2014
DOI: 10.1183/09031936.00204813
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SuHx rat model: partly reversible pulmonary hypertension and progressive intima obstruction

Abstract: 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 … Show more

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Cited by 86 publications
(87 citation statements)
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“…This was not performed in the current study owing to the present limitation in identifying pharmacological reagents that selectively target cardiac autophagy. Secondly, another potential limitation of our study is that the autophagy signatures in the RV of the MCT model associated with PH could be very different from other animal models of PH due to hypoxia, Sugen/ hypoxia, hyperflow, [34] and the PAB rat model [54]. For example, the PAB model impacts RV hypertrophy but has no impact on the pulmonary vasculature—possibly one of the important causes of RV hypoxia in the MCT model that may also impact autophagy in the RV [29].…”
Section: Discussionmentioning
confidence: 98%
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“…This was not performed in the current study owing to the present limitation in identifying pharmacological reagents that selectively target cardiac autophagy. Secondly, another potential limitation of our study is that the autophagy signatures in the RV of the MCT model associated with PH could be very different from other animal models of PH due to hypoxia, Sugen/ hypoxia, hyperflow, [34] and the PAB rat model [54]. For example, the PAB model impacts RV hypertrophy but has no impact on the pulmonary vasculature—possibly one of the important causes of RV hypoxia in the MCT model that may also impact autophagy in the RV [29].…”
Section: Discussionmentioning
confidence: 98%
“…In addition, animal models (i.e., PAB model, MCT model, and Sugen/hypoxia models) are used to duplicate aspects of compensatory hypertrophy or overt decompensated states of the RV in order to investigate common mechanisms underlying RV remodeling, respectively. This may be problematic as the cardiac hemodynamics and mechanisms of RV remodeling in different animal models may differ in terms of mechanisms and severity [34, 40]. To avoid potential confounding effects, Paulin and Sutendra objectively measured hemodynamic criteria, clinical features, and echocardiography of the MCT rat model to establish the time course of the specific RV remodeling stages [2, 7].…”
Section: Discussionmentioning
confidence: 99%
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“…3,[7][8][9][10][11][12][13] However, in almost all classical animal models, and in humans with some secondary forms of PH, when the damaging stimulus is removed, inflammation spontaneously resolves with time. [14][15][16] This is not true in human PAH, as inflammation is an integral part of PAH vascular lesions, thus, becoming an important contributing factor to the disease manifestation rather than only being a consequence of the disease. 17 Macrophages can function as agents of defense or destruction 18 to orchestrate pathophysiology of a disease.…”
Section: Introductionmentioning
confidence: 99%
“…7 Of the PH animal models reviewed recently, 6 the most commonly utilized plexogenic arteriopathy PAH rat model that most closely mimics the human phenotype is the Sugen 5416 (SU5416)/hypoxia/normoxia model. 8 SU5416 is a potent and selective vascular endothelial growth factor (VEGF) receptor 1 9 and 2 10 antagonist. It has been well established that SU5416 primarily causes initial endothelial cell (EC) injury and later hyperproliferation of apoptosisresistant ECs, 11 a characteristic of angio-obliterative (plexiform/complex) lesion formation in the development of severe PAH.…”
Section: Introductionmentioning
confidence: 99%