title: Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.
abstract: The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of TurkuTurku, Finland; Heart Center, Turku University Hospital and University of TurkuTurku, Finland.
authors.forename: Christoffer K-J
authors.initials: CK
authors.lastname: Stark
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Miikka
authors.initials: M
authors.lastname: Tarkia
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Kentala
authors.affiliation: Heart Center, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Markus
authors.initials: M
authors.lastname: Malmberg
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of TurkuTurku, Finland; Heart Center, Turku University Hospital and University of TurkuTurku, Finland.
authors.forename: Tommi
authors.initials: T
authors.lastname: Vähäsilta
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Savo
authors.affiliation: Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku University Hospital Turku, Finland.
authors.forename: Ville-Veikko
authors.initials: VV
authors.lastname: Hynninen
authors.affiliation: Children's Hospital, Pediatric Cardiology, Helsinki University Hospital Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Helenius
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.
authors.forename: Saku
authors.initials: S
authors.lastname: Ruohonen
authors.affiliation: Department of Vascular Surgery, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Jalkanen
authors.affiliation: Department of Pathology, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Taimen
authors.affiliation: Children's Hospital, Pediatric Cardiology, Helsinki University Hospital Helsinki, Finland.
authors.forename: Tero-Pekka
authors.initials: TP
authors.lastname: Alastalo
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: Turku PET Centre, Turku University Hospital and University of Turku Turku, Finland.
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Savunen
authors.affiliation: Research Center of Applied and Preventive Cardiovascular Medicine, University of Turku Turku, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Koskenvuo
keywords: cardioprotection; cardiopulmonary bypass; coagulation; ischemia-reperfusion injury; thymosin beta 4; vasoconstriction