Evaluating Systolic and Diastolic Cardiac Function in Rodents Using Microscopic Computed Tomography

The use of microscopic computed tomography 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 microscopic computed tomography can assess the dynamics of both left ventricle and right ventricle (RV) diastolic filling and systolic emptying in an experimental model of pulmonary arterial hypertension Methods and Results: The Wistar-Kyoto rats were injected subcutaneously with the VEGF (vascular endothelial growth factor)-receptor inhibitor SU5416 (20 mg/kg body weight) and were then exposed to chronic hypoxia (10% oxygen) for 21 days (SU5416-hypoxia) followed by normoxia for an additional 2 weeks. Thereafter, multiphase cine cardiac images were acquired using a microscopic computed tomography scanner in conjunction with a blood-pool iodinated contrast agent. Examination of the 3-dimensional images of SU5416-hypoxia rats confirmed the presence of severe pulmonary arterial hypertension. Functional parameters that describe the dynamics of ventricular systolic ejection and diastolic filling were calculated. RV peak ejection rate was significantly decreased ( P<0.03) in SU5416-hypoxia rats compared with controls. RV peak filling rate 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 peak filling rate ( P<0.03) and total filling time ( P<0.06). Spearman analysis between microscopic computed tomography RV diastolic indices and invasively derived RV end-diastolic pressure indicated excellent correlation.

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.