Litten ( 1 ) observed in 1881 that temporary occlusion of the renal artery in dog and rabbit for 11/2 to 2 hours was followed by tubular necrosis. In 1926 McEnery, Meyer and Ivy (2) clamped the blood vessels of both kidneys in dogs for periods of 30 minutes to 1 hour. This led to an increase in BUN 2 and some animals died in uremia. Recently, Emmel (3) described the mitochondrial and pH changes in the rat's kidney following interruption and restoration of the renal circulation. Scarff and Keele (4) removed the right kidney of rabbits and then clamped the left renal pedicle for periods up to 120 minutes. After release the BUN rose rapidly until death or reached a peak and declined with recovery. Outcome did not always depend on time of occlusion. Van Slyke et al (5) found that in the dog, if one kidney was removed and the renal artery of the other clamped for 3 hours, the animal would recover following an elevation of BUN. With clamping of 4 hours, only half of the dogs recovered and at 6 hours the procedure was Uniformly fatal with uremic death in 4 to 8 days. Thus renal occlusion of more than 4 hours was considered irreversible. Selkurt (6) studied the effect of temporary clamping of the left renal artery of the dog on subsequent left renal clearances. Ischemia of 20 minutes' duration practically eliminated creatinine and paraamino-hippuric acid clearances during observations extending for 136 minutes after release of clamp.In the following experiments a study was made of the effects of temporary complete renal ischemia in rats. With aseptic technique the kidneys were then exposed by lumbar incisions extending through the oblique abdominal muscles, the renal pedicles isolated, and the renal artery and vein occluded by means of bulldog clamps. The latter were applied on right and left sides usually within an interval of 20 seconds. Ureters were not occluded. Except for separation of adrenal from the kidney, no dissection of peri-renal fat was made. In all rats 0.5 ml. heparin was injected into the tail vein about 10 minutes before clamping to retard intrarenal thrombosis during the period of vascular occlusion. The heparin did not cause excessive bleeding. Food and water were withheld for about 10 hours prior to anesthesia, and were given ad libitum following the operation.Complete renal ischemia was maintained bilaterally for exact periods of time, i.e., 30 minutes, 1 hour, 90 minutes, and 2 hours. The kidneys were generally dark purple at the end of these periods, but all became uniformly pink either within a matter of seconds or a few minutes after removal of the clamps. A group of 15 rats was studied at each time interval.Renal function was followed by determination of BUN, made according to the method of Ormsby (7) with 0.1 or 0.2 ml. of blood from the tail. A control level was obtained prior to operation and then values were determined at fixed intervals following removal of the clamps, i.e., 6 hours, 24 hours, 2, 3, and 4 days, and in some instances 6 and 8 days. A sample of heart's blood was taken for ...

Release of a high unilateral tourniquet producing complete interruption of blood flow to a hind limb of the rat for about 5 hours almost invariably results in fatal shock. The development of shock is accompanied by progressive edema of the limb. The main object of the following experiments was to determine the magnitude and the rapidity of the fluid loss in the injured extremity. METHODSAdult white male rats weighing about 150 to 300 grams were used. These were anesthetized with sodium pentobarbital, given intraperitoneally in dosage of 25 to 35 mgm. per kgm. of body weight (0.3 to 0.4 ml. of a 2 per cent solution). Circulation in the left lower extremity was then entirely occluded by 2 tightly wound rubber band tourniquets. The first was placed around the knee in order to obtain extension of the leg. This facilitated the application of the second tourniquet, which was placed as high as possible in the groin, anchorage being obtained over a redundant segment of skin drawn down beneath the rubber band.Constriction was maintained for 5 hours and 10 minutes, at the end of which time the rats were alert and showed complete outward recovery from the anesthesia. The animals were then sacrificed by decapitation, either without release of tourniquet, or at fixed time intervals after release, i.e., 15 minutes, 30 minutes, and 1, 2 and 3 hours. The experiments were performed with small groups of rats sacrificed at different periods by random selection, until there was a total of 20 rats for each time interval.In each group there were 1 or more control rats which developed shock after removal of tourniquet and went on to death. Since these yielded only little blood at the time of death, an additional group of 11 rats was sacrificed at 5 to 6 hours following removal of constriction, in order to obtain sufficiEnt blood for chemical determinations. In 18 rats sacrificed by ether at various intervals after tourniquet release, the figures for fluid loss were of the same order as those obtained from decapitated animals.There were a few deaths apparently due to anesthesia. In addition, several rats which chewed their leg before or after removal of tourniquet were discarded. Food and water were withheld for a period of about 10 hours be-1 Aided by a grant from the Elisabeth Severance Prentiss Foundation.fore anesthesia was given, and also during the course ot the experiments. The latter were performed at room temperature during the summer and autumn seasons.The amount of fluid lost in the leg following removal of tourniquet was determined by the method of bisection (1, 2). An anterior midline incision was made from sternum to symphysis pubis and follow.ed by evisceration. A similar posterior midline incision extended down across the base of the tail. The spine was then transected at about the level of the first or second lumbar vertebra, and the lower extremities separated by bilateral paravertebral incisions passing through the hip joints.The difference in weight between the normal and the edematous extremity gave the gain in wei...

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