Studies on the pathogenesis of ischemic cell injury. II. Morphological changes of the pars convoluta (P1 and P2) of the proximal tubule of the rat kidney made ischemic in vivo.

The pars convoluta of the proximal tubules of the rat kidney was examined by means of light and electron microscopy after 15, 30, 60 and 120 min of complete ischemia produced by clamping of the aorta. The same ischemia periods were also examined after 24 hrs of blood reflow. It was found that the vast majority of the cells of pars convoluta survived 60 min of ischemia as seen after 24 hrs of reflow. The following pattern of changes were observed at time intervals up to 60 min: progressive clumping of chromatin, progressive distortion of microvilli with bleb formation, increasing dilatation and finally vesiculation of rough-surfaced endoplasmic reticulum and initially condensation and later high amplitude swelling of mitochondria. It is concluded that these subcellular changes are compatible with cell survival. Also tubule cells containing swollen mitochondria with small flocculent densities are potential candidates for survival. 120 min of ischemia was associated with marked mitochondrial swelling with large flocculent densities, severe cell damage and necrosis and was not compatible with cell survival. A working hypothesis is presented relative to the pathogenesis of acute renal failure caused by complete ischemia.