Involvement of calpain in myonephropathic metabolic syndrome (MNMS).
Myonephropathic metabolic syndrome (MNMS) is a serious muscle reperfusion injury associated with acute renal failure. The exact pathogenesis of MNMS has not been fully elucidated, nor effective treatment, through the renal failure is thought to be a consequence of rhabdomyolysis. In the present study, the possible involvement of calpain in the lysis was investigated in a MNMS animal model employing a cell permeable calpain antagonist calpeptin. Male rabbits were subjected to bilateral hind leg ischaemia for 5 hours by clamping the distal aorta, followed by reperfusion for 3 hours. Blood pressure, plasma N-acethyl-beta-D-glucosaminidase (NAG) and the presence of myoglobinuria were serially determined. Blood pressure remained constant during the ischemic period but dropped by about 25% immediately after reperfusion. This was significantly attenuated by intraaortic administration of calpeptin. NAG gradually increased during ischemia and during reperfusion and this was also significantly reduced by calpeptin. Myoglobinuria appeared immediately after reperfusion, and was also attenuated by calpeptin. Calpeptin prevented lytic and degenerative changes of the hind leg muscles, determined by light and electron microscopy. Thus it is concluded that activation of calpain in skeletal muscle is an important etiologic factor of MNMS and that the occurrence of MNMS may be prevented by administration of a calpain antagonist.
Tsuji
Y
Y
Department of Surgery II, Osaka University Medical School, Japan.
Kambayashi
J
J
Shiba
E
E
Sakon
M
M
Kawasaki
T
T
Mori
T
T
D000118:Acetylglucosaminidase / Q000097:blood; D058186:Acute Kidney Injury / Q000150:complications; D000818:Animals; D002154:Calpain / Q000037:antagonists & inhibitors* / Q000502:physiology*; D004151:Dipeptides / Q000627:therapeutic use*; D006614:Hindlimb; D008297:Male; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D011817:Rabbits; D015427:Reperfusion Injury / Q000209:etiology* / Q000517:prevention & control; D012206:Rhabdomyolysis / Q000150:complications* / Q000473:pathology; D013577:Syndrome
D004151:Dipeptides; C071482:calpeptin; D000118:Acetylglucosaminidase; D002154:Calpain