Imaging the Proangiogenic Effects of Cardiovascular Drugs in a Diabetic Model of Limb Ischemia

Figure 2

(a) Retention of [¹⁸F]FtRGD measured by longitudinal PET imaging (∼10 MBq, acquired from 70–90 min postinjection under isoflurane anaesthesia). Closed circles represent data from the ischemic leg and open circles represent data from the contralateral intact leg. Retention was significantly higher in the combination-treated ischemic limb from day 8 to day 28 postligation (whereas the nondiabetic ischemic limb and simvastatin-treated ischemic limb were only significantly higher on days 8 and 14 and metformin on day 8 only) compared to the vehicle-treated ischemic limb (, , , 1-way ANOVA with post hoc Tukey’s test, data shown as %ID/g ± SD). (b) Hind limb vascular volume measured by TOF MRI. Vascular volume was significantly higher in the nondiabetic ischemic limb, combined treatment ischemic limb, simvastatin-treated ischemic limb, and metformin-treated ischemic limb from day 21 to 28 postligation compared to the vehicle-treated ischemic limb (, , 1-way ANOVA with post hoc Tukey’s test, mean volume in mm³ ± SD). (c) Blood glucose concentration measured by venous blood sampling. Both metformin and combined treatment decreased the blood glucose levels from day 2 (, , , 1-way ANOVA with post hoc Tukey’s test, mean % area stained ± SD). (d) Observational measures of disease progression and functional limb use. Functional foot use was severely impaired in all animals early in the study with gradual improvement observed in the treated and nondiabetic groups in comparison to the vehicle-treated diabetic group. Development of progressive necrosis was observed in the vehicle-treated group; a slower progression was observed in the simvastatin-treated group, metformin-treated group, and nondiabetic group, whereas no necrosis was observed in the combined treatment group (, , , 1-way ANOVA with post hoc Tukey’s test, mean impairment score ± SD).

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