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A1182 - Evaluating Systolic and Diastolic Biventricular Function in Experimental Pulmonary Arterial Hypertension Using Microscopic Computed Tomography
Author Block: B. Kojonazarov1, A. Belenkov2, S. Shinomiya3, M. Kampschulte1, S. Mizuno4, H. A. Ghofrani1, F. Grimminger1, N. Weissmann1, W. Seeger1, R. T. Schermuly1; 1Universities of Giessen and Marburg Lung Center, Giessen, Germany, 2PerkinElmer, Waltham, MA, United States, 3Respiratory medicine, Kanazawa Medical University, Ishikawa, Japan, 4Division of Respiratory Disease, Kanazawa Medical University, Ishikawa, Japan.
Rationale. Microscopic computed tomography (microCT) is a powerful imaging modality for non-invasive and longitudinal investigation of animal models of human disease. Numerous research groups have demonstrated the usefulness of microCT for quantification of cardiac morphology and global ventricular systolic indices such as stroke volume, ejection fraction, and cardiac output. To our knowledge, however, the use of microCT to assess other key functional parameters of systolic emptying or diastolic filling has not been previously reported. Methods. Rats (Wistar-Kyoto, male, 7-10 weeks old) purchased from Charles River Laboratories (Wilmington, MA, USA) were used for experimental data. The rats were injected subcutaneously with the VEGFr 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. Quantitative multi-phase cine cardiac images were acquired 35 days after SU5416 injection using a Quantum GX microCT scanner (Rigaku, Japan) in conjunction with a blood-pool iodinated contrast agent, eXIA160XL (Binitio Biomedical, Inc., Canada). Results. Examination of 3D images from SuHx rats confirmed the presence of severe PAH, indicated by marked right-sided cardiac chamber enlargement and dilation of the pulmonary artery, flattening interventricular septum with septal shift towards the LV and a compressed “D-shaped” LV. Functional parameters that describe the dynamics of LV and RV systolic emptying and diastolic filling were calculated. Normalized peak ejection rate (PER) was significantly decreased in the RV (P =0.0001) and increased in the LV (P = 0.02) in SuHx rats compared with controls. RV peak filling rate (PFR) a significant decrease compared with controls (P=0.0002), particularly in the early phase of diastole (Mean Filling Rate1/3/End-Diastolic volume, P =0.001). This was accompanied by increased normalized RV time to PFR (P = 0.01) and total filling time (P = 0.004). Linear regression analysis between microCT RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation. Conclusion. Our data for the first time demonstrate the ability of microCT to distinguish differences between the dynamics of diastolic and systolic function in an animal model of PAH with well-documented diastolic dysfunction and normal controls. We have developed a method allows rapid and accurate assessment of cardiac functional indices and paves the way for more extensive preclinical cardiovascular research.