97o 



II Wlll',1 H IK HI I'HYMM OCY 



CIRCULATION II 



120 



100 



bO 



40 



20 



Histamine IA 

 -2-1—6-1 14—1 43- 



Brachial Artery 



Small Artery 



r 



V 



V. 



\ 



\ 





■*\- 



SmallVein <** 



/- 



Subcutaneous Tmsue 



25 50 75 100 125 



Time in Minutes 



ISO 17 5 20 



fig. 2.5. Effect of histamine infused intra-arterially upon 

 vascular and interstitial pressures in the dog's foreleg. Num- 

 bers at top refer to /ig/min histamine base administered into 

 the brachial artery. [From Haddy (133).] 



mental resistances and pressures has been observed 

 during one or another arrangement." The true signifi- 

 cance of these findings is correspondingly difficult to 

 evaluate. In the case of histamine (fig. 2.5), which 

 has been more thoroughly studied at controlled flow- 

 rates, this elevation was ascribed for small doses 

 simply to arteriolar dilatation, and for large doses 

 to an added selective constriction of small veins. This 

 constriction in turn was ascribed in part to the direct 

 action of histamine and in part to indirect effects 

 stemming from release of norepinephrine from the 

 adrenal medulla. It was suggested also that the result- 

 ing changes of capillary pressure might be sufficient 

 to explain the protein-rich edema, produced by 

 histamine, on hydrostatic grounds by passive con- 

 gestion, increased capillary pressure and stretching 

 of the capillary wall, without invoking injury of the 

 wall by histamine. The production of a protein-poor 

 filtrate is certainly possible, but the production of a 

 protein-rich filtrate seems unlikely. The small vein 

 pressures reported were all below 40 mm Hg, whereas 

 it has been shown, with venous pressures of 40 to 60 

 mm Hg, that capillary filtrate contained at most 

 0.7 g per cent of protein and averaged only 0.3 g 

 per cent (211), not the 4 or 5 g per cent found in 

 the histamine wheal (217). 



The validity of conclusions based on such catheteri- 

 zation of small veins is doubtful for several reasons. 

 In addition to inescapable, even though slight, ob- 

 struction to venous outflow and false elevations of 

 "small vein pressure" there is the possibility of effects 

 from trauma to the intima of the venules under 

 study. Davis & Hamilton (65-67) stimulated the 



sympathetic nerves to the rabbit's ear and the dog's 

 paw and found that the pressures developed in the 

 small veins depended upon the nerve stimulated, 

 upon the frequency of stimulation, upon the rate of 

 blood flow, and upon the presence or absence of 

 mechanical obstruction to venous outflow. They 

 found also that the highest small vein pressures oc- 

 curred while flow in the region had stopped. Pressures 

 in the small veins sometimes exceeded those in the 

 small arteries (fig. 2.6, right). They concluded that 

 when this occurred the walls of the small veins were 

 constricting against a static column of blood isolated 

 probably from the capillaries, and certainly from the 

 arterioles. Burch (29) observed similar elevations of 

 pressure in isolated segments of large veins in man. 



More recently still, an isovolumetric technique has 

 been used by Mellander (243) to measure the effects 

 of sympathetic stimulation on the resistance and 

 capacitance vessels in cats with hind legs placed in a 

 plethysmograph. As shown in figure 2.7, frequency of 

 stimulation was kept within physiological limits, 

 i.e., from 0.25 to 16 stimuli per sec. Both the capaci- 

 tance vessels and resistance vessels constricted. The 

 former responded more actively at first and reached 

 maximum constriction at 8 stimuli per sec. The re- 

 sistance vessels were influenced less at low stimulation 

 rates and more at higher rates. Precapillary resistance 

 increased more than postcapillary resistance and 

 increasing absorption was found, with calculated 

 reductions of capillary blood pressure ranging from 

 2 to 15 mm Hg. Mellander suggested that Kelly 

 and Yisscher, by manipulating and cannulating the 

 small veins, may have produced local constriction of 

 their walls. In addition to the obstruction already 

 mentioned, it is also possible that intimal irritation, 

 secondary to catheterization or cannulation, may 

 make the small veins abnormally susceptible to 

 vasoconstrictor impulses. In any event it seems clear 

 that, under some conditions, stimulation of sym- 

 pathetic vasoconstrictor nerves increases arteriolar 

 resistance more than venous resistance, reduces 

 capillary blood pressure, and leads to rapid and 

 significant absorption of fluid and not to elevated 

 capillary pressure and filtration. 



By the same technique Mellander showed that 

 epinephrine in small doses, and in muscle, relaxed 

 the arterioles and probably constricted the venules 

 slightly, producing filtration and hence indirect 

 evidence of a rise of capillary blood pressure. In 

 skin, all doses, and in muscle large doses of epinephrine 

 produced effects like those of sympathetic stimula- 

 tion, but only 20 to 25 per cent as great. Norepi- 



