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/m(2); p < 0.05) and stroke volume index (22 +/- 2 vs. 17 +/- 1 L/m(2)/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.