SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

• Published in: The European respiratory journal Vol. 44; no. 1; pp. 160 - 168
• Main Authors: DE RAAF, Michiel Alexander, SCHALIJ, Ingrid, GOMEZ-ARROYO, Jose, ROL, Nina, HAPPE, Chris, DE MAN, Frances S, VONK-NOORDEGRAAF, Anton, WESTERHOF, Nico, VOELKEL, Norbert F, BOGAARD, Harm Jan
• Format: Journal Article
• Language: English
• Published: Leeds Maney 01-07-2014
• Subjects: Angiogenesis Inhibitors - chemistry; Animals; Biological and medical sciences; Circadian Rhythm; Disease Models, Animal; Disease Progression; Echocardiography; Heart Ventricles - pathology; Hemodynamics; Humans; Hypertension, Pulmonary - physiopathology; Hypertrophy, Right Ventricular - physiopathology; Hypoxia - physiopathology; Indoles - chemistry; Lung - physiopathology; Male; Medical sciences; Pneumology; Pulmonary Artery - pathology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pyrroles - chemistry; Rats; Rats, Sprague-Dawley; Systole; Telemetry; Tunica Intima - pathology; Vascular Remodeling; Progressive; Animal model; Vertebrata; Mammalia; Rat; Respiratory disease; Rodentia; Intima; Cardiovascular disease; Obstruction; Pulmonary hypertension
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00204813

The SU5416 combined with hypoxia (SuHx) rat model features angio-obliterative pulmonary hypertension resembling human pulmonary arterial hypertension. Despite increasing use of this model, a comprehensive haemodynamic characterisation in conscious rats has not been reported. We used telemetry to characterise haemodynamic responses in SuHx rats and associated these with serial histology. Right ventricular systolic pressure (RVSP) increased to a mean±sd of 106±7 mmHg in response to SuHx and decreased but remained elevated at 72±8 mmHg upon return to normoxia. Hypoxia-only exposed rats showed a similar initial increase in RVSP, a lower maximum RVSP and near-normalisation of RVSP during subsequent normoxia. Progressive vascular remodelling consisted of a four-fold increase in intima thickness, while only minimal changes in media thickness were found. The circadian range in RVSP provided an accurate longitudinal estimate of vascular remodelling. In conclusion, in SuHx rats, re-exposure to normoxia leads to a partial decrease in pulmonary artery pressure, with persisting hypertension and pulmonary vascular remodelling characterised by progressive intima obstruction.