Anatomical and functional organization of cardiac fibers in the porcine cervical vagus nerve allows spatially selective efferent neuromodulation.

Cardiac disease progression reflects the dynamic interaction between adversely remodeled neurohumoral control systems and an abnormal cardiac substrate. Vagal nerve stimulation (VNS) is an attractive neuromodulatory option to dampen this dynamic interaction; however, it is limited by off-target effects. Spatially-selective VNS (sVNS) offers a promising solution to induce cardioprotection while mitigating off-target effects by specifically targeting pre-ganglionic parasympathetic efferent cardiac fibers. This approach also has the potential to enhance therapeutic outcomes by eliminating time-consuming titration required for optimal VNS. Recent studies have demonstrated the independent modulation of breathing rate, heart rate, and laryngeal contraction through sVNS. However, the spatial organization of afferent and efferent cardiac-related fibers within the vagus nerve remains unexplored. By using trial-and-error sVNS in vivo in combination with ex vivo micro-computed tomography fascicle tracing, we show the significant spatial separation of cardiac afferent and efferent fibers (179±55° SD microCT, p<0.05 and 200±137° SD, p<0.05 sVNS - degrees of separation across a cross-section of nerve) at the mid-cervical level. We also show that cardiac afferent fibers are located in proximity to pulmonary fibers consistent with recent findings of cardiopulmonary convergent neurons and circuits. We demonstrate the ability of sVNS to selectively elicit desired scalable heart rate decrease without stimulating afferent-related reflexes. By elucidating the spatial organization of cardiac-related fibers within the vagus nerve, our findings pave the way for more targeted neuromodulation, thereby reducing off-target effects and eliminating the need for titration. This, in turn, will enhance the precision and efficacy of VNS therapy in treating cardiac pathology, allowing for improved therapeutic efficacy.

Ischemia-induced ventricular proarrhythmia and cardiovascular autonomic dysreflexia after cardioneuroablation.

BACKGROUND: Cardioneuroablation (CNA) is an attractive treatment of vasovagal syncope. Its long-term efficacy and safety remain unknown. OBJECTIVE: The purpose of this study was to develop a chronic porcine model of CNA to examine the susceptibility to ventricular tachyarrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]) and cardiac autonomic function after CNA. METHODS: A percutaneous CNA model was developed by ablation of left- and right-sided ganglionated plexi (n = 5), confirmed by histology. Reproducible bilateral vagal denervation was confirmed after CNA by extracardiac vagal nerve stimulation (VNS) and histology. Chronic studies included 16 pigs randomized to CNA (n = 8) and sham ablation (n = 8, Control). After 6 weeks, animals underwent hemodynamic studies, assessment of cardiac sympathetic and parasympathetic function using sympathetic chain stimulation and direct VNS, respectively, and proarrhythmic potential after left anterior descending (LAD) coronary artery ligation. RESULTS: After CNA, extracardiac VNS responses remained abolished for 6 weeks despite ganglia remaining in ablated ganglionated plexi. In the CNA group, direct VNS resulted in paradoxical increases in blood pressure, but not in sham-ablated animals (CNA group vs sham group: 8.36% ± 7.0% vs -4.83% ± 8.7%, respectively; P = .009). Left sympathetic chain stimulation (8 Hz) induced significant corrected QT interval prolongation in the CNA group vs the sham group (11.23% ± 4.0% vs 1.49% ± 4.0%, respectively; P < .001). VT/VF after LAD ligation was more prevalent and occurred earlier in the CNA group than in the control group (61.44 ± 73.7 seconds vs 245.11 ± 104.0 seconds, respectively; P = .002). CONCLUSION: Cardiac vagal denervation is maintained long-term after CNA in a porcine model. However, chronic CNA was associated with cardiovascular dysreflexia, diminished cardioprotective effects of cardiac vagal tone, and increased susceptibility to VT/VF in ischemia. These potential long-term negative effects of CNA suggest the need for rigorous clinical studies on CNA.

Vagal Nerve Stimulation Reduces Ventricular Arrhythmias and Mitigates Adverse Neural Cardiac Remodeling Post-Myocardial Infarction.

This study sought to evaluate the impact of chronic vagal nerve stimulation (cVNS) on cardiac and extracardiac neural structure/function after myocardial infarction (MI). Groups were control, MI, and MI + cVNS; cVNS was started 2 days post-MI. Terminal experiments were performed 6 weeks post-MI. MI impaired left ventricular mechanical function, evoked anisotropic electrical conduction, increased susceptibility to ventricular tachycardia and fibrillation, and altered neuronal and glial phenotypes in the stellate and dorsal root ganglia, including glial activation. cVNS improved cardiac mechanical function and reduced ventricular tachycardia/ventricular fibrillation post-MI, partly by stabilizing activation/repolarization in the border zone. MI-associated extracardiac neural remodeling, particularly glial activation, was mitigated with cVNS.

Analysis of Palatine and Adenoid Calcification in a Sample of the Lebanese Population Using Cone­Beam Computed Tomography Technology.

Objectives Tonsilloliths and adenoid calcifications are usually an incidental finding in radiologic studies. Several studies were done to evaluate the presence of tonsillar calcifications using different radiological techniques that include panoramic radiographs, computed tomography (CT), and cone-beam computed tomography (CBCT). These percentages varied in different populations and changed with the technique used. A CBCT is used to allow the visualization of the calcifications to make a better diagnosis. To the best of our knowledge, this is the first study conducted in Lebanon to study tonsillar and adenoid calcifications using CBCT. This study aims to assess the epidemiology and the demographic criteria of tonsilloliths and adenoid calcifications in a sample of the Lebanese population using the CBCT. Methods In this retrospective study, CBCT images of 125 patients attending a private clinic in Jbeil, Lebanon from May 2016 to July 2019 were selected. Images were evaluated by a maxillofacial radiologist. Adenoid and palatine calcifications were recorded. Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) software, version 21 (IBM SPSS Statistics, Armonk, NY, USA). The level of statistical significance was established at a p-value < 0.05. Results A total of 21 patients (17.35%) had palatine calcifications and two patients (1.65%) had adenoid calcifications. From those with tonsilloliths, 12 female patients (16.43%) and nine male patients (18.75%) had palatine calcifications. Moreover, one male (2.08%) and one female (1.36%) had adenoid calcifications. There was no statistically significant difference in the distribution of calcifications with respect to gender. There was a non-statistically significant difference in the mean age of the patients with respect to the distribution of palatine and adenoid calcifications. The pattern of palatine calcifications showed a statistically significant difference in various age groups. Palatine calcifications distribution, with respect to the side, were statistically significant. Conclusion The prevalence of tonsilloliths in our sample was found to be 17.35%. The high prevalence detected was due to the technique used, the CBCT, which ensured a more detailed examination. The distribution was not affected by gender and age. However, multiple patterns of calcification were identified in younger age groups as opposed to other studies. Moreover, adenoid calcifications were present in 1.65% of the sample.

The Infraorbital Foramen in a Sample of the Lebanese Population: A Radiographic Study.

Purpose The infraorbital foramen (IOF) is an important structure in the maxillofacial region through which important structures pass. Wide variability in the shape and location of the infraorbital foramen among different populations and ethnic groups is present. So we conducted this study to specify the IOF shape, the presence of accessory foramina, and the IOF location with respect to anatomic landmarks in the Lebanese population. Patients and method A cross-sectional retrospective study was conducted on cone-beam computed tomography (CBCT) scans of 105 Lebanese adult patients. Images were reviewed and the shape, diameter, and location of the IOF were recorded. The presence of an accessory foramen was also noted. Then, SPSS version 21 (IBM Corp., Armonk, NY, US) was used for the statistical analysis. Results Concerning the distances from the IOF to the anatomic landmarks, the distance from the IOF to the infraorbital margin measured 7.98 ± 1.41 mm, to the lateral nasal wall 10.61 ± 2.39 mm, and to the midline 24.71 ± 2.09 mm. When distances were compared, a statistical difference was only identified in the distance between the IOF and the lateral nasal wall (p=0.00), and the distance between the IOF and the middle of the face (p=0.016) between genders. For the shape of the IOF, 54.8% of the IOF were circular in shape, and this shape was the most common shape in females. An accessory foramen was present in 8.6% of the cases. Finally, the mean diameter of the foramina measured 3.71 ± 0.63 mm. Conclusion The IOF shows a lot of variability between different populations. Thus, the exact location should always be remembered during an infraorbital nerve (ION) block, during maxillofacial surgeries, and during esthetic procedures involving the facial region in order to prevent unnecessary complications.