Role of the NO/cGMP pathway in postoperative vasodilation in perforator flaps

The nitric oxide (NO)/cyclic guanylyl monophosphate (cGMP) pathway is one of the most important regulators of tissue perfusion. Here, we sought to elucidate the protective effects of the NO/cGMP pathway on the microcirculation of axial pattern skin flaps.

Overall 40 rats were divided into four groups (n = 10 each): group A, sildenafil was administered orally at 10 mg/kg daily; group B, sildenafil citrate (10 mg/kg, oral) and nitro-amino-methyl-L-arginine (L-NAME, intraperitoneal injection), a nitric oxide synthase inhibitor, were administered daily; group C, L-NAME was administered alone; and group D, no drugs were administered. After surgery, the surviving flap area was calculated as a percentage of total flap dimensions using the paper template technique. Angiography and imaging were performed to compare the macrovascular changes of the choke zones in the flaps. Histological examinations were performed to compare the differences in microvascular changes between the two choke zones.

A significant improvement of flap survival area and a significant dilation of vessels in both choke zones were found after administration of sildenafil. We also found that the postoperative vasodilation of choke vessels could be altered by inhibition of NO synthase (NOS). Moreover, the vasodilatory effect prolonged by the phosphodiesterase 5 inhibitor sildenafil was attenuated after administration of L-NAME. L-NAME significantly reversed the protection afforded by sildenafil.

Targeting the NO/cGMP pathway can dilate vessels along the axis of the flap, including the choke vessels, thus augmenting flap viability. Therefore, targeting of this pathway may have therapeutic applications.