Electrical Dysynchrony Acutely Increases Interstitial Matrix Metalloproteinase Activity

Increased matrix metalloproteinase (MMP) abundance occurs with adverse LV remodeling in a number of cardiac disease states, including those induced by long-standing arrhythmias. However, whether regionally contained dyssynchronous electrical activation of the LV, with consequent dyskinesia, alter interstitial MMP activation remained unknown. Electrical activation of the LV of pigs (n=10, 30–35 kg) was achieved by pacing (120 bpm) at left atrial ( A ) and LV sites ( V) such that normal A-V electrical activation (60 min) was followed by regional early V activation for 60 min within 1.5 cm of the V site , and restoration of normal A-V pacing for 120 min. Regional shortening (piezoelectric crystals) and interstitial MMP activity (microdialysis with MMP fluorogenic substrate) at the V pacing site and a remote LV site were monitored at 30 min intervals. With early V activation, segmental shortening was reduced (8.4±0.6% vs 1.2±0.9%, p<0.05) at the V site, but not at the remote site (8.5±0.3%). Interstitial MMP activity was similar at remote and V sites during initial A-V pacing (1172±187 vs. 1332±87 fluoro units, resp). Dyssynchrony increased interstitial MMP activity at the V site compared to the remote region (Figure ). Restoration of A-V pacing normalized segmental shortening (8.5±0.4%), but MMP activity remained elevated. This study, for the first time, demonstrates that despite restoration of mechanical function, disturbances in electrical conduction - in and of itself - can directly cause regional MMP activation, and therefore, contribute to myocardial remodeling.