Abstract
Ions, particularly calcium ions, play an important role in ischemia-reperfusion cell injury. In this study, we investigated the action of verapamil on the mitochondrial function of kidneys submitted to ischemia without blood reperfusion in order to study isolated early and late ischemic effects. 44 rats were submitted to bilateral warm renal ischemia for 30 minutes. The kidneys were then immediately reperfused with saline or Euro-Collins (EC) solution, with and without previous administration of 0.35 mg/kg of verapamil. Mitochondrial function was assessed at the end of renal perfusion and after 24 hours of cold preservation. In kidneys perfused with saline, verapamil allowed a significant early preservation of state III mitochondrial respiration, a result that was no longer evident after 24 hours. In kidneys perfused with EC solution, verapamil did not change state III for either early or late evaluations. Comparison of the groups showed that the results obtained for kidneys perfused with EC were always superior to those obtained for the saline group, except for the initial analysis of kidneys treated with saline and verapamil, which showed results similar to those obtained with EC perfusion alone. Administration of verapamil before warm ischemia provides partial and short-lasting functional protection of the mitochondrial function in kidneys perfused with sodium rich saline. With Euro-Collins solution, verapamil did not show any additional beneficial effect. This fact permits us to conclude that protective action is effective only under conditions that facilitate increased sodium uptake and/or potassium loss.
Highlights
Despite the care taken to preserve vital functions in brain dead patients and candidates for organ donation, organs removed from them may pass through a variable period of hypoxia and/or ischemia secondary to a low renal blood flow with a consequent deleterious effect on renal cell metabolism that may affect function after transplantation [1].In an attempt to reduce renal cell damage, kidney preservation for transplantation currently consists of arterial perfusion with solutions whose composition is similar to that of the intracellular medium used at low temperature
Comparison of the groups showed that the results obtained for kidneys perfused with EC were always superior to those obtained for the saline group, except for the initial analysis of kidneys treated with saline and verapamil, which showed results similar to those obtained with EC perfusion alone
Administration of verapamil before warm ischemia provides partial and shortlasting functional protection of the mitochondrial function in kidneys perfused with sodium rich saline
Summary
Despite the care taken to preserve vital functions in brain dead patients and candidates for organ donation, organs removed from them may pass through a variable period of hypoxia and/or ischemia secondary to a low renal blood flow with a consequent deleterious effect on renal cell metabolism that may affect function after transplantation [1].In an attempt to reduce renal cell damage, kidney preservation for transplantation currently consists of arterial perfusion with solutions whose composition is similar to that of the intracellular medium used at low temperature. Despite the care taken to preserve vital functions in brain dead patients and candidates for organ donation, organs removed from them may pass through a variable period of hypoxia and/or ischemia secondary to a low renal blood flow with a consequent deleterious effect on renal cell metabolism that may affect function after transplantation [1]. Verapamil has shown a protective effect on renal function in animal models, acute ischemic renal failure when administered before an ischemic episode ranging from 40 to 60 minutes, usually with blood reperfusion after the period of ischemia [5,6,7,8,9], as well as in renal transplantation [10]. There is an anti-oxidant protective effect against tissue injury attributable to oxidative stress [11]
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