Ultrasound Imaging of Renal Vaso-Occlusive Events in Transgenic Sickle Mice Exposed to Hypoxic Stress

Abstract 

One of the major clinical manifestations of sickle cell disease (SCD) is vaso-occlusive crisis in response to hypoxic exposure, leading to acute and chronic organ damages, especially in kidneys. In a SCD transgenic murine model, ultrasound imaging allowed us to characterize the circulatory changes in renal arteries during vaso-occlusive crisis. Cardiac output, heart rate and renal blood flow velocities (BFV) were measured in 10 male transgenic and 10 male wild-type (WT) mice with a conventional echograph (Vivid 7, GE Medical), before and after hypoxic exposure (8%O₂, 18h). To assess entrapment of red cells, histologic study of the kidneys was performed in both groups. Hypoxic exposure decreased heart rates in both groups (–17%, p < 0.001). Cardiac output remained stable in WT, and decreased in transgenic (–26%, p < 0.01). Peak systolic BFV in the renal artery was not modified in both groups. End-diastolic and mean BFV remained stable in WT, but decreased in sickle transgenic (–56%, p < 0.01 and –47%, p < 0.001, respectively). Transgenic mice displayed marked congestion in peritubular capillaries and glomerular abnormalities with trapped sickle red cells, whereas WT did not present any histologic injury. Five hours after hypoxic exposure, blood flow velocities returned to basal values in both groups. Decrease in end-diastolic and mean BFV in absence of peak systolic BFV after hypoxic exposure strongly indicated that the increase in vascular resistance in kidneys related to sickling of red cells. Thus, ultrasound imaging of the renal artery in mouse is a powerful, noninvasive, easy-to-repeat method to evidence circulatory changes in murine models of vascular renal human diseases. (E-mail: philippe.bonnin@lrb.aphp.fr)

Key Words: Sickle cell disease, Mouse, Vaso-occlusive crisis, Ultrasound imaging, Pulsed Doppler, Blood flow velocity, Renal artery, Kidney