Abstract
Advances in neurobiology have led to a surge of clinical interest in the development of protective and regenerative neuromodulatory strategies, as surgical therapies for prostate cancer often result in neuronal damage and debilitating loss of sexual function. To investigate the dose-dependent efficacy of FK1706, a nonimmunosuppressant immunophilin ligand, for the recovery of erectile function following bilateral cavernous nerve crush injury in the rat. Recovery of erectile function was assessed by cavernous nerve electrostimulation and reported as maximal increase of intracavernous pressure (ICP) and area under the curve (AUC). Changes in animal weights, percentage completion of treatment course, and survival were compared between groups. METHODS; Thirty-five Sprague-Dawley male rats were randomly divided into five equal groups: seven animals received a sham operation, whereas 28 animals underwent bilateral cavernous nerve crush injury, followed by subcutaneous injection of vehicle alone (1.0 mL/kg), or low (0.1 mg/kg), medium (0.32 mg/kg), or high dose (1.0 mg/kg) FK1706 5 days per week for 8 weeks. Erectile dysfunction did not occur in the sham group (mean maximal ICP increase of 100.8 +/- 6.3 cmH(2)O), whereas nerve injury and vehicle treatment produced a significant reduction in ICP response to 34.4 +/- 12.8 cmH(2)O. The mean ICP increase for high-dose FK106 treatment was 73.9 +/- 6.3 cmH(2)O (P < 0.01 vs. vehicle) compared with 58.3 +/- 7.4 cmH(2)O and 56.9 +/- 8.3 for low and medium doses (P > 0.05). Similar stepwise findings were observed using AUC data. No significant maximal aortic blood pressure or weight differences occurred between groups and all animals completed treatment. High-dose subcutaneous FK1706 therapy promoted recovery of erectile function following bilateral cavernous nerve crush injury in the rat. No significant differences between groups were observed for changes in weight, and the 8-week treatment course was completed for all animals.
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