EXCHANGE OF SUBSTANCES THROUGH CAPILLARY WALLS 



969 



obstruction of a venule in the frog's mesentery (198) 

 and also when the human extremity was congested 

 by inflating a cuff previously placed on the upper 

 arm (88, 203). When blood flow was normal, capil- 

 lary pressure equalled cuff (and venous) pressure 

 within 15 to 45 sec and eventually exceeded cuff 

 (and venous) pressure by 8 to 1 4 mm Hg in the 

 2nd to 4th minute of congestion (203). When blood 

 flow was very slow, however, as in the arteriolar 

 constriction of acrocyanosis (220), capillary pressure 

 rose much more slowly, requiring up to 8 min to 

 equal venous pressure and finally exceeding that 

 pressure by only 1 or 2 mm Hg. Other direct measure- 

 ments have shown that capillary pressure is elevated 

 in congestive heart failure (92) and also in glomerulo- 

 nephritis (225) whenever venous pressure is high, 

 returning to normal as venous pressure declines. 

 In all these measurements the variability of normal, 

 resting capillary pressures prevents making any 

 meaningful comparison of the increment of capillary 

 pressure which corresponds to any given increment 

 of venous pressure. 



The effect of venous pressure on capillary pressure 

 was emphasized in 1894 on the basis of indirect 

 evidence by Bayliss & Starling (12) when they ob- 

 served that elevating venous pressure increased 

 lymph flow more than similar changes of arterial 

 pressure. In the absence of a direct method of measur- 

 ing capillary pressure they suggested using changes 

 of venous pressure to deduce changes of capillary 

 blood pressure. Also, from studies of lymph formation, 

 Drinker & Field (76) in 1933 suggested that, other 

 things remaining constant, the state of the veins might 

 modify capillary pressure and thereby influence 

 filtration of fluid through the capillary wall. In 1948 

 Pappenheimer & Soto-Rivera (282) found in the 

 denervated, perfused extremities of cats and dogs 

 that a given change of venous pressure influenced 

 filtration and absorption five to ten times more than 

 did a similar change of arterial pressure. They 

 formulated the dependence of mean capillary pressure 

 on arterial and venous pressures and resistances as 

 follows: 



p c 



r P + P 



r a 'a h v 



'* t 



(2.1) 



in which r,. and r a are, respectively, the precapillary 

 and postcapillary resistances, while p A and p v are, 

 respectively, arterial and venous pressures. From this 

 equation it follows that at given values of arterial 



and venous pressures the mean capillary pressure 

 depends on the ratio of the postcapillary to pre- 

 capillary resistance to blood flow. Contractility of 

 the large veins has been well established for a long 

 time, but even in 1950 a general review (210) re- 

 vealed little information concerning reactions of small 

 veins or venules and only a few instances of inde- 

 pendence of such reactions from those of the arterioles. 



Beginning in 1954 Haddy et al. (137) approached 

 the question of differential changes in precapillary 

 and postcapillary resistances by threading catheters, 

 outside diameter 0.2 to 0.5 mm, as far as possible into 

 "small veins" and "small arteries'' for measurement 

 of pressures. Under control conditions small artery 

 pressures averaged 65 ± 25 mm Hg, while small 

 vein pressures, under local anesthesia, averaged 13 

 mm Hg with a range of 8 to 25 mm. Small vein 

 pressure varied independently of the relatively con- 

 stant large vein pressure, indicating that the small 

 vein system must be responding independently to 

 nervous or humoral stimuli. Kelly & Visscher (171) 

 found that independent pressure changes in small 

 arteries and small veins were produced by stimulating 

 the lumbar sympathetic chain in dogs. Variability 

 of these changes in timing, magnitude, and even 

 direction was considerable and three main types or 

 combinations of pressure changes had to be described. 

 In further studies small vein pressure increased to 

 as much as 36 mm Hg and led to the suggestion by 

 Lee & Visscher (2 1 4) that edema of the skin could 

 have a neural origin. However, were this an impor- 

 tant possibility one would expect that cutaneous 

 edema would be observed at some stage in the pro- 

 gressive, neural vasoconstriction found in hemorrhage 

 and shock. This is, however, not the case. It must 

 be remembered, too, that if arterial pressure remains 

 constant, or especially if it falls, any constriction, 

 whether arteriolar or venous, tends to reduce blood 

 flow and this then tends to limit edema formation 

 to the extent that renewed volumes of blood plasma 

 are not available for filtration; at zero blood flow- 

 even the wheal of histamine does not appear (216, 

 217, 219). 



Extending this method to humoral agents, Haddy 

 and others found that independent, and sometimes 

 opposite, reactions of arteries, small arteries, small 

 veins, and large veins were produced by change of 

 tissue temperature (135, 364), change of pH (105), 

 epinephrine (134), norepinephrine (134, 364), 

 serotonin (134, 136) and histamine (133). As sum- 

 marized by Haddy et al. (134), "almost every possible 

 combination of active and passive change in seg- 



