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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



accurate. The variable of cardiac output can be 

 eliminated by controlling the rate of inflow into the 

 vascular bed with a constant output pump (101). It 

 can remain as a variable when blood flow rate and 

 pressure are monitored simultaneously in the vascular 

 bed under study (148). Additionally, this type of 

 approach can give direct information concerning 

 vascular tonus in different segments of a given bed. 

 At the present time, in vivo studies carried out in this 

 manner are the best available. 



The alterations of the environment attainable with 

 this approach are exceedingly limited if the circula- 

 tion of the bed is continuous with that of the general 

 systemic pool. The imposed change must not be great 

 enough to elicit a systemic reaction and the change of 

 milieu induced must be analytically confirmed. To 

 avoid these difficulties many studies have been carried 

 out using totally isolated vascular beds, e.g., rabbit 

 ear, dog hind limb, rat hind limb, perfused with 

 artificial solutions. The gain in control of the medium 

 does not, however, compensate for the loss of a physio- 

 logical preparation; hence such studies have not been 

 extensively used for our particular problem. 



Microscopic observations of various circulatory 

 beds have yielded useful information concerning the 

 physiology and pharmacology of these beds (114). 

 Because the mesoappendix or meso-omentum, the 

 beds usually studied (217), have rather special 

 properties, they have not been extensively or profit- 

 ably used to study the effects of ions. 



MEASUREMENT OF TENSION IN THE VASCULAR STRIP 

 OR RING OR IN AN ANALOGOUS SMOOTH MUSCLE STRIP. 



The in vitro approach has the value of enabling the 

 experimenter to control the environment although, 

 of course, the results must later be fitted to the in vivo 

 framework. This type of study has suffered greatly 

 from the fact that, so far, no one has been able to 

 mount a representative of the vessels that actually 

 control peripheral resistance. As substitutes, rings of 

 large arteries or strips of aorta (87) have been used, 

 although Bohr & Goulet (14) have recently reported 

 briefly that a spiral strip of rabbit mesoappendix 

 arteriole may be practicable. 



The aorta seems to us a particularly poor choice 

 because of its specialized elastic tissue content. It be- 

 haves quite differently from peripheral vasculature in 

 vivo and, in particular, shows a slow and prolonged 

 response time (11, 48, 88). An additional criticism is 

 that the smooth muscle cells are abnormally oriented 

 in the spiral strip. One would hope that a suitable 

 preparation using a length of artery under intra- 



luminal pressure distributed radially from its fluid 

 content will soon be devised to replace the present 

 strip techniques. Pa ton (157) and Davey (44) have 

 both had some success with this approach and our 

 own preliminary studies seem promising. For the 

 present, we must discuss the results derived from cur- 

 rent techniques with necessary reservation. 



Although it is clear that different types of smooth 

 muscle differ in their drug responses, they do have 

 certain histological features in common. We shall, 

 therefore, round out this part of the discussion by 

 surveying the findings with uterus and gut strips in 

 order to recognize generalizations where possible. 



Studies oj the Milieu During Manipulation of Vascular 

 or Analogous Smooth Muscle Tension 



In these studies, vascular smooth muscle tension 

 has been increased or decreased, acutely or chroni- 

 callv, by a diversity of procedures ranging from hor- 

 mones through drugs to direct ionic manipulation. 

 Some well-defined parameter outside and/or inside 

 the cell has been measured. The principal analyses are 

 as follows: 



MEASUREMENT OF EXTRACELLULAR AND OR INTRA- 

 CELLULAR ions and water. The external environ- 

 ment of the smooth muscle cell has for a long time 

 been estimated from measurements chiefly of plasma 

 Na, K, CI, and Ca. The analytical procedures have 

 gradually been improved but Na determination by 

 flame photometry with greater than 1 per cent error, 

 exclusive of the sampling error, has made the world 

 of small changes in plasma or serum Xa unapproach- 

 able. 



More recently it has become apparent that a knowl- 

 edge of the extracellular fluid volume is required if 

 extracellular ionic quantities are to have any mean- 

 ing. The volume distribution of exogenously ad- 

 ministered inulin so far gives the most reliable estimate 

 of this (89, 206, 207). Earlier studies used chloride 

 which, under basal conditions, was thought to be 

 almost entirely extracellular. It is now generally 

 realized, however, that not only is the chloride space 

 larger than the extracellular space but also that pro- 

 cedures which alter cation distribution of necessity 

 produce variable chloride shifts for the preservation 

 of electroneutrality within the cell. Accordingly, we 

 must interpret the ion partitions based on chloride 

 measurements with caution. Other substances such as 

 bromide or thiosulfate used as measures of extra- 

 cellular space suffer from similar criticisms. 



