The Role of the Nervous System in the Maintenance of Pulmonary Arterial Hypertension in Heart Failure

Abstract

Elevation of pressure in the pulmonary veins, with a consequent elevation of pressure in the pulmonary capillaries and pulmonary artery has for many years been invoked to explain pulmonary hypertension in both mitral stenosis and left ventricular failure. Ignoring the possibility of pulmonary vasoconstriction, this hypothesis was in complete accordance with the " mechanistic " concept of the regulation of pulmonary pressure, emphasized recently by Cournand (1947Cournand ( , 1950 and Hamilton (1951). It was based mainly on the relative refractoriness of the pulmonary circulation towards substances affecting the systemic circulation.It was soon established, however, that elevation of the pulmonary venous pressure is only partly responsible for the high pressure in the pulmonary artery that is observed in heart failure. Elevation of pulmonary " capillary " pressure beyond the colloid osmotic pressure of plasma causes an increase in the pulmonary pressure gradient (Dexter et al., 1950), as a result of an increase of the pulmonary arteriolar resistance. Lewis et al. (1952), emphasize that in mitral stenosis this increased arteriolar resistance is a physiological counterpart to the anatomical changes observed in the small pulmonary arteries by Parker and Weiss (1936) and Larrabee et al. (1949). In face of this " static " theory of increased pulmonary arteriolar resistance it seems hard to understand why the presence or absence of heart failure raises or lowers the pressure in the pulmonary artery, presumably without a change in the size of the stenosed orifice (Bloomfield et al., 1949;Bayliss et al., 1951), or in the lumen of the " statically" narrowed pulmonary arterioles. Not even an increase of the circulating blood volume explains this apparent contradiction. Nor does the decrease of pulmonary arteriolar resistance following mitral commissurotomy (Draper et al., 1951; favour this theory. On the other hand, no corresponding narrowing of the pulmonary vessels can be demonstrated in hypertensive heart failure despite a similar elevation of pulmonary arteriolar resistance (Borden et al., 1950). These data seem sufficient to support the view that anatomical factors alone cannot account for all the increase in pulmonary arterial pressure. The mechanism of this reversible elevation of pulmonary vascular resistance, therefore, needs further study.Anoxia, by producing widespread vasoconstriction in all parts of the circulation, elevates also pulmonary vascular resistance (Motley et al., 1947; LiUjestrand, 1948 ;Dirken and Heemstra, 1948; Doyle et al., 1951, etc.). Pulmonary hypertension following the administration of histamine was also observed in dogs by Dixon and Hoyle (1930). The vasomotor response to both these stimuli is a consequence of their direct chemical action on the pulmonary vessels. The significance of the nervous system as a source of vasomotor stimuli affecting the pulmonary circuit is generally underestimated. Kuntz (1946)

The Effect of Acetylcholine on the Human Pulmonary Circulation Under Normal and Hypoxic Conditions1

“…Whether the small vessels of the lungs exercise similar control over the pressure in the pulmonary artery is not so certain. This uncertainty has stemmed largely from the fact that the human pulmonary vessels have exhibited an erratic response to many vasoactive drugs (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). As a consequence, most physiologists have concluded either that the pulmonary vessels are incapable of intrinsic changes in tone, or that the effect of such changes, if they occur, is less important in determining the pulmonary arterial pressure than is the effect of mechanical factors alone.…”

Peripheral Circulation

“…Analyses of different types of secondary pulmonary hypertension have also been presented (161,203,463,464), and there is evidence that when the pulmo nary vessels are exposed for some length of time to increased pressure hyper trophic changes, first of the media, then of the intima, occur. The flow resist ance increases concomitantly (compare discussion under "Biophysical as pects," p. 162).…”

Intrinsic Mechanisms of the Lung

“…A fall in pulmonary arteriolar pressure has been reported following the administration of ganglionic blocking agents in pulmonary hypertensive cases [Fowler, Westcott, Hauenstein, Scott and McGuire, 1950; see also Greene an dBunnel, 1950;Halmagyi, Felkai, lvanyi, Zsoter, Tenyi and Szuics, 1953]. Of more than passing interest is that sleep reduces the pulmonary arterial pressure in patients with pulmonary hypertension arising from mitral stenosis or left heart failure [Halmagyi et al, 1953]. Werko, Frisk, Wade and Eliasch [1951], however, considered that the haemodynamic changes caused by ganglionic blocking agents were due to pooling of blood in the systemic circulation with a resultant diminution in venous return.…”

“…Werko, Frisk, Wade and Eliasch [1951], however, considered that the haemodynamic changes caused by ganglionic blocking agents were due to pooling of blood in the systemic circulation with a resultant diminution in venous return. Of more than passing interest is that sleep reduces the pulmonary arterial pressure in patients with pulmonary hypertension arising from mitral stenosis or left heart failure [Halmagyi et al, 1953].…”