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.
Highlights
Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature; it is subsequent right ventricular (RV) failure that is the main cause of morbidity and mortality in patients
Compared to normoxic rats (23.87 Æ 4.1 mmHg), RV systolic pressure (RVSP) was significantly elevated in SuHx rats at both five and eight weeks (40.95 Æ 15.5 mmHg, p 1⁄4 0.03; 48.89 Æ 9.6 mmHg, p 1⁄4 0.002, respectively)
There were no significant differences in RVSP between SuHx rats at five and eight weeks
Summary
Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature; it is subsequent right ventricular (RV) failure that is the main cause of morbidity and mortality in patients. Cardiac magnetic resonance (CMR) is a non-invasive imaging tool providing high-resolution. During CMR, ventricular short axis stacks are used to reconstruct a 3D image of the right and the left ventricle (LV), and ventricular volumes, mass, and function can be measured.[1] Many CMR measurements have shown to be strongly predictive of mortality and survival offering potential for assessing response to treatment. Stroke volume,[2] RV ejection fraction,[3] and RV and LV end-diastolic volume (EDV)[4] have all shown to be prognostic markers in PAH patients
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