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

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Abstract

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.

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