title: Neuropeptide Y improves myocardial perfusion and function in a swine model of hypercholesterolemia and chronic myocardial ischemia.
abstract: Pharmacologically induced angiogenesis could be a promising option in clinical situations with diffuse inoperable coronary artery disease e.g. metabolic syndrome and diabetes mellitus. The failure of focused cytokine, stem cell and gene therapies to achieve both perfusion and functional improvement in clinical trials suggests a more centralized control mechanism. Neuropeptide-Y (NPY) is one such natural neurotransmitter that is known to exert a multifaceted role during neo-angiogenesis and can possibly act as the central control. To date, the ability to harness the 'master switch' nature of NPY in a specific experimental model of metabolic syndrome and chronic myocardial ischemia has not been conclusively demonstrated. We hypothesized that infiltration of NPY into an area of chronic ischemia in a metabolic syndrome swine model would induce angiogenesis and improve myocardial perfusion and function. An osmotic pump was inserted three weeks after surgical induction of focal myocardial ischemia. We delivered either NPY or placebo for five weeks, after which the myocardial tissue was harvested for analysis. Assessments of myocardial perfusion and function were performed at each stage of the experiment. Local infiltration of NPY significantly improved collateral vessel formation, blood flow and myocardial function. We believe activation of NPY receptors may be a potential target therapy for patients with diffuse coronary artery disease.
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Anesthesia and Critical Care, Boston, MA, USA.
authors.forename: Robina
authors.initials: R
authors.lastname: Matyal
authors.forename: Louis
authors.initials: L
authors.lastname: Chu
authors.forename: Feroze
authors.initials: F
authors.lastname: Mahmood
authors.forename: Michael P
authors.initials: MP
authors.lastname: Robich
authors.forename: Angela
authors.initials: A
authors.lastname: Wang
authors.forename: Philip E
authors.initials: PE
authors.lastname: Hess
authors.forename: Sajid
authors.initials: S
authors.lastname: Shahul
authors.forename: Duane S
authors.initials: DS
authors.lastname: Pinto
authors.forename: Kamal
authors.initials: K
authors.lastname: Khabbaz
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000188:drug therapy / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013552:Swine
chemical_list: D043925:Angiogenesis Inducing Agents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y