4-AMINOPYRIDINE IMPROVES PULMONARY-FUNCTION IN QUADRIPLEGIC HUMANS WITH LONGSTANDING SPINAL-CORD INJURY

Study Objective. To test the hypothesis that 4-aminopyridine (4-AP) mi ght cause clinically evident improvement in pulmonary function in huma ns with chronic spinal cord injury (chronic SCT). Design. Balanced, op en-label study with subjects consecutively enrolled. Setting. Spinal C ord Injury Service, university-affiliated tertiary level care Departme nt of Veterans Affairs Medical Center. Patients. Seventeen healthy men and women suffering from traumatic SCI (11 quadriplegic, 6 paraplegic patients) for more than 1 year. Interventions. Each subject was given a single dose of 4-AP 10 mg orally in an immediate-release formulatio n. Measurements and Main 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 pre ssure (MEP) that persisted for at least 12 hours were demonstrated in quadriplegic patients beginning 6 hours after 4-AP administration. Tes ts of pulmonary function that demonstrated statistically significant i ncreases at any time were also numerically, if not statistically, incr eased at 24 hours compared with pretreatment values obtained in 4-AP-n aive subjects. Conclusions. The administration of a single dose of an immediate-release formulation of 4-AP to humans with longstanding, tra umatic quadriplegia is associated with sustained, clinically meaningfu l, and statistically significant improvements in pulmonary function. W e suggest that the administration of 4-AP may have a salutary effect i n patients suffering from SCI and appears to be associated with potent ially clinically significant reductions in the pathophysiologic pulmon ary sequelae of SCI.