i 72 a 



HANDBOOK OF PHYSIOLOGY -" CIRCULATION II 



♦ Q • 2 87 L/min 



pH- 7 38 



L Ac " 10 mgm V. 



Q ■ 2 94 L/min 

 pH -7 21 

 L Ac ■ 56 mgm °/. 



fig. 45. A continuous record of the pulmonary arterial (PA) and left ventricular (LV) blood 

 pressures in the dog prior to, and during, an infusion of 0.3 M lactic acid. The arrow above the 

 pressure tracing indicates the start of the infusion. The values for cardiac output (Ql, blood pH and 

 blood lactate concentration (L Ac) on the left were obtained during the control period; those on the 

 right are after 3 min of the infusion. Time lines occur at i-sec intervals; the duration of the entire 

 record is 3 min 15 sec. [Unpublished records of Bergofsky et at. (24).] 



four categories: isolated lungs, unilateral hypercapnia, 

 controlled ventilation, and spontaneous ventilation 

 (132). But, even though results tend to be consistent 

 within each category, the differences between cate- 

 gories may be quite striking. Thus, in spontaneously 

 breathing animals and man, acute hypercapnia is 

 generally without effect on pulmonary hemodynamics 

 (132); conversely, in anesthetized animals which are 

 being passively ventilated, acute hypercapnia usually 

 increases pulmonary vascular resistance (24). Recent 

 observations have suggested a basis for this disparity: 

 for example, during anesthesia and controlled CO2 

 breathing — when the ventilatory response to inspired 

 CO2 is limited by the apparatus — respiratory acidosis 

 is common; on the other hand, during spontaneous 

 breathing — when the increase in ventilation is quite 

 marked — respiratory acidosis is ordinarily mild. In 

 the next section it will be shown that severe acidosis 

 increases pulmonary vascular resistance. Accordingly, 

 the effects of breathing CO2 on the pulmonary circula- 

 tion appear to depend on the degree of acidosis which 

 it produces. 



Acute Acidosis 



For a long while, observations on the isolated lung 

 (1 16, 305) and on the lungs perfused in situ (423) led 

 to the opinion that acidosis played no role in the 

 regulation of the pulmonary circulation. Recently, this 

 view was challenged by experiments on similar 

 preparations which not only indicated that acute 

 acidosis is capable of eliciting an increase in pulmo- 

 nary vascular resistance, but also suggested that it 

 might be involved in the pulmonary vascular response 



to acute hypoxia (269). That acidosis can also elicit 

 an increase in the pulmonary vascular resistance in 

 the intact anesthetized dog is shown in figure 45; in 

 these animals, the pressor response seems to arise 

 from pulmonary vasoconstriction and to depend upon 

 the degree of acidosis rather than upon specific 

 anions (24, 30). It should be noted that this constrictor 

 effect of acidosis on pulmonary vascular smooth mus- 

 cle stands in marked contrast to the inhibitory effects 

 of acidosis on systemic vascular smooth muscle (402). 

 Another use of alkali and amine buffer has been to 

 test the idea that acidosis may underlie the pulmonary 

 arterial pressor response to acute hypoxia (269). This 

 idea could not be substantiated in normal man (24). 

 Instead, the conclusion was reached that acute 

 hypoxia and acute acidosis constitute independent 

 stimuli for pulmonary vasoconstriction; however, it is 

 conceivable that in subjects with regional hypoventi- 

 lation, the two separate stimuli may act synergistically 

 to divert pulmonary blood flow to the well-ventilated 

 portions of the lung (24). 



Alveolar Hypoventilation 



Alveolar hypoventilation may be uniform, as in 

 patients with kyphoscoliosis or extreme obesity (25), 

 or spotty, as in chronic bronchitis and emphysema. 

 During ambient-air breathing, the designation "alveo- 

 lar hypoventilation" implies a combination of alveolar 

 hypoxia and hypercapnia; the state achieves clinical 

 significance when sufficiently severe to produce sys- 

 temic arterial hypoxemia and respiratory acidosis (138). 

 Experimentally, it has been deliberately induced by 

 artificial underventilation during general anesthesia 

 (359). Largely on the basis of such experiments, it has 



