Peripheral plasma adenosine release in patients with chronic heart failure.

OBJECTIVE: Chronic heart failure (CHF) is accompanied by increased adenosine plasma levels (APLs). It is unknown whether adenosine release occurs at the peripheral level or whether the myocardium itself is the source of adenosine release. To answer this question, we evaluated APLs in the coronary sinus of CHF patients during a resynchronisation procedure and compared the values with those at the peripheral level. We also investigated a possible correlation between APLs and ischaemia-modified albumin (IMA) levels, a useful marker of tissue ischaemia. METHODS: 19 men and seven women were prospectively included. Blood samples for APLs were collected simultaneously from a brachial vein (peripheral) and from the coronary sinus. Blood samples for brain natriutretic peptide (BNP) and IMA were collected from a brachial vein. RESULTS: APLs from the brachial vein were higher than those from the coronary sinus (1.69 vs 0.75 muM p<0.01). IMA levels were correlated with APLs from the brachial vein (r = 0.59, p<0.01). BNP concentrations were correlated with APLs from the brachial vein (r = 0.73, p<0.001) but not with APLs from the coronary sinus (r = 0.38, p>0.05). BNP concentrations and IMA levels were correlated (r = 0.71, p<0.001). CONCLUSIONS: In CHF patients, adenosine release occurs at a peripheral level and not at the myocardium level.

[Cardioversion by external electric shock for atrial fibrillation: does patient age affect immediate results?]. / Cardioversion par choc électrique externe de la fibrillation auriculaire: l'âge des patients affecte-t-il les résultats immédiats?

The restoration of sinus rhythm by external electric shock in patients with persistent atrial fibrillation is a well established treatment. However, in current practice this treatment is generally indicated less in the elderly subject although this attitude is not factual. The objective of this work was to evaluate the immediate results of cardioversion by external electric shock, comparing the success rates in four age groups: under 60 years, between 60 and 69 years, between 70 and 79 years, and over 80 years. This study was performed on 182 consecutive patients aged from 25 to 89 years: 35 patients aged less than 60 years, 52 patients aged from 60 to 69 years, 65 patients aged from 70 to 79 years, and 30 patients aged 80 years or over. The success rates were 91.4% before 60 years, 90.4% between 60 and 69 years, 90.8% between 70 and 79 years, and 83.3% after 80 years. There was no significant difference between the success rates in the four age groups (p = 0.68). Among the other factors analysed, only the duration of atrial fibrillation and the body mass index significantly influenced the results of external electric shock in this series. This work suggests that age does not significantly influence the immediate results of external electric shock. According to these data it does not appear justified to contra-indicate cardioversion by external electric shock on the sole criterion of age.

Influence of residual myocardial ischaemia on induced ventricular arrhythmias following a first acute myocardial infarction.

OBJECTIVES: The purpose of this study was to assess the possible effect of residual myocardial ischaemia on induced ventricular arrhythmia during programmed ventricular stimulation in survivors of a first acute myocardial infarction. BACKGROUND: Most deaths after hospital discharge for acute myocardial infarction are sudden and presumably arrhythmic. Sudden cardiac death results from a dynamic interaction of structural abnormalities and transient triggering factors. The role of myocardial ischaemia as a trigger for ventricular arrhythmias remains unclear. We hypothesized that residual myocardial ischaemia after a first acute myocardial infarction is a potent trigger for sustained ventricular tachyarrhythmias, particularly in the presence of an abnormal myocardium. METHODS AND RESULTS: In this prospective study, programmed electrical stimulation, coronary angiography and dipyridamole-thallium-201 scintigraphy single-photon emission computed tomography were performed in 90 consecutive survivors of a first acute myocardial infarction. Patients, divided in two groups - group 1 with induced ventricular tachyarrhythmia (n=24) and group 2 without induced ventricular tachyarrhythmia (n=66) - were compared regarding residual myocardial ischaemia. The two groups were comparable in terms of mean left ventricular ejection fraction, infarct size and location, gender ratio, peak creatine kinase value, and extent of coronary disease. Residual myocardial ischaemia was detected in 32 patients: 15 (42.5%) belonged to group 1 and 17 (25.7%) to group 2. There was a statistically significant difference between the two groups regarding the presence and the extent of residual myocardial ischaemia (P<0.05). CONCLUSION: Residual myocardial ischaemia, revealed by dipyridamole-thallium-201 scintigraphy following a first acute myocardial infarction, might contribute to electrical instability evaluated by programmed ventricular stimulation.

Effects of digoxin on chemoreflex in patients with chronic heart failure.

The effects of digitalis on the baroreflexes in human chronic heart failure have been well studied. Similarly, since it has been recently shown that chemoregulation remains generally effective during cardiac failure, the goal of this study was to evaluate the effects of a chronic administration of digoxin on the chemoreflexes. Hemodynamic and blood gas parameters were assessed in 7 patients with chronic congestive heart failure before and after chronic administration for 10 days of digoxin therapy (0.25 mg daily). In both situations measurements were performed 1/ in baseline conditions at room air and, 2/ after inhalation of pure O2 for 30 min, in order to inhibit the activation of the chemoreflexes. At room air, acute O2 inhalation resulted in a significant decrease in heart rate and cardiac output. After digoxin therapy, comparatively to pre-treatment values, cardiac output, stroke volume and PaO2 were significantly higher while heart rate, systemic resistance and pulmonary wedge pressure were lower. Furthermore, acute O2 inhalation did not modify heart rate or any hemodynamic variables. These results suggest that after digoxin therapy chemoreflex was no more activated in these patients. This effect may be related to the sympatho-inhibitory and to the positive inotropic effects of digoxin: improving hemodynamic and blood gas parameters may result in the inactivation of the reflex.

Plasma beta-endorphin and adenosine concentration in pulmonary hypertension.

To determine whether beta-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and beta-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 +/- 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 +/- 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 +/-5 mm Hg). Plasma beta-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher beta-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (-60% in COPD [p <0.005] and -70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and beta-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between beta-endorphin and adenosine concentrations (r = -0.751, p <0.001): the higher the adenosine, the lower the beta-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased beta-endorphin release.

Effects of percutaneous transluminal coronary angioplasty on coronary adenosine concentrations in humans.

BACKGROUND: Even minimal amounts of adenosine is released during myocardial ischemia. Its role in coronary blood flow has been extensively studied, but little is known about its behaviour during percutaneous transluminal angioplasty (PTCA) in man. MATERIAL AND METHODS: Using in situ samples the aim of this study was to evaluate adenosine plasma concentration before and after PTCA. Ten patients (8 men and 2 women, mean age 65 +/- 9 years) with a single stenosis of the left anterior descending coronary artery (LAD) of at least 70% and 10 healthy volunteers (4 men and 6 women, mean age 55 +/- 9 years) were included in the study. RESULTS AND DISCUSSION: We found that there is a close relationship between the degree of the stenosis and the adenosine concentrations in the great cardiac vein and in the LAD, and that after PTCA there is a drop in adenosine concentration downstream from the stenosis. This study confirms the crucial role of adenosine in coronary blood flow control.

[Tolerance and efficacy of carvedilol prescription in patients with mild to moderated chronic heart failure]. / Tolérance et efficacité du carvédilol prescrit chez des patients atteints d'insuffisance cardiaque chronique légère à modérée.

The current treatment for heart failure, i.e., carvedilol administration, has brought about a significant reduction in cardiovascular morbidity and mortality. The European Cardiology Association task-force has recently recalled that the treatment for heart failure should be considered differently according to the regions within Europe. However, most studies have involved North American or Australasian subjects. The results of these studies have shown that carvedilol improves the symptomatic status of patients with mild to moderate chronic heart failure, but their extrapolation to the situation in Europe is questionable. In the present study, the authors have reported on the use of this beta-blocker over a 6-month period in 48 European subjects (an older patient population, and more frequently given digitalis treatment) with mild to moderate stage II and III chronic heart failure (mean NYHA functional stage = 2.75 +/- 0.2; mean left ventricular ejection fraction = 32.4 +/- 3.4). Six patients (12.5%) were obliged to withdraw from the study due to adverse reactions to carvedilol, i.e., 2 subjects during the test-dose (4.2%) and 4 others who were subsequently unable to withstand the progressive stepping up of drug dosage (8.3%). In the remaining 42 patients, the mean NYHA scores dropped significantly from 2.75 +/- 0.2 to 1.8 +/- 0.1 (p < 0.05) at the end of the study period, indicating an increase in symptomatic improvement with a favorable hemodynamic tolerance profile, even in cases of combined therapy with digitalis. This study confirms the positive action of carvedilol on functional symptomatology in southern European patients presenting with mild to moderate chronic heart failure. However, it should be emphasized that this beta-blocker should only be administered under strict and specialized medical surveillance as its effect of significantly slowing down the heart rate could also result in cardiac insufficiency.

Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.

Hemodynamic effects of bilevel nasal positive airway pressure ventilation in patients with heart failure.

AIMS: Benefits of nasal continuous positive airway pressure (CPAP) in patients presenting with chronic heart failure (CHF) are controversial. The purpose of this study was to compare the hemodynamic effects of CPAP and bilevel positive airway pressure (BiPAP) in patients with or without CHF. METHODS AND RESULTS: Twenty patients with CHF and 7 with normal left ventricular function underwent cardiac catheterization. Measurements were made before and after three 20-min periods of BiPAP: expiratory positive airway pressure (EPAP) = 8 cm H2O and inspiratory positive airway pressure (IPAP) = 12 cm H2O, EPAP = 10 cm H2O and IPAP = 15 cm H2O, and CPAP = EPAP = IPAP = 10 cm H2O administered in random order. Positive pressure ventilation decreased cardiac output (CO) and stroke volume. No change was observed in either pulmonary or systemic arterial pressure. There was no difference in the hemodynamic effects of the three ventilation settings. Only mean pulmonary wedge pressure (MPWP) and heart rate were lower with CPAP than with BiPAP. CO decreased only in patients with low MPWP (

Hemodynamic response to oxygen administration in chronic heart failure: role of chemoreflexes.

The aim of this study was to assess whether arterial chemoreceptors are activated in chronic heart failure and to appreciate whether this activation is related to the degree of cardiac dysfunction. We examined whether administration of pure oxygen for 30 min to 35 patients with chronic heart failure was followed by hemodynamic modifications that would suggest a negative feedback (inactivation) of such chemoregulation. A decrease in heart rate and cardiac output was observed in all patients. The decrease in cardiac output and stroke volume was inversely correlated to the left ventricular ejection fraction. We observed that the lower the left ventricular ejection fraction, the smaller the decrease in heart rate and the greater the increase in systemic vascular resistance. The variation of stroke volume was related to the variation of systemic vascular resistance. In 12 patients, keeping heart rate constant during oxygen inhalation by adequate right atrial pacing prevented the decrease of cardiac output. These results suggest that chemoregulation remains generally effective in chronic heart failure: increase in Pao2 resulted in a reduction of cardiac output mainly related to the decrease of heart rate. However, when the left ventricular function is very poor, the central chemomediated regulation is impaired, and the direct peripheral effect of oxygen on systemic circulation appears to play a leading part.

Long-term effects of cicletanine on secondary pulmonary hypertension.

Cicletanine, a furopyridine-derivative drug, was shown to enhance the production of endogenous prostacyclin. The potent vasodilating properties of prostacyclin are used to treat severe primary pulmonary hypertension. Prostacyclin has a short half-life and can be administered only as an i.v. infusion. The aim of this study was to evaluate the effects of cicletanine on pulmonary artery hypertension (PAH) resulting from chronic obstructive lung disease (COLD). In a double-blind controlled study, we evaluated the effects of short- and long-term administration of cicletanine (50 mg daily, orally) on hemodynamics and blood gases of patients with PAH resulting from COLD. The initial dose of 50 mg of cicletanine had no effect. A significant decrease in the mean pulmonary artery pressure (15%) and in total pulmonary resistance (20%) was observed after 3 or 12 months of treatment in the cicletanine group (11 patients), when compared with placebo (12 patients). PaO2 decreased slightly in the cicletanine group, but the difference from the control group was not significant. These results suggest that long-term treatment with cicletanine can induce effective pulmonary vasodilation in patients with PAH caused by COLD and that this is probably responsible for a small venous admixture.

Effect of almitrine bismesylate on pulmonary vasoreactivity to hypoxia in chronic obstructive pulmonary disease.

The aim of this double-blind, placebo-controlled study was to determine whether acute administration of almitrine enhances hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease (COPD). Haemodynamics and blood gases were studied at various inspiratory fractional concentrations of oxygen (FIO2): 0.15, 0.21, 0.30 and 1.0, randomly administered for 20 min periods under constant infusion of either placebo or almitrine (8 micrograms.kg-1.min-1) in 20 patients with COPD. The almitrine group exhibited a significant increase in mean pulmonary artery pressure, pulmonary vascular resistance and arterial oxygen tension (PaO2) at FIO2 0.15, 0.21 and 0.30. During hypoxia, the increase in mean pulmonary pressure and pulmonary vascular resistance was three times greater in the almitrine group than the placebo group. No significant difference in cardiac output and systemic haemodynamics was found. These results suggest that almitrine at the dose used, enhances pulmonary vasoconstriction in COPD patients.

[Acute effects of nicardipine on the vascular reactivity of oxygen in patients with respiratory insufficiency and pulmonary hypertension]. / Effets aigus de la nicardipine sur la réactivité vasculaire à l'oxygène chez les patients insuffisants respiratoires hypertendus pulmonaires.

Pulmonary vascular response to the inhalation of various concentrations of oxygen (FIO2) was studied under basal conditions and after nicardipine in 10 patients with pulmonary hypertension secondary to chronic bronchitis. Hemodynamic data and blood gases were measured during inhalation of 3 gas mixtures: hypoxia (FIO2 = 0.15), normoxia (FIO2 = 0.21) and hyperoxia (FIO2 = 0.30). Each gas mixture was administered for 20 minutes, initially during an infusion of placebo and then of nicardipine giving a steady plasma concentration of 29 +/- 4 ng/ml. This was obtained by continuous I.V. infusion of 0.06 mg/kg/hour. Under basal conditions with placebo, the heart rate, cardiac output and pulmonary hypertension increased with decreasing concentrations of inhaled oxygen. The systemic blood pressure was unchanged with hypoxia but decreased during hyperoxia. Nicardipine increased the heart rate and the cardiac output but reduced the blood pressure with every inhaled oxygen mixture. The blood pressure was independent of FIO2 and the reduction observed during hyperoxia with placebo no longer occurred with nicardipine. However, the pulmonary hypertension was unaffected. At the dosage used in this study, nicardipine modified the systemic vascular response to oxygen but not the pulmonary vascular response. The vasodilation induced was much greater in the systemic than in the pulmonary circulation. In relation to the absence of significant pulmonary vasodilation, no changes in blood gases, due to a possible pulmonary shunting effect, were observed. At this dosage, nicardipine is ineffective in reducing pulmonary hypertension. However, its systemic hypotensive action may be used in patients with respiratory failure due to chronic bronchitis without deleterious effects on blood gases.

Nifedipine inhibits the effects of almitrine in patients suffering from pulmonary artery hypertension secondary to chronic obstructive pulmonary disease.

It has been suggested that almitrine improves the local ventilation/perfusion ratio by enhancing hypoxic pulmonary vasoconstriction (HVC), leading to an increase in pulmonary vascular resistance (PVR) and PaO2. The goal of the present study was to determine if pulmonary vasodilation induced by nifedipine inhibits the enhancement of HVC (and consequently of PaO2), in patients suffering from chronic obstructive pulmonary disease (COPD). Two groups of 10 patients were compared in a controlled, double-blind study. Hemodynamics and blood gases were measured during continuous infusion of placebo or almitrine (8 micrograms/kg/min). Two hours after the onset of the infusion, a single dose of nifedipine (10 mg) was given sublingually. Almitrine infusion was followed by an increase in PaO2 (20%) and PVR (48%). In the almitrine group, after nifedipine, the PVR decreased 33% and PaO2 dropped to baseline while in the placebo group the PVR decreased 22% and PaO2 fell to 11% below baseline. In COPD patients, nifedipine inhibits almitrine-induced pulmonary vasoconstriction.

Vascular and cardiac reactivity in pulmonary hypertension due to chronic obstructive lung disease: assessment with various oxygen concentrations.

The aim of the present work was to evaluate vasoreactivity in patients with pulmonary hypertension related to chronic obstructive lung disease. This was done by comparing haemodynamic data recorded while patients were breathing room air, and hypoxic and hyperoxic mixtures. We estimated the role of vasoconstriction in determining the level of pulmonary hypertension. This study included 26 patients with moderate pulmonary hypertension mean pulmonary arterial pressure (MPAP) = 27.3 +/- 1.2 mmHg) secondary to chronic obstructive lung disease (COLD), forced expiratory volume in one second (FEV1) = 0.95 +/- 0.13 l; arterial oxygen tension (PaO2) = 8.7 +/- 0.25 kPa). After insertion of a thermodilution catheter in the pulmonary artery and a cannula in the femoral artery, mixtures containing 15, 21, 30 and 100% oxygen were randomly administered for 20 min each. As fractional inspiratory oxygen (FIO2) increased, MPAP decreased relatively less than cardiac index. Cardiac output was at its highest during room air breathing and the hypoxic mixture did not lead to a further increase. Unlike normal subjects, in whom adjustment of cardiac output is achieved by heart rate alone, haemodynamic regulation in these patients also involved stroke volume. Variations in MPAP and cardiac index were strongly correlated with arterial oxygen saturation (SaO2). The greatest variations were noted in the patients with the highest pulmonary hypertension. Under normoxic and hyperoxic condition the relationship between pulmonary artery driving pressure and cardiac index was linear and its slope steeper in patients having the highest pulmonary hypertension at steady-state.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pulmonary hypertension secondary to talc microemboli in a HIV seropositive heroin-addict woman]. / Hypertension artérielle pulmonaire secondaire à des micro-emboles de talc chez une héroïnomane séropositive au virus immunodépresseur humain.

Severe pulmonary hypertension presenting as acute cor pulmonare was observed in a HIV positive heroin addict. The usual aetiological investigations were negative. The apparently primary pulmonary hypertension was resistant oxygen and vasodilator therapy and was fatal in 6 months. Anatomopathological examination revealed the presence of talc microemboli in the pulmonary arterioles, severe medial hypertrophy and fibrous subendothelial thickening. The presence of the talc suggests that the pulmonary hypertension in this case was due to obstruction of the pulmonary vascular bed by the obstructive arterial lesions, despite the context of HIV infection.

[Treatment of pulmonary artery hypertensions]. / Traitement des hypertensions artérielles pulmonaires.

The pulmonary hypertension (PAH) in chronic obstructive lung disease include therapy of the respiratory disease i.e. bronchodilator, kinesitherapy. Long-term oxygen therapy (more than 15 h/day) reverse the course of PAH and increase survey. Long-term efficiency of vasodilators is not well demonstrated. Primary PAH could benefit from vasodilators, especially waiting lung or heart-lung transplantation. Patients with PAH secondary to respiratory insufficiency could also be successfully transplanted. In post embolic PAH, antithrombotic agents are useful. Thrombectomy or transplantation are sometimes proposed.

Effects of nicardipine on pulmonary and systemic vascular reactivity to oxygen in patients with pulmonary hypertension secondary to chronic obstructive lung disease.

We compared the acute effects of nicardipine and a placebo on the response of pulmonary and systemic circulation to different inspiratory fractional concentrations of O2 (FiO2) in 10 patients with pulmonary hypertension secondary to chronic obstructive lung disease. After catheterization of the pulmonary and femoral arteries, gas mixtures containing 15, 21, and 30% O2 were randomly administered for 20 min each during infusion of saline and then nicardipine (0.06 mg/kg/min). Plasma nicardipine level was maintained at 30 ng/ml. During nicardipine infusion, cardiac index (CI) was significantly higher (+20%, p less than 0.05) than during placebo infusion, with no change in mean pulmonary artery pressure (MPAP). Pulmonary resistances also decreased significantly (-20%) during nicardipine. No change in arterial or mixed venous O2 contents was noted. Mean arterial pressure (MAP) and systemic resistances decreased significantly with nicardipine. Inhaling a hyperoxic mixture was followed by a significant decrease in arterial pressure during placebo infusion; this was not observed during nicardipine. In contrast with systemic circulation, the response of the pulmonary circulation to different FiO2 levels was unaffected by nicardipine.

Uvulopalatopharyngoplasty in snorers with sleep apneas: predictive value of presurgical polysomnography.

To determine its predictive value, polysomnography was performed on 14 snorers with sleep apnea syndrome (SAS) before and 3 months after uvulopalatopharyngoplasty (UPPP). In the 8 patients considered as cured (less than 10 apneas per hour after UPPP), total apnea index (TAI) decreased from 29.7 +/- 22.6 to 4.9 +/- 3.5. Rapid eye movement sleep (REM) increased from 10.9 +/- 3.6 to 14 +/- 5.7% of the total sleep period (TSP). In the 6 uncured patients, TAI decreased from 59.7 +/- 15.7 to 32 +/- 15.7 and REM increased from 7.7 +/- 5.6 to 15.8 +/- 7.2% of TSP. Snoring and drowsiness decreased in both cured and uncured patients. A presurgical apnea index less than 40 seems to be a reliable predictor of successful UPPP. The association of obstructive apnea with either central apnea or mixed apnea was not a factor of poor prognosis. Better sleeping could explain in part the clinical improvement in both cured and uncured patients, but postoperative polysomnography is needed to detect asymptomatic SAS.