Generalized convulsive seizures are associated with ketamine anesthesia in a rhesus macaque (<i>Macaca mulatta</i>) undergoing urodynamic studies and transcutaneous spinal cord stimulation

Gad, Parag; Salyards, Gregory W; Garzel, Laura; Christe, Kari L.; Edgerton, V. Reggie; Havton, Leif A.

doi:10.1111/jmp.12287

Cited by 2 publications

(4 citation statements)

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“…In the present study, we have investigated the potential utility of TSCS for neuro-urological applications. The studies were performed in adult rhesus macaques, a clinically relevant and translational research model for studies of pelvic organ physiology, reflex micturition and LUT function (Chang and Havton, 2016;Gad et al, 2017;Gad et al, 2018aGad et al, , 2018bGad et al, , 2018c.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

Havton

Christe

Edgerton

et al. 2019

Experimental Neurology

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Dysfunction of the lower urinary tract (LUT) is prevalent in neurological disorders, including multiple sclerosis, stroke, spinal cord injury and neurodegenerative conditions. Common symptoms include urgency, incontinence, and urinary retention. Recent advances in neuromodulation have resulted in improved treatments for overactive bladder symptoms of urgency, frequency, and nocturia. However, there are presently no treatments available for the induction of voiding to overcome urinary retention. We demonstrate that transcutaneous spinal cord stimulation (TSCS), a non-invasive intervention, applied over the thoracolumbar spine in neurologically intact rhesus macaques can activate the LUT, including activation of the bladder detrusor muscle, the urethral sphincter and pelvic floor muscles. Urodynamic studies show improved voiding efficiency and decreased post-voiding residual volumes in the bladder, while maintaining coordinated activity in the detrusor and sphincter with physiologic detrusor peak pressure, contraction duration, and urine flow rate remaining unchanged. We conclude that TSCS may represent a novel approach to activate the LUT and enable voiding in select neurological conditions.

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Section: Introductionmentioning

confidence: 99%

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

Havton

Christe

Edgerton

et al. 2019

Experimental Neurology

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“…Concurrent urodynamic recordings and EMG tracings from multiple muscle groups showed that involuntary muscle activity was rhythmic and synchronized, suggesting that the neuromuscular component of a ketamine reaction has an origin in the central nervous system (CNS) and not in the peripheral nervous tissues or at the neuromuscular junction. Prior studies have demonstrated a similarly coordinated onset of neuromuscular activity across multiple recording sites in rhesus macaques experiencing convulsive seizures associated with ketamine sedation [ 11 , 32 ]. At this time, however, it remains unclear whether the presence of ketamine-associated neuromuscular reactivity may suggest an increased risk for ketamine-associated seizures in primates.…”

Section: Discussionmentioning

confidence: 99%

“…The use of ketamine as a single agent was demonstrated to be superior to flurane anesthesia for cystometrogram recordings in rhesus macaques, and ketamine has been suggested as a suitable agent for studies on lower urinary tract function [9]. When ketamine is administered by intravenous constant rate infusion (CRI) in rhesus macaques, a stable and light plane of sedation may be achieved with relative sparing of spinal reflexes and neuromuscular function, thereby allowing for both cystometrogram and external sphincter electromyography (EMG) studies in male and female subjects [10,11]. However, the effects of aging on subject sensitivity to ketamine anesthesia has been largely unexplored in non-human primates, especially with regards to spinal reflex actions.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we investigated the effects of aging on the prevalence of ketamine-associated neuromuscular reactivity and ketamine infusion rate to maintain a light plane of sedation and immobilization. The present study represents an expansion of scope of our ongoing physiologic and functional mapping studies of the lower urinary tract and pelvic floor in neurologically intact rhesus macaques and during aging [10][11][12][13]. Comprehensive urodynamic and EMG studies of the pelvic floor were analyzed to provide insights about possible underlying mechanisms for neuromuscular reactivity during ketamine exposures.…”

Section: Introductionmentioning

confidence: 99%

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Ketamine-induced neuromuscular reactivity is associated with aging in female rhesus macaques

et al. 2020

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Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized. Urodynamic recordings and electromyography (EMG) studies were performed in aged (>20 years old) and adult (3.9-14.9 years old) female rhesus macaques under an equal and light plane of sedation by constant rate infusion (CRI) of ketamine. A total of 4 of 41 adult subjects (9.7%) showed clinical signs of ketamine-induced abnormal neuromuscular reactivity, whereas a larger portion of 14 of 26 aged subjects showed similar ketamine-induced neuromuscular reactivity (53.8%; P< 0.001). The ketamine CRI rate was 19.8±0.9 mg/kg/h in adults and lower in aged subjects at 16.5±1.4 mg/kg/h (P<0.05). The ketamine CRI rate was negatively correlated with age (r =-0.30, P<0.05, n = 64). The incidence of ketamine reactivity or CRI rate was not different between aged pre-and post-menopausal females. EMG recordings during neuromuscular reactivity showed coordinated activation of multiple muscles, suggesting a central nervous system (CNS) mechanism for ketamine-associated neuromuscular reactivity. The incidence of ketamine-induced neuromuscular reactivity is age related but not affected by the estrous cycle in female rhesus macaques. A coordinated activation of multiple muscles, innervated by different peripheral nerves, suggests that ketamine-induced neuromuscular reactivity originates in the CNS.

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Generalized convulsive seizures are associated with ketamine anesthesia in a rhesus macaque (Macaca mulatta) undergoing urodynamic studies and transcutaneous spinal cord stimulation

Cited by 2 publications

References 10 publications

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

Noninvasive spinal neuromodulation to map and augment lower urinary tract function in rhesus macaques

Ketamine-induced neuromuscular reactivity is associated with aging in female rhesus macaques

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