Preconditioning of the rat random-pattern skin flap: modulation by opioids

Opioid receptors have been implicated in protecting several organ systems from ischaemic events. The authors have studied the effects of opioid receptors on random-pattern skin flap survival. Sixty-nine male Sprague-Dawley rats were used. Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. Different doses of morphine (0.01, 0.1, 1 and 5 mg/flap) were administered locally in the cranial half of the flap and systemically through intraperitoneal injections (5 and 10 mg/kg). In another experiment, 0.4 mg/flap of naloxone was injected followed by 5 mg/flap injection of morphine to determine whether the effect of morphine is receptor mediated. The role of the opioid receptors in the ischaemic preconditioning (IPC) phenomenon was investigated by administration of naloxone (0.4 mg/flap) 1 h before clamping the cranial pedicle for 20 min followed by 40 min of reperfusion. Appropriate control groups were included. The cranial pedicle was cut 2 h after saline or drug administration in all groups and flap survival area was evaluated on the seventh postoperative day. Local administration of morphine in higher doses (1 and 5 mg/flap) significantly reduced the amount of flap necrosis when compared to that of the control cohort (P < 0.05). Naloxone abolished this protective effect of morphine. Furthermore naloxone significantly decreased the anti-ischaemic effect of the IPC. Systemic administrations of morphine had no significant effect on flap survival area in compare with the control group.