HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



are virtually worthless. Large portions of the venous 

 bed are in a state of partial collapse, in which case 

 pressures are not conditioned by vascular tone but 

 b\ the interplay of extravascular pressures with intra- 

 vascular dynamics. The small magnitude of venous 

 pressure further complicates the problem, since an 

 adequate definition of zero reference levels, appro- 

 priate to the specific conditions of the experiment, 

 is often extremely difficult. Finally, in situations where 

 venomotor activity exhibits any significant change, 

 there are usually associated changes in cardiac ac- 

 tivitv and blood flow which produce passive changes 

 in venous pressure. These further confound any valid 

 assessment of venous tone. 



Measurement of Pressure Gradients 



Errors in attempting to draw inferences from iso- 

 lated venous pressure might be reduced by measuring 

 successive venous pressures along the venous gradient 

 in conjunction with determinations of blood flow. 

 Unfortunately, this approach is still confronted by 

 the obstacle of collapse phenomena, aggravated in 

 the case of intrathoracic and intra-abdominal veins 

 by respiratory variations in extravascular pressure. 

 The author is not alone among investigators who 

 have spent frustrating hours attempting to interpret 

 pressure gradients in such veins. 



An older method for surmounting this obstacle in 

 the larger veins was introduced by Donegan (19). 

 He selected appropriate vein segments which could 

 be isolated and perfused artifically, at sufficient rates 

 to keep them well distended, and could yield mean- 

 ingful pressure gradients. By judicious selection of 

 the segment to be perfused, it is possible to preserve 

 innervation to the vein and thus study the normal 

 venomotor responses of such a vein segment in vivo. 

 This technique has yielded a great deal of significant 

 information in the hands of Fleisch (25), Gollwitzer- 

 Meier (35, 36), and others. Unfortunately such prepa- 

 rations are rather difficult to prepare and maintain 

 in good reactive condition, perhaps due to the trauma 

 of isolation and double cannulation, possible inter- 

 ferences with vasa venarum circulation, temperature 

 changes, and other artifacts introduced by the arti- 

 ficial perfusion. Fleisch particularly stresses the pre- 

 cautions which must be observed if a reactive 

 preparation is to be obtained. This technique can 

 therefore only be trusted when significant positive 

 results are obtained; it is difficult to dissociate valid 

 negative responses from deterioration of the prepa- 

 ration. 



Another method of avoiding the collapse problem 

 would be to proceed out far enough into the periph- 

 eral venous system to areas of steeper pressure gradi- 

 ents and higher absolute pressure levels, preferably 

 in superficial areas where one can be confident that 

 extravascular pressures will never approach the order 

 of magnitude of intravascular pressures. A very sig- 

 nificant advance is therefore represented by the work 

 of Haddy (27, 41-45) who has employed fine plastic 

 catheters and passed them in a retrograde direction 

 into minute peripheral blood vessels, such as those of 

 the paw. This retrograde catheterization must avoid 

 areas with valves. By simultaneously recording pres- 

 sures from minute vessels approached from both the 

 arterial and the venous sides, and also from the corre- 

 sponding large arteries and veins, he has been able 

 to plot the pressure gradient through the total vascular 

 bed. When combined with flow measurements, the 

 flow resistance of each segment of the bed may be 

 calculated. As has been previously discussed, moderate 

 changes in the pattern of flow resistance and pressure 

 gradient in local segments of the peripheral venous 

 bed may not produce any alterations in the total 

 capillary-to-heart pressure flow gradient; yet these 

 changes will signify alterations in venous tone and 

 the shifts in venous capacity which presumably result. 

 With more intense venoconstrictor responses, venous 

 resistance may become elevated to the point that 

 capillary pressure rises, in which case this technique 

 also becomes a very useful adjunct to the study of 

 factors leading to tissue edema (41). 



This technique has proven quite fruitful in the 

 analysis of the effect of a variety of agents on the pe- 

 ripheral venous system. One example is shown in 

 figure 9. The upper part of this figure indicates the 

 pressures recorded from the vessels in the foreleg of a 

 dog that was being perfused artificially at a constant 

 rate; below are plotted the resistances calculated from 

 the flow and pressure gradient data. On the left of 

 the figure, the innervation was intact and vascular 

 tone was high, as reflected in a high arterial pressure. 

 Administration of 5-hydroxytryptamine (serotonin) 

 produced a significant drop in pressure and resistance 

 on the arterial side, particularly in the smaller vessels, 

 attributed to antagonism of the adrenergic constrictor 

 mechanism. In contrast, there was a dramatic rise 

 in small vein pressure, interpreted as due to a direct 

 constrictor action of this drug on the veins. Following 

 denervation, the right of the figure indicates a low 

 initial pressure on the arterial side because of a loss 

 of sympathetic tone. Under these conditions, 5-hy- 

 droxvtn ptamine is observed to produce a significant 



