FUNCTIONAL, HISTOLOGIC, AND ULTRASTRUCTURAL-STUDY OF THE PROTECTIVE EFFECTS OF VERAPAMIL IN EXPERIMENTAL ISCHEMIC ACUTE-RENAL-FAILURE IN THE RABBIT

The present study was performed in vivo in rabbits to evaluate the fun ctional and morphologic effects of verapamil in a model of ischemic ac ute renal failure (ARF). Particularly impressive was the ultrastructur al integrity of renal tubules in the animals exposed to both ischemia and verapamil. Three groups were studied: Group A: no ischemia; Group B: renal ischemia alone; and Group C: renal ischemia with verapamil. C reatinine clearance was higher in Group C (0.77 mL/min/kg) compared to Group B (0.13 mL/min/kg) at 24 h of reperfusion (p < .005) as well as at 48 and 72 h (0.73 mL/min/kg vs. 0.35 mL/min/kg; p < .05 and 0.90 m L/min/kg vs. 0.46 mL/min/kg; p < 0.05, respectively). Light microscopi c evaluation of Group C rabbits revealed significantly better preserva tion of proximal tubule (PT) brush border (p < .0005) and less desquam ation of PT (p < .05) compared to Group B. Ultrastructural examination of in vivo perfused kidneys also demonstrated decreased loss of micro villi of PT (p < .0005) as well as less cellular edema (p < .005), few er cells with apical PT membrane rupture (p < .01), better preservatio n of mitochondria (p < .005), less flattening of the PT basolateral la byrinth (p < .05), and few er hypertrophic actin bands at the basal su rface of PT epithelial cells (p < .05). These results suggest that ver apamil markedly attenuates PT morphologic injury in a rabbit model of reversible ischemic ARF. The functional protection observed in these s tudies may be related, in part, to the improved structural integrity o f the renal tubules. Renal transplantation and anticipated renal ische mia (i.e., surgical interventions) are two important situations,where treatment with verapamil or other calcium channel blockers may prove t o be clinically beneficial.-