Histological and SEM Assessment of Blood Stasis in Kidney Blood Vessels after Repeated Intra-Arterial Application of Radiographic Contrast Media
Creators: name: Lamby, Philipp
name: Minkow, Alexander
name: Handt, Stefan
name: Falter, Johannes
name: Schellenberg, Eva-Lotte
name: Graf, Stefanie
name: Hiebl, Bernhard
name: Haerteis, Silke
name: Gemeinhardt, Ole
name: Krüger-Genge, Anne
name: Klosterhalfen, Bernd
name: Jung, Ernst-Michael
name: Franke, Ralf-Peter
name: Momeni, Arash
name: Prantl, Lukas
name: Jung, Friedrich
Publisher: name: Universität Regensburg
Year: 2020
Subjects: subject: INDUCED NEPHROPATHY; ERYTHROCYTE MORPHOLOGY; IODINATED CONTRAST; CUTANEOUS MICROCIRCULATION; ECHINOCYTE FORMATION; DOUBLE-BLIND; IN-VIVO; IODIXANOL; RISK; IOPROMIDE; acute kidney injury; nephrotoxicity; nephropathy; renal pathology; iodinated contrast media; electron microscopy; histopathology
subject: 570 Biowissenschaften, Biologie
subject: 610 Medizin

description: Background: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. Methods: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n= 8), or Iopromide (n= 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H &amp; E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. Results: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p&lt; 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p= 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert's fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and "box-like" deformations. Conclusions: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide.