The relationship between the components of pulmonary artery pressure remains constant under all conditions in both health and disease.

Background: The relationships among systolic pulmonary artery pressure (SPAP), diastolic pulmonary artery pressure (DPAP), and mean pulmonary artery pressure (MPAP) have been found to be constant in humans breathing air, at rest, while supine. It would be important for those studying the pulmonary circulation if this relationship were maintained under other circumstances, such as change in posture, during exercise, or after pharmacologic manipulation. In particular, it would be useful if the relationship were maintained when treating pulmonary hypertension because this would allow different methods of measurement to be compared, such as SPAP from echocardiography and MPAP from right heart catheterization.

Pulmonary artery adventitial fibroblasts cooperate with vasa vasorum endothelial cells to regulate vasa vasorum neovascularization: a process mediated by hypoxia and endothelin-1.

The precise cellular and molecular mechanisms regulating adventitial vasa vasorum neovascularization, which occurs in the pulmonary arterial circulation in response to hypoxia, remain unknown. Here, using a technique to isolate and culture adventitial fibroblasts (AdvFBs) and vasa vasorum endothelial cells (VVECs) from the adventitia of pulmonary arteries, we report that hypoxia-activated pulmonary artery AdvFBs exhibited pro-angiogenic properties and influenced the angiogenic phenotype of VVEC, in a process of cell-cell communication involving endothelin-1 (ET-1). We demonstrated that AdvFBs, either via co-culture or conditioned media, stimulated VVEC proliferation and augmented the self-assembly and integrity of cord-like networks that formed when VVECs where cultured on Matrigel.

Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage.

Vascular remodeling in chronic hypoxic pulmonary hypertension includes marked fibroproliferative changes in the pulmonary artery (PA) adventitia. Although resident PA fibroblasts have long been considered the primary contributors to these processes, we tested the hypothesis that hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage, termed fibrocytes. Using two neonatal animal models (rats and calves) of chronic hypoxic pulmonary hypertension, we demonstrated a dramatic perivascular accumulation of mononuclear cells of a monocyte/macrophage lineage (expressing CD45, CD11b, CD14, CD68, ED1, ED2).

Consensus statement on chronic and subacute high altitude diseases.

This is an international consensus statement of an ad hoc committee formed by the International Society for Mountain Medicine (ISMM) at the VI World Congress on Mountain Medicine and High Altitude Physiology (Xining, China; 2004) and represents the committee's interpretation of the current knowledge with regard to the most common chronic and subacute high altitude diseases. It has been developed by medical and scientific authorities from the committee experienced in the recognition and prevention of high altitude diseases and is based mainly on published, peer-reviewed articles. It is intended to include all legitimate criteria for choosing to use a specific method or procedure to diagnose or manage high altitude diseases.

Distensibility of the normal human lung circulation during exercise.

Increasing pulmonary arterial (Ppa) and wedge (Pw) pressures at high flow (Q) during exercise could distend the thin-walled vessels. A mechanical descriptor of vascular distension, the distensibility (alpha, fractional diameter change/mmHg pressure), has been reported to be approximately 0.02 for isolated large and small arteries, i.

Hypoxia, leukocytes, and the pulmonary circulation.

Data are rapidly accumulating in support of the idea that circulating monocytes and/or mononuclear fibrocytes are recruited to the pulmonary circulation of chronically hypoxic animals and that these cells play an important role in the pulmonary hypertensive process. Hypoxic induction of monocyte chemoattractant protein-1, stromal cell-derived factor-1, vascular endothelial growth factor-A, endothelin-1, and tumor growth factor-beta(1) in pulmonary vessel wall cells, either directly or indirectly via signals from hypoxic lung epithelial cells, may be a critical first step in the recruitment of circulating leukocytes to the pulmonary circulation. In addition, hypoxic stress appears to induce release of increased numbers of monocytic progenitor cells from the bone marrow, and these cells may have upregulated expression of receptors for the chemokines produced by the lung circulation, which thus facilitates their specific recruitment to the pulmonary site.

Insights by Peruvian scientists into the pathogenesis of human chronic hypoxic pulmonary hypertension.

Pulmonary hypertension had long been suspected in high-altitude natives of the Andes. However, it remained for a team of Peruvian scientists led by Dante Penaloza to provide not only the first clear evidence that humans living at high altitude did indeed have chronic, and occasionally severe, pulmonary hypertension, but more importantly, that this was a consequence of structural changes in the pulmonary vascular bed. Novel histological findings by one of the team, Javier Arias-Stella, indicated that hypoxia-induced thickening of the pulmonary arteriolar walls was the primary cause of the elevated pressure.

High-altitude pulmonary edema in children with underlying cardiopulmonary disorders and pulmonary hypertension living at altitude.

Background: Pulmonary hypertension has not been described as a predisposing risk factor for high-altitude pulmonary edema (HAPE) in children. Previous studies have shown an association of HAPE with abnormally increased pulmonary vasoreactivity to hypoxia but generally normal pulmonary artery pressure (PAP) after recovery.

Objective: To describe HAPE of relatively rapid onset and its management in a series of children residing at moderate to high altitudes, all of whom had underlying pulmonary hypertension.

Chronic mountain sickness: recent studies of the relationship between hemoglobin concentration and oxygen transport.

Although an increase in hemoglobin concentration [Hb] in high altitude residents assists oxygen transport, excessive polycythemia ([Hb] > or = 21 g/100 mL) may cause the syndrome of chronic mountain sickness (CMS). A recent theoretical analysis has suggested that increasing [Hb] above 18 g/100 mL provides no further benefit in oxygen transport at rest. To test this hypothesis, we examined oxygen transport at rest for given arterial oxygen saturations (Sa(O2), in classes at intervals of 5%) as reported in 206 residents of various altitudes.

Bovine distal pulmonary arterial media is composed of a uniform population of well-differentiated smooth muscle cells with low proliferative capabilities.

The media of the normal bovine main pulmonary artery (MPA) is composed of phenotypically heterogeneous smooth muscle cells (SMC) with markedly different proliferative capabilities in response to serum, mitogens, and hypoxia. Little, however, is known of the SMC phenotype in distal pulmonary arteries (PA), particularly in arterioles, which regulate the pulmonary circulation. With a panel of muscle-specific antibodies against alpha-smooth muscle (SM)-actin, SM-myosin heavy chains (SM-MHC), SM-MHC-B isoform, desmin, and meta-vinculin, we demonstrate a progressive increase in phenotypic uniformity and level of differentiation of SMC along the proximal-to-distal axis of normal adult bovine pulmonary circulation so that the media of distal PA (1,500- to 100-microm diameter) is composed of a phenotypically uniform population of "well-differentiated" SMC.

Hypoxia-induced pulmonary artery adventitial remodeling and neovascularization: contribution of progenitor cells.

Information is rapidly emerging regarding the important role of the arterial vasa vasorum in a variety of systemic vascular diseases. In addition, increasing evidence suggests that progenitor cells of bone marrow (BM) origin may contribute to postnatal neovascularization and/or vascular wall thickening that is characteristic in some forms of systemic vascular disease. Little is known regarding postnatal vasa formation and the role of BM-derived progenitor cells in the setting of pulmonary hypertension (PH).

Adrenergic contribution during acclimatization to high altitude: perspectives from Pikes Peak.

We have examined the sympathoadrenal responses to both acute and chronic high-altitude exposure at the summit of Pikes Peak, CO, in both men and women. A dissociation between the adrenal medullary response (acute) with that of the sympathetic nervous system (chronic) is observed. Both alpha- and beta-adrenergic contributions to key metabolic and physiologic adjustments to high-altitude exposure are evident.

Exercise-dependent ventilatory sensitivity to hypoxia in Andean natives.

In Andean natives (NAT), the ventilatory response to hypoxia is blunted at rest but potential interaction with exercise has been little studied. Therefore, during three levels of submaximal exercise, 13 NAT were compared with 6 sojourners (SOJ) acclimatized at 4,360 m for an average of 7 months. Exercise ventilation was measured first breathing oxygen (PI(O(2)) 410 Torr) and then ambient air (PI(O(2)) 86 Torr).

Circulatory responses to high altitude in the cat and rabbit.

Cats were taken from Denver (5,200 ft.) to Mt. Evans (14,150 ft.

Pulmonary vasoconstriction in steers at high altitude.

Each of ten steers taken for 9 weeks to 12,700 ft. (Mt. Evans, Colorado) showed a marked increase in pulmonary artery (PA) pressure.

Pulmonary circulation and oxygen transport in lambs at high altitude.

The oxygen transport and pulmonary hemodynamics of lambs native to low altitude were evaluated in Denver and on Mount Evans (12,700 ft.). Because the Hb-O2 dissociation curve is placed well to the right of most other mammals, markedly depressed arterial O2 saturations (59%) occurred at high altitude.