Types Of Pulmonary Hypertension Research Articles

The endothelium and genetics in pulmonary arterial hypertension.

There have been tremendous progresses in research and improvement in therapeutic options for pulmonary arterial hypertension (PAH) and other types of pulmonary hypertension (PH) over the last 15 years. PAH and other PH have been shown to present similar histopathologic changes and therefore, do not indicate lung biopsies for a specific diagnosis. This may be due to shared physiopathologic mechanisms, involving initially endothelial alterations, leading to three main changes: vasoconstrictive phenomena, growth factor releases, leading to small vessel remodelling and to thrombotic phenomena. Genetic polymorphisms have been discovered in two genes of the transforming growth factor family (the bone morphogenetic protein receptor II and the activin receptor-like kinase) and one in the serotonin transporter gene. The genetic findings are not yet applicable for genetic counselling, but the physiopathologic discoveries have allowed major therapeutic progresses.

Pulmonary Hypertension, Antiphospholipid Antibodies, and Syndromes

Antiphospholipid antibodies have been associated with two types of pulmonary hypertension (PHT), the thromboembolic type, after deep venous thromboses in the lower limbs complicated by pulmonary embolism and the "primary" plexogenic type. The PHT may occur in the absence of any other manifestations of the antiphospholipid syndrome (APS), and cases have been recorded with very high levels of antiphospholipid antibodies. It may also accompany systemic lupus erythematosus (SLE) and may manifest with or without other features of the APS. It may also form part of the clinical presentation of a "primary" APS. Its prevalence is of the order of 1.8-3.5% of the manifestations of the APS depending on the series. Primary "idiopathic" PHT has long been regarded as an "immunological" disorder. Its manifestations are essentially to the primary type seen with the connective tissue disorders such as SLE, APS, mixed connective tissue disease, calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia variety of systemic sclerosis and Sjögren's syndrome. The high prevalence of PHT in patients with human immunodeficiency virus infection who demonstrate low CD4 counts points to a close relationship between the T regulatory cells (Treg) and the development of PHT, and this hypothesis is discussed in this review. Genetic and chromosomal aspects of PHT are also discussed.

Chronische Lungenembolie – Radiologische Bildmorphologie und Differenzialdiagnose

In chronic pulmonary embolism branches of the pulmonary arterial tree remain partially or totally occluded. This may lead to pulmonary hypertension with the development of right ventricular hypertrophy as well as structural changes of pulmonary arteries. Imaging of chronic pulmonary embolism should prove vessel occlusions (pulmonary angiography, MSCT, MRI) and reduction of regional lung perfusion (lung scanning, MSCT, MRI). According to current guidelines ventilation-perfusion lung scanning and pulmonary angiography are still recommended as the methods of choice. MSCT and MRI provide technical alternatives which are helpful in differential diagnosis versus other types of pulmonary hypertension. In spite of medical and surgical measures (in rare cases pulmonary thromboendarterectomy) the prognosis of chronic pulmonary embolism remains unfavourable.

Pulmonary hypertension and β-thalassemia major: Report of a case, its treatment, and a review of the literature

Pulmonary hypertension is a common complication of beta-thalassemia major. We report a case of successful treatment of pulmonary hypertension in a patient with beta-thalassemia major and review the literature on pulmonary hypertension and beta-thalassemia major. A 28-year-old man with beta-thalassemia major, splenectomy, hepatitis C, and hemosiderosis who presented with increasing dyspnea on exertion was diagnosed with pulmonary hypertension. After receiving continuous epoprostenol infusion and desferoxamine, his functional capacity and hemodynamic status improved. To our knowledge, this is the first case of pulmonary hypertension associated with beta-thalassemia treated with continuous epoprostenol infusion and desferoxamine. Epoprostenol, beneficial in the treatment of other types of pulmonary hypertension, may ameliorate the morbidity and mortality of pulmonary hypertension associated with thalassemia.

Superoxide and Chronic Hypoxia-Induced Pulmonary Hypertension in Newborn Piglets

Free radicals, including superoxide, O2−, have been implicated in the pathogenesis of certain types of pulmonary hypertension. Yet, the role of O2− in chronic hypoxia-induced pulmonary hypertension in newborns is unknown. Moreover, there is little information regarding the influence of chronic hypoxia on the expression of O2− enzymatic scavenging systems, such as the cytosolic copper/zinc containing enzyme, superoxide dismutase (SOD)-1 or mitochondrial manganese SOD (SOD-2). Our purpose was to determine whether O2− is involved with the abnormal constrictor responses that develop in resistance pulmonary arteries (RPAs) of newborn pigs exposed to 3 days of hypoxia.

Diagnostic et classification des hypertensions artérielles pulmonaires

The clinical classification of types of pulmonary hypertension has made it possible to better standardize the approach to the diagnosis and treatment of patients, to perform clinical studies among homogeneous patients, and to discover common laboratory abnormalities that may serve as markers or help elucidate mechanisms of disease. Pulmonary arterial hypertension groups together different diseases that affect the small-caliber pulmonary arteries and lead to a progressive increase in pulmonary arterial resistance and right heart failure. A specific diagnosis of pulmonary arterial hypertension is generally based on a detailed and methodical clinical evaluation. Pulmonary biopsy is rarely indicated. Work-up in a center specialized in the management of this disease is frequently appropriate when the cause of the hypertension is not clear or when a specific treatment is envisaged.

Safety and hemodynamic effects of pulmonary angiography in patients with pulmonary hypertension: 10-year single-center experience.

We sought to examine the incidence of complications and change in pulmonary artery pressure in patients with pulmonary hypertension who were undergoing pulmonary angiography. A retrospective review was performed for all patients who underwent pulmonary angiography over a 10-year period at a single institution. Patients with moderate pulmonary hypertension (pulmonary artery pressure, 30-59 mm Hg) and severe pulmonary hypertension (pulmonary artery pressure, >/= 60 mm Hg) served as the study population. Demographic data, clinical indication, pre- and postcontrast pulmonary artery pressure measurements, type of pulmonary hypertension, contrast agent volume, complications, and American Society of Anesthesiologists (ASA) classification were recorded for all patients and compared. Two hundred two of 612 patients who underwent pulmonary angiography had pulmonary hypertension. Moderate pulmonary hypertension was present in 155 patients (77%) and severe pulmonary hypertension, in 47 patients (23%). Three (2.0%) of four complications were fatal. The complication rate was higher in patients with severe pulmonary hypertension compared with patients with moderate pulmonary hypertension but not statistically significant (6.3% vs 0.6%, p = 0.63). Patients with complications had a higher mean ASA score than those without complications (4.0 vs 3.0, p = 0.03). Patients with lung transplants had the greatest increase in pulmonary artery pressure after pulmonary angiography compared with all other clinical indications (16.75 +/- 12.97 mm Hg vs 5.46 +/- 6.86 mm Hg, p = 0.003). The complication rate of pulmonary angiography in patients with pulmonary hypertension is low. However, in severely ill patients with acute pulmonary hypertension, pulmonary angiography should be undertaken with extreme caution.

Inflammation in pulmonary arterial hypertension.

Inflammatory mechanisms appear to play a significant role in some types of pulmonary hypertension (PH), including monocrotaline-induced PH in rats and pulmonary arterial hypertension of various origins in humans, such as connective tissue diseases (scleroderma, systemic lupus erythematosus, mixed connective disease), human immunodeficiency virus infection, or plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal (M) protein and skin changes (POEMS) syndrome. Interestingly, some patients with severe pulmonary arterial hypertension associated with systemic lupus erythematosus have experienced significant improvements with immunosuppressive therapy, emphasising the relevance of inflammation in a subset of patients presenting with PH. Patients with primary PH (PPH) also have some immunological disturbances, suggesting a possible role for inflammation in the pathophysiology of this disease. A subset of PPH patients have been shown to have circulating autoantibodies, including antinuclear antibodies, as well as elevated circulating levels of the pro-infammatory cytokines, interleukins -1 and -6. Lung histology has also revealed inflammatory infiltrates in the range of plexiform lesions in patients displaying severe PPH, as well as an increased expression of the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) and fractalkine. Further analysis of the role of inflammatory mechanisms is necessary to understand whether this component of the disease is relevant to its pathophysiology.

Different types of pulmonary hypertension require different treatment strategies

Different types of pulmonary hypertension require different treatment strategies

Nitric Oxide in Systemic and Pulmonary Hypertension.

Endothelium-derived nitric oxide (NO) is an important gas molecule in the regulation of vascular tone and arterial pressure. It has been considered that endothelial dysfunction with impairment of NO production contributes to a hypertensive state. Alternatively, long-term hypertension may affect the endothelial function, depress NO production, and thereby reduce the dilator action on vasculatures. There were many studies to support that endothelium-dependent vasodilatation was impaired in animals and humans with long-term hypertension. However, results of some reports were not always consistent with this consensus. Recent experiments in our laboratory revealed that an NO synthase inhibitor, N(G)-nitro-L-arginine monomethyl ester (L-NAME) caused elevation of arterial pressure (AP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The magnitude of AP increase following NO blockade with L-NAME was much higher in SHR than WKY. In other experiments with the use of arterial impedance analysis, we found that L-NAME slightly or little affected the pulsatile hemodynamics including characteristic impedance, wave reflection and ventricular work. Furthermore, these changes were not different between SHR and WKY. The increase in AP and total peripheral resistance (TPR) following NO blockade in SHR were significantly greater than those in WKY, despite higher resting values of AP and TPR in SHR. In connection with the results of other studies, we propose that heterogeneity with respect to the involvement of NO (impairment, no change or enhancement) in the development of hypertension may exist among animal species, hypertensive models and different organ vessels. Our study in SHR provide evidence to indicate that the effects of basal release of NO on the arterial pressure and peripheral resistance are not impaired, but enhanced in the hypertensive state. The increase in NO production may provide a compensatory mechanism to keep the blood pressure and peripheral resistance at lower levels. The phenomenon of enhanced NO release also occurs in certain type of pulmonary hypertension. We first hypothesized that a decrease in NO formation might be responsible for the pulmonary vasoconstriction during hypoxia. With the measurement of NO release in the pulmonary vein, we found that ventilatory hypoxia produced pulmonary hypertension accompanying an increase in NO production. Addition of NO inhibitor (L-NAME), blood or RBC into the perfusate attenuated or abolished the NO release, while potentiating pulmonary vasoconstriction. During hypoxia, the increased NO formation in the pulmonary circulation similarly exerts a compensatory mechanism to offset the degree of pulmonary vasoconstriction.

Different distribution of plexiform lesions in primary and secondary pulmonary hypertension

Despite much interest in plexiform lesions, no published work compares their distribution in different types of pulmonary hypertension. Scattered reports of plexiform lesions in bronchial arteries oppose the consensus view that the lesions develop in pulmonary arteries. To compare the localization of plexiform lesions in different types of pulmonary hypertension, and to assess the role of the bronchial arteries in their formation, we examined by light microscopy lung tissue from five patients with primary plexogenic pulmonary arteriopathy (PPPA), six with pulmonary hypertension secondary to congenital cardiac malformations (CCM), and one with pulmonary hypertension complicating hepatic cirrhosis. We classified the 270 plexiform lesions observed as either preacinar or intra-acinar based on the type of pulmonary artery in which they were located, and computed the frequencies of each type of lesion within each etiologic group. We searched for lesions developing in bronchial arteries. Then, postulating that a close anatomic relationship between plexiform lesions and bronchial arteries would necessitate a clustering of the lesions near sites in the lung subserved by the bronchial circulation, we measured, for 211 of the 270 lesions previously classified, the distance from the lesion to the nearest airway and computed the mean lesion-to-airway distance in each etiologic group. The frequencies of preacinar plexiform lesions were 34% in PPPA, 67% in CCM ( P < .01), and 21% in the case of cirrhosis. We found no plexiform lesions within bronchial arteries, and the mean plexiform lesion-to-airway distances were 1,680 ± 180 μm in PPPA, 1,330 ± 220 μm in CCM, and 2,050 ± 1,090 μm in cirrhosis ( P > .05). Our data suggest that (1) the distribution of plexiform lesions within the pulmonary arterial tree varies depending on the etiology, (2) plexiform lesions rarely if ever arise in bronchial arteries, and (3) plexiform lesions are not preferentially distributed near parts of the lung subserved by the bronchial circulation.

Pulmonary vascular pressure-flow plots in canine oleic acid pulmonary edema. Effects of prostaglandin E1 and nitroprusside.

We investigated the effects of prostaglandin E1 (PGE1) and of sodium nitroprusside (NP) on multipoint pulmonary arterial pressure (PAP)/cardiac index (Q) plots in 24 pentobarbital-anesthetized and ventilated dogs with pulmonary hypertension secondary to oleic acid lung injury. The PAP/Q plots were rectilinear in all experimental conditions. In control dogs (n = 8), PAP was increased over the entire range of Q studied, from 1 to 4 L/min.m2, 90 min after oleic acid 0.09 ml/kg, and remained so during 2 consecutive 5-point PAP/Q plots, each of them being constructed in about 30 min. Oleic acid increased the extrapolated pressure intercept (p less than 0.001) but not the slope of the PAP/Q plots. Infusion of PGE1 0.4 micrograms/kg.min intravenously (n = 8) reduced PAP at each level of Q, with a reduction of the extrapolated pressure intercept (p less than 0.01) and no change in slope of the PAP/Q plots. In contrast, NP 5 micrograms/kg.min intravenously (n = 8) slightly reduced PAP only at the highest Q studied, without any significant change in extrapolated pressure intercept or slope of PAP/Q plots. Systemic blood pressure was decreased by 21% after PGE1 and by 24% after NP. Neither drug affected Q nor blood gases after oleic acid. The results suggest that pulmonary hypertension secondary to oleic acid pulmonary edema may be due more to an increase in effective outflow pressure of the pulmonary circulation than to an increase in incremental vascular resistance, and that active vasoconstriction contributes to this type of pulmonary hypertension.

Pulmonary heart disease: pathophysiology, diagnostic signs, and therapy.

The anatomy and physiology of the pulmonary vasculature has been described with emphasis on several types of pulmonary hypertension and their pathophysiology. Treatment of pulmonary hypertension may be successful, especially when disease is related to emboli which respond to anticoagulant therapy. Relief of mitral valve obstruction is usually beneficial. Patients with abnormalities of blood PO2 and pH (especially in chronic obstructive lung disease) may be spared increased pulmonary pressure or may reverse existing pulmonary hypertension by giving up smoking, learning more efficient ventilatory methods, and when indicated, using supplemental oxygen, bronchodilators, digitalis, diuretics, or a combination of these.

Familial pulmonary hypertension and multiple abnormalities of large systemic arteries in Osler's disease

Two sisters with severe pulmonary hypertension and Osler's disease are described. Heart disease also occurred in other family members affected with hereditary hemorrhagic telangiectasia. Multiple abnormalities of large systemic vessels, severe intrahepatic arteriovenous fistulas and systemic-pulmonary arterial anastomoses were demonstrated in one of the patients, and we conclude that analogous manifestations may have been present in her sister and presumably in other members of the family too. The patients are discussed in relation to similar cases reported earlier and to various types of pulmonary hypertension.

Pulmonary hypertension with muscular exercise in the newborn calf

Two types of pulmonary hypertension occur with muscular exercise (walking) in the calf on the day of birth: a) Pulmonary arterial pressure increased in all calves during exercise. The increase was greatest in the youngest calves. Pulmonary arterial pressures did not rise to systemic levels and arterial oxygen saturations remained normal. Pulmonary hypertension subsided in 2 min after stopping exercise. Pulmonary arterial pressure rose again when exercise was repeated. Both an increased pulmonary flow and pulmonary vasoconstriction may have contributed to the increased pulmonary arterial pressure during exercise. b) Pulmonary hypertension was observed in five calves for 30-50 min after exercise ceased. When pulmonary arterial pressure exceeded aortic pressure, arterial oxygen unsaturation occurred. This pulmonary hypertension which occurred only once per calf resembled"spontaneous" pulmonary vasoconstriction observed in resting calves on the day of birth. It is postulated that some substance remaining in the lung after fetal life, rather than the acutely reduced oxygenation of mixed venous blood, initiated this pressor response. hypoxia; pulmonary vasoconstriction Submitted on May 11, 1964