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Trial Lecture – time and place
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Adjudication committee
- First opponent: Associate Professor Victoria Delgado, University Autonomous of Barcelona, Spain
- Second opponent: Associate Professor Helga Midtbø, University of Bergen, Norway
- Third member and chair of the evaluation committee: Professor Henrik Schirmer, University of Oslo
Chair of the Defence
Professor II Mona-Elisabeth Rootwelt Revheim, University of Oslo
Principal Supervisor
Associate Professor Emil Knut Stenersen Espe, University of Oslo
Summary
This thesis is within the field of cardiology and investigates how well non-invasive imaging biomarkers of diastolic function reflect left ventricular (LV) chamber stiffness in a rat model of pressure overload.
Pressure overload of the LV, as in aortic stenosis, can cause LV hypertrophy, myocardial fibrosis and increased LV chamber stiffness. This may eventually lead to diastolic dysfunction and heart failure. Rat models are widely used to discover and test new therapies, and non-invasive imaging plays a crucial role in characterising disease development. However, how well imaging biomarkers of diastolic function reflect LV chamber stiffness in rats has not been established. The main research question was whether imaging biomarkers from cardiovascular magnetic resonance (CMR) and echocardiography reflect invasively measured LV chamber stiffness, and whether early biomarkers predict later myocardial fibrosis.
We established a high-precision rat model in which the ascending aorta was constricted with O-rings of different inner diameters. Young male rats were examined by CMR, echocardiography, pressure-volume catheterisation, gene expression analysis and histology up to 20 weeks after surgery. LV chamber stiffness was measured invasively as the slope of the end-diastolic pressure-volume relationship.
Our results showed that imaging biomarkers from both CMR and echocardiography reflected LV chamber stiffness. Left atrial function and size were among the best performing. Over 20 weeks, banded rats developed progressive diastolic dysfunction with preserved ejection fraction, and left atrial diameter at 4 weeks independently predicted myocardial fibrosis at 20 weeks.
These findings provide a high-precision rat model of pressure overload and non-invasive imaging biomarkers validated against LV chamber stiffness as reliable endpoints for preclinical studies of diastolic dysfunction.
Additional information
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