ObjectiveTo 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. MethodsSeventy 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. ResultsThe 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. ConclusionPharmacologic delay with pioglitazone can improve extended perforator flap viability through increasing ischemia-induced angiogenesis and choke vessels vasodilation in rat models.