Ischemic acute renal failure--pathogenetic steps leading to acute tubular necrosis.
Acute renal failure in dogs occurs following 40 min of total renal ischemia induced by a 40-min infusion of norepinephrine (NE; 0.75 micrograms/kg/min) into the renal artery. Similar functional impairment is seen following 50 min of bilateral renal pedicle clamping in the rat. Attending these renal ischemic insults a progressive increase in mitochondrial (Mito) calcium (Ca++) accumulation occurs during reflow. Although Mito respiration and Mito Ca++ kinetics (uptake and release) are abnormal during ischemia, prior to reflow, as are tissue ATP levels, reflow in the first 1-3 h after ischemia is associated with recovery of these measurements to almost normal levels. Between 3 and 24 h of further reflow, however, Mito functional deterioration is again observed. Verapamil (5 micrograms/kg/min) infused intrarenally for 2 h after NE or for 30 min prior to NE protected kidneys from the low glomerular filtration rate which follows renal ischemia in untreated dogs. Since mannitol and polyethylene glycol, two solutes with relatively high reflection coefficients, also exert protection in this model, it may be that Ca++ leak into the cytosol of ischemically damaged kidney cells eventually aborts the Mito recovery which accompanies reflow; these impermeant solutes (by preventing cell swelling) and the Ca++ blocker Verapamil may work by different mechanisms to prevent increased cytosolic Ca++ after renal ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004285:Dogs; D004837:Epinephrine; D005919:Glomerular Filtration Rate; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000648:ultrastructure; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D000255:Adenosine Triphosphate; D014700:Verapamil; D002118:Calcium; D004837:Epinephrine