•7*4 



II \M>HOOK OF I'HYsioI ( IGY 



CIRCULATION II 



mmHq H. F 

 80 



10 SEC 



PA 



40 



li I L 



WW 





mmm 







10 SEC 



t i 



I 20 

 BA 

 80 



40 



fig. 46. Spontaneous rhythmic fluctuations in pulmonary arterial blood pressure in a young 

 woman with primary pulmonary hypertension. The pulmonary arterial systolic pressure is identical 

 with the systolic pressure in the right ventricle. The pulmonary arterial pressure waxes and wanes. 

 Each cycle is 1 10 sec long; the pulmonary arterial systolic pressure ranges from 57 to 74 mm Hg; the 

 diastolic pressure ranges from 26 to 36 mm. The pressure changes are not accompanied by parallel 

 changes in heart rate. The brachial arterial pressure is somewhat low. The slow cyclic variations in 

 pulmonary arterial pressure have no counterparts in the systemic blood pressure. (Unpublished 

 observations by A. P. Fishman and A. G.Jameson.) 



Recently, a pulmonary arterial rhythm, unaccom- 

 panied by fluctuations in systemic arterial blood pres- 

 sure, was observed in an unanesthetized woman with 

 primary pulmonary hypertension (fig. 46). In this 

 subject, systemic hypotension coexisted with pulmo- 

 nary hypertension, a combination which presumably 

 favors the occurrence of isolated pulmonary arterial 

 pressure waves in the experimental animal (379). 

 However, while it is intuitively attractive to accept 

 the pulmonary arterial waves in this subject as a 

 manifestation of a central vasomotor rhythm — super- 

 imposed by the central nervous system on local pulmo- 

 nary vascular controls — the probability remains that 

 the fluctuations in pulmonary arterial pressure may 

 merely reflect the passive consequences of rhythmic 

 changes in systemic hemodynamics (125). 



EFFECTS OF DRUGS 



Interests in the pharmacology of the pulmonary 

 circulation differ: at one extreme is the use of drugs to 

 display the capacity of the pulmonary vessels to 

 undergo a change in "tone"; this has led to the stuck 

 of isolated perfused lungs and vascular rings. At the 

 other extreme is the effect of a particular drug on the 

 pulmonary circulation under natural conditions; this 

 has involved the study of the unanesthetized intact 

 animal or man in whom the ventilation, circulation, 

 and the coordinating neurohumoral systems are all 



intact. Between these extremes are many shades of 

 interest which are not always defined or self-evident 

 from the experimental protocols. 



It is generally difficult, in intact animal and man, 

 to separate the direct, local vasomotor effects of a 

 drug on the pulmonary circulation from its indirect, 

 passive effects originating from afar, i.e., in the 

 systemic circulation, the left heart or the ventilation. 

 Theoretically, this distinction should be easily made 

 if the pharmacological agent, such as acetylcholine, 

 is rapidly destroyed by contact with blood (122): 

 minute quantities of acetylcholine are infused into a 

 peripheral vein or into the pulmonary artery at a rate 

 carefully adjusted to avoid the classical circulatory 

 picture of systemic vasodilatation and cardiac inhibi- 

 tion; the action of the drug is then presumed to be 

 confined to the pulmonary circulation. During this 

 venous or pulmonary arterial titration with acetyl- 

 choline, steady-state measurements are made, not 

 only of pulmonary blood flow and pressures, but also 

 of other relevant respiratory and circulatory param- 

 eters (153). 



Of more universal applicability is the procedure of 

 injecting a drug into the pulmonary artery while re- 

 cording blood pressures simultaneously from the 

 pulmonary artery, the pulmonary vein (or left 

 atrium), and a systemic artery as the drug traverses 

 the pulmonary circulation (fig. 33) (150, 187). At 

 first, the use of this approach required open thora- 

 cotomy for the cannulation of the pulmonary vessels 



