Widener L L, Mela-Riker L M
Circ Shock. 1984;13(1):27-37.
These studies were designed to test the efficacy and possible mechanisms of the prevention of mitochondrial functional deterioration in renal ischemia by the slow-channel calcium blocker verapamil. Renal ischemia was induced in guinea pigs by a unilateral ligation of the renal artery for 30 or 60 min. In the pretreated animals verapamil was given twice a day over a 5-d period prior to the induction of ischemia. Sham-operated animals were used as normal controls. After 30 and 60 minutes, the kidneys were removed and used for mitochondrial isolation and analyses, total tissue Ca2+ and Mg2+ determinations, or for electron microscopy. Verapamil pretreatment completely blocked the decrease of mitochondrial Ca2+ uptake rate induced by 30 or 60 min of ischemia. The pretreatment delayed by 30 min the ischemic decrease of state 3 respiratory activity. Total tissue Ca2+ concentration was not altered by ischemia or verapamil pretreatment. Total tissue Mg2+ concentration, however, was significantly reduced in the ischemic kidney at 60 min. This reduction was prevented completely by verapamil pretreatment. These data suggest that the mitochondrial functional deterioration induced by 30 min of ischemia is a primary cellular insult secondarily leading to loss of tissue Mg2+. The point of irreversibility in the ischemic cell injury might be initiated by lowered tissue Mg2+/Ca2+ ratios.
这些研究旨在测试慢通道钙阻滞剂维拉帕米预防肾缺血中线粒体功能恶化的疗效及可能机制。通过单侧结扎肾动脉30或60分钟在豚鼠中诱导肾缺血。在预处理的动物中，在诱导缺血前5天每天给予维拉帕米两次。假手术动物用作正常对照。30和60分钟后，取出肾脏用于线粒体分离和分析、全组织钙和镁测定或电子显微镜检查。维拉帕米预处理完全阻断了30或60分钟缺血诱导的线粒体钙摄取率的降低。预处理使状态3呼吸活性的缺血性降低延迟了30分钟。全组织钙浓度不受缺血或维拉帕米预处理的影响。然而，全组织镁浓度在缺血60分钟时在缺血肾脏中显著降低。维拉帕米预处理完全阻止了这种降低。这些数据表明，30分钟缺血诱导的线粒体功能恶化是一种原发性细胞损伤，并继发导致组织镁的丢失。缺血性细胞损伤的不可逆点可能由降低的组织镁/钙比率引发。
