C1-esterase inhibitor and a novel peptide inhibitor improve contractile function in reperfused skeletal muscle.
To determine the role of inhibition of complement activation in the contractile function of skeletal muscle ischemia-reperfusion (I/R) injury, the rat extensor digitorum longus (EDL) muscles underwent 3 h ischemia and received human C1-esterase inhibitor (C1-INH, 100 IU/kg), a synthetic C1q A chain peptide with a similar inhibitory effect on activated C1 (peptide, 5 mg/kg), or human serum albumin control. Results showed a significant overall increase in tetanic contractile forces of the reperfused EDL in both C1-INH and peptide groups compared to controls. Maximum improvement occurred with peptide treatment at 120-Hz stimulation, with an increase in force from 38 +/- 4% of normal in controls to 52 +/- 4% in peptide-treated rats. There were no significant differences between C1-INH and peptide groups. Plasma C3 and C4 activities were significantly increased in both treated groups, suggesting inhibition of complement activation. Our results suggest that complement activation is involved in I/R injury, and inhibition of complement activation may therefore represent a potential therapeutic approach to reducing or preventing I/R injury.
Toomayan
Glen A
GA
Orthopaedic Microsurgery Laboratories, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
Chen
Long-En
LE
Jiang
Hai-Xiang
HX
Qi
Wen-Ning
WN
Seaber
Anthony V
AV
Frank
Michael M
MM
Urbaniak
James R
JR
D000818:Animals; D003167:Complement Activation; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D015922:Complement C1q / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D012680:Sensitivity and Specificity
D003174:Complement C1 Inactivator Proteins; D015922:Complement C1q