Effects of soluble guanylate cyclase activator vericiguat on fracture healing in rats.

OBJECTIVES

The aim of this study was to assess the healing effects of vericiguat at various concentrations on rat femur fractures through clinical and radiological and biomechanical and histopathological assessments.

MATERIALS AND

METHODS

In this study, a total of 60 female Wistar-Albino rats were used. The study comprised of six rat groups with 10 rats in each group: Group 1 (normal controls), Group 2 (positive controls - only fracture), Group 3 (low-dose vericiguat - 3 mg/kg), Group 4 (high-dose vericiguat - 6 mg/kg), Group 5 (fracture + low-dose vericiguat), Group 6 (fracture + high-dose vericiguat). Under general anesthesia, standard closed fractures were created in the right femurs of rats in the fracture groups. Radiological examinations were performed on Days 7, 14, and 28. The Lane-Sandhu scoring system was used for radiological assessment. At the end of Day 28, the rats were sacrificed, and the fracture healing tissues were examined biomechanically and histologically using the Huo scale.

RESULTS

The 28th day biomechanical assessment showed significant differences in maximum load values between the fractured groups (Group 2: 88.75 ± 23.25 N, Group 5: 83.54 ± 23.15 N, Group 6: 39.07 ± 10.38 N; p = 0.003). The stiffness values showed similar patterns (Group 2: 64.71 ± 45.52 N/mm, Group 5: 99.20 ± 43.82 N/mm, Group 6: 40.47 ± 19.27 N/mm; p = 0.088). In the histological evaluation according to the Huo scale, Group 5 showed the highest quality of healing (8.6 ± 1.14) and a significant difference was found between Group 2 and Group 5 (p = 0.009). Group 6 demonstrated necrosis in four out of 10 animals and severe inflammation in eight out of 10 animals. In the radiological evaluation on Days 7, 14, and 28, no statistically significant differences were observed between the groups according to the Lane-Sandhu scoring system (p = 0.811 on Day 14; p = 0.299 on Day 28).

CONCLUSION

Our study results suggest that soluble guanylate cyclase (sGC) activators show promise for fracture healing treatment when used at specific concentrations, but their therapeutic range remains limited and their toxic effects at high doses need careful consideration.