Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Giraffe as a Natural Animal Model for Resistance to Heart Failure with Preserved Ejection Fraction

Version 1 : Received: 28 October 2020 / Approved: 30 October 2020 / Online: 30 October 2020 (08:06:24 CET)

How to cite: Horowitz, B.N.; Baccouche, B.; Shivkumar, T.; Bertelsen, M.F.; Aalkjær, C.; Smerup, M.; Ajijola, O.A.; Hadaya, J.; Wang, T. The Giraffe as a Natural Animal Model for Resistance to Heart Failure with Preserved Ejection Fraction. Preprints 2020, 2020100625 (doi: 10.20944/preprints202010.0625.v1). Horowitz, B.N.; Baccouche, B.; Shivkumar, T.; Bertelsen, M.F.; Aalkjær, C.; Smerup, M.; Ajijola, O.A.; Hadaya, J.; Wang, T. The Giraffe as a Natural Animal Model for Resistance to Heart Failure with Preserved Ejection Fraction. Preprints 2020, 2020100625 (doi: 10.20944/preprints202010.0625.v1).

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

Subject Areas

heart failure; cardiovascular; comparative; evolution

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