Title of article :
The Novel Glycolipid RC-552 Attenuates Myocardial Stunning and Reduces Infarct Size in Dogs
Author/Authors :
G. T. Elliott، نويسنده , , C. G. Sowell، نويسنده , , E. B. Walker، نويسنده , , P. A. Weber، نويسنده , , J. Moore، نويسنده , , G. J. Gross، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2000
Pages :
13
From page :
1327
To page :
1339
Abstract :
The novel glycolipid RC-552 shares common structural features with the natural products lipid A and the previously described cardioprotectant monophosphoryl lipid A. RC-552 administered to dogs as a bolus intravenous dose (35–70μ g/kg) either 24 h or 10 min prior to 60 min of regional myocardial ischemia and 3 h of reperfusion significantly (P<0.05 v control) reduced infarct size (IS) as assessed by triphenyltetrazolium staining from 27.0±2.3% of the area-at-risk (AAR) to 13.3±2.2% and 15.0±3.0%, respectively. Administration of the non-specific inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (30 mg/kg, subcutaneously) 1 h prior to ischemia blocked the ability of RC-552 (35 μ g/kg, 24 h pretreatment) to reduce infarct size. Intravenous pretreatment with RC-552 (35 μ g/kg) either 24 h or 10 min prior to five 5 min repetitive cycles of ischemia and reperfusion significantly improved regional myocardial segment shortening (percentage of control) at all time points during 2 h of reperfusion in dogs. These effects of RC-552 in either cardiac injury model occurred independent of differences in AAR, transmural blood flow during ischemia or hemodynamics throughout the experiment. In contrast with monophosphoryl lipid A (MLA), which has also been reported to be cardioprotective at similar doses in dogs, RC-552 was approximately 100 times less prone to cause fever in the USP rabbit pyrogen test. Likewise, RC-552 did not induce secretion of the proinflammatory cytokines TNF, IL-6 or IL-8 from THP-1 cells or alter the expression of adhesion molecules on human neutrophils at concentrations up to 10μ g/ml. MLA was active in these systems at concentrations in the range 0.1–1.0 μ g/ml. In conclusion, RC-552 reduces myocardial infarct size and stunning in dogs in the absence of residual immunomodulatory activity.
Keywords :
stunning , Aminoguanidine , nitric oxide. , RC-552 , glycolipid , ischemia , reperfusion , cardioprotection , Infarction
Journal title :
Journal of Molecular and Cellular Cardiology
Serial Year :
2000
Journal title :
Journal of Molecular and Cellular Cardiology
Record number :
527283
Link To Document :
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