Accelerated cellular recovery after an ischemic renal injury.
To determine the mode of action of the beneficial effect of adenosine triphosphate (ATP)-MgCl2, recovery of microinjected inulin, proximal tubular pressure (PTP), and cellular damage as quantitated by histomorphometric analysis of necrosis and swelling were evaluated at 2, 6, and 24 hours after 45 minutes of renal ischemia in rats treated with either normal saline or ATP-MgCl2. At 2 hours both groups of rats demonstrated increased permeability to inulin, elevated PTP, and severe ischemic damage and necrosis. By 6 hours ATP-MgCl2 rats had less tubular back leak of inulin, PTP was modestly reduced, and ultrastructural studies demonstrated improved cellular morphologic features with evidence of early regenerative changes. The saline rats had progressive ischemic cellular damage. At 24 hours ATP-MgCl2 rats had reestablished tubular integrity, PtP had fallen, and ischemic alterations were improved, with only focal evidence of necrosis. Saline-treated rats still had a back leak of inulin, elevated PTP, and progressive ischemic injury. This study demonstrates that 1) cellular damage continues to occur for 6 hours after renal ischemia; 2) ATP-MgCl2 enhances recovery of tubular integrity and cellular morphologic features. The salutary effect of ATP-MgCl2 appears related to the preservation of sublethally injured cells and acceleration of the process of restoration and repair of damaged cells.
D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000818:Animals; D006735:Horseradish Peroxidase; D007444:Inulin / Q000008:administration & dosage / Q000032:analysis; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology / Q000648:ultrastructure*; D007687:Kidney Tubules, Proximal / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D009336:Necrosis; D011312:Pressure; D051381:Rats; D011919:Rats, Inbred Strains
D000255:Adenosine Triphosphate; D007444:Inulin; D006735:Horseradish Peroxidase