LAUSR

In pre-clinical studies, matrix metalloproteinase (MMP) inhibition, particularly gelatinases (MMP-2 and -9), attenuated post-myocardial infarct (MI) remodelling.1 However, synthetic inhibitors of MMPs in the clinical setting have yielded disappointing results.2 For the first time, the TIPTOP trial3 showed that a timely short-term treatment with doxycycline, the most potent MMP inhibitor of the tetracycline, is able to reduce 6-month left ventricular (LV) remodelling in patients with a first ST-elevation MI (STEMI) and LV dysfunction [LV ejection fraction (LVEF) < 40%]. Based on the plasma profile of total MMP concentrations and their tissue inhibitors (TIMPs), it has been hypothesized that this may be due to a favourable modulation of MMP activity by TIMP-2.4 Thus, using the stored plasma samples of the TIPTOP patients,4 we now evaluated the relationship between MMP-2 and -9 activities and LV remodelling. The TIPTOP trial has already been described in detail.3,4 In brief, it was a prospective, phase 2, randomized, open-label trial, with blinded outcome assessment, in which 110 STEMI patients were randomized to receive doxycycline [100 mg oral dose immediately after primary percutaneous coronary intervention (pPCI), then twice daily for 7 days], or standard care. For MMP analysis, blood samples were collected at baseline, and at post-MI days 1, 7, 30 and 180. LV remodelling was assessed by twodimensional echocardiography on admission and at 6 months. For the present analysis, gelatinase activity was analysed by zymography in polyacrylamide gels containing gelatin as a substrate by an independent blind off-site laboratory. Statistical analyses were conducted using SPSS software (version 19; IBM Corp., Somers, NY, USA) after transformation of not normally distributed variables. Univariate linear regression was used to assess the relationship between plasma values of collagenase activities at each measurement time,