peptide and neuropeptide Y from canine heart

The effects of right cervical vagal and left sympathetic stimulation on release of immunoreactive vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) into cardiac venous and lymphatic effluent was tested in 11 anesthetized adult mongrel dogs. After stimulation of the right cervical vagus (1 ms, 20 Hz, 5 V) for 3 min, VIP output in lymphatic effluent was significantly increased at 1.90 +/- 0.56 pg/min compared with control of 0.90 +/- 0.42 pg/min. NPY output in lymphatic effluent and VIP and NPY release into coronary venous effluent, as measured by the arterial-coronary sinus concentration difference, were not changed. After stimulation of the ansae of the left sympathetic ganglion (1 ms, 10 Hz, 5 V) for 3 min, NPY output in lymphatic effluent was significantly increased at 4.72 +/- 1.58 pg/min compared with a control of 0.73 +/- 0.66 pg/min. VIP output in lymphatic effluent was not changed. VIP arterial-coronary sinus concentration difference decreased slightly but significantly, and NPY arterial-coronary sinus concentration difference decreased markedly after left sympathetic stimulation. In three additional dogs in which coronary sinus blood flow was measured, NPY overflow during left sympathetic stimulation increased from 28.2 +/- 23.5 to 129.6 +/- 212.7 pg/min. Thus VIP and NPY release from the canine heart can be evoked by right cervical vagal and left sympathetic stimulation, respectively. VIP and NPY may play a role as cardiac noncholinergic-nonadrenergic neurotransmitters.

Attenuation of the cardiac effects of cocaine by dizocilpine.

Cocaine abuse causes autonomic and cardiovascular effects that may be life threatening. Attenuation of cocaine-induced seizures has been produced by the noncompetitive antagonist of the N-methyl-D-aspartate receptor channel complex, dizocilpine. The purpose of the present study was, first, to determine effects of dizocilpine on the incidence of pacing-induced ventricular arrhythmias and, second, to evaluate the effects of dizocilpine on cocaine-induced depression of sympathetic efferent activity to the heart. Adult dogs were anesthetized and instrumented for blood pressure and an electrocardiogram. After vagotomy and thoracotomy, electrodes and strain gauges were sutured onto the right atrium and ventricle. A left thoracic sympathetic efferent nerve was isolated and stimulated for analysis of the innervation pattern. Arrhythmias were induced with programmed electrical stimulation of the heart before and during left cardiac sympathetic efferent nerve stimulation. The control incidence of induced arrhythmias was only 2%, which increased to 21% during left sympathetic stimulation. Cocaine (2 mg/kg iv) significantly increased these to 11 and 42%, respectively. Dizocilpine (0.5 mg/kg iv) reduced the incidence of induced ventricular arrhythmias to 2% with cocaine (P < 0.05) and to 19% with cocaine and left sympathetic stimulation (P < 0.01). One or two sympathetic efferent cardiac nerves were stimulated to evaluate innervation patterns. These nerves were severed and prepared for recording multifiber efferent neurograms. Nerve traffic was analyzed by counting positive spikes for 15 s. Control activities were normalized at 100%. Within 6 min, cocaine (2 mg/kg iv) reduced the sympathetic efferent activity to 83 +/- 4% of control (n = 14 nerves).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary sinus norepinephrine concentrations during ventricular tachycardia induced by left stellate ganglion stimulation in dogs.

Coronary sinus catecholamine overflow was measured in open-chest dogs, anesthetized with sodium thiopental and alpha-chloralose, during left sympathetic stimulation. Uniform ventricular tachycardias were induced in 9 out of 16 dogs during either left stellate ganglion or left ventrolateral cardiac nerve stimulations. Significant increases in norepinephrine (8.1 ng/mL, plasma) and epinephrine (0.19 ng/mL, plasma) overflows were obtained after 30 and 90 s of stimulation, respectively. Maximum norepinephrine overflow was significantly higher in dogs with ventricular tachycardia than in those without it (16.0 vs. 7.4 ng/mL, p less than 0.05). This suggests that the induction of ventricular tachycardia in the normal myocardium is related to the amount of local secretion of norepinephrine during nerve stimulation.

T Wave Amplitude as a Quantitative Index of Regional Myocardial Sympathetic Responsiveness

Alterations in T wave morphology have been quantitated in seven open chest anesthetized dogs by simultaneous recording of electrograms from 10 epicardial sites across the anterior left ventricular wall under basal conditions, following left sympathetic stimulation (LSS) at 2, 4, 8, 12, and 16 Hz and during noradrenaline infusions (NAI) of 0.125, 0.25, 0.50, and 1.0 micrograms/kg/min. Overdrive atrial pacing at 175 beats/min was employed and rate of rise of left ventricular pressure (dP/dt) monitored. Linear log dose-response relationships were found between both peak T amplitude and left ventricular dP/dt for NAI between 0.125 and 0.50 micrograms/kg/min (peak T wave amplitude 4.0 +/- 0.9 to 1.4 +/- 0.7 mV). Following LSS, T wave amplitude responses were highly variable both between animals and between electrode sites in individual studies. A linear log dose-response relationship was found at stimulation frequencies between 8 and 16 Hz (T amplitude 3.9 +/- 1.4 to 1.8 +/- 1.2 mV). Changes in QT interval were minor and inconsistent. It is concluded that changes in peak T wave amplitude may provide a useful index of regional myocardial sympathetic responsiveness following NAI, but are more variable following LSS.

Could redistribution of flow promote genesis of early ischaemic arrhythmias following left sympathetic stimulation?

Could redistribution of flow promote genesis of early ischaemic arrhythmias following left sympathetic stimulation?

Intra-SA-nodal pacemaker shifts induced by autonomic nerve stimulation in the dog.

Pacemaker shifts in the canine heart were inferred during stimulation of thoracic cardiac nerves and following norepinephrine from changes in the initial site of activation of bipolar electrodes sutured over the rostral, middle, and caudal regions of the sinus node, over the internodal pathways, and His bundle. During control periods, pacemaker activity was localized within the sinoatrial (SA) node 87% of the time, with the middle electrode most frequently showing initial activation. Stimulation of the right-sympathetic nerves enhanced sinus node pacemaker dominance, shifting it rostrally within the node. Right-vagal stimulation shifted the pacemaker caudally within the SA node, to nonnodal sites, and to the lower atrioventricular node and His bundle. Left-sympathetic stimulation shifted the pacemaker caudally within the sinus node and enhanced pacemaker activity in the vicinity of the internodal pathway electrodes and His bundle. Dispersion of pacemaker activity was particularly apparent during stimulation of the ventrolateral cervical cardiac nerve. Stimulation of the left-vagal nerves produced effects similar to those of the left-sympathetic nerves. Norepinephrine enhanced pacemaker activity particularly in the rostral region of the sinus node. Slight shifts in pacemaker activity within the sinus node produced changes in pattern of atrial excitation.

Comparison of left and right sympathetic stimulations on the phasic coronary flow.

In thirteen anesthetized open chest dogs the left sympathetic stimulation decreased the systolic flow by augmented myocardial contractility and by sympathetic coronary vasoconstriction, while the diastolic flow was increased with the elevation of blood pressure. Both systolic and diastolic flows were increased after the stimulation suggesting metabolic vasodilatation. Coronary vasoconstriction and vasodilatation revealed parallel changes in systolic and diastolic flows. The right sympathetic stimulation induced marked tachycardia and decreased systolic and diastolic flows at the initial phase. Both systolic and diastolic flows were increased during the right sympathetic stimulation, indicating less positive inotropic effcet and less remarkable coronary vasoconstriction as well as the marked metabolic response to tachycardia.