title: Myocardial infarction and functional outcome assessment in pigs.
abstract: Introduction of newly discovered cardiovascular therapeutics into first-in-man trials depends on a strictly regulated ethical and legal roadmap. One important prerequisite is a good understanding of all safety and efficacy aspects obtained in a large animal model that validly reflect the human scenario of myocardial infarction (MI). Pigs are widely used in this regard since their cardiac size, hemodynamics, and coronary anatomy are close to that of humans. Here, we present an effective protocol for using the porcine MI model using a closed-chest coronary balloon occlusion of the left anterior descending artery (LAD), followed by reperfusion. This approach is based on 90 min of myocardial ischemia, inducing large left ventricle infarction of the anterior, septal and inferoseptal walls. Furthermore, we present protocols for various measures of outcome that provide a wide range of information on the heart, such as cardiac systolic and diastolic function, hemodynamics, coronary flow velocity, microvascular resistance, and infarct size. This protocol can be easily tailored to meet study specific requirements for the validation of novel cardioregenerative biologics at different stages (i.e. directly after the acute ischemic insult, in the subacute setting or even in the chronic MI once scar formation has been completed). This model therefore provides a useful translational tool to study MI, subsequent adverse remodeling, and the potential of novel cardioregenerative agents.
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht; Interuniversity Cardiology Institute of the Netherlands; S.Koudstaal@umcutrecht.nl.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koudstaal
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Sanne
authors.initials: S
authors.lastname: Jansen of Lorkeers
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Johannes M I H
authors.initials: JM
authors.lastname: Gho
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Gerardus P J
authors.initials: GP
authors.lastname: van Hout
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Marlijn S
authors.initials: MS
authors.lastname: Jansen
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Gründeman
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht; Interuniversity Cardiology Institute of the Netherlands.
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht; Interuniversity Cardiology Institute of the Netherlands.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht.
authors.forename: Imo E
authors.initials: IE
authors.lastname: Hoefer
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht; s.a.j.chamuleau@umcutrecht.nl.
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D054059:Coronary Occlusion / Q000209:etiology; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D009203:Myocardial Infarction / Q000209:etiology* / Q000503:physiopathology*; D013552:Swine