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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



time of injection, the arteriovenous difference in con- 

 centration of the substance may be substituted. A 

 rapid injection of the substance into the blood stream 

 is used. This procedure was originally developed to 

 determine cardiac output (15). Description of the 

 method and its theoretical implications have been 

 given by Hamilton (14a) and Zierler (41). For ap- 

 plication of the method to blood flow of any organ, 

 the general formula holds: 



F- 



f °°c(t)dt 



wherein 



F = blood flow 



C = concentration of test substance in the effluent blood 



I = time elapsing during passage of test substance 



m = amount of test substance injected. 



Measurement oj Coronary Blood Flow 



Hirche & Lochner (16) have adapted the method 

 to determine coronary blood flow in anesthetized 

 dogs. A main branch of the left coronary artery (de- 

 scending branch or circumflex branch) and the cor- 

 onary sinus are catheterized. Cardiogreen (5) is used 

 as the test substance. For continuous measurement of 

 dye concentration, the mixed venous blood of the 

 heart muscle is drawn by a pump from the sinus cath- 

 eter through a cuvette photometer (27). When the 

 dye is injected either into the descending or circum- 

 flex branch, time-concentration curves of equal area 

 are obtained. The sinus catheter should be placed 

 close to the outflow. Hirche and Lochner have con- 

 cluded that the method gives values of the sinus out- 

 flow only. Since about 10 per cent of left coronary 

 artery blood may not be returned by the coronary 

 sinus, and therefore a proportionate amount of dye 

 does not appear with this venous outflow, 10 per cent 

 of the calculated blood flow must be subtracted for 

 quantitative measurement. Values obtained with this 

 method are in agreement with those measured by 

 other methods reported in the literature. The meas- 

 urements can be repeated in intervals of 1 to 2 min 

 and in practically unlimited number. 



Measurement oj Cerebral Blood 

 Flow (10, 22, 30-32, 39) 



The human brain receives nearly all of its blood 

 through two vertebral and two internal carotid ar- 



teries. The blood leaves the brain through two main 

 veins, the two internal jugulars. It would be theoreti- 

 cally justified to apply the test-substance injection 

 method if, following injection into one arterial branch, 

 one could obtain identical time-concentration curves 

 in all veins. This would indicate that the mixing of 

 the test substance in all brain vessels was complete. 

 However, the results described below show that such 

 mixing is not obtained. Injection of test substance into 

 one internal carotid vields three distinct types of time- 

 concentration curves in the separate internal jugular 

 veins. 



/) The test substance may appear only on one 

 side. This finding would allow the conclusion that 

 blood flow of only one hemisphere is measured. 2) The 

 concentration curves may be identical in both in- 

 ternal jugular veins. This would correspond to the 

 ideal case where blood flow through the brain as a 

 whole is measured. 3) Most frequently, however, it 

 happens that although the dye appears in both in- 

 ternal jugular veins, the concentrations differ to a 

 high degree. 



It is proposed to average the blood flow values 

 obtained from both time-concentration curves. How- 

 ever, it seems questionable whether this procedure 

 yields accurate quantitative values for brain blood 

 flow. Using the test-substance injection method, 

 Shenkin et al. (40) have studied the "dynamic anat- 

 omy of the brain," mainly to test the validity of the 

 nitrous oxide method. The advantage of the latter 

 lies in the fact that all cerebral arteries show the same 

 concentrations of nitrous oxide at any period of time. 

 In spite of this, the measurements made from the in- 

 ternal jugular veins sometimes do not give identical 

 values (29). When the method of sudden and short 

 injection of the test substance is applied, the inter- 

 pretation is much more complicated. Even in the 

 simple case of two identical time-concentration curves 

 cerebral blood flow cannot be correctly estimated, 

 since not all the test substance appears at the internal 

 jugular measuring points. About 22 per cent of the 

 blood flow through the external jugular vein is derived 

 from internal carotid blood, as Shenkin has shown. 

 One cannot assume that the test substance leaving 

 the brain via the external jugular vein has mixed 

 thoroughly with all the blood passing the brain. The 

 difference between two time-concentration curves 

 from the internal jugular veins speaks against it. This 

 means that accurate measurement of cerebral blood 

 flow cannot be obtained with the test-substance in- 

 jection method, even when concentration curves of 

 both internal jugular veins are recorded. 



