Hypoxia and the pulmonary vasculature.

Abstract

HYPOXIA AND THE PULMONARY VASCULATURE I. BRADLEY GORDON, M.D.* AND LOUIS N. KATZ, M.D.t That hypoxia ofvarying degrees is capable ofinitiating a rise in resting pulmonary artery blood pressure is not a new observation. As early as !937.Johnson, Hamilton, Katz, and Weinstein (?) noted a rise in pulmonary artery pressure as a response to progressive asphyxia. Through the years this has been documented time and again in many species ofanimals, and in man. However, despite an extensive literature on the subject representing intensive inquiry into mechanism, the means whereby hypoxia initiates pulmonary hypertension has remained, at best, unsettled. As late as 1955 Cournand entitled a paper "The Mysterious Influence ofUnilateral Pulmonary Hypoxia upon the Circulation in Man" (2). This presentation is an attempt to review the literature and to synthesize, wherever possible, the diffusely scattered information into a workable hypothesis suitable as a basis for further experimentation. While others had shown a relation between hypoxia and pulmonary hypertension, it was not until 1946, when von Euler and Liljestrand (3) published their data on cats, that the period ofintensive research into the problem began. I. Instrumentation and Methodology The most frequently studied laboratory animals have been dogs, cats, and, to some extent, rabbits. Humans have also been subject to intensive investigation. So variable and intricate has been the methodology employed, that at times it has introduced errors which invalidated entire experiments. Lungs have been excised and perfused and ventilated, or left intact and perfused and/or ventilated. They have been studied while innervated normally or, * Fellow on National Heart Training Grant (HTS-5252). At present, Resident in Medicine, Montefiore Hospital, New York City. J Cardiovascular Institute, Michael Reese Hospital and Medical Center, Chicago 16, Illinois. 275 contrariwise, as denervated preparations. Still other techniques have enlisted completely intact cardio-respiratory systems without artificial perfusion or extraneous mechanical ventilation. These preparations have been subjected to many different degrees ofrelative hypoxia, ranging to complete anoxia by inhalation of ioo per cent nitrogen. Measurements and calculations have been both direct and indirect, utilizing flowmeters, cardiac catheterization, bronchospirometry, and even P32 to determine blood volume in the lungs. Pulmonary blood pressure and flow as well as pulmonary blood volume have all been determined. Why, then, is the mechanism whereby hypoxia induces pulmonary hypertension so difficult to elucidate? In the systemic circulation, it is easy to measure directly changes in pressure, flow, and resistance between two points, and one can easily observe changes in the caliber ofvessels. However, these parameters are not so easily measured in the lesser circulation . In the first place, this is a low-pressure system somewhat like the systemic veins, and readily subject to changes in intrathoracic pressures. Therefore, measurements should be made in a closed-chest preparation if the intention is to mimic the natural state. This criterion has been met through various techniques. In animals the chest was opened temporarily and then closed after the cannulae were placed. When the cardiac catheter came into vogue, this technique removed the need to open and close the chest but, as a result, access to the pulmonary venous drainage was lost. Consequently, pulmonary blood flow had to be estimated by the Fick principle or by indicator dilution curves. Pulmonary venous pressures also are not directly measurable, though closely approximated, by the pulmonary artery wedge pressure. Because measurements in the lesser circuit are less direct than in the greater circuit, the exact mechanism by which hypoxia produces the rise in pulmonary artery pressure has beendifficult to elucidate. Acute hypoxia can induce a rise in pulmonary artery pressure in several ways, (a) Pulmonary vasoconstriction is the most frequently incriminated. It may be directly or reflexly induced and involves either the vasculature proximal to the alveolar capillaries or that distal to them, (b) Increasedpulmonary blood flow. The prototype ofthis mechanism is the augmented flow resulting from vigorous exercise or large left-to-right shunts across defective intracardiac septae. (c) Blood volume shiftfrom the systemic circuit to the lungs. Thisisknownto occurwhenthehumanbody changes positionfrom 276 /. Bradley Gordon and Louis N. Katz · Hypoxia Perspectives in Biology and Medicine · Spring 1962 erect to horizontal, (d) Back pressure. This may follow a rise in left atrial pressure as a...