Primary Arterial Hypertension Research Articles

Relationship of renal cell carcinoma and hypertension

The morbidity and mortality due to renal cell carcinoma has increased worldwide over the last 30 years. Renal cell carcinoma accounts for about 90-95% of all renal tumors. The mean age of patients with this type of tumor ranges between 50 and 70 years. It is important to note that primary arterial hypertension as well as obesity and smoking are considered as independent risk factors for renal cell carcinoma. The increase in both systolic and diastolic blood pressure as well as the severity of arterial hypertension may have an impact on development of renal cell carcinoma. We describe the case of a 45-year-old male patient with hypertensive crisis. Computed tomography scan revealed renal cell carcinoma, which was confirmed histologically after surgical treatment.

Crosstalk of cyclic GMP dependent kinase I and BMP signaling

Bone morphogenetic proteins (BMPs) are members of the TGFβ growth factor superfamily and have important roles in proliferation, development, differentiation of embryonic and adult cells, as well as in tissue regeneration. BMPs signal via two transmembrane serine/threonine kinase receptors, the BMP type I (BMPRIa and BMPRIb) and BMP type II (BMPRII) receptors which can form homo- and heterooligomeric complexes. They occur in distinct membrane areas, are differently modulated upon ligand binding and are subsequently endocytosed [1]. Upon ligand binding to the receptor complex a signaling cascade via Smad proteins or independent of Smads is initiated and results in expression of specific target genes. cGMP-dependent kinase I (cGKI) was identified as a BMPRII interacting protein in a proteomics-based approach using the cytoplasmic BMPRII-tail region as bait [2]. cGKI is a cytoplasmic serine/threonine kinase and signals via the NO/cGMP/cGK pathway and is involved in regulation of growth, differentiation and apoptosis of cells [3]. The involvement of cGKI in BMP signaling could be validated as it positively influences receptor and Smad activation at the plasma membrane as well as it enhances the transcription of target genes in the nucleus [4]. New results hint towards the fact that cGKI is involved in endocytotic events in BMP signaling, as it dynamically interacts with BMPRII upon BMP-2 stimulation and enhances the internalization of the receptor. Interfering with endocytosis in the cell inhibits BMP signaling mediated by BMP-2 and cGKI. Clinical evidence for the involvement of cGKI in BMP-signaling is given by the fact that mutations in the BMPRII are related to the development of primary arterial hypertension (PAH) [5]. Patients with PAH suffer from vasoconstriction and elevated pressure in the pulmonary arteries, but the distinct pathway leading to the specific phenotype is still unraveled. We could show that ineffective signaling caused by mutant BMPRII found in PAH could be compensated through cGKI [4].

Cerebral Hemorrhage Associated with Sildenafil (Revatio) in an Infant

A case of cerebral hemorrhage associated with sildenafil (Revatio) use in an infant is presented. Sildenafil is increasingly used in the treatment of primary and secondary pulmonary arterial hypertension and pulmonary arteriovenous fistula. In the reported case, sildenafil used to treat pulmonary arteriovenous fistula improved right-to-left shunting across the pulmonary fistula but resulted in cerebral hemorrhage. Cerebral hemorrhage, a previously reported complication of sildenafil, developed in an infant after a rapid increase in dose, to 4.7 mg/kg/day. Therefore, sildenafil doses must be increased only with care, and cerebral hemorrhage must be considered a potential complication.

Octreotide for recurrent intestinal variceal bleeding in patients without portal hypertension

We report on the efficacy of octreotide acetate in two patients with intestinal phlebectasia and no evidence of portal hypertension or mesenteric thrombosis. Patient 1 was a 46-year-old woman with primary pulmonary arterial hypertension. She required repeated transfusions for recurrent episodes of gastrointestinal bleeding (GIB). Intraoperative enteroscopy revealed wide-spread small bowel phlebectasia and intestinal resection was not performed. Blue rubber-bleb syndrome, portal hypertension and mesenteric thrombosis were ruled out. Octreotide acetate long-acting release was started. A transient interruption in treatment was followed by severe overt GIB. This was effectively controlled with continuous infusion of octreotide acetate. After this episode, octreotide acetate long-acting release was resumed and no further episodes of GIB have been reported until the most recent follow up (total duration of 74 months). Patient 2 was a 51-year-old woman with a history of recurrent GIB requiring multiple blood transfusions since young adulthood with negative endoscopic investigations. An enteroscopy showed numerous submucosal serpiginous varices in the colon and the terminal ileum. All putative causes including portal hypertension or mesenteric thrombosis were ruled out. Monthly intramuscular injections of long-acting octreotide acetate were initiated, and no GIB occurred since then (27 months of follow up). Somatostatin analogues are known to reduce splanchnic blood flow, to increase vascular resistance, to enhance platelet aggregation; and are thus efficacious in preventing GIB secondary to various vascular lesions (portal hypertension, intestinal angiodysplasia and blue rubber-bleb syndrome). These case reports suggest that they are also effective in preventing GIB in intestinal phlebactasia without portal hypertension.

Telmisartan in daily clinical practice

Telmisartan provides effective treatment of hypertension in a broad spectrum of patients. To evaluate factors affecting the efficacy of telmisartan in daily clinical practice. Prospective practice-based 12-week uncontrolled cohort study. Consecutive incident/prevalent outpatients with mild to moderate essential hypertension were started on telmisartan 40 mg/day with optional up-titration to 80 mg/day in order to achieve seated systolic (SSBP) and diastolic (SDBP) blood pressure < 140/90 mm Hg. Intent-to-treat (ITT, N=282) and per protocol (PP, N=275) efficacy assessment was based on SSBP/SDBP reduction and delivered doses. SSBP/SDBP decreased (165.2+/-13.1 / 98.3+/-6.7 mm Hg to 137.9+/-13.2 / 82.6+/-7.3 mm Hg), whilst telmisartan was up-titrated in 40.5% of patients during the study. Multivariate (practically identical ITT and PP) analysis indicated poorer response in obese vs. non-obese patients: lesser SDBP reduction (by around 2.2-2.3 mm Hg, P < 0.05) with higher odds of dose up-titration (odds ratio, OR around 1.90, P < 0.05); and better response in: a) patients started on telmisartan monotherapy than when added to a preexisting treatment: greater SSBP/SDBP reduction (by around 4.0 and 3.0 mm Hg, respectively, P < 0.05) with comparable odds of up-titration; b) diabetics vs. non-diabetics: greater SDBP reduction (by around 3.6-3.7 mm Hg, P < 0.05) with comparable odds of up-titration; c) men vs. women: slightly greater SDBP reduction (by around 1.2 mm Hg, 0.05 P < 0.1) with lower odds of up-titration (OR around 0.51, P < 0.05). Previous unsuccessful treatment, obesity, diabetes and gender should be considered in order to optimize the use of telmisartan for mild to moderate essential hypertension in daily clinical practice.

Tratamento da hipertensão arterial com olmesartana medoxomila em escalonamento

The national and international guidelines emphasize the importance of the effective treatment of arterial hypertension. Nevertheless, low levels of control are observed, as well as low attainment of the recommended goals, indicating that it is important to plan and implement better treatment strategies. To evaluate the efficacy of a based treatment algorithm with olmesartan medoxomil. This is an open, national, multicentric and prospective study of 144 patients with primary arterial hypertension, stages 1 and 2, naïve to treatment or after a 2-to-3 week washout period for those in whom treatment was ineffective. The use of olmesartan medoxomil was assessed in a treatment algorithm divided into 4 phases: (i) monotherapy (20 mg), (ii-iii) associated to à hydrochlorothiazide (20/12.5 mg and 40/25 mg) and (iv) addition of amlodipine besylate (40/25 mg + 5 mg). At the end of the phased-treatment, 86% of the study subjects attained the goal of BP < 130/85 mmHg. Maximum reductions in SAP and DAP were -44.4 mmHg and -20.0 mmHg, respectively. The rate of systolic responders (SAP >or= 20 mmHg) and of diastolic responders (DAP >or= 10 mmHg) was 87.5% and 92.4%, respectively. The study was based on a treatment regimen that was similar to the therapeutic approach in daily clinical practice and showed that the use of olmesartan medoxomil in monotherapy or in association with hydrochlorothiazide and amlodipine was effective in the attainment of the recommended goals for hypertension stage 1 and 2 hypertensive individuals.

Treatment of patients with spontaneous intracranial hematomas

Spontaneus intracerebral haemorrhage is a common cause of stroke especially in the young. The term "spontaneuos intracerebral haemorrhage" refers to bleeding without coincident trauma. About 80% of this haemorrhage occur supratentorial in the basal nuclei and they are associated with hypertension. Etiological factors range from congenital vascular malformations (aneurysmas, AVM, cavernomas) to acquired and degenerative vascular and brain conditions. In primary intracerebral hemorrhage arterial hypertension and consequent vascular changes are the major etiological factors. In secondary- nonhypertensive hemorrhage cause may be associated with aneurysms, AVM, tumors, coagulation disorders. Contemporary diagnosis imaging (CT, MRI) and neurological evaluation, allow early diagnosis and effective medical and/or surgical therapy in a majority patients. Without treatment, the risk of mortality and morbidity is high. Medical management involves normalization of blood pressure, reduction of intracranial pressure, control of brain edema and prevention of seizures. In design for operative treatment must be include age of the patient, hematoma size and location, clinical condition, the level of consciousness and patient outcome. The role of surgery remains contraversial.

Bosentan dans la sclérodermie: Perspectives

Systemic sclerosis (SSc) is a complex, immune-mediated disease. The etiology and pathogenesis of SSc remain incompletely understood. Vascular injury, excessive fibrosis, autoimmunity and inflammation are permanent features of the disease process leading to irreversible organ damage and significant morbidity and mortality in SSc patients. One hypothesis suggests that endothelial damage and vascular dysfunction may be some of earliest pathogenic alterations. Despite significant efforts developed in the past twenty years, no single therapy has been proven to increase survival in SSc patients in a prospective randomised trial. Endothelin-1 is considered to be a central pathogenic factor in systemic sclerosis (SSc), leading to vasoconstriction and fibrosis. Bosentan is a specific, orally active, dual endothelin receptor antagonist that has recently been approved for the treatment of primary pulmonary arterial hypertension (PAH) orPAH associated with systemic sclerosis. Furthermore, bosentan is a useful option for the prevention of ischemic digital ulcers in the setting of systemic sclerosis. These findings suggest that bosentan could have therapeutic benefits on others vascular injuries. Recent data in many experimental animal models demonstrated the fundamental role of endothelin in the pathogenesis of fibrosis, and the anti-fibrotic potential of bosentan. Nonetheless, its exact place in the management of fibrosis in patients with SSc will be clarified by results of furthers studies. Several new therapeutic approaches are currently under evaluation in ScS. An attractive therapeutic approach is the combination of drugs with different mechanisms of action, with the objective to maximize their clinical benefit.

Mixed-Expired and End-Tidal CO2 Distinguish Between Ventilation and Perfusion Defects During Exercise Testing in Patients With Lung and Heart Diseases

Mismatching of ventilation to perfusion is found in patients with COPD, left ventricular failure (LVF), and pulmonary vascular diseases. Such mismatching may be due to ventilation or perfusion defects or both. Our primary hypothesis was that pressures of mixed-expired CO2 pressure (Peco(2)), end-tidal Pco(2) pressure (Petco(2)), and their ratios would differ between groups during exercise testing, depending on whether the ventilation/perfusion (V/Q) abnormality was dominantly caused by airways or perfusion defects. We administered incremental cycle ergometry tests to 25 normal subjects and three groups of 25 patients, each group with uncomplicated COPD, LVF, or primary pulmonary arterial hypertension (PAH). We compared Peco(2), Petco(2), and their ratios at rest, unloaded pedaling, anaerobic threshold, and peak exercise. Although each patient group had mean peak O(2) uptake of approximately 50% of predicted normal, the levels and patterns of change for each group for Peco(2), Petco(2), and their ratios were surprisingly distinctive. As hypothesized, the COPD group always had markedly lower Peco(2)/Petco(2) ratios than all other groups (p < 0.001). In addition, patients with LVF had slightly lower Peco(2)/Petco(2) ratios at heavy exercise than normal subjects (p < 0.05). At all times, except for COPD group Petco(2) at peak exercise, each group had significantly lower Petco(2) and Peco(2) than normal subjects (p < 0.001). In patients with PAH, the Petco(2) decline with exercise was distinctive. The levels and changes in Peco(2), Petco(2), and their ratios during cardiopulmonary exercise testing are distinctive and explained by the differing pathophysiologies of V/Q mismatching in these disorders.

Apport de la scintigraphie rénale avec test au captopril dans l’exploration de l’hypertension artérielle rénovasculaire : à propos d’un cas

Introduction Dynamic renal scintigraphy with 99mTc-DTPA and captopril test is a non-invasive functional method for the diagnosis of renovascular hypertension. It allows differentiating between hypertension induced by renal arterial stenosis from primary arterial hypertension with an incidental stenosis. Case report A 14-year-old girl, without previous medical history, developed a severe arterial hypertension with cephalgias and ears buzzing. Auscultation revealed a murmur in the left lumbar pit. Renal angiography objectified a stenosis of the infrarenal aorta due to a circumferential parietal thickening associated to renal arteries stenosis more marked in the left side. Dynamic renal scintigraphy after administration of captopril highlighted a marked collapse of the rate of tracer uptake exceeding 40% on the left side with an increase in the time of collecting on the right side testifying a frankly positive test prevailing on the left. A transluminal angioplasty of the left renal artery and a revascularisation surgery on the right side were carried out. The evolution was marked by an improvement of blood pressure figures. Discussion Dynamic renal scintigraphy using 99mTc-DTPA with captopril test constitutes a non-invasive process with a low dosimetry for the patients. Its principal goal is to affirm the role of renovascular stenosis in the origin of arterial hypertension and to determine which hypertensive patients with renal arterial stenosis can be treated successfully by surgical or endoscopic revascularisation of the kidney.

Role of zinc in regulation of arterial blood pressure and in the etiopathogenesis of arterial hypertension

Increased gastrointestinal absorption and urinary excretion of zinc has been confirmed in experimental and clinical studies on primary arterial hypertension as a result from changes of intracellular and extracellular zinc content. In arterial hypertension, the levels of zinc in serum, lymphocyte, and bone decrease while increasing in heart, erythrocytes, kidney, liver, suprarenal glands and spleen. These changes result in the loss of zinc homeostasis that leads to various degrees of deficiency, not entirely compensated by nutritional factors or increased absorption in the gastrointestinal tract. Loss of zinc homeostasis can be both cause and effect of high blood pressure. In the present review, the role of zinc metabolism changes and its mechanisms in arterial hypertension are discussed.

Selected zinc metabolism parameters in premenopausal and postmenopausal women with moderate and severe primary arterial hypertension

The aim of this study was to compare zinc (Zn) metabolism parameters in groups of premenopausal and postmenopausal women with moderate and severe primary arterial hypertension. The study included 38 women, of which 15 were premenopausal and 23 were postmenopausal. Postmenopausal women had a positive correlation between total (ERCt- Zn) and oubain-dependent (ERCos-Zn) rate constants of Zn efflux from lymphocyte (k = 0.52). In premenopausal women's ERCos-Zn was negatively but weakly correlated with serum Zn (Zn-s) (k = 0.35). The Zn ERCt- Zn and ERCos-Zn did not show any correlation with age, as did Zn-s. Lymphocyte Zn correlated negatively with age only in premenopausal women (k = -0.62). The renin-angiotensin-aldosterone system correlated with Zn metabolism parameters. In premenopausal women, plasma renin activity and serum aldosterone showed positive correlations with lymphocyte Zn (Znl) (k = 0.63 and k = 0.41, respectively), and in postmenopausal women, it correlated negatively with Zn-s (k = -0.38) and whole aldosterone correlated negatively with ERCos-Zn (k = -0.41). Positive correlations between Zn metabolism parameters and arterial blood pressure in premenopausal women were as follows: ERCt-Zn with diastolic blood pressure (dRR) (k = 0.40) and ERCos-Zn with dRR (k = 0.47). In postmenopausal women, the correlations between ERC-t-Zn and dRR and systolic blood pressure (sRR) were negative (k = -0.53 and k = -0.63, respectively). A similar situation was observed between dRR and sRR and Zn-s (k = -0.40 and k = -0.38, respectively). The body mass index (BMI) was positively correlated with ERCt-Zn in premenopausal women (k = 0.36), whereas in postmenopausal, it was negatively correlated with ERCos-Zn (k = -0.42). For the whole group, negative correlations were seen between Zns and dRR and sRR (k = -0.36 and k = -0.39, respectively) and between ERCos-Zn and BMI (k = -0.39). The results presented show differences in Zn metabolism in arterial hypertension between premenopausal and postmenopausal women. The role of estrogens in these differences is disscused.

Selected Zinc Metabolism Parameters and Left Ventricle Mass in Echocardiographic Examination in Primary Arterial Hypertension

The basal systolic and diastolic blood pressure, body mass index, left ventricular mass, serum and lymphocyte zinc levels, serum aldosterone, plasma rennin and angiotensin-converting enzyme activities, sodium and potassium levels, and the total and ouabain-dependent rate constants of zinc efflux from lymphocytes were measured in a group of 41 individuals of both sexes (overall age 46.3 +/- 11.4 years), of which 18 were women (48.5 +/- 7.1 years old) and 23 were men (44.7 +/- 13.8 years old). There were no significant differences between these parameters while dividing the subjects into groups according to sex, despite differences in weight, left ventricle mass, plasma rennin activity, and serum aldosterone content. Only the total and ouabain-dependent rate constants of zinc efflux from lymphocytes slightly negatively correlated to left ventricular mass, r = -0.30 to r = -0.36. This may constitute indirect evidence of zinc deficiency in cardiomyocytes of some hypertensive individuals with left ventricular hypertrophy.

Role of rat α adducin in angiogenesis: Null effect of the F316Y polymorphism

Rat alpha adducin point mutation (F316Y) has been associated with primary systemic arterial hypertension. As microcirculatory abnormalities are present in most forms of hypertension, the aim of the present study was to investigate whether rat alpha adducin may regulate endothelial cell (EC) functions in vitro and in vivo. The overexpression of rat wild type alpha adducin (WT-Add1) in ECs induced capillary-like structure development in Matrigel in vitro and enhanced capillary formation in Matrigel implants in vivo in CD1 mice. In contrast, the overexpression of the mutated form (MUT-Add1) of rat alpha adducin had a Null effect in vitro and lacked any significant activity in vivo. Further, adenovirus-mediated rat WT-Add1 but not MUT-Add1 gene transfer to murine ischemic hindlimb enhanced capillary formation in skeletal muscles. Gene profiling of human umbilical vein endothelial cells overexpressing alpha adducin was performed in order to identify putative effector molecules of alpha adducin-mediated activities on ECs. Interestingly, among a number of genes involved in angiogenesis regulation, retinoic acid-induced protein (RAI17) was found to be upregulated in WT-Add1 vs MUT-Add1 overexpressing cells, possibly representing a key molecule/axis for the functional Add1-induced effect. Rat WT alpha adducin enhanced EC functions both in vitro and in vivo. The expression of the F316Y variant, associated with the hypertensive phenotype, had a Null effect and might contribute to endothelial rarefaction/dysfunction in hypertension. RAI17 was found to be a putative effector molecule differentially regulated by the overexpression of the two forms of Add1 in endothelial cells.

Correlations between serum zinc concentrations and oxygen balance parameters in patients with primary arterial hypertension

It has been postulated that increased blood pressure is related to hypersensitivity of arterial chemoreceptors and increased tissue oxygen supply. Arterial blood pressure has been found to be negatively correlated to serum zinc and positively correlated to age, body mass index, and hemoglobin concentrations. The aim of the present investigation was to further explore the relationship between blood pressure and zinc concentrations in serum and blood morphology parameters, iron concentrations, and venous blood gasometry parameters. The study was carried out in two groups. Group Aconsisted of 23 subjects of both sexes suffering from moderate to severe arterial blood pressure. Their mean age was 53.13+/-10.45 yr (range: 23-74 yr). Group B included 48 subjects of mean age 36.7+/-10.0 yr (range: 26-60 yr). This group included 5 patients with arterial hypotension, 37 with hypertension, and the remaining 6 with normal blood pressure. Significant positive correlations between serum zinc and red blood cell count (r = 0.51) and negative with age (r = -0.52) were found. By multiple regression, negative correlations were also found between serum zinc and the diastolic blood pressure and with hemoglobin (r = -0.5). Age was positively correlated to systolic (r = 0.49) and diastolic (r = 0.45) blood pressure parameters and to hemoglobin concentrations (r = 0.33 and r = 0.38, respectively). Buffered and excess bases in blood were negatively correlated to zinc (r = -0.29 in both cases) and to systolic and diastolic blood pressure (r = -0.31 and r = -0.40, respectively). In turn, the systolic and diastolic blood pressure also correlated negatively to the partial pressure of carbon dioxide and positively to venous blood oxygen saturation and to the partial pressure of oxygen. The role of zinc and acid-balance realtionships in blood pressure regulation and in arterial hypertension ethiopatogenesis is disscused.

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. Amajor research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and thallium have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed.

Correlations between serum zinc concentrations and oxygen balance parameters in patients with primary arterial hypertension

Correlations between serum zinc concentrations and oxygen balance parameters in patients with primary arterial hypertension

Role of trace elements in primary arterial hypertension

A negative relationship between water hardness and cardiovascular mortality rate was demonstrated and became a source of interest regarding minerals and trace metals in the pathogenesis of atherosclerosis, cardiovascular diseases, and arterial hypertension. Higher incidences of sudden death, cerebrovascular diseases, arterial hypertension, and coronary heart disease have been reported in soft water areas. Amajor research effort has been devoted to the problem in an attempt to find a protective factor in hard water or a detrimental factor or element in soft water. The roles of calcium, magnesium, cobalt, lithium, vanadium, silicon, manganese, and copper have been considered potentially beneficial, whereas those of cadmium, lead, silver, zinc, and thallium have been considered potentially harmful. Cobalt and zinc have been attributed both roles. In the present article, the role of trace quantities of several elements in mineral water in the etiopathogenesis of primary arterial hypertension is reviewed.

PREVALENCE OF ARTERIAL HYPERTENSION, ASSOCIATED DISEASES AND END-ORGAN DAMAGES IN REPUBLIC OF BASHKORTOSTAN

Aim. To estimate arterial hypertension (AH) prevalence among population of Republic of Bashkortostan (RB), prevalence of end-organ damages and the associated clinical conditions in hypertensive patients. Material and methods. 1648 people from 10 regions of RB were examined. Standard questionnaires were used - socially-demographic, health con???dition, WHO cardiologic questionnaire, women’s health. Results. The urban and rural AH prevalence, AH prevalence in men and women, as well as AH comorbidities prevalence is studied. There is a high fre???quency of myocardial infarction and cerebral strokes in AH patients. Prevalence of end-organ damage and the associate clinical conditions is various in men and in women. С onclusion. Available data will help to develop primary and secondary AH prevention taking into account risk factors.

Low-dose oral sildenafil for patients with pulmonary hypertension: a cost-effective solution in countries with limited resources

Pulmonary arterial hypertension, both primary and secondary, continues to pose a therapeutic problem. In this study, we evaluate the efficacy and safety of a low-dose of oral sildenafil in 10 patients with pulmonary arterial hypertension. We administered a single daily dose of 0.5 milligrams per kilogram of sildenafil for 3 months to 10 patients with pulmonary arterial hypertension. Their average age was 26.8 years. Diagnoses were primary pulmonary arterial hypertension in 3 patients, and secondary pulmonary arterial hypertension due to congenital cardiac disease in the remaining 7 patients. Outcome measures included the clinical state, the mean pulmonary arterial pressure, and the indexed pulmonary vascular resistance; the latter two assessed at the beginning and at the end of the treatment period by cardiac catheterization. We also analysed the cost of the treatment. Oral treatment was well tolerated, and resulted in an improvement of the functional capacity in 9 of the 10 patients. Pulmonary arterial pressure decreased from 70 to 60 millimetres of mercury (p equal to 0.05), and indexed pulmonary vascular resistance decreased from 21.8 to 15.8 Wood units per square metre (p equal to 0.006). The mean cost per patient for 3 months on oral treatment with sildenafil was 120.99 American dollars. A low dose of 0.5 milligrams per kilogram per day of oral sildenafil, instead of 1 to 4 milligrams per kilogram per day, provided early clinical and haemodynamic improvements, and proved less expensive. Additional experience is now required to define more reliably the true long-term benefits of this therapy.