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. As a perfect example of how clinical imperative can drive basic physiological investigation, studies of the effect of pulmonary venous hypertension (PVH) on the lung's circulation were in full swing by the very early 1950s, 1 close on the heels of the development of surgical relief of mitral valve stenosis. Cardiac catheterization of patients with mitral valve disease has characterized the physiology of PVH, and histological investigations demonstrated the microvascular changes provoked by PVH. Just as important, the effect of relief of left atrial (LA) hypertension on the circulation has been extensively reported, usually for patients who have had mitral valve intervention. We have learned that the circulatory alterations provoked by PVH share some characteristics with other forms of pulmonary hypertension (PH), such as the idiopathic variety, PH due to chronic alveolar hypoxia, and PH secondary to congenital cardiac shunting lesions. For example, acute "reactivity" to vasodilators may be observed, and there is overlap in the microarchitectural abnormalities seen. On the other hand, the "natural history" of PVH-PH is very different than that of the idiopathic variety or that seen with shunting defects: in the former (as demonstrated with mitral valve disease), PH is likely to largely or completely resolve if PVH is relieved, even with long-standing and severely increased pulmonary vascular resistance (PVR), 2,3 while in the latter two, PH is more likely to inexorably increase. PVH-PH is ther...

Imatinib relaxes the pulmonary venous bed of guinea pigs

“…Though, some patients develop severe PH characterized by a TPG ≥12, by proliferative pulmonary vascular disease and elevated pulmonary vascular resistance (PVR) [ 6 ]. PH due to LHD primarily affects the pulmonary veins (PVs) [ 7 ], thus it is also called postcapillary PH or pulmonary venous hypertension (PVH) [ 1 , 4 , 8 ]. This feature is pivotal for the therapy of PH due to LHD, as vasodilators acting primarily in the pulmonary arterial bed may increase pulmonary perfusion leading to elevated hydrostatic pressure, pulmonary edema and elevated PVR [ 8 ].…”

Murine Models of Heart Failure With Preserved Ejection Fraction

“…Although the mechanisms of hypoxia-induced vascular remodeling are partially understood, the complex obliterate lesions found in human patients with severe primary pulmonary hypertension do not develop in this rodent model (265) . Instead of these obliterate lesions in the pulmonary vasculature of humans with left-sided heart disease, HF and pulmonary hypertension (266) , there is evidence of alveolar septa thickening, cellular proliferation, and collagen deposition (234) . It has been described that chronic hypoxia causes right ventricle 258 , 259 and LV 267 , 268 hypertrophy in rats/mice, but to our knowledge there are no in vivo studies of HFpEF induced by chronic hypoxia, although this might be an applicable model of pulmonary hypertension-associated HFpEF 62 , 260 .…”

The impact of right ventricular pressure and function on survival in patients with pulmonary vein stenosis

“…Both vasodilator gases (iNO, O2) and PV dilation acutely reduced the PA:Ao in over half of the patients. Since patients with mitral stenosis show an acute fall in PAP with reduction in left atrial pressure and iNO, 17 and some patients with Group 1 PH are “reactive,” 10 this is not surprising. Given the small number of patients who had reactivity testing, and multiple confounding factors, we did not attempt to relate reactivity to survival or other outcome endpoints.…”

“…Targeted therapy is generally thought to not be indicated for PH due to pulmonary venous hypertension or lung disease, although the effect of these drugs in these contexts is still not definitively established. 10 , 17 Although it would be clearly desirable to reduce PAP, several concerns need to be considered before broadly utilizing targeted therapy: unknown efficacy of targeted therapy in decreasing PVR in this setting; possibly unfavorable effects on ventilation-perfusion matching and/or lung water; questionable utility if the PVS proves relentless despite therapy. Also relevant to future clinical studies, phosphodiesterase inhibitors, endothelin receptor antagonists, and prostanoids may affect vascular remodeling and thus make it hard to determine the effect of other therapies on pathological remodeling in PVS.…”