Chemically Modified Tetracycline Improves Contractility in Porcine Coronary Ischemia/Reperfusion Injury

Background: Reperfusion of ischemic myocardium has been implicated in extension of infarct size and deleterious clinical outcomes. Anti‐inflammatory agents reduce this reperfusion injury. Chemically modified tetracycline‐3 (CMT‐3) (Collagenex Pharmaceuticals, Newtown, PA, USA) lacks antimicrobial properties yet retains anti‐inflammatory activity. We examined infarct size and myocardial function in a porcine coronary artery occlusion/reperfusion model in CMT‐3‐treated and control animals. Methods: Yorkshire pigs (n = 8) underwent median sternotomy, pretreatment with heparin (300 U/kg and 67 U/kg/hr IV) and lidocaine (1 mg/kg IV) and were divided into two groups. Group one (n = 4) had the left anterior descending artery (LAD) occluded for 1 hour, after which it was reperfused for 2 hours. Group two (n = 4) had an identical protocol to group one except CMT‐3 (2 mg/kg IV) was administered prior to occlusion of the LAD. Results: Animals receiving CMT‐3 had significantly decreased infarct size in relation to the ventricular area‐at‐risk (AAR) (28 ± 9% vs. 64 ± 8%; p < 0.05). Myocardial contractile function was superior in the CMT‐3 treatment, indicated by a higher cardiac index (2.9 ± 0.3 vs. 2.0 ± 0.3 L/min/m2; p < 0.05) and stroke volume index (22 ± 2 vs. 17 ± 1 L/m2/beat; p < 0.05). Conclusions: CMT‐3 decreased infarct size in relation to the AAR resulting in relative preservation of contractility, suggesting CMT‐3 may improve outcomes during myocardial ischemia reperfusion.