piperidines and Paraplegia

Heartburn, bloating, and abdominal discomfort are common problems in patients with spinal cord injury but, despite its clinical significance, little is known about the gastrointestinal effects of spinal transections. To address the potential gastrointestinal pathophysiology of spinal cord injury, we measured mouth-to-cecum transit time (MCTT) in seven subjects with paraplegia and seven with quadriplegia. Gastric emptying was studied in six subjects with quadriplegia. MCTT was significantly prolonged in patients with quadriplegia, an abnormality corrected by the administration of cisapride. Patients with paraplegia, in contrast to those with quadriplegia, have normal mouth-to-cecum transit time. In addition, patients with quadriplegia had neither a prolonged gastric emptying time nor a change in gastric emptying time, with cisapride. Changes in gastrointestinal transit after spinal cord injury and the improvement of mouth-to-cecum transit time in subjects with quadriplegia, but not in those with paraplegia, may be explained by an imbalance between parasympathetic and sympathetic outflows to the gastrointestinal tract in this group of subjects.

Topics: Adult; Aged; Cisapride; Double-Blind Method; Gastric Emptying; Gastrointestinal Transit; Humans; Male; Middle Aged; Paraplegia; Piperidines; Quadriplegia; Serotonin Antagonists; Spinal Cord Injuries

Topics: Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Arteriovenous Malformations; Edema; Femoral Vein; Humans; Male; Methyl Ethers; Neuromuscular Nondepolarizing Agents; Paraplegia; Piperidines; Radial Artery; Remifentanil; Sevoflurane; Thiopental; Thorax; Upper Extremity; Vecuronium Bromide; Young Adult

Spontaneous spinal-epidural hematoma is uncommon and rare during pregnancy. We were presented with a 31-year-old patient who developed back pain with lower extremity paralysis at 36 weeks of gestation. A magnetic resonance imaging scan demonstrated an acute spinal-epidural hematoma and therefore, an emergency cesarean delivery was performed followed by hemilaminectomy with hematoma removal. Anesthesia was initiated with a volatile-based technique which, following delivery of the baby, was changed to target-controlled infusions of propofol and remifentanil. Postoperatively, dopamine was infused to maintain the blood pressure within the high-normal range to optimize spinal cord perfusion. Successful anesthetic and postoperative management is described together with a review of the literature.

Topics: Adult; Androstanols; Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Back Pain; Cesarean Section; Dopamine; Emergency Treatment; Female; Follow-Up Studies; Hematoma, Epidural, Spinal; Humans; Laminectomy; Magnetic Resonance Imaging; Methyl Ethers; Neuromuscular Nondepolarizing Agents; Paraplegia; Piperidines; Pregnancy; Pregnancy Complications; Propofol; Remifentanil; Rocuronium; Sevoflurane; Treatment Outcome

Centrally expressed 5-HT3 receptors (5-HTR3) are well known for their role in wakefulness, cognition, and nociception. However, clear evidence of their participation in motor control is still lacking despite specific 5-HTR3 expression in hindlimb motor areas of the spinal cord (i.e., lumbar laminae VII-IX). Here, we studied the acute effects of 4-amino-(6-chloro-2-pyridyl)-1-piperidine hydrochloride (SR 57227A), a potent and selective 5-HTR3 agonist, on hindlimb movement generation in complete paraplegic mice. The induced movements were assessed in open-field, air-stepping, and treadmill conditions using a combination of qualitative and quantitative methods. The results revealed that SR 57227A (1-4 mg/kg ip) produced hindlimb movements corresponding to scores ranging from 1 to 5 on the motor scales of Basso, Beattie, and Bresnahan and of Antri, Orsal, and Barthe. Additional analyses revealed that one-third of the movements displayed on a treadmill were "locomotor-like" (i.e., bilateral alternation), whereas only nonlocomotor movements were observed in the other testing conditions suggesting a task-dependent contribution of peripheral afferent inputs to these effects. Locomotor-like movements could also be induced in open field and air stepping if SR 57227A was combined with subthreshold doses of 5-carboxytryptamine (5-HT1A/7 receptor agonist), suggesting synergistic actions of these drugs on central neurons. These results demonstrate that 5-HTR3 activation can induce motor activity and, under some conditions, rhythmic locomotor-like movements in the hindlimbs of paraplegic mice providing evidence of an unsuspected role for this receptor subtype in hindlimb motor control.

Topics: Animals; Biological Clocks; Hindlimb; Injections, Intraperitoneal; Ion Channels; Locomotion; Male; Mice; Muscle Contraction; Muscle, Skeletal; Paraplegia; Piperidines; Receptors, Serotonin, 5-HT3; Serotonin Receptor Agonists; Spinal Cord Injuries

Chronic constipation in patients with spinal cord injury (SCI) has significant impact on quality of life. To measure baseline clinical functioning, colonic transit time and anorectal manometry and the effect of cisapride on these clinical and physiological parameters, we studied 12 SCI patients. Patients initially received baseline clinical scoring, measurement of colonic transit time and anorectal manometry. Patients then received cisapride 20 mg orally three times each day. After one and three months of cisapride therapy, all measurements were repeated. The mean duration cisapride treatment was 5.2 months. Six of 12 (50 percent) reported that symptoms of constipation improved. No patient had worsening of symptoms. Prior to cisapride treatment, 23 percent of patients passed colonic transit markers by day five and 57 percent by day seven; baseline anal manometry revealed variable resting and squeeze pressures. After treatment, 33 percent of patients passed their colonic transit markers by day five and 71 percent by day seven. Six of 12 (50 percent) demonstrated a 10 percent or more increase in resting anal canal pressures. We conclude that about 50 percent of SCI patients have subjective improvement in constipation after cisapride therapy. Cisapride appears to improve both colonic and anorectal function.

Topics: Cisapride; Colostomy; Constipation; Gastrointestinal Motility; Gastrointestinal Transit; Humans; Manometry; Paraplegia; Parasympathomimetics; Piperidines; Quadriplegia; Spinal Cord Injuries

Paraplegic patients have intractable constipation associated with prolonged colonic transit time. The agent Cisapride significantly reduced the colonic transit time from 7.7 days to 5.1 days. It also improved the intraluminal tone in the rectum, resulting in a significant reduction in maximal rectal capacity from 305.8 ml to 224.3 ml. There was a reduction in residual urine volume from 51.5 ml to 27.7 ml. The increased number of stools containing transit markers showed that intraluminal mixing was increased by cisapride. Faecal water remained unchanged. A side effect was retention of urine in one subject after sudden withdrawal of the drug but this was avoided by its gradual reduction over 2 days.

Topics: Administration, Oral; Adult; Anal Canal; Chronic Disease; Cisapride; Constipation; Female; Gastrointestinal Transit; Humans; Male; Middle Aged; Paraplegia; Piperidines; Rectum; Urination