THE CEREBRAL CIRCULATION 



t757 



Effects of Drugs 



Most drugs which affect the cerebral circulation 

 do so also by altering cerebrovascular tone. Their 

 effects have been studied by local application, by 

 arterial injection or by intravenous administration in 

 a wide range of dosages in animals and, in man, under 

 conditions of therapeutic dosage and administration. 

 The conclusions have been quite variable if not con- 

 tradictory because of the tendency to generalize 

 regarding the effects of a drug from results of its 

 administration by one route at a particular concen- 

 tration in a single species. It is possible to test under 

 appropriate clinical conditions the effects of a number 

 of agents reputed to possess some action on the 

 cerebral circulation. Although in many cases clinical 

 impressions have been quantitatively substantiated, 

 often the results have been somewhat disillusioning. 



Reference has been made to the effects of the nor- 

 mal blood gases, oxygen and carbon dioxide. A recenl 

 study has suggested that the bicarbonate ion may be 

 an important vasodilator for the brain and has demon- 

 strated a marked increase in cerebral blood flow fol- 

 lowing the intravenous administration of 3 per cent 

 sodium bicarbonate (93). Although not nearly as 

 effective as carbon dioxide, papaverine administered 

 intravenously has produced a moderate relaxation of 

 cerebral vessels and a modest increase in the cerebral 

 circulation (99). 



Contrary to a widespread belief based upon studies 

 in lower animals, the xanthine drugs consistently 

 produce in man a significant cerebral vasoconstriction 

 (99, 1 10). In convalescent patients the administration 

 of aminophvlline intravenously is consistently followed 

 by a marked reduction in cerebral blood flow on the 

 basis of an increase in cerebral vascular resistance. 

 Similar findings have been reported with caffeine. 



A number of agents have enjoyed the reputation of 

 being potent vasodilators in the brain, although 

 studies in man with therapeutic dosage have not con- 

 firmed their therapeutic efficacy on that basis. Nico- 

 tinic acid, while producing facial vasodilatation, has 

 been shown to produce no significant effects upon the 

 cerebral blood flow or cerebral vascular resistance 

 (88). Histamine (2, 99), administered intravenously, 

 although it dilates cerebral vessels, produces at the 

 same time a corresponding decrease in the arterial 

 pressure with the result that the cerebral blood flow 

 is not augmented. When administered intravenously 

 to the point of mild intoxication, ethyl alcohol has 

 produced no significant increase in cerebral blood 

 flow or change in vascular resistance in the brain (5). 



Experiments in lower animals have not been con- 



sistent with regard to the effects of epinephrine on 

 cerebral vessels (14, 26, 96), and this agent has been 

 listed as a dilator or as a constrictor, depending upon 

 the conditions of the particular experiment. The two 

 studies (59, 98) in man are not in agreement and that 

 may very well be because one group studied the 

 administration of epinephrine intravenouslv and the 

 other intramuscularly. With intravenous injection at 

 a rate sufficient to elevate the mean arterial pressure 

 by approximately 20 per cent, some interesting differ- 

 ences have been found between the effects of epineph- 

 rine and norepinephrine (59). The latter was found to 

 constrict cerebral vessels somewhat more severelv 

 than it raised the arterial pressure with the result that 

 there was a slight fall in the cerebral blood flow. 

 Epinephrine itself, on the other hand, neither con- 

 stricted nor dilated cerebral vessels with the result 

 that the increased arterial pressure produced a sig- 

 nificant increase in cerebral blood flow. An excellent 

 and exhaustive review of the effects of drills on the 

 cerebral circulation has recently been written (103). 



CEREBRAL CIRCt I ATION IN lit MAN DISEASE 



Cert bt 11I Artt rwsclerosis 



Studies upon patients with cerebral arteriosclerosis 

 and senile psvrlmsis (28, 104) have demonstrated a 

 significant decrease in the cerebral circulation and 

 the oxygen consumption of the brain when compared 

 to values found in healthy young men. The restriction 

 of cerebral blood flow is upon the basis of an increased 

 cerebrovascular resistance which was found to be 

 about twice the normal value and which represents 

 a physiological confirmation during life of the well- 

 known sclerotic changes observed in these brains 

 post-mortem. 



Essential Hypertension 



This disease is characterized by an elevation in 

 mean arterial pressure and a corresponding: increase 

 in the tone of cerebral vessels witli the result that the 

 cerebral circulation remains within normal limits 

 (50). This indicates that the vessels of the brain par- 

 take in the generalized vasoconstriction which occurs 

 in this condition. It has also been demonstrated that 

 in essential hypertension, uncomplicated by cerebral 

 arteriosclerosis, the narrowing of the vessels is a func- 

 tional one which is capable of relaxation should the 

 arterial pressure of such a patient be reduced (22, 37, 



