Nocturnal oxygen therapy in patients with the Eisenmenger syndrome.

This prospective and controlled pilot study evaluates the long-term effects of nocturnal oxygen therapy (NOT) on exercise endurance, hematology variables, quality of life, and survival of 23 adult patients (mean age, 32 +/- 6 yr) with post-tricuspid congenital heart defects (ventricular septal defect = 10; patent ductus arteriosus = 13) and Eisenmenger Syndrome. All had pulmonary hypertension (mean pulmonary artery pressure = 88 +/- 20 mm Hg), severe hypoxemia (Pa(O(2)) = 44 +/- 5 mm Hg), and secondary erythrocytosis (hematocrit = 61.5 +/- 7%). Exercise endurance (6-min walk test = 380 +/- 88 m) was limited. In a random fashion, NOT was given to one group of patients (n = 12) but withheld from a comparable control group (n = 11). At 2 yr of close follow-up, two patients in the group of control patients, and three in the treatment group died. Mean survival estimates were similar in both groups (20.7 versus 20.8 mo; chi-square log-rank, 0.08; p = NS). Likewise, none of the hematology, exercise capacity, and quality of life variables examined showed statistically significant changes that were dependent on treatment regimen. We conclude that NOT does not modify the natural history of patients with advanced Eisenmenger Syndrome.

[Development of a canine model of chronic progressive right ventricular hypertension]. / Desarrollo de un modelo canino de hipertensión ventricular derecha crónica progresiva.

INTRODUCTION: Several animal models of right ventricle hypertension (RVH) have been produced through pulmonary artery banding with linen, tygon or teflon. Nevertheless few devices attempting a progressive, step by step graduated chronic development of RVH have been reported. The present study describes the results in our animal model of chronic RVH. MATERIAL AND METHODS: We designed a software programmed to obtain hemodynamic data and installed a small occlusive hydraulic device (OHD) at the pulmonary artery trunk producing a raise in the right ventricular systolic pressure (RVSP); this pressure can be modified externally through the OHD. We studied 12 healthy mongrel dogs (18 to 28 kg of weight) in the course of 6 months. Hemodynamic measurements were performed at different RVSP at two months intervals; (Baseline, 40 mmHg and 60 mmHg). RESULTS: The software was useful to analyze several hemodynamic variables at each RVSP. At 60 mmHg, the end diastolic pressure of the right ventricle (RVEDP) increased from 4.2 +/- 0.4 mmHg to 13.2 +/- 1.1 mmHg, p < 0.000, accompanied with a fall in cardiac output adjusted to the dogs weight from 0.16 +/- 0.03 L/min/kg to 0.09 +/- 0.01 L/min/kg, p > 0.000. Also an increase of the end diastolic pressure of the left ventricle (LVEDP) from 7.4 +/- 0.8 mmHg to 16.3 +/- 2.8 mmHg, p < 0.000, was observed. RVSP was maintained in chronic condition and the intraclass correlation coefficient was 0.83, P < 0.005. CONCLUSIONS: Right ventricular chronic hypertension is created. The device is useful and reliable to maintain chronic increments of RVSP. The software permits a versatile analysis.

[Helical computerized tomography of the thorax in the diagnosis of unresolved chronic pulmonary thromboembolism]. / La tomografía computarizada helicoidal del tórax en el diagnóstico de la tromboembolia pulmonar crónica no resuelta.

We assessed the diagnostic usefulness of helical CT scan of the thorax in the setting of chronic thromboembolic pulmonary hypertension by prospectively comparing the results of helical CT scan to those of the pulmonary angiogram (gold standard). We studied 40 patients with diagnosis of pulmonary hypertension of diverse etiology (mean age: 40.7 +/- 12 y.o.; mean systolic pulmonary artery pressure: 91 +/- 33 mmHg)). Thirty of these patients fulfilled the diagnostic criteria of chronic thromboembolic pulmonary hypertension and the other ten were used as controls. Diagnosis in control patients included: primary pulmonary hypertension (4); patent ductus arteriosus (2); atrial septal defect (1); rheumatic valve disease (1); ischemic heart disease (1); and acute pulmonary embolism (1). Both helical CT scan and pulmonary angiogram were part of the routine diagnostic work up of these patients, and were, performed and interpreted almost simultaneously (within one week) by a different group of investigators in a blind manner. Only the diagnostic accuracy of the method regarding central (major arteries) vascular lesions was evaluated. Helical CT scan had an overall sensitivity of 100% (29/29), and a specificity of 91% (10/11). Positive predictive and negative predictive values were 96.6% (29/30) and 100% (10/10), respectively. Overall diagnostic accuracy was 97.5% (39/40). We conclude that helical CT scan of the thorax is an excellent alternative approach for the diagnosis of major arteries lesions in the setting of chronic thromboembolic pulmonary hypertension.

[Pulmonary vascular reactivity and the development of edema in the presence of prostaglandin inhibitors in the isolated canine lobe]. / Reactividad vascular pulmonar y formación de edema en presencia de inhibidores de prostaglandinas en el lóbulo canino aislado.

UNLABELLED: Alveolar hypoxia is the most powerful pulmonary vasoconstrictor. In a previous work, we did not demonstrate significant changes in vascular reactivity and edema formation in an isolated canine lobe model during alveolar hypoxia. The purpose of this study is to define vascular pulmonary reactivity and edema formation after induction of pulmonary vasoconstriction using a prostaglandin inhibitor like tiaprofenic acid and alveolar hypoxia. Six isolated canine pulmonary lobules were instrumented and studied, all of them under two conditions (normoxia FIO2 21% and hypoxia FIO2 5%) four starting in normoxia condition and 2 starting in hypoxia condition. RESULTS: No significant changes in filtration rate were found, normoxia 0.42 +/- 0.41, hypoxia 0.37 +/- 0.51 ml/min/100 g pulmonary tissue P = NS. The arterial pressure in basal conditions was 25.1 +/- 6.21, and during hypoxia increased to 37 +/- 7.19 cm H2O (Delta 12.0 +/- 1.2 cm H2O). P < 0.001. CONCLUSION: Hypoxia vascular reactivity was significantly increased in tiaprofenic acid pretreated isolated canine lobes, no changes in pulmonary permeability was found nor increased rate in edema formation.

Effect of body position changes on pulmonary gas exchange in Eisenmenger's syndrome.

Preliminary studies on sleep of patients with congenital heart disease and Eisenmenger's syndrome (ES) at our institution demonstrated nocturnal worsening arterial unsaturation, which appeared to be a body position-related phenomenon. To investigate the potential effect of body position on gas exchange in ES, we carried out a prospective study of 28 patients (mean age, 34.8 +/- 11.7 yr) with established ES due to congenital heart disease. In every patient, arterial blood gases were performed during both sitting and supine positions under three different conditions: room air, while breathing 100% oxygen, and after breathing oxygen at a flow rate of 3 L/min through nasal prongs. Alveolar oxygen pressure (PaO2) for the calculation of alveolar-arterial oxygen tension differences (AaPO2) was derived from the alveolar gas equation using PaCO2 and assuming R = 1. We used paired t test, repeated-measures two-way ANOVA with Bonferroni's test, and regression analysis. From sitting to supine position on room air, there was a significant decrease in PaO2 (from 52.5 +/- 7.5 to 47.5 +/- 5.5 mm Hg; p < 0. 001) and SaO2 (from 86.7 +/- 4.6 to 83.3 +/- 4.9%; p < 0.001), both of which were corrected by nasal O2 (to 68.2 +/- 21 mm Hg and to 92 +/- 4%, respectively, p < 0.005). PaCO2 and pH remained unchanged. The magnitude of the change in PaO2 correlated with the change in AaPO2 on room air (r = 0.77; p < 0.01) but not with the change in AaPO2 on 100% oxygen. It is concluded that in adult patients with ES there is a significant decrease in PaO2 and SaO2 when they change from the sitting to the supine position. A ventilation-perfusion (V/Q) distribution abnormality and/or a diffusion limitation phenomenon rather than an increase in true shunt may be the mechanisms responsible for this finding. The response to nasal O 2 we observed warrants a trial with long-term nocturnal oxygen therapy in these patients.

Graded balloon dilation atrial septostomy in severe primary pulmonary hypertension. A therapeutic alternative for patients nonresponsive to vasodilator treatment.

OBJECTIVES: We sought to investigate the acute hemodynamic effects of graded balloon dilation atrial septostomy (BDAS) and to define the long-term impact of this procedure on New York Heart Association functional class and survival in adult patients with primary pulmonary hypertension (PPH). BACKGROUND: Current treatment strategies for patients with severe and refractory PPH are limited by either technical difficulties and high mortality or cost. METHODS: We studied 15 patients with severe PPH. BDAS was successfully performed in all patients by crossing the interatrial septum with a Brockenbrough needle, followed by progressive dilation of the orifice with a Mansfield balloon in a hemodynamically controlled, step-by-step manner. RESULTS: BDAS caused an immediate significant fall in right ventricular end-diastolic pressure and in systemic arterial oxygen saturation and an increase in cardiac index. One patient died, and 14 survived the procedure and significantly improved their mean functional class (from 3.57 +/- 0.6 to 2.07 +/- 0.3 [mean +/- SD], p < 0.001). Exercise endurance (6-min test) also improved from 107 +/- 127 to 217 +/- 108 m (p < 0.001). Because of spontaneous closure, BDAS was repeated in four patients. The survival rate among patients who survived the procedure was 92% at 1, 2 and 3 years, which is better than that for historical control PPH patients (73%, 59% and 52%, respectively). CONCLUSIONS: With careful monitoring, BDAS is a safe and useful palliative treatment for selected patients with severe PPH.

Primary antiphospholipid syndrome presenting as chronic thromboembolic pulmonary hypertension. Treatment with thromboendarterectomy.

Pulmonary hypertension may occur in the antiphospholipid syndrome as a result of recurrent pulmonary embolism or microthrombosis of pulmonary vessels. We describe 3 cases of primary antiphospholipid syndrome (APS) and cor pulmonale that fulfilled the criteria for chronic major vessel thromboembolic pulmonary hypertension. Pulmonary thromboendarterectomy was performed in all 3 patients and it was successful in 2. One patient died in the immediate postoperative period from hemorrhagic pulmonary edema. Chronic thromboembolic pulmonary hypertension should be added to the list of pulmonary vascular complications of primary APS. Despite its risk, pulmonary thromboendarterectomy represents a treatment option for this otherwise lethal condition.

[Continuous spectrophotometry as a method to study pulmonary edema in isolated canine pulmonary lobe]. / Espectrofotometría continua como método para el estudio del edema pulmonar en una preparación de lóbulo pulmonar canino aislado.

The aim of this paper is to introduce the spectrophotometric method to the study of pulmonary edema in isolated ex-vivo canine pulmonary lobe preparation. This spectrophotometric method is based on the on-line measure of light transmission in a column of blood, that is proportional to hematocrit. A second light is used to follow Evans blue dyed proteins. With this method we were able to measure the amount of edema in 10 isolated canine lobes. Both the filtration and reflection coefficient of the membrane as well as the characteristics of the filtrate could be calculated. The filtration coefficient was 0.6 +/- 0.4 ml/min (1.3 +/- 0.9 ml/min/100 g pulmonary, tissue) at maximum capillary pressure and the reflection coefficient was 0.53 +/- 0.07. With the spectrophotometric method we have the capability to study different aspects of lung edema formation. This method has the advantage of being exact and independent from pressure and volume induced vascular changes. It also allows the measurement of solute transport.

Primary pulmonary hypertension in children: clinical characterization and survival.

OBJECTIVES: This study characterized mortality in a group of Mexican children (n = 18, mean [+/- SD] age 9.9 +/- 3 years) with primary pulmonary hypertension and investigated the factors associated with their survival. BACKGROUND: Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Establishing the diagnosis earlier in life may influence prognosis. METHODS: A dynamic cohort of children with primary pulmonary hypertension were enrolled between December 1977 and May 1991 and followed up through September 1992. Measurements included hemodynamic and pulmonary function variables in addition to demographic data, medical history and response to vasodilator treatment. We also compared the survival estimates of these children with those of our adult patients with primary pulmonary hypertension (n = 42, mean age 27.9 +/- 8.5 years). RESULTS: Baseline mean (+/- SD) pulmonary artery pressure was similar in children and adults (66 +/- 15 vs. 65 +/- 18 mm Hg, p = NS), but a higher cardiac index resulted in a lower mean pulmonary vascular resistance index in children (18 +/- 7 vs. 26 +/- 12 U/m2, p < 0.01). The proportion of patients who had a positive hemodynamic response to vasodilator treatment was higher in children than in adults (41% vs. 25%). Estimated median survival in children was 4.12 years (95% confidence interval [CI] 0.75 to 8.66) and 3.12 years in adults (95% CI 0.5 to 13.25, chi-square log-rank 0.81, p = NS). Elevated right atrial pressure (rate ratio 10.2) and decreased stroke volume index (rate ratio 32.9) were the only significant predictors of mortality (Cox proportional hazards model). CONCLUSIONS: Children with primary pulmonary hypertension have a poor survival expectancy, which does not appear to differ from that in adults with primary pulmonary hypertension. Mortality in childhood primary pulmonary hypertension is also associated with variables that assess right ventricular dysfunction.

Survival in primary pulmonary hypertension. Validation of a prognostic equation.

BACKGROUND: The prognosis of patients with primary pulmonary hypertension (PPH) remains a major problem for the planning and assessment of therapeutic interventions. The objectives of this study were (1) to characterize mortality in a Mexican population of patients with PPH and to investigate factors associated with survival and (2) to test the applicability in this population of the prognostic equation proposed by the US National Institutes of Health study on PPH. METHODS AND RESULTS: A dynamic cohort of patients with PPH at our institution were enrolled between June 1977 and August 1991 and prospectively followed at regular intervals through September 1992. Measurements at diagnosis included hemodynamic and pulmonary function variables in addition to information on demographic data and medical history. The response to vasodilator treatment was also analyzed. The estimated median survival of the group was 4.04 years (95% confidence interval, 2.98 to 5.08 years). Variables associated with poor survival (univariate analysis) included an elevated mean right atrial pressure, a decreased cardiac index, and a decreased mixed venous PO2. A reduced forced vital capacity and the absence of vasodilator treatment were also associated with poor survival. A multivariate Cox proportional-hazards regression analysis was used to assess the adjusted hazard ratios, hence the relative contributions of the variables controlling for confounding. Reduced forced vital capacity and cardiac index and increased right atrial pressure were still significantly associated as risk factors for survival in patients with PPH. Survival as computed by the equation correlated with real survival of PPH patients with positive predictive values of 87%, 91%, and 89% at 1, 2, and 3 years, respectively. The equation, however, was relatively unable to predict deaths in our population, in part because of the strict limits of poor prognosis. CONCLUSIONS: Mortality in PPH is largely associated with hemodynamic variables that assess right ventricular function. The proposed prognostic equation had a high sensitivity and a relatively low specificity to predict survival in our PPH population. To improve this specificity it may be necessary to increase the limits of poor prognosis as defined by the equation.

Pulmonary arterial hypertension and cor pulmonale associated with chronic domestic woodsmoke inhalation.

We describe the clinical, radiologic, functional, and pulmonary hemodynamic characteristics of a group of 30 nonsmoking patients with a lung disease that may be related to intense, long-standing indoor wood-smoke exposure. The endoscopic and some of the pathologic findings are also presented. Intense and prolonged wood-smoke inhalation may produce a chronic pulmonary disease that is similar in many aspects to other forms of inorganic dust-exposure interstitial lung disease. It affects mostly country women in their 60s, and severe dyspnea and cough are the outstanding complaints. The chest roentgenograms show a diffuse, bilateral, reticulonodular pattern, combined with normalized or hyperinflated lungs, as well as indirect signs of pulmonary arterial hypertension (PAH). On the pulmonary function test the patients show a mixed restrictive-obstructive pattern with severe hypoxemia and variable degrees of hypercapnia. Endoscopic findings are those of acute and chronic bronchitis and intense anthracotic staining of the airways appears to be quite characteristic. Fibrous and inflammatory focal thickening of the alveolar septa as well as diffuse parenchymal anthracotic deposits are the most prominent pathologic findings, although inflammatory changes of the bronchial epithelium are also present. The patients had severe PAH in which, as in other chronic lung diseases, chronic alveolar hypoxia may play the main pathogenetic role. However, PAH in wood-smoke inhalation-associated lung disease (WSIALD) appears to be more severe than in other forms of interstitial lung disease and tobacco-related COPD. The patients we studied are a selected group and they may represent one end of the spectrum of the WSIALD.

Diclofenac potasico como coadyuvante en el tratamiento de la bronquitis aguda. / Potassium diclofenac as adjuvant in the treatment of acute bronchitis

Se valoro con el metodo doble ciego la respuesta sintomatica de 90 pacientes adultos con bronquitis infecciosa aguda a la administracion de diclofenac potasico, metoxipropiocin sodico y placebo en los tres grupos se asocio ampicilina. Los resultados obtenidos permiten concluir que ambos preparados activos ejercen efecto sintomatico sobre la fiebre e inflamacion, que fue mas notable con la administracion de diclofenac potasico. Una vez mas se comprobo la conveniencia del tratamiento sintomatico en este tipo de procesos agudos

[Pulmonary function in chronic ischemic cardiopathy]. / Estudio de la función pulmonar en la cardiopatía isquémica crónica.

Twenty patients with heart disease were prospectively studied. Seven of them had an old myocardial infarction and thirteen, ischemic symptoms without infarction. Pulmonary function was studied focusing on small airway disease and gas exchange abnormalities. Our results showed that a mild degree of abnormality exists as reflected by bronchial obstruction with origin in small airways, V/Q disturbed and hypoxemia. In 88% these seem to be related to left ventricular disfunction. Twenty four hours after pulmonary function test all patients underwent left heart catheterization with coronarography and ventriculography.

[Alveolar-arterial oxygen gradient in cardiopulmonary patients breathing ambient air at rest and during exercise]. / Estudio del gradiente A-a de oxígeno en pacientes cardiopulmonares, respirando aire ambiente, en reposo y en ejercicio.

The alveolar to arterial difference of oxygen [(A-a)DO2] depends on variables such as ventilation, cardiac output, respiratory exchange ratio and arterial PO2. The arterial PO2 itself depends on the ventilation to perfusion ratio (V/Q) pulmonary shunt, (a-v) O2 difference, and the metabolic status of the patient. When the alveolar-ventilation is normal, the (A-a)DO2 reflects gas exchange abnormalities and when the alveolar-ventilation is increased, the (A-a)DO2 can increase because of a decrease in PaCO2. The factors capable of altering the alveolar to arterial oxygen difference were investigated in ninety patients with pulmonary disease: (pulmonary embolism, lung fibrosis and chronic obstructive lung disease), both at rest and during exercise. At rest when alveolar ventilation was increased, the (A-a)DO2 broadened due to the decrease in PaCO2. During exercise the (A-a)DO2 also increased and the PaCO2 was not significantly modified, therefore admixture it is the result of an increase in the proportion of venous. The difference between the mixed venous and arterial PO2 decreased due to alveolar hypoventilation reducing in consequence the (A-a)DO2. We conclude that in the group studied the increase in the (A-a)DO2 is mainly due to V/Q imbalance at rest and during exercise.

Peripheral airways obstruction in idiopathic pulmonary artery hypertension (primary).

The mechanical properties of the lung were studied in ten nonsmokers with idiopathic pulmonary artery hypertension (IPAH) (mean pulmonary artery pressure 65.7 +/- 30 mm Hg). In the routine lung test, residual volume was found to be abnormal (greater than 120 percent of the predicted) in seven patients, and measured airway resistance was normal in eight out of the ten patients. A decreased FEF 75-85 percent, abnormal values for the helium-air flow ratios and increased closing capacities were documented in eight of ten patients in whom lung elastic recoil was normal (six of ten) or increased (four of ten). These features suggest peripheral airways obstruction (PAO) which was also supported by histopathologic findings in three cases (one biopsy and two necropsies). The observed changes in lung compliance could be related to the behavior of the coupling of the air-space and vascular compartments. The etiology of PAO in IPAH patients is not known, but our results indicate that both the peripheral airways and the pulmonary circulation are affected. The knowledge of PAO in IPAH patients could help to better understand the observed V/Q inequality in this entity.

[Pulmonary mechanics and small airways in patent ductus arteriosus and interventricular communication, in relation to pulmonary arterial flow and pressure]. / La mecánica pulmonary y la vía aérea menor en la persistencia del canal arterial y la comunicación interventricular, en relación al flujo y a la presión arterial pulmonar.

Eighteen patients with ventricular septal defect or patent ductus arteriosus were studied to investigate the effects of an increase of pulmonary hypertension. In general group II showed similar results as previously reported in patients with atrial septal defect without pulmonary hypertension. In group I, we found an increased frequency of functional abnormalities in the small airways. We do not have a definitive explanation for the origin of these differences.

[Effects of body posture on mechanical lung function in the obese patient]. / Los effectos de la posición corporal sobre la función mecánica del pulmón en el obeso.

The pulmonary mechanics of twelve obese patients were studied: the static and dynamic compliance, the maximum pressure of elastic recoil, and the expiratory flow curves breathing room air and a mixture of He-O2. Also analyzed were the closing capacity, the closing volume and the slope of the alveolar plateau (phase III), in the erect and supine positions. Our data confirm that the tests that explore the small airways are abnormal in the obese patients. The results obtained, allow us to assure that the pulmonary mechanics in the obese patients are affected by the change of position, as is shown by the closing volume and closing capacity when assuming the supine position when compared to orthostatism, as well as the decrease in vital capacity. These alterations were not found in non-obese patients which were used as controls.

[Arteriovenous shunting in obesity, its relation to lung volume]. / El corto-circuito venoarterial en al obesidad, su dependencia del volumen pulmonar.

Thirty-five patients with an average overweight of 67.1% were studied. Pulmonary restriction of a variable degree was found in 68.6/; in 60% due to reduction of respiratory reserve volume. Bronchial obstruction was detected in 57% as measured by forced midexpiratory flow (25-75%). In addition, 14% showed a decrease of 75-85% in forced expiratory flow, which suggested that the pathology was located in the small respiratory airways. The PaO2 while breathing room air and in a resting state was of 52.6 +/- 9.42 mmHg, and after breathing it increased to 69.07 +/- 11.01 mmHg. The PaO2 breathing inspiratory fractions of 99.6% O2 in a resting condition was 309.34 +/- 70.07 mmHg, and after deep breathing it rose to 354.0 +/- 64.27 mmHg. The mechanisms which produce hypoxemia in the obese were analysed and it was concluded that they were due fundamentally to alterations of the ventilation perfusion ratio and to an increase of the venous-arterial shunt. In some cases, alveolar hypoventilation contributed (Pickwick syndrome). By increasing the pulmonary volume with deep breathing, the ventilation perfusion ratio improves or becomes normal, likewise, the venous-arterial shunt can improve or persist as the only cause of hypoxemia.