| Nowadays, cardiovascular disease is a serious threat to human health, and has become number one cause of death in the worldwide, the number of death from cardiovascular disease each year is equal to the number of death from any other causes. According to World Health Organization statistics, in 2008, about 1,730 people died from cardiovascular disease, accounting for 30% of global deaths. It is predicted that by 2030 the number of death from cardiovascular disease will increase to 2330 million. Cardiovascular disease is expected to continue to be the single most important cause of death.Autonomic nervous system (ANS) is the peripheral nervous system of vertebrates, which is differentiated and developed from somatic nerves, functioning largely below the level of consciousness. It is composed primarily by efferent fibers, and dominated by the brain, but more independence, most autonomous functions are involuntary, so J. N. Langley named it autonomic nervous system in 1905, and it is also known as involuntary nervous system. The autonomic nervous system is mainly distributed to the organs, cardiovascular and glands, can regulate visceral and vascular smooth muscle, cardiac muscle and glandular activity and it affects heart rate, digestion, respiratory rate, salivation, perspiration, pupillary dilation, micturition (urination), and sexual arousal. The ANS is classically divided into two subsystems:the parasympathetic nervous system (PSNS) and sympathetic nervous system (SNS), which operate independently in some functions and interact co-operatively in others.Autonomic nervous system is closely related to the cardiovascular system, and many cardiovascular diseases are closely associated with autonomic dysfunction, such as hypertension, vasovagal syncope, heart failure and arrhythmias. This article mainly focuses on the effects and mechanisms of autonomic nervous system on vasovagal syncope and the regulation of blood pressure and heart rate.Clinical studies found that ganglionated plexi (GP) ablation prevented vasovagal syncope (V-VS). However, animal models which could provide mechanistic insights, are lacking. This article present an experimental model which closely simulates the clinical vasovagal syndrome (V-VS) manifesting the cardioinhibitory response and provide clues to potential procedures for preventing or terminating these clinical events and their sequelae.Experimental studies for many previous decades up to the present have utilized cervical vagosympathetic stimulation (VS) mainly for slowing the heart rate and prolonging atrioventricular conduction. A recent study demonstrated that tyrosine hydroxylase-positive sympathetic nerve fibers are invariably present in the cervical vagosympathetic trunks of normal dogs and are present in the periphery of the vagus nerves. Until now, the precise mechanism of action of VNS and how these efferent and afferent fibers, sympathetic and parasympathetic component work is still far from completely elucidated.In previous experimental studies we used endovascular electrical stimulation within the right and left pulmonary arteries to induce both parasympathetic as well as sympathetic effects. Recent studies have focused on the adventitial nerves overlying the renal arteries as playing an important role in the regulation of blood pressure as well as heart rate in patients undergoing renal artery denervation, primarily for the treatment drug resistant hypertension. Sympathetic innervation of an individual vascular structure that modulates the local and systemic vascular tone is not unique for the renal artery, other arteries like subclavian artery and carotid artery also have their sympathetic impact on cardiac function.Based on these three aspects, the following abstract will demonstrate the methods, results and conclusion of each aspects.Part 1 Experimental Model for Induction and Ablation of Vaso-Vagal SyncopePurposes:The purpose of the present study was to present an experimental model which closely simulates the clinical vasovagal syndrome (V-VS) manifesting the cardioinhibitory response and provide clues to potential procedures for preventing or terminating these clinical events and their sequelae.Methods:All animal studies were reviewed and approved by the Institutional Animal Care and Use Committee of the University of Oklahoma Health Sciences Center, In 16 pentobarbital anesthetized dogs, wire electrodes were inserted into the left and right cervical vagosympathetic trunks (LVG and RVG) for electrical stimulation. After thoracotomies, electrodes were attached to the anterior right GP (ARGP) (n=10) or superior left GP (SLGP) (n=6). We then determined the ventricular rate (VR) slowing by RVG, LVG, GP, RVG+LVG, RVG+GP, LVG+GP and RVG+LVG+GP simulation at the voltages required to induce sinus rate slowing by 50% or 2:1 atrioventricular block for each of the 3 modalities alone, or in combination. Lidocaine was then injected into the ARGP or SLGP to induce autonomic block. The above procedures were repeated after lidocaine injection. The ventricular rate (VR) slowing by RVG, LVG, ARGP, RVG+LVG, RVG+ARGP, LVG+ARGP and RVG+LVG+ARGP simulation after 3 hours rapid right atrial pacing.Results:Combined LVG+RVG stimulation induced a greater SR slowing (71.8 ± 12.9%) versus either RVG or LVG alone (both P<0.01). LVG+ARGP and RVG+ARGP induced 68.2 ±10.6% and 68.3±10.9% HR slowing, respectively, greater than either RVG, LVG or ARGP alone (both P<0.01). Combined RVG+LVG+ARGP stimulation induced the greatest slowing of (76.8±10.9%) with preceding asystolic periods of 3 to 7.3 seconds. Similarly, LVG+SLGP and RVG+SLGP stimulation induced 63.6±9.5% and 69.7±4.7% SR slowing (both P<0.01). The combination of RVG+LVG+SLGP induced 80.6±6.3% SR slowing with preceding asystolic periods of 3 to 6.3 seconds. Lidocaine was injected into the ARGP and SLGP in 5 cases, respectively, and both markedly attenuated the slowed SR and prevented ventricular asystole. After 3 hours rapid right atrial pacing, the capacity of ARGP stimulation to decrease the ventricular rate was attenuated.Conclusion:Combined stimulation of the vasosympathetic trunks and GP simulates the cardioinhibitory form of V-VS and has a common pathway mediated through the GP. This could possibly explain the efficacy of GP ablation in the treatment of syncope clinically.Part 2:Differential Cardiovascular Effects Induced by Electrical Stimulation of the Cervical Vagosympathetic Trunks in the Cephalad vs. Caudal DirectionPurposes:Vagosympathetic trunk stimulation (VS) is known to slow the sinus rate (SR) and AV conduction. In the present study, we compared the effects of VS in the cepahlad and caudal direction on SR and systolic and diastolic blood pressure (SBP; DBP).Methods:Sixteen adult mongrel dogs were anesthetized with Na-pentobarbital. The right and left cervical vagosympathetic trunks were dissected. A pair of wire electrodes was inserted in the cephalad end and another pair in the caudal end.Results:VS before vagotomy induced SR slowing and SBP/DBP reduction. After bilateral vagotomy, there was no significant change in SR with either right (RVS), left (LVS) or bilateral VS (BVS) by stimulating vagosympathetic trunks in the cephalad direction in 16 dogs. RVS, LVS and BVS all induced a significant increase in SBP (mmHg; RVS:181.1±38.1 vs 119.9±30.3, LVS:181.0±58.7 vs119.8±30.3, BVS 219.8±56.9 vs 119.8±30.3, all P<0.01 compared to baseline) and DBP (RVS:134.4± 30.2 vs 86.6±24.3; LVG:128.2±36.7 vs 86.6±24.3; bilateral VS:153.23±5.9 vs 86.6±24.3, P<0.01). After esmolol injection, the hypertensive response induced by cephalad VS was attenuated. After atropine injection, the hypertensive response induced by cephalad VS was not affected. The capacity of VNS in the cephalad direction to increase the blood pressure was attenuated after bilateral stellate ganlion ablation. After bilateral stellate ganglion, the capacity to increase BP of VNS in the cephalad direction was attenuated.Conclusion:These data suggest that caudal VS cause decreased HR and BP via vagal efferents to the heart, whereas cephalad VS significantly increased BP via a central neuro-circuitry whose end result is an increased sympathetic efferent outflow causing vascular constriction without affecting SR.Part 3 The Effects Induced by Stimulation of Adventitial Nerves on the Pulmonary Artery in The Dog HeartPurposes:The present study was undertaken to determine if electrical or neurohumoral stimulation on the adventitial surface of another vascular structures, namely, the pulmonary artery would have effects on blood pressure, heart rate and ventricular arrhythmias.Methods:The protocol was reviewed and approved by the Institutional Animal Care and Use Committee at the University of Oklahoma Health Sciences Center. Adult mongrel dogs were anesthetized with Na-pentobarbital,30 mg/kg, with additional 50 mg doses each hour to maintain a surgical level of anesthesia. A left-sided thoracotomy was performed at the 4th intercostal space. An electrode catheter was sutured to the left atrial appendage (LAA) for atrial pacing. A blunt-tip hook was used to guide a 20-pole adjustable Lasso catheter to go underneath the LPA, so as to make the catheter contact the entire Epicardial surface of LPA. A 40-msec train of high-frequency electrical stimulation (200 Hz,0.1 msec pulse duration,1-12 V) was applied at all of the bipolar pairs of the catheter around the LPA. Atrial pacing via a catheter attached to the left atrial appendage was coupled to the train of high-frequency stimulation (HFS). The coupling interval was adjusted so that the 40-msec train occurred immediately after the QRS interval of each cardiac cycle, that is, during the ventricular refractory period, in order not to directly stimulate the myocardial tissue adjacent to the LPA. A gauze pad (2.0 cm2) was moistened with 0.25,0.5 and l.Omg/ml epinephrine (Epi) and sequentially applied to the LPA. After each application, the effects on systemic BP, HR and VA was determined (n=11). At the end of the experiment we applied a formaldehyde moistened gauze pad on the LPA for 5 minutes, followed by the application of Epi (1.0 mg/ml) again on the LPA. The effects on BPs, HR were then determined and compared to those parameters obtained when Epi alone was applied to the LPA.Results:comparing of the hemodynamic effect in response to the application of various concentrations of Epi to the adventitial surface of the LPA, as the concentration increased, the effect was increment, the HR became progressively faster, the SBP progressively increased and the same for the DBP. The heart rates were unchanged compared to baseline (BS) values when electrical stimulation of LPA, but SBP increased significantly, DBP had the tendency to increase, but didn’t reach significance. At the end of the experiments, HR and BP were not changed from the baseline values when Epi (1 mg/ml) Application to the LPA after Formaldehyde Applied to the same site (.P>0.05), but there was a trend for a reduction of HR and BP when the values after formaldehyde were compared to those for the same concentration of Epi(P>0.05).Conclusion:Both electrical stimulation and sympathomimetics, e.g., epinephrine, topically applied to the adventitial surface of the left pulmonary artery induce marked increases in systemic BP. However, there were significant qualitative and quantitative differences in these responses. |
PDF Full Text Request