Preconditioning reduces myocardial complement gene expression in vivo.
This investigation examined the effect of preconditioning in an in vivo model of ischemia-reperfusion injury. Anesthetized New Zealand White rabbits underwent 30 min of regional myocardial ischemia followed by 2 h of reperfusion. Hearts preconditioned with two cycles of 5 min ischemia-10 min reperfusion (IPC) or with the ATP-sensitive K (K(ATP)) channel opener, diazoxide (10 mg/kg), exhibited significantly (P < 0.05) smaller infarcts compared with control. These treatments also significantly (P < 0.001 to P < 0.05) reduced C1q, C1r, C3, C8, and C9 mRNA in the areas at risk (AAR). The K(ATP) channel blocker 5-hydroxydecanoate (5-HD; 10 mg/kg) attenuated infarct size reduction elicited by IPC and diazoxide treatment. 5-HD partially reversed the decrease in complement expression caused by IPC but not diazoxide. There were no significant differences in complement gene expression in the nonrisk regions and livers of all groups. Western blot analysis revealed that IPC also reduced membrane attack complex expression in the AAR. The data demonstrate that preconditioning significantly decreases reperfusion-induced myocardial complement expression in vivo.
Tanhehco
E J
EJ
Department of Pharmacology, University of Michigan Medical School Ann Arbor, Michigan 48109-0632, USA.
Yasojima
K
K
McGeer
P L
PL
McGeer
E G
EG
Lucchesi
B R
BR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D015153:Blotting, Western; D003165:Complement System Proteins / Q000235:genetics* / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015427:Reperfusion Injury / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D012333:RNA, Messenger; D014665:Vasodilator Agents; C052853:5-hydroxydecanoic acid; D003165:Complement System Proteins; D003981:Diazoxide