Author + information
- Received May 6, 2015
- Revision received June 22, 2015
- Accepted June 29, 2015
- Published online November 1, 2015.
- Navin K. Kapur, MD∗,†,‡∗ (, )
- Xiaoying Qiao, PhD∗,
- Vikram Paruchuri, MD∗,†,‡,
- Kevin J. Morine, MD∗,
- Wajih Syed, BSc‡,
- Sam Dow, MD∗,
- Nimish Shah, MD∗,
- Natesa Pandian, MD‡ and
- Richard H. Karas, MD, PhD∗,†,‡
- ∗The Molecular Cardiology Research Institute, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
- †Surgical and Interventional Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
- ‡The Cardiovascular Center, Tufts Medical Center and Tufts University School of Medicine, Boston, Massachusetts
- ↵∗Reprint requests and correspondence:
Dr. Navin K. Kapur, Tufts Medical Center, 800 Washington Street, Box #80, Boston, Massachusetts 02111.
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, ischemia–reperfusion injury contributes to residual myocardial damage and subsequent heart failure. Stromal cell-derived factor (SDF)-1α is a chemokine that activates cardioprotective signaling via Akt, extracellular regulated kinase, and glycogen synthase kinase-3β.
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° Reperfusion) group, the LAD was reperfused for 120 min. In the primary unloading (1° 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° Reperfusion, 1° Unloading reduced LV wall stress and increased myocardial levels of SDF-1α, CXCR4, and phosphorylated Akt, extracellular regulated kinase, and glycogen synthase kinase-3β in the infarct zone. 1° Unloading increased antiapoptotic signaling and reduced myocardial infarct size by 43% compared with 1° 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-1α/CXCR4 expression, increases cardioprotective signaling, reduces apoptosis, and limits myocardial damage in AMI.
Funding for this study was received from Abiomed Inc.
Dr. Kapur has received research funding from Abiomed Inc., CardiacAssist Inc., HeartWare Inc., and Maquet Cardiovascular Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 6, 2015.
- Revision received June 22, 2015.
- Accepted June 29, 2015.
- American College of Cardiology Foundation