title: Non-invasive technology that improves cardiac function after experimental myocardial infarction: Whole Body Periodic Acceleration (pGz).
abstract: Myocardial infarction (MI) may produce significant inflammatory changes and adverse ventricular remodeling leading to heart failure and premature death. Pharmacologic, stem cell transplantation, and exercise have not halted the inexorable rise in the prevalence and great economic costs of heart failure despite extensive investigations of such treatments. New therapeutic modalities are needed. Whole Body Periodic Acceleration (pGz) is a non-invasive technology that increases pulsatile shear stress to the endothelium thereby producing several beneficial cardiovascular effects as demonstrated in animal models, normal humans and patients with heart disease. pGz upregulates endothelial derived nitric oxide synthase (eNOS) and its phosphorylation (p-eNOS) to improve myocardial function in models of myocardial stunning and preconditioning. Here we test whether pGz applied chronically after focal myocardial infarction in rats improves functional outcomes from MI. Focal MI was produced by left coronary artery ligation. One day after ligation animals were randomized to receive daily treatments of pGz for four weeks (MI-pGz) or serve as controls (MI-CONT), with an additional group as non-infarction controls (Sham). Echocardiograms and invasive pressure volume loop analysis were carried out. Infarct transmurality, myocardial fibrosis, and markers of inflammatory and anti-inflammatory cytokines were determined along with protein analysis of eNOS, p-eNOS and inducible nitric oxide synthase (iNOS).At four weeks, survival was 80% in MI-pGz vs 50% in MI-CONT (p< 0.01). Ejection fraction and fractional shortening and invasive pressure volume relation indices of afterload and contractility were significantly better in MI-pGz. The latter where associated with decreased infarct transmurality and decreased fibrosis along with increased eNOS, p-eNOS. Additionally, MI-pGz had significantly lower levels of iNOS, inflammatory cytokines (IL-6, TNF-α), and higher level of anti-inflammatory cytokine (IL-10). pGz improved survival and contractile performance, associated with improved myocardial remodeling. pGz may serve as a simple, safe, non-invasive therapeutic modality to improve myocardial function after MI.
authors: Division of Neonatology, Mount Sinai Medical Center, Miami Beach, FL, United States of America.
authors: Arkady
authors: A
authors: Uryash
authors: Division of Neonatology, Mount Sinai Medical Center, Miami Beach, FL, United States of America.
authors: Jorge
authors: J
authors: Bassuk
authors: Columbia Heart Source, Columbia University College of Physicians and Surgeons, New York, NY, United States of America.
authors: Paul
authors: P
authors: Kurlansky
authors: Departments of Molecular Bioscience, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: Francisco
authors: F
authors: Altamirano
authors: Departments of Molecular Bioscience, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America.
authors: Jose R
authors: JR
authors: Lopez
authors: Division of Neonatology, Mount Sinai Medical Center, Miami Beach, FL, United States of America.
authors: Jose A
authors: JA
authors: Adams
mesh_terms: D000054:Acceleration; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D033081:Shear Strength; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III