D28-13 A Time Course Evaluation of Pulmonary Hypertension Using Ultrasound, Catheterization, and Fulton Index

Abstract

Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance, and the primary cause of increased resistance is a decrease in intraluminal diameter due to sustained pulmonary vasoconstriction, concentric pulmonary arterial wall thickening, and obliterative lesions in small pulmonary arteries. Assessment of right ventricular systolic pressure (RVSP) is commonly used as a surrogate for pulmonary artery systolic pressure in small animals (e.g., mice) because direct measurement of mean pulmonary arterial pressure is technically challenging. Pulmonary arterial flow and velocity are influenced by resistance in pulmonary circulation, pulmonary arterial diameter, as well as cardiac output, and the pulmonary artery acceleration time to ejection time (PAT/PET) ratio is also used as a surrogate measure of pulmonary artery pressure and vascular resistance. PAT/PET assessment can be performed using noninvasive echocardiography; therefore, many investigators have recently begun using this method. Those two methods have advantages and disadvantages; RVSP measurement provides more stable, reproducible data across researchers than echocardiography, which can be influenced by technical skills and anatomical differences, including transducer angles and fat volumes. A major disadvantage of RVSP is that it requires a terminal experiment. In this study, we determined the sensitivity and reproducibility of RVSP and PAT/PET assessment in PH mice. Mice were induced to PH using Sugen 5416 (20 mg/kg, s.c.) once a week injection with constant exposure to hypoxia (10% O2). We measured PAT/PET, 3D RV strain, RVSP, and Fulton index in mice 1, 2, and 3 weeks after Sugen injection and found that RVSP was the most sensitive assessment, with a significant increase even 1 week after PH induction. On the other hand, PAT/PET shows a significant increase at the later stage of PH. Surprisingly, the Fulton index increased slightly, but significantly, even 1 week after PH induction, and continued to progress over the weeks. The most insensitive or unreproducible assessment was 3D strain measurement in our laboratory; however, this might be partially due to differences in individual skill development, and there is still room to improve this technique and its stabilization. In summary, although RVSP is an invasive and terminal experiment, it can yield sensitive, stable data to detect PH development. PAT/PET assessment also provides relatively reproducible data compared to 3D strain assessment, but early/small changes cannot be detected. Therefore, this method might be suited to a restation study in mice with fully developed PH, but not to a time-course study of PH development.

This abstract is funded by: HL146764