04 February 2019 by Baktybek Kojonazarov

Multi-phase analysis of the right ventricular systolic and diastolic function in rats with severe pulmonary hypertension using microCT

Background:

The use of microCT to assess the key functional parameters of systolic emptying or diastolic filling in small animals has not been previously reported. The aim of the study was to test whether microCT can assess the dynamics of both left ventricle (LV) and right ventricle (RV) diastolic filling and systolic emptying in an experimental model of pulmonary arterial hypertension (PAH)

Methods and Results.

The Wistar-Kyoto rats were injected subcutaneously with the VEGF-receptor inhibitor SU5416 (20 mg/kg body weight) and were then exposed to chronic hypoxia (10% oxygen) for 21 days (SuHx) followed by normoxia for an additional two weeks. Thereafter, multi-phase cine cardiac images were acquired using a microCT scanner in conjunction with a blood-pool iodinated contrast agent. Examination of the 3D images of SuHx rats confirmed the presence of severe PAH. Functional parameters that describe the dynamics of ventricular systolic ejection and diastolic filling were calculated. RV peak ejection rate (PER) was significantly decreased (P<0.03) in SuHx rats compared with controls. RV peak filling rate (PFR) had a significant decrease compared with controls (P<0.03), particularly in the early phase of diastole (P<0.03). This was accompanied by increased time to PFR (P<0.03) and total filling time (P<0.06).
Spearman analysis between microCT RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation.

Conclusions.

We developed a method that allows rapid and accurate assessment of cardiac functional indices and that paves the way for more extensive preclinical cardiovascular research.

Key Contributors

Baktybek Kojonazarov, MD, PhD* 1, Alexander Belenkov, MD, PhD 2, Shohei Shinomiya, MD 3, Jochen Wilchelm, PhD 1, Marian Kampschulte, MD 1, Shiro Mizuno, MD 3, Hossein Ardeschir Ghofrani, MD 1, Friedrich Grimminger, MD, PhD 1, Norbert Weissmann PhD 1, Werner Seeger, MD 1,4 & Ralph Theo Schermuly, PhD* 1 : 1.Justus Liebig University of Giessen, German Center for Lung Research (DZL), Giessen, Germany; 2.PerkinElmer, Waltham, USA; 3.Kanazawa Medical University, Ishikawa, Japan; 4.Max-Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.


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