Journal
ASAIO JOURNAL
Volume 61, Issue 2, Pages 161-169Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MAT.0000000000000178
Keywords
heart failure; left ventricular assist device; extracellular matrix
Categories
Funding
- CorMatrix Cardiovascular, Inc
- HeartWare, Inc
- Roger M. Prizant Research Trust Fund
- University of Louisville Cardiac Implant Science Endowment
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Myocardial recovery with left ventricular assist device (LVAD) support is uncommon and unpredictable. We tested the hypothesis that injectable particulate extracellular matrix (P-ECM) with LVAD support promotes cell proliferation and improves cardiac function. LVAD, P-ECM, and P-ECM + LVAD therapies were investigated in chronic ischemic heart failure (IHF) calves induced using coronary embolization. Particulate extracellular matrix emulsion (CorMatrix, Roswell, GA) was injected intramyocardially using a 7 needle pneumatic delivery tool. Left ventricular assist devices (HVAD, HeartWare) were implanted in a left ventricle (LV) apex to proximal descending aorta configuration. Cell proliferation was identified using BrdU (5 mg/kg) injections over the last 45 treatment days. Echocardiography was performed weekly. End-organ regional blood flow (RBF) was quantified at study endpoints using fluorescently labeled microspheres. Before treatment, IHF calves had an ejection fraction (EF) of 33 +/- 2% and left ventricular end-diastolic volume of 214 +/- 18 ml with cardiac cachexia (0.69 +/- 0.06 kg/day). Healthy weight gain was restored in all groups (0.89 +/- 0.03 kg/day). EF increased with P-ECM + HVAD from 36 +/- 5% to 75 +/- 2%, HVAD 38 +/- 4% to 58 +/- 5%, and P-ECM 27 +/- 1% to 66 +/- 6%. P-ECM + HVAD demonstrated the largest increase in cell proliferation and end-organ RBF. This study demonstrates the feasibility of combined LVAD support with P-ECM injection to stimulate new cell proliferation and improve cardiac function, which warrants further investigation.
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