Objective: To investigate the effect of pharmacologic delay with pioglitazone, a peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, on extended perforator flap survival in a rat model.
Methods: Seventy male Sprague Dawley rats, weighing 250-300 g, were randomly divided into control group (n=35) and experimental group (n = 35). A three-territory flap was made, including two choke zones. Pioglitazone was dissolved in 1.5 mL saline. Oral doses of pioglitazone [10 mg/(kg · d)] was given by gavaged for 5 days in the experimental group, while the same volume of saline was given in the control group at same time point. After 7 days, the flap survival area was measured and angiographic diagnosis was made. The tissue samples were harvested from choke zone II for histological study and vascular endothelial growth factor (VEGF) expression detection by immunohistochemical staining. The content of nitric oxide (NO) in choke zones I and II was measured at immediate, 1, 3, 5, and 7 days after operation.
Results: The flap general change of 2 groups was similar. Varying degrees of necrosis occurred with the extension of time in 2 groups. At 7 days after operation, the flap survival rate was 87.73% ± 3.25% in the experimental group and 76.07% ± 2.92% in the control group, showing a significant difference (t = -10.338, P = 0.000). The number of true anastomosis in choke zones I and II was 5.40 ± 1.14 and 3.00 ± 0.71 in the experimental group, and was 3.20 ± 0.84 and 0.80 ± 0.84 in the control group respectively, showing significant differences between the 2 groups (t = -3.479, P = 0.008; t = -4.491, P = 0.002). The microvessel density and the expression of VEGF in choke zone II of experimental group were (33.16 ± 7.73)/mm2 and 4,368.80 ± 458.23, respectively, which were significantly higher than those of control group [(23.29 ± 5.91)/mm2 and 2,241.24 ± 554.43] (t = 5.073, P = 0.000; t = -14.789, P = 0.000). The content of NO in the experimental group were significantly higher than those in the control group at other time points (P < 0.05) except for at immediate after operation.
Conclusion: Pharmacologic delay with pioglitazone can improve extended perforative flap viability through increasing ischemia-induced angiogenesis and choke vessels vasodilation in rat models.