The Effect of Angiotensin (1–7) on Survival of Random Pattern Skin Flaps With Nicotine-Induced Ischemia in Rats

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The purpose of this study was to reveal the effect of angiotensin (1–7) on survival of random pattern, nicotinized, ischemic flap model in rats.

Materials and Methods:

We used female Sprague Dawley rats weighing between 250 and 300 g. The study was performed on 3 groups each of them was consisted of 30 rats (control [C], angiotensin (1–7) [A] and vehicle [V]).

Materials and Methods:

While group C was subjected to 1 mL saline subcutaneous injection once daily for 28 days, groups A and V were nicotinized by 2 mg/kg nicotine subcutaneous injection, twice a day. At the end of this period, McFarlane random flap was constructed in all rats. No drug was applied to the flap bed in the group C, whereas for group A angiotensin (1–7) (A [1–7]) was delivered and a vehicle without an active ingredient was applied to the group V.

Materials and Methods:

Following surgery, immediately, Na-fluorescein diffusion tests were performed on 10 subjects of every group and necrotic areas were determined by millimetric paper method. After this, for determining angiogenesis, 10 subjects were killed from each group on the second day and fourth day. Finally, on the seventh day, necrotic areas were measured in 10 subjects of each group. They were then killed after photographs were taken. Specimens were collected from distal and critical zones of flaps, in all the groups, for immunohistochemical and histopathologic analyses.


Macroscopic measurements revealed equal ischemic areas for groups A and V in 30 minutes which were both larger than those of the group C (P < 0.005). Measurements performed on the seventh day showed a significant decrease of ischemia, which advanced to necrosis in the group A (P < 0.005). Groups V and C showed a direct progress to necrosis without changes in ischemia levels. Microscopic analysis exhibited a statistically significant increase in the number of microvascular structures and diameters of mature vascular structures in the group A compared with those of groups C and V (P < 0.005).


A (1–7) increased vasodilatation in nicotinized flaps, triggered angiogenesis in the first 2 days, and contributed remarkably to the flap survival.

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