1504 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



anccs arc used a washout •"overshoot" could occur 

 (62, 298), some reasons for the variability can be per- 

 ceived. 



Thirty minutes of ischemia (unilateral) in dogs (76) 

 resulted in a fall in C PAH and C,„ to less than 50 per 

 cent of control, but recovery occurred in 30 min. No 

 significant change in E FAS occurred, indicating con- 

 tinued authenticity of the clearance. Following 45 

 min of ischemia, C PAH and C In were still much reduced 

 1 35 min after release, but now the validity of the 

 clearance could be questioned because of possible 

 tubular damage. Unquestionably, 2 hours of ischemia 

 results in marked and persistent reduction of £p AH 

 (control 0.90-0.94, to o. 1 1-0.43) ( 2 46). 



The mechanism of the persistent ischemia is of 

 great interest. One speculation is that prolonged 

 clamping of the artery results in the excessive produc- 

 tion and accumulation of pressor substances which act 

 locally (269). Other possible factors should be con- 

 sidered. A locally activated, persisting reflex, either 

 intrarenal (93) or caused by mechanical compression 

 of the arteries and intramural nerve fibers, could be 

 involved. It is noteworthy that renal artery blockade 

 does not have the same effect as venous blockade. 

 Neely & Turner (231) found that renal blood flow in 

 the dog kidney (direct method) after 1 hour of uni- 

 lateral occlusion of the artery was reduced to 44 per 

 cent of control immediately after release, but was re- 

 stored to 79 per cent 1 hour later. Venous occlusion 

 for 30 min resulted in a decrease to 58 per cent of con- 

 trol and blood flow remained at this value 1 hour 

 later. Combined occlusion of artery and vein also 

 resulted in poor recovery of flow. With venous 

 occlusion, a persistent weight increase occurred; but 

 with combined artery and vein occlusion the weight 

 was constant, so that congestion of the kidney did not 

 appear to be the answer. The possibility of intra- 

 vascular thrombosis was raised. 



With prolonged ischemia, tubular damage, uremia, 

 and death in renal failure is the outcome. Hamilton 

 et al. (128) found that anesthetized dogs with the 

 right kidney previously removed uniformly survived 

 2 hours of clamping of the left renal artery, and some 



survived ischemia of 3 to 4 hours. When the kidney 

 was cooled to 5 to 17 C, percentage survival was im- 

 proved even with longer periods of ischemia, because 

 of greatly reduced cellular metabolism (20). 



The pattern of recovery of renal clearance following 

 2 hours of clamping of the remaining kidnev after 

 unilateral nephrectomy in the clog is nicely shown in 

 the work of Friedman et al. [table 15 (97)]. 



It can be seen that the clearances lose their validity 

 for measuring plasma flow because of tubular damage, 

 revealed by the low £ PA h and reduced Tm PAH . When 

 plasma flow is estimated by the Fick application, al- 

 though reduced to less than half of control 3 hours 

 after ischemia, blood flow is fairly well restored in 24 

 hours. The low C C r is probably the result of continued 

 back diffusion of creatinine, so that the FF has little 

 meaning for some time after ischemia. 



Hypercapnia and Acidosis 



Dowds et al. (75) studied the effects of progressive 

 hypercapnia in anesthetized dogs rebreathing from a 

 spirometer flushed with pure oxygen to prevent 

 hypoxia. During about 2.5 hours, the carbon dioxide 

 content of the inspired air increased to an average of 

 16.8 vol per cent (13.5-19.9). This was accompanied 

 by a marked increase in respiratory rate. Arterial 

 blood carbon dioxide increased from 35 vol per cent 

 to an average peak of 52.8 vol per cent. Heart rate 

 slowed and blood pressure declined about 10 per cent 

 below the control. In this range of carbon dioxide in- 

 crease, C'pah and C'cr did not change remarkably; if 

 anything they decreased with the fall in blood pres- 

 sure. Brooker et al. (37) subjected dogs to 30 per cent 

 carbon dioxide in oxygen for 30-min periods. All dogs 

 became acidotic, with decreased urinary output. Blood 

 flow decreased to an average of 45 per cent of control 

 (25 to 64 % ). Renal resistance increased from 0.68 to 

 1. 1 7 mm Hg per ml per min, despite a fall of blood 

 pressure to 93 per cent of control. In similar experi- 

 ments, Stone et al. (296) studied the effects on intact 

 and pharmacologically denervated kidneys of anes- 

 thetized dogs. With carbon dioxide inhalation, blood 



table 15. Effects of 2-Hour Renal Ischemia 



[After Friedman el al . (97).] 



