Red cell trapping and postischemic renal blood flow. Differences between the cortex, outer and inner medulla

Abstract

The distribution of blood flow in the rat kidney after 60 minutes of renal ischemia was studied by single-fiber laser-Doppler flowmetry. Blood flow in superficial cortex and inner medulla was measured with a probe directed towards the kidney surface and exposed papilla, respectively. Outer medullary blood flow was measured with a probe introduced through the renal core. After ischemia the blood flow decreased to 60% of the preischemic value (P less than 0.01) in superficial cortex and to 16% (P less than 0.01) in outer medulla, while inner medullary blood flow increased paradoxically to 125% (P less than 0.01). There was extensive trapping of red blood cells (RBC) in the outer medulla, but not in the inner medulla or cortex. The fractional RBC volume as measured by radiolabeled RBCs was 21% in the inner stripe of the outer medulla, but 2% in this area in a normal kidney. To investigate the influence of RBC trapping on intrarenal distribution of blood flow after ischemia, the hematocrit was reduced from 46% to 31% by isovolemic hemodilution. When performed before ischemia, this maneuver almost completely abolished RBC trapping. In this group blood flow in both outer and inner medulla was almost unchanged after ischemia, while superficial cortical blood flow decreased to 66% (P less than 0.01) of the pre-ischemic value. It is concluded that RBC trapping in the outer medulla causes a large decrease in blood flow in this area and, at the same time, shunting of blood to the inner medulla. In the absence of RBC trapping, blood flow of both outer and inner medulla is well preserved after ischemia.

Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.

“…6 A, there was a good correlation between peak creatinines at 24 h and absolute neutrophil counts at the time of ischemia. Protection against ischemic injury was seen only in those animal groups in which ANS treatment resulted in a reduction in the absolute neutrophil count to Ͻ 100 cells/mm 3 . As shown in Fig.…”

“…These leukocyte-endothelial interactions may contribute to residual obstruction of blood flow and prolonged local ischemia after the pedicle clamps are removed and may explain the medullary vascular congestion in the postischemic renal outer medulla (2,3). We propose that the protection afforded by knockout of the ICAM-1 gene is due to prevention of leukocyte accumulation in the kidney with consequently less release of proteases, reactive oxygen species, and other toxic and vasoactive metabolites.…”

“…For example, ICAM-1 is a fibrinogen receptor (26), and one possible consequence of mutation of the ICAM-1 gene is decreased intravascular coagulation. Hellberg et al (3) have suggested a role for erythrocytes in postischemic injury. To evaluate further the importance of the neutrophil, we tested whether neutrophil depletion could protect against ischemic injury in the normal mouse.…”

“…There is no clinically accepted therapy that prevents cellular injury after ischemic injury to the kidney (1). We have proposed that the outer medullary vascular congestion that is seen in ischemic acute renal failure (2) may result, at least in part, from intercellular adhesion molecule (ICAM) 1 -1-mediated adhesion of leukocytes to the endothelium with obstruction of the venous vasa recta and/or leukocyte-mediated increases in endothelial permeability leading to erythrocyte aggregation and edema (2,3). Interference with outer medullary blood flow would then result in sustained ischemia to the outer medulla, even after systemic blood pressure and total renal blood flow were returned to normal.…”

Production of heparin binding epidermal growth factor-like growth factor in the early phase of regeneration after acute renal injury. Isolation and localization of bioactive molecules.

“…HB-EGF immunoreactivity was detected in the distal nephron in the areas where injured proximal tubular cells were located. In postischemic kidney, the straight portion of proximal tubules in the outer medulla (S3 segment) is vulnerable to ischemic injury because of the heterogeneous oxygen delivery and generation of reactive oxygen species that occur upon reperfusion (60). However, evidence also suggests the existence of sublethal cell injury in distal tubules in response to ischemia/reperfusion.…”