Pulmonary hypertension caused by pulmonary venous hypertension

Abstract

The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility.

Keywords: pulmonary hypertension; pulmonary venous hypertension.

Figure 1

How pulmonary venous hypertension (PVH) causes increased pulmonary vascular resistance (PVR). Increased intravascular pressure increases wall stress in resistance-level pulmonary arteries (PAs), increasing stretch/tension in medial smooth muscle cells (SMCs). This stimulates mechanoreceptors in these cells, causing vasoconstriction, which reversibly increases PVR and also provokes structural changes. The latter may result from shared pathways for smooth muscle contraction and growth and/or reduction in blood flow in very small end and branch PAs. Increased stretch/tension may also directly (independent of vasoconstriction) stimulate medial hypertrophy and intimal hyperplasia. In the upper right panel, pulmonary capillary wedge pressure (PCWP) is plotted against PVR (pulmonary vascular resistance) in 114 adult patients with mitral stenosis (data from Wood et al.); PVR ranges from normal, despite very high left atrial pressure, to markedly elevated, despite only a modest increase in pulmonary venous pressure. The upper left panel shows the effect of inhaled nitric oxide (iNO) on PVR in 13 children with left atrial hypertension (data from Atz et al.), demonstrating that a component of increased PVR with PVH is often acutely reversible. BL: baseline, before iNO. The lower right panel shows the relative rate of protein synthesis in the media of rabbit PA strips in tissue culture was measured at wall stresses equivalent to various mean PA pressures using quantitative autoradiography. Protein synthesis increased with wall stress in an endothelium-independent manner; hydrostatic pressure did not alter protein synthesis. Adapted from Kolpakov et al. DE: endothelium removed; EN: endothelium present; PS: hydrostatic pressure.

Figure 2

Change in pulmonary vascular resistance (PVR) after mitral valve intervention to effect relief of mitral stenosis/regurgitation (circles; n = 61 patients) or closure of ventricular septal defect (VSD; dots, n = 110 patients). Nearly all patients with mitral valve disease had a large decrease in PVR after relief of left atrial hypertension. Conversely, for patients with a VSD, the response was quite variable, and many had unchanged or increased PVR after repair. Adapted from Kulik. MVI: mitral valve intervention.