Mechanically reducing left ventricular work for 30 minutes before coronary reperfusion limited infarct size, reduced scar size, and improved cardiac function 28 days after AMI in swine.
Does primary unloading with a transvalvular axial-flow pump before reperfusion reduce infarct size and improve cardiac function in a swine model of acute myocardial infarction?
In a preclinical swine model of acute myocardial infarction, mechanically unloading the left ventricle for 30 minutes prior to reperfusion reduces infarct size and improves long-term cardiac function.
BACKGROUND Heart failure after an acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. We recently reported that activation of a transvalvular axial-flow pump in the left ventricle and delaying myocardial reperfusion, known as primary unloading, limits infarct size after AMI. The mechanisms underlying the cardioprotective benefit of primary unloading and whether the acute decrease in infarct size results in a durable reduction in LV scar and improves cardiac function remain unknown. OBJECTIVES This study tested the importance of LV unloading before reperfusion, explored cardioprotective mechanisms, and determined the late-term impact of primary unloading on myocardial function. METHODS Adult male swine were subjected to primary reperfusion or primary unloading after 90 min of percutaneous left anterior descending artery occlusion. RESULTS Compared with primary reperfusion, 30 min of LV unloading was necessary and sufficient before reperfusion to limit infarct size 28 days after AMI. Compared with primary reperfusion, primary unloading increased expression of genes associated with cellular respiration and mitochondrial integrity within the infarct zone. Primary unloading for30 min further reduced activity levels of proteases known to degrade the cardioprotective cytokine, stromal-derived factor (SDF)-1α, thereby increasing SDF-1α signaling via reperfusion injury salvage kinases, which limits apoptosis within the infarct zone. Inhibiting SDF-1α activity attenuated the cardioprotective effect of primary unloading. Twenty-eight days after AMI, primary unloading reduced LV scar size, improved cardiac function, and limited expression of biomarkers associated with heart failure and maladaptive remodeling. CONCLUSIONS The authors report for the first time that first mechanically reducing LV work before coronary reperfusion with a transvalvular pump is necessary and sufficient to reduce infarct size and to activate a cardioprotective program that includes enhanced SDF-1α activity. Primary unloading further improved LV scar size and cardiac function 28 days after AMI.
“If you take a patient with STEMI and if you unload the ventricle, you decrease wall stress, decrease myocardial oxygen demand and increase coronary perfusion, but you do a lot more. You provoke a whole series of cardioprotective reflexes that actually reduce reperfusion injury and apoptosis. It totally changes the transcriptome of the patient while you've got left ventricular unloading.”
Esposito et al. (Sun,) conducted a other in Acute myocardial infarction. Primary unloading (LV unloading before reperfusion) vs. Primary reperfusion was evaluated on Infarct size 28 days after AMI. Mechanically reducing left ventricular work for 30 minutes before coronary reperfusion limited infarct size, reduced scar size, and improved cardiac function 28 days after AMI in swine.
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