Functional, Histologic, and Ultrastructural Study of the Protective Effects of Verapamil in Experimental Ischemic Acute Renal Failure in the Rabbit

Abstract

The present study was performed in vivo in rabbits to evaluate the functional and morphologic effects of verapamil in a model of ischemic acute renal failure (ARF). Particularly impressive was the ultrastructural 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. Creatinine 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 mL/min/kg vs. 0.46 mL/min/kg; p < 0.05, respectively). Light microscopic evaluation of Group C rabbits revealed significantly better preservation of proximal tubule (PT) brush border (p < .0005) and less desquamation of PT (p < .05) compared to Group B. Ultrastructural examination of in vivo perfused kidneys also demonstrated decreased loss of microvilli of PT (p < .0005) as well as less cellular edema (p < .005), fewer cells with apical PT membrane rupture (p < .01), better preservation of mitochondria (p < .005), less flattening of the PT basolateral labyrinth (p < .05), and fewer hypertrophic actin bands at the basal surface of PT epithelial cells (p < .05). These results suggest that verapamil markedly attenuates PT morphologic injury in a rabbit model of reversible ischemic ARF. The functional protection observed in these studies may be related, in part, to the improved structural integrity of the renal tubules. Renal transplantation and anticipated renal ischemia (i.e., surgical interventions) are two important situations where treatment with verapamil or other calcium channel blockers may prove to be clinically beneficial.