Ischemia in the isolated erythrocyte-perfused rat kidney. Protective effect of hypothermia.
We have examined the effects of 25 min of ischemia in the isolated erythrocyte-perfused rat kidney (IEPK). We have previously shown that, in this model, perfusate flow rate is close to blood flow rates in vivo and morphology is normal. The functional and morphological consequences of both warm ischemia (at 37 degrees C) and ischemia induced during mild hypothermia (27 degrees C) were compared. (1) Warm ischemia resulted in a 51% increase in renal vascular resistance (RVR) during the reflow period, while glomerular filtration rate (GFR) was reduced to 24% of control levels. (2) Kidneys subjected to warm ischemia showed marked morphological damage localized to the proximal tubule. There was dilatation of the proximal segments and widespread loss of the proximal brush border due both to shedding into the lumen and interiorization into the cell. In contrast to the proximal tubular damage, the cells of the medullary thick ascending limb segments were intact. However, the lumena of many of these segments were filled with cytoplasmic blebs and necrotic cell debris. There was also pronounced vascular congestion of the capillary plexus in the inner stripe of the outer medulla. (3) Hypothermia to 27 degrees C resulted in almost complete protection against ischemic injury: RVR and GFR were not different from control values. Also, kidneys subjected to cold ischemia showed only isolated areas of mild brush border damage; no evidence of tubular obstruction or vascular congestion was present. (4) Thus, warm ischemia in the IEPK results in functional and morphological effects comparable to those found in vivo. Post-ischemic vasoconstriction as well as medullary congestion occur in the absence of systemic hormones and renal nerves. These consequences of ischemia are prevented by modest hypothermia.