4-Aminopyridine improves pulmonary function in quadriplegic humans with longstanding spinal cord injury.
OBJECTIVE
To test the hypothesis that 4-aminopyridine (4-AP) might cause clinically evident improvement in pulmonary function in humans with chronic spinal cord injury (chronic SCI).


METHODS
Balanced, open-label study with subjects consecutively enrolled.


METHODS
Spinal Cord Injury Service, university-affiliated tertiary level care Department of Veterans Affairs Medical Center.


METHODS
Seventeen healthy men and women suffering from traumatic SCI (11 quadriplegic, 6 paraplegic patients) for more than 1 year.


METHODS
Each subject was given a single dose of 4-AP 10 mg orally in an immediate-release formulation.


RESULTS
Significant increases in mean values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) that persisted for at least 12 hours were demonstrated in quadriplegic patients beginning 6 hours after 4-AP administration. Tests of pulmonary function that demonstrated statistically significant increases at any time were also numerically, if not statistically, increased at 24 hours compared with pretreatment values obtained in 4-AP-naive subjects.


CONCLUSIONS
The administration of a single dose of an immediate-release formulation of 4-AP to humans with longstanding, traumatic quadriplegia is associated with sustained, clinically meaningful, and statistically significant improvements in pulmonary function. We suggest that the administration of 4-AP may have a salutary effect in patients suffering from SCI and appears to be associated with potentially clinically significant reductions in the pathophysiologic pulmonary sequelae of SCI.
Segal
J L
JL
Medicine Service, Department of Veterans Affairs Medical Center, Long Beach, CA 90822, USA.
Brunnemann
S R
SR
D015761:4-Aminopyridine / Q000627:therapeutic use*; D000328:Adult; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010264:Paraplegia / Q000209:etiology / Q000503:physiopathology; D026902:Potassium Channel Blockers; D011782:Quadriplegia / Q000209:etiology / Q000503:physiopathology*; D012129:Respiratory Function Tests; D012133:Respiratory Paralysis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000503:physiopathology*
D026902:Potassium Channel Blockers; D015761:4-Aminopyridine