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Vol. 303, Issue 3, 1007-1013, December 2002

C-Reactive-Protein-Associated Increase in Myocardial Infarct Size After Ischemia/Reperfusion

Terrance D. Barrett, James K. Hennan, Rory M. Marks and Benedict R. Lucchesi

University of Michigan Medical School, Departments of Pharmacology (T.D.B., J.K.H., B.R.L.) and Internal Medicine (R.M.M.), Ann Arbor, Michigan

C-Reactive protein (CRP), a marker for acute inflammation, is associated with increased risk of cardiovascular events. The mechanism underlying this association is uncertain. An acute inflammatory response was induced in rabbits by subcutaneous injection of croton oil (CO) 1 to 3 days before 30 min of regional myocardial ischemia/180 min of reperfusion. CO treatment increased plasma CRP from below the limit of detection to 2.5 ± 0.5 mg/dl and was associated with an increase in infarct size expressed as percentage of risk region [32 ± 6% vehicle controls (n = 7) to 47 ± 9% CO-treated rabbits (n = 7; P < 0.05]. After 10 min of ischemia and 180 min reperfusion, no infarct was found in controls; however, an infarct of 7 ± 1% was found in CO-treated rabbits (P < 0.05; CRP, 2.3 ± 0.4 mg/dl). The CRP-related increase in infarct size was not observed in croton oil-treated, C6-deficient rabbits (n = 5/group), indicating the involvement of complement. In these rabbits, infarct size was 22 ± 2% (P < 0.05) despite having plasma CRP of 4.3 ± 0.4 mg/dl. The CRP-associated increase in infarct size was ameliorated by pretreatment with heparin (n = 7; infarct size 33 ± 3%; CRP, 2.3 ± 0.3 mg/dl; P < 0.05) or N-acetylheparin (n = 7; infarct size 23 ± 4%; CRP, 3.1 ± 0.5 mg/dl; P < 0.05). These observations may explain why increased serum CRP is associated with an augmented risk for cardiovascular events.

0022-3565/02/3033-1007$07.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2002 by The American Society for Pharmacology and Experimental Therapeutics


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