Renal Ne/De tumor cells and related microcirculatory changes in a rat model

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Abstract Introduction: The development of malignant tumors and their abnormal vasculature may result in severe alterations in tissue perfusion. The aim of this study was to investigate the alterations in the kidney microcirculation, related micro-rheological changes, and parenchymal structural differences in a rat-origin mesenchymal mesoblastic nephroma (Ne/De) tumor cell implantation model. Materials and Methods: Sixteen female Fischer-344 rats (bodyweight: 190.17±4.96 g) were anesthetized (3% isoflurane) (permission reg. nr.: 21/2017/UDCAW), the retroperitoneum was opened in the lumbar region. The left kidney was exposed and the Gelaspon® disc containing 0.9 % NaCl or tumor cells (1x106 Ne/De tumor cells, established by Prof. Dr. Pál Kertai) was placed under the renal capsule. The wound was closed in two layers. The microcirculation of the kidney was monitored by Cytocam IDF camera on the 1st and the 9th postoperative (p.o.) days. Blood samples were taken on the day of implantation, and on the 4th and 9th p.o. days for testing hematological parameters, red blood cell (RBC) deformability and aggregation. Results: Leukocyte count significantly increased by the 4th p.o. day (p=0.002 vs. base) followed by a decrease on day 9 (p=0.002 vs. day 4). Platelet count increased on p.o. days 4 and 9 (p<0.001 vs. base). In all RBC aggregation index values a continuous and significant increase was observed (M5 index value on 4th day: p=0.034, on 9th day: p<0.001 vs. base; M10 index values on 4th day: p=0.034, on 9th day: p=0.008 vs. base). The RBC deformability describing parameter SS1/2 [Pa] was remarkably increased on day 9 (p=0.007 vs. base), representing worsened RBC deformability. On day 9 the structural features of the tumor tissue and a heterogenous blood flow pattern were detected by the Cytocam compared to healthy or to the contralateral intact kidney. Vessels with abnormal geometry and shape were often seen in the recordings, where flow parameters were increased, while in other territories RBC aggregates and microcirculatory deterioration was observed. Conclusion: The growing malignant renal tumor caused significant deterioration and heterogeneity in the microcirculation, of which background can be the abnormal vessels and impaired blood micro-rheology. The model seems to be suitable for further investigations of tumor growth and related microcirculatory changes(1.08 MB)
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Abstract Introduction: The development of malignant tumors and their abnormal vasculature may result in severe alterations in tissue perfusion. The aim of this study was to investigate the alterations in the kidney microcirculation, related micro-rheological changes, and parenchymal structural differences in a rat-origin mesenchymal mesoblastic nephroma (Ne/De) tumor cell implantation model.

Materials and Methods: Sixteen female Fischer-344 rats (bodyweight: 190.17±4.96 g) were anesthetized (3% isoflurane) (permission reg. nr.: 21/2017/UDCAW), the retroperitoneum was opened in the lumbar region. The left kidney was exposed and the Gelaspon® disc containing 0.9 % NaCl or tumor cells (1x106 Ne/De tumor cells, established by Prof. Dr. Pál Kertai) was placed under the renal capsule. The wound was closed in two layers. The microcirculation of the kidney was monitored by Cytocam IDF camera on the 1st and the 9th postoperative (p.o.) days. Blood samples were taken on the day of implantation, and on the 4th and 9th p.o. days for testing hematological parameters, red blood cell (RBC) deformability and aggregation. Results: Leukocyte count significantly increased by the 4th p.o. day (p=0.002 vs. base) followed by a decrease on day 9 (p=0.002 vs. day 4). Platelet count increased on p.o. days 4 and 9 (p<0.001 vs. base). In all RBC aggregation index values a continuous and significant increase was observed (M5 index value on 4th day: p=0.034, on 9th day: p<0.001 vs. base; M10 index values on 4th day: p=0.034, on 9th day: p=0.008 vs. base). The RBC deformability describing parameter SS1/2 [Pa] was remarkably increased on day 9 (p=0.007 vs. base), representing worsened RBC deformability. On day 9 the structural features of the tumor tissue and a heterogenous blood flow pattern were detected by the Cytocam compared to healthy or to the contralateral intact kidney. Vessels with abnormal geometry and shape were often seen in the recordings, where flow parameters were increased, while in other territories RBC aggregates and microcirculatory deterioration was observed.

Conclusion: The growing malignant renal tumor caused significant deterioration and heterogeneity in the microcirculation, of which background can be the abnormal vessels and impaired blood micro-rheology. The model seems to be suitable for further investigations of tumor growth and related microcirculatory changes

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Micro-rheology, Ne/De tumor, rodent model
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