title: Feasibility study of particulate extracellular matrix (P-ECM) and left ventricular assist device (HVAD) therapy in chronic ischemic heart failure bovine model.
abstract: 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.
authors.affiliation: From the *Department of Cardiovascular and Thoracic Surgery, University of Louisville, Louisville, Kentucky; †Department of Bioengineering, University of Louisville, Louisville, Kentucky; ‡Cardiovascualr Innovation Institute, University of Louisville, Louisville, Kentucky; §Department of Medicine, University of Louisville, Louisville, Kentucky; ¶Department of Pediatrics, University of Louisville, Louisville, Kentucky; ‖CorMatrix Cardiovascular, Inc., Roswell, Georgia; and #Research Resource Facilities, University of Louisville, Louisville, Kentucky.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Soucy
authors.forename: Erin F
authors.initials: EF
authors.lastname: Smith
authors.forename: Gretel
authors.initials: G
authors.lastname: Monreal
authors.forename: Gregg
authors.initials: G
authors.lastname: Rokosh
authors.forename: Brad B
authors.initials: BB
authors.lastname: Keller
authors.forename: Fangping
authors.initials: F
authors.lastname: Yuan
authors.forename: Robert G
authors.initials: RG
authors.lastname: Matheny
authors.forename: Anna M
authors.initials: AM
authors.lastname: Fallon
authors.forename: Beecher C
authors.initials: BC
authors.lastname: Lewis
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Sherwood
authors.forename: Michael A
authors.initials: MA
authors.lastname: Sobieski
authors.forename: Guruprasad A
authors.initials: GA
authors.lastname: Giridharan
authors.forename: Steven C
authors.initials: SC
authors.lastname: Koenig
authors.forename: Mark S
authors.initials: MS
authors.lastname: Slaughter
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods*; D002417:Cattle; D004195:Disease Models, Animal; D004655:Emulsions; D005109:Extracellular Matrix / Q000502:physiology*; D005240:Feasibility Studies; D006333:Heart Failure / Q000503:physiopathology / Q000601:surgery* / Q000628:therapy*; D006353:Heart-Assist Devices; D006439:Hemodynamics; D007267:Injections; D009206:Myocardium / Q000473:pathology; D010316:Particle Size; D012039:Regional Blood Flow; D013552:Swine; D054457:Tissue Scaffolds; D016277:Ventricular Function, Left
chemical_list: D004655:Emulsions