998 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



table 6.4. Effects of C0 2 , 2 , f>H, and Severe 

 Chemical Injury on Frog's Mesenteric Capillaries 



Filtration Coefficient, 



Effective n p i 



(in vivo) 

 cm H2O 



sec X if- X cm H2O 

 .004B-.0074* 8. 6-1 I. 7 



.0088 11.8 



Capillaries Irrigated by 

 Ringer's Fluid with 



Usual aeration 



Saturated CO» 



pH 8.0 

 HC1 to pH 6.0 

 5-o 

 4.0 

 3-5 

 3-o 



()■. lack and arrested blood 



How for 3 min 

 After 15 min recovery 



10% alcohol or mercuric chlo- 

 ride, 1 : 10,000 



* Accumulated control measurements (23, 200, 201). 



is shown the still greater effect of chemical injury 

 severe enough to produce irreversible capillary stasis. 



In contrast to the effects of extreme local hypoxia 

 just described, studies of graded hypoxemia have 

 demonstrated that the capillary wall tolerates less 

 severe grades of oxygen lack very well. In the human 

 forearm, Henry el al. ( 1 50) found that oxygen tension 

 of venous blood must be reduced to between 1 5 and 

 25 mm Hg before protein passage was increased 

 above normal. This corresponds to an oxygen satura- 

 tion of 15 to 25 per cent or an oxygen content of 4 to 

 6 vol per cent, assuming the blood has a normal 

 hemoglobin content. The method used to measure 

 protein passage was, however, indirect and the 

 protein content of capillary filtrate varied widely. 



DiPasquale & Schiller (70) and Hendley & Schiller 

 (148) studied the effects of hypoxemia on the rate of 

 edema formation in limbs of rats perfused with Krebs- 

 Ringer solution containing 20 per cent washed red 

 cells of dog and 0.33 per cent gelatin. When the 

 oxygen content of the perfusing fluid was kept above 

 5 vol per cent, the rate of edema formation remained 

 at the control level. Reducing oxygen content to 

 between 0.88 and 2.60 vol per cent increased the 

 rate of edema formation above control levels by 42 

 per cent in the first 20 min, by 87 per cent in the 

 next 20 min, and by 151 per cent in the third 20- 

 min period. Blood flow having been kept constant 

 to exclude effects of the vasodilatation which ac- 

 companied this hypoxemia, they concluded that the 

 critical level below which hypoxemia influences 



the permeability of a capillary wall was probably 

 about 2.6 vol per cent. No observations on protein 

 passage were made. In further studies Hendley & 

 Schiller (149) found, however, that either histaminic 

 (Xeo-Antergan) or adrenergic (Dibenzyline) blockade 

 eliminated these results on the basis either of specific 

 blocking action or of hemodynamic effects, and the 

 meaning of these studies therefore remains a chal- 

 lenging problem. 



Systemic hypoxemia, within the range compatible 

 with the life of the organism, has no certain effect on 

 capillary permeability. Maurer (228, 229) and 

 Warren & Drinker (367) found, in dogs, that breath- 

 ing 8.0 to 1 1 .5 per cent oxygen in nitrogen augmented 

 the flow of lymph from the lungs and cervical region, 

 increased the total amount of lymph protein col- 

 lected in unit time, but decreased the concentration 

 of protein in that lymph. Although an increase of 

 capillary permeability was postulated, the decreased 

 protein concentration in lymph, taken together with 

 the studies of Courtice & Korner (53, 1 79) make 

 it unlikely that permeability to protein was changed. 

 In the human forearm McMichael & Morris (242) 

 found that breathing 9.5 per cent oxygen did not 

 increase filtration hum capillaries during venous 

 congestion. Moreover, in patients with generalized 

 hypoxemia sufficient to impair cerebral function, 

 Stead & Warren (351) observed no significant in- 

 crease in the protein content of edema fluids collected 

 from the extremities. 



Only in agonal or antemortem stages of asphyxia 

 (34) or anoxemia ( 1 60 ) is there some slight evidence 

 of increased capillary permeability. In shock the 

 possibility that generalized hypoxemia might increase 

 capillary permeability has been considered on many 

 occasions. Careful studies with labeled plasma proteins 

 (45, 101, 102) have shown the expected rapid passage 

 of protein through capillary walls locally in burned 

 or crushed tissues. However, no abnormal passage 

 through capillary walls elsewhere in the body has 

 been found until just before death, again as an 

 agonal or antemortem occurrence. 



In view of the many uncertainties already men- 

 tioned it is important to note that Bayliss & Lunds- 

 gaard fii) perfused isolated kidneys with cyanide- 

 containing blood and found that some tubular 

 functions were reduced conspicuously, but that the 

 glomerular capillaries and membranes remained 

 nevertheless normally impermeable to protein in the 

 two instances tested. In an earlier study Starling & 

 Verney (348) found that the urine contained only a 

 trace of protein after 1 5 min of cyanide perfusion, 



