title: Hemodynamic changes in a model of chronic heart failure induced by multiple sequential coronary microembolization in sheep.
abstract: Although a large variety of animal models for acute ischemia and acute heart failure exist, valuable models for studies on the effect of ventricular assist devices in chronic heart failure are scarce. We established a stable and reproducible animal model of chronic heart failure in sheep and aimed to investigate the hemodynamic changes of this animal model of chronic heart failure in sheep. In five sheep (n = 5, 77 +/- 2 kg), chronic heart failure was induced under fluoroscopic guidance by multiple sequential microembolization through bolus injection of polysterol microspheres (90 microm, n = 25.000) into the left main coronary artery. Coronary microembolization (CME) was repeated up to three times in 2 to 3-week intervals until animals started to develop stable signs of heart failure. During each operation, hemodynamic monitoring was performed through implantation of central venous catheter (central venous pressure [CVP]), arterial pressure line (mean arterial pressure [MAP]), implantation of a right heart catheter {Swan-Ganz catheter (mean pulmonary arterial pressure [PAP mean])}, pulmonary capillary wedge pressure (PCWP), and cardiac output [CO]) as well as pre- and postoperative clinical investigations. All animals were followed for 3 months after first microembolization and then sacrificed for histological examination. All animals developed clinical signs of heart failure as indicated by increased heart rate (HR) at rest (68 +/- 4 bpm [base] to 93 +/- 5 bpm [3 mo][P < 0.05]), increased respiratory rate (RR) at rest (28 +/- 5 [base] to 38 +/- 7 [3 mo][P < 0.05]), and increased body weight 77 +/- 2 kg to 81 +/- 2 kg (P < 0.05) due to pleural effusion, peripheral edema, and ascites. Hemodynamic signs of heart failure were revealed as indicated by increase of HR, RR, CVP, PAP, and PCWP as well as a decrease of CO, stroke volume, and MAP 3 months after the first CME. Multiple sequential intracoronary microembolization can effectively induce myocardial dysfunction with clinical and hemodynamic signs of chronic ischemic cardiomyopathy. The present model may be suitable in experimental work on heart failure and left ventricular assist devices, for example, for studying the impact of mechanical unloading, mechanisms of recovery, and reverse remodeling.
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University of Goettingen, Goettingen, Germany. schmitto@med.uni-goettingen.de
authors.forename: Jan Dieter
authors.initials: JD
authors.lastname: Schmitto
authors.forename: Kasim Oguz
authors.initials: KO
authors.lastname: Coskun
authors.forename: Sinan Tolga
authors.initials: ST
authors.lastname: Coskun
authors.forename: Philipp
authors.initials: P
authors.lastname: Ortmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Vorkamp
authors.forename: Florian
authors.initials: F
authors.lastname: Heidrich
authors.forename: Samuel
authors.initials: S
authors.lastname: Sossalla
authors.forename: Aron-Frederik
authors.initials: AF
authors.lastname: Popov
authors.forename: Theodor
authors.initials: T
authors.lastname: Tirilomis
authors.forename: José
authors.initials: J
authors.lastname: Hinz
authors.forename: Jan
authors.initials: J
authors.lastname: Heuer
authors.forename: Michael
authors.initials: M
authors.lastname: Quintel
authors.forename: Frederick Yen-Ching
authors.initials: FY
authors.lastname: Chen
authors.forename: Friedrich Albert
authors.initials: FA
authors.lastname: Schöndube
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004562:Electrocardiography; D004617:Embolism / Q000601:surgery; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology* / Q000601:surgery; D006439:Hemodynamics; D008863:Microspheres; D009206:Myocardium / Q000473:pathology; D012756:Sheep