Understanding longitudinal biventricular structural and functional changes in a pulmonary hypertension Sugen-hypoxia rat model by cardiac magnetic resonance imaging

Geeshath Jayasekera; Kathryn S Wilson; Hanna Buist; Rosemary Woodward; Aysel Uckan; Colin Hughes; Margaret Nilsen; A Colin Church; Martin K Johnson; Lindsay Gallagher; James Mullin; Mandy R MacLean; William M Holmes; Andrew J Peacock; David J Welsh

doi:10.1177/2045894019897513

Understanding longitudinal biventricular structural and functional changes in a pulmonary hypertension Sugen-hypoxia rat model by cardiac magnetic resonance imaging

Pulm Circ. 2020 Feb 10;10(1):2045894019897513. doi: 10.1177/2045894019897513. eCollection 2020 Jan-Mar.

Authors

Affiliations

¹ ICAMS, University of Glasgow, Glasgow, UK.
² Scottish Pulmonary Vascular Unit, Glasgow Caledonian University, Glasgow, UK.
³ CRF, University of Glasgow, Glasgow, UK.
⁴ GEMRIC, INP, University of Glasgow, Glasgow, UK.

Abstract

Cardiac magnetic resonance-derived ventricular variables are predictive of mortality in pulmonary arterial hypertension. Rodent models which emphasize ventricular function, allowing serial monitoring, are needed to identify pathophysiological features and novel therapies for pulmonary arterial hypertension. We investigated longitudinal changes in the Sugen-hypoxia model during disease progression. Sprague Dawley rats (n = 32) were divided into two groups. (1) Sugen-hypoxia: a dose of subcutaneous Sugen-5416 and placed in hypobaric hypoxia for two weeks followed by normoxia for three weeks. (2) Normoxia: maintained at normal pressure for five weeks. Rats were examined at five or eight weeks with right-heart catheter, cardiac magnetic resonance, and autopsy. Compared to normoxic controls (23.9 ± 4.1 mmHg), right ventricular systolic pressure was elevated in Sugen-hypoxia rats at five and eight weeks (40.9 ± 15.5 mmHg, p = 0.026; 48.9 ± 9.6 mmHg, p = 0.002). Right ventricular end-systolic volume index was increased in eight weeks Sugen-hypoxia (0.28 ± 0.04 µlcm^-2, p = 0.003) compared to normoxic controls (0.18 ±0.03 mlcm^-2). There was progressive dilatation of the right ventricular at eight weeks Sugen-hypoxia compared to normoxic controls (0.75 ± 0.13 µlcm^-2 vs 0.56 ± 0.1 µlcm^-2 p = 0.02). Ventricle mass index by cardiac magnetic resonance at five weeks (0.34 ± 0.06, p = 0.003) and eight weeks Sugen-hypoxia (0.34 ± 0.06, p = 0.002) were higher than normoxic controls (0.21 ± 0.04). Stroke volume, right ventricular ejection fraction, and left ventricular variables were preserved in Sugen-hypoxia. Ventricular changes during the course of illness in a pulmonary arterial hypertension rodent model can be examined by cardiac magnetic resonance. These changes including right ventricular hypertrophy and subsequent dilatation are similar to those seen in pulmonary arterial hypertension patients. Despite the persisting pulmonary hypertension, there are features of adaptive cardiac remodeling through the study duration.

Keywords: cardiac magnetic resonance (CMR); left ventricle; pulmonary arterial hypertension; right ventricle.