Abstract 16199: From Door to Balloon to Door to Unload: Shifting the Paradigm of Cardioprotective Therapy for Ischemia Reperfusion Injury in Acute Myocardial Infarction
Management of an acute myocardial infarction (AMI) focuses on rapid coronary reperfusion to limit myocardial injury, known as the Door to Balloon time. Despite timely coronary recanalization, myocardial ischemia-reperfusion injury (mIRI) remains a major determinant of morbidity and mortality. No studies have targeted initially reducing left ventricular stroke work (LVSW) as a method to limit mIRI. The TandemHeart centrifugal-flow pump (TH-CFP, Cardiac Assist Inc) is a percutaneous left atrial to femoral arterial bypass system. We tested the hypothesis that reducing LVSW with the TH-CFP, while delaying coronary recanalization limits mIRI.
Methods and Results: Percutaneous left anterior descending artery (LAD) occlusion was induced by angioplasty for 120 minutes in 50kg male Yorkshire swine (n=4/group). LV pressure-volume loop analysis via a conductance catheter was performed in all animals. After 120 minutes of ischemia we observed no significant change in LV end-diastolic volume or pressure (LVEDV; LVEDP) and LVSW in all animals. In Group 1, 120 minutes after LAD reperfusion, LVEDV and LVEDP increased (p<0.05 for each vs baseline) with no change in LVSW. In Group 2, after 120 minutes of ischemia a TH-CFP was placed and activated and the LAD left occluded for an additional 30 minutes, followed by 120 minutes of reperfusion. The TH-CFP was active throughout reperfusion and reduced LVSW (2964+117 vs 703+42 mL-mmHg, p<0.01). Compared to Group 1, 120 minutes after LAD reperfusion, Group 2 had significantly reduced LVEDV and LVEDP (p<0.05 for each versus baseline). Mean arterial pressure (54+4 vs 45+4, p<0.05) and the slope of end-systolic pressure and volume (ESPVR: 1.7+0.5 vs 0.84+0.2, p<0.05) were higher with TH-CFP support after reperfusion. Group 2 showed increased myocardial phosphorylation of the reperfusion injury salvage kinases, ERK and AKT. Compared to Group 1, total myocardial infarct size was significantly reduced in Group 2 (54+14% vs 28+7%, p<0.05; Fig B) as quantified by triphenyltetrazolium chloride staining.
Conclusion: In contrast to the paradigm of rapid coronary reperfusion in AMI, we report the potential benefit of initially reducing LVSW with a support device (Door to Unload) and delaying coronary reperfusion to limit mIRI in AMI.
- Ischemia reperfusion
- Ventricular assist devices
- Interventional cardiology
- Myocardial infarction
- © 2012 by American Heart Association, Inc.