ATP-sensitive potassium channels mediate the anti-ischemic properties of ischemic and pharmacologic preconditioning in rat random-pattern skin flap.
Ischemic preconditioning (IPC) and pharmacologic preconditioning by morphine and adenosine may significantly decrease the amount of necrosis in rat random pattern skin flaps. We examined the role of ATP-sensitive potassium channels (K(ATP) channels) in mediating these protective phenomenon by using glibenclamide a nonspecific blocker of these channels. We also investigated whether administration of diazoxide an opener of the K(ATP) channels could mimic the same protective effect. Ninety male Sprague-Dawley rats were randomly divided into either control or treatment groups (n = 6 each). Bipedicled dorsal skin flaps (2 x 8 cm) were elevated at the midline. In pharmacologic preconditioning groups, 1 mL of morphine (5 mg/flap), adenosine (0.5 mg/flap), or different doses of diazoxide (0.5, 1, 5, and 15 mg/flap) were administered locally in the cranial half of the flap, respectively. One milliliter of saline was locally injected in the control group. In the IPC group, 1 hour after local saline injection the cranial pedicle was clamped for 20 minutes, and then 40 minutes' reperfusion was performed. In another experiment, 0.3 mg/kg of glibenclamide was injected intraperitoneally 30 minutes before local administration of saline or drug in ischemic or pharmacologic preconditioning groups. Regardless of the group, all flaps were cut at the cranial side 2 hours after elevation and were sutured back. Flap survival area was evaluated on the seventh postoperative day. IPC and pharmacologic preconditioning with morphine, adenosine, and diazoxide (in higher doses; 1, 5, and 15 mg/flap) improved survival area compared with the control group. Glibenclamide abolished their protective effect. K(ATP) channels may have a key role in anti-ischemic properties of IPC and pharmacologic preconditioning.
Beheshtian
Azadeh
A
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Demehri
Shadpour
S
Kiumehr
Saman
S
Salmasi
Amirali Hassanzadeh
AH
Nezami
Behtash Ghazi
BG
Ghazinezami
Behtash
B
Rahimpour
Sina
S
Amanpour
Saeed
S
Rabbani
Shahram
S
Mohagheghi
Mohammad Ali
MA
Dehpour
Ahmad Reza
AR
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D062109:Dermatologic Surgical Procedures; D003981:Diazoxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005905:Glyburide / Q000008:administration & dosage / Q000009:adverse effects; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D007511:Ischemia / Q000517:prevention & control*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D013524:Surgical Flaps / Q000098:blood supply*; D014022:Tissue Survival / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology
D007004:Hypoglycemic Agents; D009294:Narcotics; D015221:Potassium Channels; D014665:Vasodilator Agents; D009020:Morphine; D000255:Adenosine Triphosphate; D000241:Adenosine; D003981:Diazoxide; D005905:Glyburide