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Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

Sakao S, Voelkel NF, Tanabe N, Tatsumi K - Respir. Res. (2015)

Bottom Line: Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown.Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage.Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. sakaos@faculty.chiba-u.jp.

ABSTRACT
Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

No MeSH data available.


Related in: MedlinePlus

The determinants of severe pulmonary hypertension. The determinants of the elevation of the pulmonary arterial pressure in principle are vasoconstrictive reactivity which may be treatable with currently available vasodilator drugs. Fully developed and endstage disease may be characterized by complex vascular lesions and vasoconstriction that is refractory to treatment with presently available drugs. Ppa: pulmonary arterial perssure, PVR: pulmonary vascular resistance
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Fig1: The determinants of severe pulmonary hypertension. The determinants of the elevation of the pulmonary arterial pressure in principle are vasoconstrictive reactivity which may be treatable with currently available vasodilator drugs. Fully developed and endstage disease may be characterized by complex vascular lesions and vasoconstriction that is refractory to treatment with presently available drugs. Ppa: pulmonary arterial perssure, PVR: pulmonary vascular resistance

Mentions: Almost five decades ago, the high pulmonary blood pressure associated with Heath-Edwards classification grades 1-3 was shown to be reversible following surgery that primarily eliminated the left to right shunt in PAH patients with CHD. However, PH associated with Heath-Edwards classification grade 4 was not reversible, at least acutely, after surgery [31]. These differences between grade 3 and 4 are due to the presence of complex intimal lesions that are composed of phenotypically altered mesenchymal-like cells [18, 22, 28, 29], indicating that the determinants of a fixed high pulmonary arterial pressure include complex vascular lesions, but not necessarily a high pulmonary blood flow. Oka et al. investigated the Sugen/Hypoxia rat model and found that pulmonary vascular tone remained to be an important contributing factor to the high Ppa even in the late stages of the disease. The role of increased vascular tone, in particular during exercise and perhaps also controlled by diurnal rhythms, may be underestimated in patients with fully developed angioobliterative disease [14] (Fig. 1). As the disease further progresses, a decrease in the cardiac output due to right ventricle dysfunction and failure results in a drop in Ppa while the pulmonary vascular disease is ongoing.Fig. 1


Determinants of an elevated pulmonary arterial pressure in patients with pulmonary arterial hypertension.

Sakao S, Voelkel NF, Tanabe N, Tatsumi K - Respir. Res. (2015)

The determinants of severe pulmonary hypertension. The determinants of the elevation of the pulmonary arterial pressure in principle are vasoconstrictive reactivity which may be treatable with currently available vasodilator drugs. Fully developed and endstage disease may be characterized by complex vascular lesions and vasoconstriction that is refractory to treatment with presently available drugs. Ppa: pulmonary arterial perssure, PVR: pulmonary vascular resistance
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493808&req=5

Fig1: The determinants of severe pulmonary hypertension. The determinants of the elevation of the pulmonary arterial pressure in principle are vasoconstrictive reactivity which may be treatable with currently available vasodilator drugs. Fully developed and endstage disease may be characterized by complex vascular lesions and vasoconstriction that is refractory to treatment with presently available drugs. Ppa: pulmonary arterial perssure, PVR: pulmonary vascular resistance
Mentions: Almost five decades ago, the high pulmonary blood pressure associated with Heath-Edwards classification grades 1-3 was shown to be reversible following surgery that primarily eliminated the left to right shunt in PAH patients with CHD. However, PH associated with Heath-Edwards classification grade 4 was not reversible, at least acutely, after surgery [31]. These differences between grade 3 and 4 are due to the presence of complex intimal lesions that are composed of phenotypically altered mesenchymal-like cells [18, 22, 28, 29], indicating that the determinants of a fixed high pulmonary arterial pressure include complex vascular lesions, but not necessarily a high pulmonary blood flow. Oka et al. investigated the Sugen/Hypoxia rat model and found that pulmonary vascular tone remained to be an important contributing factor to the high Ppa even in the late stages of the disease. The role of increased vascular tone, in particular during exercise and perhaps also controlled by diurnal rhythms, may be underestimated in patients with fully developed angioobliterative disease [14] (Fig. 1). As the disease further progresses, a decrease in the cardiac output due to right ventricle dysfunction and failure results in a drop in Ppa while the pulmonary vascular disease is ongoing.Fig. 1

Bottom Line: Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown.Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage.Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Respirology (B2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. sakaos@faculty.chiba-u.jp.

ABSTRACT
Given the difficulty of diagnosing early-stage pulmonary arterial hypertension (PAH) due to the lack of signs and symptoms, and the risk of an open lung biopsy, the precise pathological features of presymptomatic stage lung tissue remain unknown. It has been suggested that the maximum elevation of the mean pulmonary arterial pressure (P pa) is achieved during the early symptomatic stage, indicating that the elevation of the mean P pa is primarily driven by the pulmonary vascular tone and/or some degree of pulmonary vascular remodeling completed during this stage. Recently, the examination of a rat model of severe PAH suggested that the severe PAH may be primarily determined by the presence of intimal lesions and/or the vascular tone in the early stage. Human data seem to indicate that intimal lesions are essential for the severely increased pulmonary arterial blood pressure in the late stage of the disease.However, many questions remain. For instance, how does the pulmonary hemodynamics change during the course of the disease, and what drives the development of severe PAH? Although it is generally acknowledged that both pulmonary vascular remodeling and the vascular tone are important determinants of an elevated pulmonary arterial pressure, which is the root cause of the time-dependent progression of the disease? Here we review the recent histopathological concepts of PAH with respect to the progression of the lung vascular disease.

No MeSH data available.


Related in: MedlinePlus