Mechanical Pre-Conditioning With Acute Circulatory Support Before Reperfusion Limits Infarct Size in Acute Myocardial Infarction

OBJECTIVES This study tested the hypothesis that first reducing myocardial work by unloading the left ventricle (LV) with a novel intracorporeal axial flow catheter while delaying coronary reperfusion activates a myocardial protection program and reduces infarct size. BACKGROUND Ischemic heart disease is a major cause of morbidity and mortality worldwide. Primary myocardial reperfusion remains the gold standard for the treatment of an acute myocardial infarction (AMI); however, ischemiareperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1 alpha is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3 beta. METHODS AMI was induced by occlusion of the left anterior descending artery (LAD) via angioplasty for 90 min in 50-kg male Yorkshire swine (n = 5/group). In the primary reperfusion (1 degrees Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1 degrees Unloading) group, after 90 min of ischemia the axial flow pump was activated and the LAD left occluded for an additional 60 min, followed by 120 min of reperfusion. Myocardial infarct size and kinase activity were quantified. RESULTS Compared with 1 degrees Reperfusion, 1 degrees Unloading reduced LV wall stress and increased myocardial levels of SDF-1 alpha, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3 beta in the infarct zone. 1 degrees Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1 degrees Reperfusion (73 +/- 13% vs. 42 +/- 8%; p = 0.005). Myocardial levels of SDF-1 correlated inversely with infarct size (R = 0.89; p < 0.01). CONCLUSIONS Compared with the contemporary strategy of primary reperfusion, mechanically conditioning the myocardium using a novel axial flow catheter while delaying coronary reperfusion decreases LV wall stress and activates a myocardial protection program that up-regulates SDF-1 alpha/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI. (C) 2015 by the American College of Cardiology Foundation.