Effect of dibutyryl cyclic adenosine monophosphate on skeletal muscle reperfusion injury in the rat.
To clarify the action of dibutyryl cyclic adenosine monophosphate (DBcAMP) on reperfused ischemic muscle, experiments were conducted using the hindlimbs of 18 male Lewis rats. At the midportion of the thigh all tissues except for the femoral artery and vein were transected, and a route for continuous intravenous infusion was secured in a contralateral limb vein. After inducing total ischemia by clamping the femoral artery and vein with a vascular clamp for 4 h, the limb was reperfused for 1 h. Blood flow was then compared using the hydrogen gas clearance method in a group in which DBcAMP 10 mg was continuously infused from a vein in the contralateral hindlimb from 1 h prior to the induction of ischemia to 1 h after the completion of ischemia (DBcAMP group), a group in which saline was infused in the same manner (control group), and a group which was subjected to biopsy alone (biopsy group). The percent change in blood flow was significantly higher in the DBcAMP group than in the control group at 15 and 30 min after the release of the clamp. Adenosine triphosphate (ATP), phosphocreatine (PCr), and lipid peroxide (LPO) were measured in tissue samples obtained 1 h after reperfusion. Serum LPO was measured in blood samples collected at the same time. ATP values were higher in the DBcAMP group than in the control group. PCr was significantly higher in the DBcAMP group than in the control group. LPO levels in skeletal muscle tissue did not differ significantly between the DBcAMP and control groups. In contrast, serum LPO levels were significantly lower in the DBcAMP group than the control group. On morphologic analysis the control and DBcAMP groups showed normal vascular endothelial cells and absence of the 'no-reflow' phenomenon. These data confirm that in this reperfusion model the administration of DBcAMP enhances the viability of skeletal muscle cells. Moreover, mediated by an effect on vascular endothelial cells this agent is thought to be of help in mitigating the vascular endothelial cell injury occurring in acute ischemic injury. DBcAMP may be a useful agent in mitigating skeletal muscle ischemia-reperfusion injury.
Ohshima
T
T
Department of Orthopaedic Surgery, Nagoya University School of Medicine, Japan.
Yabe
Y
Y
Ishiguro
N
N
Iwata
H
H
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D003994:Bucladesine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D008054:Lipid Peroxides / Q000097:blood / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000227:Adenine Nucleotides; D008054:Lipid Peroxides; D010725:Phosphocreatine; D003994:Bucladesine