RevaTen platelet-rich plasma improves cardiac function after myocardial injury.
OBJECTIVE
Cell therapy is an exciting area of investigation for repair of injured myocardial tissue. Platelet-rich plasma (PRP) is an autologous fractionation of whole blood containing high concentrations of growth factors including vascular endothelial growth factor and insulin-like growth factor, among many others. PRP has been shown to safely and effectively enhance healing of musculoskeletal tissue primarily by reparative cell signaling. Despite a growing body of evidence on PRP's safety and efficacy, limited studies have been performed using PRP in cardiovascular tissues. Utilizing a murine myocardial permanent ligation and ischemia/reperfusion model, this study sought to determine whether RevaTen PRP (Menlo Park, CA, USA), a proprietary formulation of PRP, improves cardiac function as measured by left ventricular ejection fraction (LVEF).


METHODS
Via thoracotomy, the left anterior descending arteries (LAD) of 28 mice were occluded by suture either permanently or for 45 min to induce ischemic injury and then reperfused. Mice undergoing permanent ligation had intramyocardial injections of either RevaTen PRP (n=5) or phosphate-buffered saline (PBS; n=4). Magnetic resonance (MR) imaging was performed to calculate LVEF at 7 days. Mice undergoing ischemia and reperfusion had intramyocardial injections of either PRP (n=10) or PBS (n=9) and underwent MR imaging to calculate LVEF at 21 days. Hearts were harvested for histologic examination following imaging.


RESULTS
Compared with PBS controls, RevaTen PRP-treated animals that underwent LAD ligation had a 38% higher LVEF 7 days after injury (PRP=36.1±6.1%; PBS=26.4±3.6%, P=.027). Compared with PBS controls, PRP-treated animals who underwent ischemia-reperfusion of the LAD had a 28% higher LVEF 21 days after injury (PRP=37.6±4.8%, control=29.3±9.7%, P=.038). Histologic analysis suggested the presence of more scar tissue in the control group compared to the PRP-treated animals.


CONCLUSIONS
MR imaging demonstrated a positive effect of RevaTen PRP on left ventricular function in both a ligation and ischemia-reperfusion murine model. Our results suggest RevaTen PRP should be investigated further as a potential point-of-care biologic treatment following myocardial injury.
BioParadox, Inc., Menlo Park, CA, USA. Electronic address: am@bioparadox.com.
Allan
A
Mishra
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Jeff
J
Velotta
Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, USA.
Todd J
TJ
Brinton
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Xi
X
Wang
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Stephanie
S
Chang
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Owen
O
Palmer
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Ahmad
A
Sheikh
Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, USA.
Jaehoon
J
Chung
Division of Cardiovascular Medicine, Stanford University Medical Center, Stanford, CA, USA.
Phillip Chung-Ming
PC
Yang
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Robert
R
Robbins
Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, CA, USA.
Michael
M
Fischbein
D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019028:Magnetic Resonance Imaging, Cine; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D053657:Platelet-Rich Plasma; D020127:Recovery of Function; D013318:Stroke Volume; D013997:Time Factors; D016277:Ventricular Function, Left