Abstract
Swine are important translational research models for developing and gaining regulatory approval for novel therapies for heart failure. Three swine species in particular are utilized in these studies, the Domestic Yorkshire (DY), Yucatan Minipigs (Yuc), and Göttingen minipigs (Gott). Selecting the right swine breed is important to the translational success of novel therapies and is the source of debate in the field. The current study compared interventionally induced Ischemia-reperfusion injury (IRI), a method that mimics clinical myocardial infarction and subsequent heart failure, in these breeds. Interventional IRI was induced by occluding the Left Anterior Descending Coronary Artery for 90 minutes using a PTCA balloon placed distal to the first diagonal branch. Yuc have the highest rate of survival of the three breeds following a 90 min occlusion (81%; 56 out of 69), Gott survival was 70% (28 out of 40), and DY survival was 57% (75 out of 131). Assessment of serum levels of Cardiac Troponin I (CTnI) revealed significant increases in this parameter that peak at 3 hrs following occlusion. Gott have the highest levels at 122ng/mL, followed by Yuc (99ng/mL), and DY (85ng/mL) at this time point. Functionally, all three breeds displayed an Ejection Fraction assessed by echocardiography of less than 40%, with Gott having the lowest mean, followed by Yuc, and DY. These levels remain low or decrease slightly over 1 to 4 months. Magnetic Resonance imaging demonstrates infarct sizes are approximately 25% of the left ventricle following 1 month and decreasing over time to 22% at 2 months post and 13% 4 months post. Additionally, all three species lose their hemodynamic responsiveness to dobutamine challenge following IRI. All three breeds respond similarly to IRI functionally and structurally, and they develop the clinical features of congestive heart failure, the main distinguishing factor in the current study was survival of the IRI procedure. Based on this data, factors such as rate of body weight gain in relation to the ability to obtain functional endpoints, availability, and other practical considerations should drive the selection of breed for translational studies.
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