Hypoxia and Pulmonary Vascular Resistance. The Relative Effects of Pulmonary Arterial and Alveolar P_O2

Abstract

HAUGE, A. Hypoxia and pulmonary vascular resistance. The relative efects of pulmonary arterial and alveolar PO,. Acta physiol. scand. 1969. 76. 121-130. The relative effects of pulmonary arterial and alveolar Poz on pulmonary vascular resistance (PVR) have been studied in isolated and ventilated rat lung preparations. The experimental arrangement included two such preparations perfused in series with homologuous blood. Pulmonary arterial hypoxemia (Poz 28-44 mm Hg) without alveolar hypoxia did not elicit vasoconstrictor response. High pulmonary arterial Poz (120-320 mm Hg) reduced the pressor response to alveolar hypoxia. This effect of arterial Po2 could be counteracted by a rise in ventilation frequency. Pulmonary arterial hypoxemia during periods with arrest of ventilation caused brisk vasoconstrictor responses. I t was apparent that the combined effect of alveolar and arterial Po2 on PVR depends on the relative intensities of ventilation and perfusion, the alveolar Po2 being the main denominator for the vasoconstriction effect. The results have been discussed in relation to the possible shape of the Po, gradient from alveolar gas to lumen of small resistance vessels.There is general agreement among investigators in the field that ventilation hypoxia elicits increased pulmonary vascular resistance in several mammalian species. Direct evidence has been presented which indicates that constriction of arterial vessels is involved in the response (Kato and Staub 1966). Much less is known about the intrinsic mechanism triggered by the hypoxic stimulus. The possibilities of hypoxia releasing or activating a local vasoactive substance as well as that of a more direct effect of reduced oxygen tension on the vascular smooth muscle have been suggested. Bergofsky and Holtzman (1967) reported a reversible loss of potassium from pulmonary arterial strips under hypoxic conditions. They calculated that this would correspond to a partial depolarization of the vascular smooth muscle cells bringing them closer to their excitatory threshold. These authors suggest that this change, at least in part, is the mechanism responsible for the pulmonary vasoconstrictor response during hypoxia. The findings of Hauge ( 1968a) and of Haavik Nilsen and Hauge (1968) seemed to indicate that interference with the metabolism of a vasoactive component in the lung, possibly histamine, could be involved. 121

Cardiac index, oxygen delivery, and tissue oxygen extraction in slow and fast growing chickens, and in chickens with heart failure and ascites: A comparative study

“…First, in view of the evidence presented here, cardiac output is not likely to be a factor in pulmonary hypertension in fast growing broilers. Furtherm ore, although, hypoxa emia would be a very likely cause of pulm onary hypertension at high altitude, it would not explain increased pressure in pulm onary circulation in broilers raised at low altitude, since hypoxa emia without ventilation hypoxi a does not elicit a vasoconstrictor response (Reeves et al, 1962;Hauge, 1969) . Therefore, in broiler chickens raised at low altitude, the pressor effect of hypoxa emia (if any) is not likely a signi® cant factor causing pulm onary arteries constriction.…”

Influence of perfusate PO2 on hypoxic pulmonary vasoconstriction in rats.

“…and independent of the inspired oxygen tension of the lung. Of the several previous studies that have not detected an influence of perfusate P02 on HPV (Nisell, 1951;Barer et al, 1969;Hauge, 1969;Hyman, 1975), most did not adequately define or control the alveolar and perfusate oxygen tensions, and for the in vivo studies, an additional difficulty is introduced by the circulating response to systemic hypoxemia. For these reasons, the suggestion that species or age may determine the influence of perfusate or mixed venous P02 (Hyman, 1981) should be regarded cautiously.…”

“…These studies confirm and extend previous hypotheses that alveolar and perfusate oxygen tensions together, determine the P02 at a precapillary site to stimulate hypoxic pulmonary vasoconstriction. (Circ Res 52: 691 -696, 1983) PULMONARY alveolar oxygen tension has long (Euler et al, 1946) been regarded as the primary stimulus for hypoxic pulmonary vasoconstriction (HPV), and a number of investigators have detected essentially no effect on HPV when pulmonary artery oxygen tension has been altered (Nisell, 1951;Duke, 1954;Reeves et al, 1962;Lloyd, 1964;Barer et al, 1969;Hauge, 1969;Hyman, 1975). In contrast, others have reported that the pressor response to alveolar hypoxia was modified by the pulmonary artery oxygen tension (Benumof et al, 1981;Bergofsky et al, 1968;Hyman et al, 1981), and a study from this laboratory suggesting such an interaction has led us to reexamine this controversy.…”

“…The basic preparation consisted of a ventilated and perfused rat lung maintained in a constant temperature chamber. Whereas such models have been described previously (Hauge, 1969), the present one was developed to achieve independent control of the alveolar and perfusate oxygen tensions. The special features of the preparations are described below for study 1 and illustrated in Figure 1.…”

Pathological changes in metabolism of poultry related to increasing production levels

“…Low oxygen tensions in blood, or hypoxaemia, also may occur due to an inadequately functioning circulatory system under normal conditions or due to intensive utilization of oxygen in the systemic circulation as a result of a high metabolic rate. Several experiments with different animals have shown that a low mixed venous oxygen tension influences pulmonary vasoconstriction (2,5,7). Other experiments have shown that reduced oxidative phosphorylation in vascular smooth muscle of pulmonary arterioles can result in vasoconstriction.…”