Abstract 036: The Role Of Spinal Modulation On The Ventricular Electrophysiology In A Porcine Model

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Wei Zhou ◽  
Kentaro Yamakawa ◽  
Olujimi Ajijola ◽  
Daigo Yagishita ◽  
Mariko Takemoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Ventricular Arrhythmias ◽  
Stellate Ganglion ◽  
Afferent Pathways ◽  
Beneficial Effects ◽  
Thoracic Epidural ◽  
Yorkshire Pigs ◽  
Efferent Pathways ◽  
Intact Roots

Background: Enhanced cardiac sympathetic tone has been associated with ventricular arrhythmias and sudden cardiac death. The spinal cord is an important integrative region of afferent and efferent pathways that participate in cardiovascular regulation. The purpose of this study is to investigate the role of spinal processing of cardiac afferent information on ventricular electrophysiology during cardiac sympathoexcitation. Methods: Female Yorkshire pigs (n=5) underwent surgical exposure of the heart and left stellate ganglion (LSG) through thoractomy as well as the dorsal and ventral roots of the spinal cord through laminectomy. A 56-electrode sock was placed over the ventricles to record epicardial electrograms. Animals underwent LSG stimulation in intact, after dorsal root transaction (DRTx), and followed by ventral root transaction (DVRTx). Activation recovery intervals (ARIs) were measured at each electrode before and during LSG stimulation. Results: With intact roots LSG stimulation resulted in significant global ARI shortening by 12.9% (p<0.05). After DRTx, mean global ARI shortened by 7.2%. LSG stimulation after DRTx and DVRTx resulted in greater ARI shortening compared to LSG stimulation with intact roots (21.5 and 18.4 vs 12.9%, p<0.05, see figure 1 below). ARI shortened more during LSG stimulation after DRTx than that after DVRTx (21.5 vs. 18.4%, p<0.05). Conclusion: Spinal afferent pathways play an inhibitory role in sympathoexcitation of ventricle induced by LSG stimulation. This finding provides insight into the mechanism underlying the beneficial effects of thoracic epidural anesthesia in reducing ventricular arrhythmias.

scholarly journals Role of Adenosine Kinase In Sphingosine-1-Phosphate Receptor 1-Induced Mechano-Hypersensitivities

2021 ◽  
Author(s):  
Filomena Lauro ◽  
Luigino Antonio Giancotti ◽  
Grant Kolar ◽  
Caron Harada ◽  
Taylor A Harmon ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Adenosine Kinase ◽  
Receptor Subtype ◽  
Beneficial Effects ◽  
Pyrin Domain ◽  
Sphingosine 1 Phosphate ◽  
Expression Activity ◽  
Receptor Family ◽  
Adenosine Signaling

Abstract Emerging evidence implicates the sphingosine-1-phosphate (S1P) receptor subtype 1 (S1PR1) in the development of neuropathic pain. Continued investigation of the signaling pathways downstream of S1PR1 are needed to support development of S1PR1 antagonists. In rodents, intrathecal (i.th.) injection of SEW2871, a selective S1PR1 agonist, activates the nod-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, increases interleukin-1β (IL-1β) and causes behavioral hypersensitivity. I.th. injection of a IL-1β receptor antagonist blocks SEW2871-induced hypersensitivity, suggesting that IL-1β contributes to S1PR1’s actions. Interestingly, previous studies have suggested that IL-1β increases the expression/activity of adenosine kinase (ADK), a key regulator of adenosine signaling at its receptors (ARs). Increased ADK expression reduces adenosine signaling whereas inhibiting ADK restores the action of adenosine. Here, we show that SEW287-induced behavioral hypersensitivity is associated with increased expression of ADK in astrocytes of the dorsal horn of the spinal cord (DH-SC). Moreover, the ADK inhibitor, ABT702, blocks SEW2871-induced hypersensitivity. These findings link ADK activation to S1PR1. If SEW2871-induced pain is mediated by IL-1β, which in turn activates ADK and leads to mechano-allodynia, then blocking ADK should attenuate IL-1β effects. In support of this idea, recombinant rat (rrIL-1β)-induced allodynia was blocked by at least 90% with ABT702, functionally linking ADK to IL-1β. Moreover, the selective A3AR antagonist, MRS1523, prevents the ability of ABT702 to block SEW2871 and IL-1β-induced allodynia, implicating A3AR signaling in the beneficial effects exerted by ABT702. Our findings provide novel mechanistic insight into how S1PR1 signaling in the spinal cord produces hypersensitivity through IL1-b and ADK activation.

scholarly journals Central vs. peripheral neuraxial sympathetic control of porcine ventricular electrophysiology

2016 ◽  
Vol 310 (5) ◽  
pp. R414-R421 ◽  
Author(s):  
Kentaro Yamakawa ◽  
Kimberly Howard-Quijano ◽  
Wei Zhou ◽  
Pradeep Rajendran ◽  
Daigo Yagishita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Stellate Ganglion ◽  
Afferent Input ◽  
Ventral Root ◽  
Spinal Root ◽  
Sympathetic Control ◽  
Thoracic Spinal ◽  
Yorkshire Pigs ◽  
Heart Electrophysiology

Sympathoexcitation is associated with ventricular arrhythmogenesis. The aim of this study was to determine the role of thoracic dorsal root afferent neural inputs to the spinal cord in modulating ventricular sympathetic control of normal heart electrophysiology. We hypothesize that dorsal root afferent input tonically modulates basal and evoked efferent sympathetic control of the heart. A 56-electrode sock placed on the epicardial ventricle in anesthetized Yorkshire pigs ( n = 17) recorded electrophysiological function, as well as activation recovery interval (ARI) and dispersion in ARI, at baseline conditions and during stellate ganglion electrical stimulation. Measures were compared between intact states and sequential unilateral T1–T4 dorsal root transection (DRTx), ipsilateral ventral root transection (VRTx), and contralateral dorsal and ventral root transections (DVRTx). Left or right DRTx decreased global basal ARI [Lt.DRTx: 369 ± 12 to 319 ± 13 ms ( P < 0.01) and Rt.DRTx: 388 ± 19 to 356 ± 15 ms ( P < 0.01)]. Subsequent unilateral VRTx followed by contralateral DRx+VRTx induced no further change. In intact states, left and right stellate ganglion stimulation shortened ARIs (6 ± 2% vs. 17 ± 3%), while increasing dispersion (+139% vs. +88%). There was no difference in magnitude of ARI or dispersion change with stellate stimulation following spinal root transections. Interruption of thoracic spinal afferent signaling results in enhanced basal cardiac sympathoexcitability without diminishing the sympathetic response to stellate ganglion stimulation. This suggests spinal dorsal root transection releases spinal cord-mediated tonic inhibitory control of efferent sympathetic tone, while maintaining intrathoracic cardiocentric neural networks.

scholarly journals Supraspinal Mechanisms of Spinal Cord Stimulation for Modulation of Pain

2019 ◽  
Vol 130 (4) ◽  
pp. 651-665 ◽  
Author(s):  
Eellan Sivanesan ◽  
Dermot P. Maher ◽  
Srinivasa N. Raja ◽  
Bengt Linderoth ◽  
Yun Guan
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Spinal Cord Stimulation ◽  
Pain Treatment ◽  
Neurologic Diseases ◽  
Beneficial Effects ◽  
Chronic Pain Treatment ◽  
Sites Of Action ◽  
Pain Inhibition

Abstract The field of spinal cord stimulation is expanding rapidly, with new waveform paradigms asserting supraspinal sites of action. The scope of treatment applications is also broadening from chronic pain to include cerebral ischemia, dystonia, tremor, multiple sclerosis, Parkinson disease, neuropsychiatric disorders, memory, addiction, cognitive function, and other neurologic diseases. The role of neurostimulation as an alternative strategy to opioids for chronic pain treatment is under robust discussion in both scientific and public forums. An understanding of the supraspinal mechanisms underlying the beneficial effects of spinal cord stimulation will aid in the appropriate application and development of optimal stimulation strategies for modulating pain signaling pathways. In this review, the authors focus on clinical and preclinical studies that indicate the role of supraspinal mechanisms in spinal cord stimulation–induced pain inhibition, and explore directions for future investigations.

scholarly journals Role of M2 and M3 Muscarinic Acetylcholine Receptor Subtypes in Activation of Bladder Afferent Pathways in Spinal Cord Injured Rats

Urology ◽  
2012 ◽  
Vol 79 (5) ◽  
pp. 1184.e15-1184.e20 ◽  
Author(s):  
Yoshihiro Matsumoto ◽  
Minoru Miyazato ◽  
Hitoshi Yokoyama ◽  
Masafumi Kita ◽  
Yoshihiko Hirao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Acetylcholine Receptor ◽  
Muscarinic Acetylcholine Receptor ◽  
Receptor Subtypes ◽  
Afferent Pathways ◽  
Muscarinic Acetylcholine ◽  
M3 Muscarinic Acetylcholine Receptor ◽  
Spinal Cord Injured

RESEARCH THE VALUE OF THE COMBINATION OF T WAVE ALTERNANS AND NT-PROBNT IN PREDICTING SUDDEN CARDIAC DEATH

2012 ◽  
pp. 74-83
Author(s):  
Anh Tien Hoang ◽  
Nhat Quang Nguyen
Keyword(s):  
Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Ventricular Arrhythmias ◽  
Healthy Person ◽  
Treadmill Test ◽  
T Wave ◽  
T Wave Alternans

Background: Decades of research now link TWA with inducible and spontaneous clinical ventricular arrhythmias. This bench-to-bedside foundation makes TWA, NT-ProBNP a very plausible index of susceptibility to ventricular arrythmia, and motivates the need to define optimal combination of TWA and NT-ProBNP in predicting ventricular arrythmia in myocardial infarction patients. We research this study with 2 targets: 1. To evaluate the role of TWA in predicting sudden cardiac death in myocardial infarction patients. 2. To evaluate the role of NT-ProBNP in predicting sudden cardiac death in myocardial infarction patients 3. Evaluate the role of the combined NT-ProBNP and TWA in predicting sudden cardiac death in myocardial infarction patients. Methods: Prospective study with follow up the mortality in 2 years: 71 chronic myocardial infarction patients admitted to hospital from 5/2009 to 5/20011 and 50 healthy person was done treadmill test to caculate TWA; ECG, echocardiography, NT-ProBNP. Results: Cut-off point of NT-ProBNP in predicting sudden cardiac death is 3168 pg/ml; AUC = 0,86 (95% CI: 0,72 - 0,91); Cut-off point of TWA in predicting sudden cardiac death is 107 µV; AUC = 0,81 (95% CI: 0,69 - 0,87); NT-ProBNP can predict sudden cardiac death with OR= 7,26 (p<0,01); TWA can predict sudden cardiac death with OR= 8,45 (p<0,01). The combined NT-ProBNP and TWA in predicting ventricular arrythmia in heart failure patients: OR= 17,91 (p<0,001). Conclusions: The combined NT-ProBNP and TWA have the best predict value of sudden cardiac death in myocardial infarction patients, compare to NT-ProBNP or TWA alone

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