Microcirculatory effects of selective endothelin-A receptor antagonism in testicular torsion.

PURPOSE

Testicular torsion without timely intervention causes incurable damage to the testis. We examined the causative role of microcirculatory injury in torsion induced testicular damage with particular regard to endothelin-A receptor activation.

MATERIALS AND METHODS

The microcirculatory consequences of testicular torsion were assessed in the presence or absence of endothelin-A receptor antagonism in rats. Microcirculatory perfusion changes (red blood cell velocity and pulsatile flow pattern alterations) were examined by an orthogonal polarization spectral imaging technique. Microcirculatory inflammatory alterations were assessed by fluorescence intravital video microscopy after 60-minute torsion followed by 240-minute reperfusion. As a specific endothelin-A receptor inhibitor, the antisense homology box derived peptide ETR-p1/fl was applied 10 minutes before reperfusion. Tissue accumulation of leukocytes was estimated by myeloperoxidase activity in tissue biopsies taken at the end of the 4-hour reperfusion period. In further experiments testicular weight as a marker of permanent damage was evaluated 45 days after torsion.

RESULTS

The physiological pulsatile flow pattern ceased in the initial phase of reperfusion while leukocyte-endothelial interactions increased throughout the examined reperfusion period. Endothelin-A receptor antagonism caused earlier return of pulsatile flow and recovery of red blood cell velocity, and alleviated microcirculatory inflammatory reactions and atrophy.

CONCLUSIONS

Results suggest a pathophysiological role of endothelin-A receptor activation in the pathogenesis of testicular torsion. This effect is related to deterioration in testicular perfusion and activation of microcirculatory inflammatory reactions.