PT - JOURNAL ARTICLE AU - Terrance D. Barrett AU - James K. Hennan AU - Rory M. Marks AU - Benedict R. Lucchesi TI - C-Reactive-Protein-Associated Increase in Myocardial Infarct Size After Ischemia/Reperfusion AID - 10.1124/jpet.102.040600 DP - 2002 Dec 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 1007--1013 VI - 303 IP - 3 4099 - http://jpet.aspetjournals.org/content/303/3/1007.short 4100 - http://jpet.aspetjournals.org/content/303/3/1007.full SO - J Pharmacol Exp Ther2002 Dec 01; 303 AB - 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.