Complete cervical or thoracic spinal cord transections delay gastric emptying and gastrointestinal transit of liquid in awake rats

Gondim, Francisco de Assis Aquino; Alencar, Hamilton Menezes Piancó de; Rodrigues, Cleonísio Leite; Graça, José Ronaldo Vasconcelos da; Santos, Armênio Aguiar dos; Rola, Francisco H.

doi:10.1038/sj.sc.3100923

Cited by 30 publications

(29 citation statements)

References 12 publications

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“…Hence, it appears that hemodynamic status has a major role in drug bioavailability changes observed after SCI. On the other hand, there is also evidence that SCI diminishes gastrointestinal motility, 4,19,20 leading to a slow gastric emptying that has been suggested to result in a reduced drug absorption at the duodenum. 4,[7][8][9][10]12 It is notable that the effect of SCI on absorption is of such magnitude that it not only compensates for reduced clearance, but also overrides it.…”

Section: Discussionmentioning

confidence: 99%

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

et al. 2012

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Study design: Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). Objective: To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Methods: Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg À1 of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Results: Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Conclusion: Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

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Section: Discussionmentioning

confidence: 99%

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

et al. 2012

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“…15) (138, 335). Mid-thoracic SCI models demonstrate inhibition of gastric emptying and duodenal transit (114,116,158,287). Noninvasive breath tests for gastric emptying that utilize […”

Section: Upper Gi Dysfunctionmentioning

confidence: 97%

“…After a nontoxic, nonabsorbable marker or dye is fed to the stomach, the movement of the substance can be detected by X-ray or spectrophotometry throughout transportation in the GI tract during the period of any time interval (114,117,285). Visualization techniques including video fluoroscopy and magnetic resonance imaging (MRI) have been used in clinical or experimental settings to visualize GI motility by detection of solid food labeled with tracer (62,202,295).…”

Section: Techniques For Functional Assessmentsmentioning

confidence: 99%

Autonomic Consequences of Spinal Cord Injury

Hou

Rabchevsky

2014

Comprehensive Physiology

179

112

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Spinal cord injury (SCI) results not only in motor and sensory deficits but also in autonomic dysfunctions. The disruption of connections between higher brain centers and the spinal cord, or the impaired autonomic nervous system itself, manifests a broad range of autonomic abnormalities. This includes compromised cardiovascular, respiratory, urinary, gastrointestinal, thermoregulatory, and sexual activities. These disabilities evoke potentially life-threatening symptoms that severely interfere with the daily living of those with SCI. In particular, high thoracic or cervical SCI often causes disordered hemodynamics due to deregulated sympathetic outflow. Episodic hypertension associated with autonomic dysreflexia develops as a result of massive sympathetic discharge often triggered by unpleasant visceral or sensory stimuli below the injury level. In the pelvic floor, bladder and urethral dysfunctions are classified according to upper motor neuron versus lower motor neuron injuries; this is dependent on the level of lesion. Most impairments of the lower urinary tract manifest in two interrelated complications: bladder storage and emptying. Inadequate or excessive detrusor and sphincter functions as well as detrusor-sphincter dyssynergia are examples of micturition abnormalities stemming from SCI. Gastrointestinal motility disorders in spinal cord injured-individuals are comprised of gastric dilation, delayed gastric emptying, and diminished propulsive transit along the entire gastrointestinal tract. As a critical consequence of SCI, neurogenic bowel dysfunction exhibits constipation and/or incontinence. Thus, it is essential to recognize neural mechanisms and pathophysiology underlying various complications of autonomic dysfunctions after SCI. This overview provides both vital information for better understanding these disorders and guides to pursue novel therapeutic approaches to alleviate secondary complications.

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“…Traditionally, numerous experimental methodologies, some with similarities to those found in clinical practice 1 , have been employed to directly quantify changes in GI contraction rate 2-5 , intraluminal pressure 6, 7 , or the GI transit of non-absorbable markers 8, 9 or stable isotopes 10-12 . Each of these techniques has unique advantages and disadvantages, which have been addressed previously in the literature.…”

Section: Introductionmentioning

confidence: 99%

Fabrication and Implantation of Miniature Dual-element Strain Gages for Measuring <em>In Vivo</em> Gastrointestinal Contractions in Rodents.

Holmes

Swartz

McLean

2014

JoVE

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Gastrointestinal dysfunction remains a major cause of morbidity and mortality. Indeed, gastrointestinal (GI) motility in health and disease remains an area of productive research with over 1,400 published animal studies in just the last 5 years. Numerous techniques have been developed for quantifying smooth muscle activity of the stomach, small intestine, and colon. In vitro and ex vivo techniques offer powerful tools for mechanistic studies of GI function, but outside the context of the integrated systems inherent to an intact organism. Typically, measuring in vivo smooth muscle contractions of the stomach has involved an anesthetized preparation coupled with the introduction of a surgically placed pressure sensor, a static pressure load such as a mildly inflated balloon or by distending the stomach with fluid under barostatically-controlled feedback. Yet many of these approaches present unique disadvantages regarding both the interpretation of results as well as applicability for in vivo use in conscious experimental animal models. The use of dual element strain gages that have been affixed to the serosal surface of the GI tract has offered numerous experimental advantages, which may continue to outweigh the disadvantages. Since these gages are not commercially available, this video presentation provides a detailed, step-by-step guide to the fabrication of the current design of these gages. The strain gage described in this protocol is a design for recording gastric motility in rats. This design has been modified for recording smooth muscle activity along the entire GI tract and requires only subtle variation in the overall fabrication. Representative data from the entire GI tract are included as well as discussion of analysis methods, data interpretation and presentation.

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Complete cervical or thoracic spinal cord transections delay gastric emptying and gastrointestinal transit of liquid in awake rats

Cited by 30 publications

References 12 publications

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction

Autonomic Consequences of Spinal Cord Injury

Fabrication and Implantation of Miniature Dual-element Strain Gages for Measuring <em>In Vivo</em> Gastrointestinal Contractions in Rodents.

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