4-aminopyridine influences heart rate variability in long-standing spinal cord injury.

Humans with traumatic spinal myelopathy exhibit intralesional conduction block and autonomic failure as pathophysiologic sequelae of their injury. Analysis of heart rate variability (HRV) provides a means of assessing changes in the function of the autonomic nervous system (ANS) and the cardiac sequelae of injury. Thirteen patients with long-standing spinal cord injury (SCI) and 13 able-bodied controls were studied. Each patient received a single 10-mg dose of an immediate release (IR) formulation of 4-aminopyridine (4-AP). Twenty-four hour heart rate (HR) and HRV data were acquired using a Holter ambulatory electrocardiographic (ECG) monitor. Analysis of acquired data was carried out using a minicomputer programmed to separate ECG R-R intervals into frequency patterns that appear as peaks dispersed along a frequency range of 0.0 to 1.0 Hz. Twenty-four hour baseline, pretreatment low-frequency (LF) HRV power was diminished in all patients with SCI compared with able-bodied-controls and was significantly decreased in tetraplegic patients (P = 0.03). This difference in LF HRV power disappeared during the 24 hours immediately after administration of 4-AP, and mean LF HRV power in tetraplegic patients became indistinguishable from LF HRV power in controls. 4-Aminopyridine appears to influence ANS function and LF HRV in humans with long-standing SCI.

A Nonparametric Alternative to Modeling Population Pharmacokinetics in Patients with Spinal Cord Injury: Comparison with the Standard Two-Stage Method.

The estimation of population-specific pharmacokinetic parameters from sparse of fragmentary data obtained during routine patient care is a powerful analytical tool in drug development and therapeutic drug monitoring. The Nonparametric Expectation Maximization program (NPEM) performs this function and generates robust parameter estimates which are distribution-free and unconstrained by assumption-rich parametric, for example, Gaussian, analyses. We compared standard two-stage method (STS) estimates of amikacin pharmacokinetic parameters (V, CL) derived from a sampling rich strategy (11 patients with spinal cord injury, SCI; 7 able-bodied controls) to estimates of pharmacokinetic parameters obtained from an NPEM one-compartment analysis incorporating the 11 optimally sampled SCI patients and 8 sparse data sets (19 patients with SCI; 7 controls). The STS (n = 11) and NPEM (n = 19) analyses provided similar V and CL parameter estimates in patients with SCI: 0.20 plus minus 0.04 L kg(minus sign1), 0.93 plus minus 0.24 ml min(minus sign1) kg(minus sign1) and 0.20 plus minus 0.06 L kg(minus sign1), 1.12 plus minus 0.26 ml min(minus sign1) kg(minus sign1), respectively. NPEM is a useful, user-friendly, distribution-free computational program for estimating the central tendency and interindividual variability of amikacin pharmacokinetic parameters in spinal cord injured humans.