The effect of verapamil on renal function after warm and cold ischemia in the isolated perfused rat kidney

Abstract

The potential usefulness of verapamil, a calcium channel blocker to renal allograft preservation, was investigated using the isolated perfused rat kidney. Two models of ischemic injury were used. In the first model, rat kidneys were exposed to 40 min of 37 degrees C ischemia on the perfusion circuit. Addition of verapamil in doses of 2.5, 5, and 100 microM concentration to the perfusate significantly improved inulin clearance (Cin) and total sodium absorption (TNa) in the hour of reperfusion following ischemia. Regeneration of adenosine triphosphate (ATP) and total adenine nucleotide TAN levels during reperfusion following warm ischemia were also significantly higher in verapamil-treated kidneys. In the second model, rat kidneys were flushed in situ with Collins C2 solution and stored at 0 degrees C for 8 hr. After this period of cold ischemia, they were perfused on a perfusion circuit with perfusion media. Verapamil 2.5 microM was absent from both flush and perfusate (control), or added to just the flush, both the flush and perfusate, or just the perfusate. Addition of verapamil to the flush or the flush and perfusate significantly improved Cin, urine flow rate (V) and TNa during reperfusion, compared with control. Addition of verapamil to just the perfusate did not effect Cin, TNa, or V but did significantly increase RPF. These findings suggest the verapamil may protect against organ damage occurring during both warm and cold ischemia in the absence of any systemic effects and thus may be useful for renal allograft preservation.