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Biomedical subjects

D Annane

Publications and source records attributed to D Annane.

At least 37 records · Page 2Linked to original sources
PubMed2000

A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin.

CONTEXT: The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress. The relationship between its activation and patient outcome is not known. OBJECTIVE: To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock. DESIGN AND SETTING: Prospective inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France. PARTICIPANTS: A total of 189 consecutive patients who met clinical criteria for septic shock. INTERVENTION: A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin; blood samples were taken immediately before the test (T0) and 30 (T30) and 60 (T60) minutes afterward. MAIN OUTCOME MEASURES: Twenty-eight-day mortality as a function of variables collected at the onset of septic shock, including cortisol levels before the corticotropin test and the cortisol response to corticotropin (delta max, defined as the difference between T0 and the highest value between T30 and T60). RESULTS: The 28-day mortality was 58% (95% confidence interval [CI], 51%-65%) and median time to death was 17 days (95% CI, 14-27 days). In multivariate analysis, independent predictors of death (P < or = .001 for all) were McCabe score greater than 0, organ system failure score greater than 2, arterial lactate level greater than 2.8 mmol/L, ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg, cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified: good (cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 26%), intermediate (cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 67%), and poor (cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL; 28-day mortality rate, 82%). CONCLUSION: Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death.

Adult↗
PubMed2000

Nocturnal mechanical ventilation for chronic hypoventilation in patients with neuromuscular and chest wall disorders.

BACKGROUND: Chronic alveolar hypoventilation is a common complication of many neuromuscular and chest wall disorders. Long term nocturnal mechanical ventilation is used to treat an increasing number of patients. OBJECTIVES: To examine the efficacy of nocturnal mechanical ventilation in relieving hypoventilation related symptoms in patients with neuromuscular or chest wall disorders. SEARCH STRATEGY: Search of the Cochrane Neuromuscular Disease Group register for randomized trials and enquiry from authors of trials and other experts in the field. SELECTION CRITERIA: Types of studies: quasi-randomized or randomized controlled trials TYPES OF PARTICIPANTS: patients with neuromuscular or chest wall disorder-related stable chronic hypoventilation of all ages and all degrees of severity. Types of interventions: any type and any mode of nocturnal mechanical ventilation. Types of outcome measures: Primary: short term and long term reversal of hypoventilation related clinical symptoms Secondary: unplanned hospital admission rate, one year mortality, short term and long term reversal of day time hypercapnia, improvement of lung function and improvement of sleep breathing disorders. DATA COLLECTION AND ANALYSIS: We identified four randomized trials. One author extracted the data and another checked them. Individual data were available from the authors of the largest study. MAIN RESULTS: The four eligible trials included a total of 51 patients. The risk difference (proportion of patients) of no improvement of hypoventilation related clinical symptoms in the short term following nocturnal mechanical ventilation was significant and favoured treatment, -0.417 (95% CI -0.639 to -0.194). However, there was significant heterogeneity across the studies (p<0.001). Similarly, the risk difference of no reversal of day time hypercapnia in the short term following nocturnal ventilation was significant and favoured treatment, -0.635 (95% CI -0.874 to -0.396). The weighted mean difference of nocturnal mean oxygen saturation percent was 5.5 (95% CI 1.5 to 9.4) more improvement in patients treated with nocturnal mechanical ventilation. For the primary and most of the secondary outcome measures there was no significant difference between nocturnal mechanical ventilation and no ventilation in the long term, except for one-year mortality. Indeed, the risk difference of death one year following implementation of nocturnal mechanical ventilation was significant and favoured treatment, -0.259 (95% CI -0.478 to -0. 041). However, there was significant heterogeneity across the studies (p<0.001). Most of the secondary outcomes were not assessed in the eligible trials. No data could be summarised for the comparisons between invasive and non-invasive mechanical ventilation, between intermittent positive pressure and negative pressure ventilation, and between volume-cycled and pressure-cycled ventilation. REVIEWER'S CONCLUSIONS: Current evidence about the therapeutic benefit of mechanical ventilation is weak, but consistent, suggesting alleviation of the symptoms of chronic hypoventilation in the short term, and in two small studies survival was prolonged. Mechanical ventilation should be offered as a therapeutic option to patients with chronic hypoventilation due to neuromuscular diseases. Further larger randomized trials are needed to confirm long term beneficial effects of nocturnal mechanical ventilation on quality of life, morbidity and mortality, to assess its cost-benefit ratio, and to compare the different types and modes of ventilation.

Chronic Disease↗
PubMed2000

Effect of hydrocortisone on phenylephrine--mean arterial pressure dose-response relationship in septic shock.

BACKGROUND: Septic shock is characterized by decreased responsiveness to catecholamines. Because endogenous steroids are known to play a role in the modulation of vasomotor tone, the purpose of our study was to investigate the phenylephrine-mean arterial pressure dose-response relationship in patients with septic shock and the effect of a physiological dose of hydrocortisone on it. METHODS: Twelve patients meeting usual criteria for septic shock and 12 age-matched control subjects were investigated before and 1 hour after receiving 50 mg intravenous hydrocortisone. Sixteen incremental doses of phenylephrine (microg/kg/min) were infused, and the effects on mean arterial pressure (mm Hg) were recorded. A sigmoid model, E = E0 + [Emax x Dgamma/(ED50gamma + Dgamma)], was fitted to individual data. In this model, E is the predicted effect and D is the dose of phenylephrine infused. E0 represents the basal value of effect (ie, the value of mean arterial pressure without drug), Emax is the maximum theoretical effect, ED50 is the dose of phenylephrine for which an effect of 50% of Emax is observed, and gamma is the Hill coefficient which accounts for the sigmoidicity of the curve. RESULTS: As compared with in control subjects, in patients, E0 was decreased before (58 +/- 8 versus 73 +/- 7 mm Hg) and after (64 +/- 12 versus 82 +/- 10 mm Hg) administration of hydrocortisone (P = .0001 for group), Emax was reduced before (39 +/- 17 versus 84 +/- 18 mm Hg) and after (77 +/- 26 versus 106 +/- 21 mm Hg) administration of hydrocortisone (P = .0001 for group), ED50 was not modified, and gamma was increased before (3.5 +/- 1.8 versus 1.3 +/- 0.3) and after (1.9 +/- 1.1 versus 1.3 +/- 0.3) administration of hydrocortisone (P = .0010 for group). Hydrocortisone similarly increased E0 in both groups (P = .0003 for sequence, P = .2883 for interaction), increased more Emax in patients than in control subjects (P < .0001 for sequence; P = .0280 for interaction), did not change ED50, and decreased y in patients but not in control subjects (P = .0025 for sequence, P = .0025 for interaction). CONCLUSIONS: In patients with septic shock, the Emax of phenylephrine is decreased, whereas its ED50 is not modified, both before and after administration of hydrocortisone. A physiological dose of hydrocortisone tends to normalize the relationship.

Analysis of Variance↗
PubMed2000

[Corticotherapy in severe infectious states].

Septic shock is one of the leading cause of death in modern countries. Scientists have made huge improvement in the understanding of mechanisms of inflammation, and the sequence of activation of the various pro and anti-inflammatory markers is now well known. By contrary, physicians have failed to improve survival from septic shock, in spite of the development of specific targets of the various points of the cytokine cascade sought to have a key role in host survival to sepsis. Corticosteroids were among the first anti-inflammatory drugs, which have been tested in high quality randomised controlled trials. These trials clearly showed that patients with septic shock are unlikely to benefit from a short course of a large dose of an anti-inflammatory steroid. More recent findings highlighting the role of the integrity of the hypothalamic-pituitary -adrenal axis to appropriately respond to a septic insult, have led to a reappraisal of the use of steroids in septic shock. Several high quality randomised controlled trials have evaluated the efficacy and safety of a prolonged treatment with low dose hydrocortisone in severe sepsis. These trials strongly suggested that this strategy of corticotherapy reduced the morbidity of septic shock and may favourably affect survival from septic shock.

Adrenal Cortex Hormones↗
PubMed1999

Inappropriate sympathetic activation at onset of septic shock: a spectral analysis approach.

The autonomic cardiovascular control was investigated in 10 patients with septic shock, 10 patients with sepsis syndrome, and six tilted healthy subjects. Overall variability, high- and low-frequency components (AUC, HF, and LF, beats/min(2)/Hz or mm Hg(2)/Hz) from heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures spectra were obtained from 5-min recordings. LF(HR)/HF(HR) and the square root of LF(SBP)/LF(HR) (alpha) were used as indices of sympathovagal interaction and baroreflex control of the heart, respectively. Compared with tilted control subjects and patients with sepsis syndrome, septic shock is characterized by reduction in: (1) HR variability, i.e., decreased AUC(HR) (p = 0.007), LF(HR) (p = 0.002), and LF(HR)/HF(HR) (p = 0.0002); (2) DBP variability, i.e., decreased AUC(DBP) (p = 0.003) and LF(DBP) (p = 0.001), (3) alpha (p = 0.003). In septic shock, LF(HR)/HF(HR), alpha, and LF(DBP) correlated with mean blood pressure (r = 0.67, p = 0.04, r = 0.64, p = 0.03, and r = 0.88, p = 0.0008, respectively), and with plasma norepinephrine levels (r = -0.65, p = 0.03, r = -0.79, p = 0.006, and r = -0.69, p = 0.03, respectively). In conclusion, onset of septic shock is characterized by high concentrations of circulating catecholamines but impaired sympathetic modulation on heart and vessels, suggesting that central autonomic regulatory impairment contributes to circulatory failure.

Adult↗
PubMed1999

Mechanisms underlying effects of nocturnal ventilation on daytime blood gases in neuromuscular diseases.

The hypothesis that, in neuromuscular and chest wall diseases, improvement in central respiratory drive explains the effects of night-time ventilation on diurnal gas exchanges was tested. The effects at 6 months, 1, 2 and 3 yrs of intermittent positive pressure ventilation (IPPV) on arterial blood gas tension, pulmonary function, muscle strength, sleep parameters, respiratory parameters during sleep and ventilatory response to CO2 were evaluated in 16 consecutive patients with neuromuscular or chest wall disorders. As compared with baseline, after IPPV daytime arterial oxygen tension (Pa,O2) increased (+2.3 kPa at peak effect) and arterial carbon dioxide tension (Pa,CO2) and total bicarbonate decreased (-1.8 kPa and -5 mmol x L(-1), respectively) significantly; vital capacity, total lung capacity, maximal inspiratory and expiratory pressures and alveolar-arterial oxygen gradient did not change; the apnoea-hypo-opnoea index and the time spent with an arterial oxygen saturation (Sa,O2) value <90% decreased (-24 and -101 min, respectively), sleep efficiency and mean Sa,O2 increased (+16% and +5%, respectively); and ventilatory response to CO2 increased (+4.56 L x min(-1) x kPa(-1)) significantly. The reduction in Pa,CO2 observed after IPPV correlated solely with the increase in the slope of ventilatory response to the CO2 curve (r=-0.68, p=0.008). In neuromuscular or chest wall diseases, improvement of daytime hypoventilation with nocturnal intermittent positive pressure ventilation may represent an adaptation of the central chemoreceptors to the reduction of profound hypercapnia during sleep or reflect change in the quality of sleep.

Adult↗
PubMed1999

Is early noninvasive mechanical ventilation of first choice in stable restrictive patients with chronic respiratory failure?

Noninvasive long-term ventilation is consensually advocated when daytime hypercapnia > 6 kPa at steady state in chronic restrictive pulmonary syndromes. Several mechanisms can cause the occurrence of hypercapnia in these diseases. They may involve impairment of lung mechanics or airway function and cough, ventilation-perfusion mismatching, blunted central ventilatory drive or respiratory muscle fatigue. These abnormalities may occur while awake or during sleep. From a practical point of view, imperative ventilation, a palliative technique that aims to supply respiratory muscle weakness, and preventive ventilation, aimed at delaying respiratory handicap, should be distinguished between. The latter is offered to patients who do not fulfil any criteria for mechanical ventilation. Otherwise, the underlying disease markedly influences both pathophysiology and outcome. This implies that the available modes of ventilatory support should be assessed in each disease. Several findings have been published about Duchenne's muscular dystrophy. Mechanical ventilation, usually using noninvasive methods, is offered to patients with either hypercapnia or a forced vital capacity < 20% of the predicted value. Nevertheless, based on our experience, deterioration of the restrictive syndrome should be followed by a tracheostomy. By contrast, early ventilation, offered to patients free of symptoms and whose forced vital capacity are within 20-50% pred and with normal arterial blood gas levels, achieves no benefit.

Humans↗
PubMed1999

Short-term variability of blood pressure and heart rate in Guillain-Barré syndrome without respiratory failure.

The effect of Guillain-Barré syndrome (GBS) on the short-term variability of blood pressure and heart rate was evaluated in six patients presenting with a moderate form of the syndrome, i.e. unable to stand up unaided and without respiratory failure, at the height of the disease and during recovery. The patients were compared with six age-matched healthy volunteers. During the acute phase of the syndrome, GBS patients exhibited a significant heart rate elevation (+26 beats/min compared with healthy subjects), but the acceleratory response to atropine, or to 60 degrees head-up tilt, was maintained. Resting plasma noradrenaline levels were high in acute GBS, but the secretory response to tilt was preserved. Desensitization to noradrenaline was observed in acute GBS with a reduced pressor action of this alpha-adrenoceptor agonist. Blood pressure levels were normal and head-up tilt did not induce orthostatic hypotension in this moderate form of GBS. Power spectral analysis demonstrated marked alterations in cardiovascular variability. The overall heart period variability was markedly reduced with the reduction predominantly in the high-frequency (respiratory) range (-73%). The low-frequency component of heart period variability was also reduced (-54%). This cardiovascular profile of moderate GBS at the height of the disease could result from a demyelination of the reflex loop controlling respiratory oscillations in heart rate and from a desensitization of the arterial tree to an elevated plasma noradrenaline. Sympathetic nervous activation may contribute to the high resting heart rate in acute GBS.

Acute Disease↗
PubMed1998

Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size dependent phenomenon.

Myotonic dystrophy (DM) is caused by an expansion of a CTG triplet repeat sequence in the 3'-noncoding region of a protein kinase gene, yet the mechanism by which the triplet repeat expansion causes disease remains unknown. Impaired glucose penetration into brain tissues has been described in DM patients and is a phenomenon that remains unexplained. The present study shows that altered brain glucose metabolism is triplet repeat dependent. We studied brain glucose metabolism (CMRGlu, mumol/100 g/min) by the use of positron emission tomography and 18F-fluoro-2-deoxy-D-glucose in 11 ambulatory non-obese DM patients and in 11 age and sex matched healthy subjects. All subjects underwent a glucose tolerance test with plasma insulin determinations. The expansion of CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. As compared to controls, in DM patients, the CMRGlu was significantly decreased (26.26 +/- 5.05 vs. 33.43 +/- 2.18, mumol/100 g/min, P = 0.004), and after oral glucose loading, plasma insulin levels were significantly higher and plasma glucose levels remained unchanged (respectively, F = 11.21, P = 0.004 and F = 0.20, P = 0.66). Subsequently, the glucose/insulin ratio was significantly lower in DM patients (F = 6.25, P = 0.02). The length of the expansion of the CTG repeats correlated negatively with the CMRGlu (r2 = 0.63, P = 0.003) and positively with the area under the curve for insulin changes over time after oral glucose (r2 = 0.49, P = 0.016). We conclude that, in DM patients, the brain metabolism of glucose is impaired in a repeat dependent manner.

Activities of Daily Living↗
PubMed1998

Impaired pressor sensitivity to noradrenaline in septic shock patients with and without impaired adrenal function reserve.

AIMS: To investigate the relationship between adrenal gland function and pressor response to noradrenaline in septic shock. METHODS: Basal cortisol level, noradrenaline--mean arterial pressure dose-response curve and cortisol response to intravenous corticotrophin bolus were obtained in nine patients fulfilling usual criteria for septic shock and in six normal volunteers. In patients with septic shock, dose-response curve to noradrenaline was determined a second time 60 min after a 50 mg intravenous hydrocortisone bolus. RESULTS: As compared with controls, patients with septic shock had increased basal cortisol levels (mean+/-s.d.: 1564+/-818 vs 378+/-104 nmol l(-1) , P=0.002, 95% confidence interval for difference in means: [452, 1920]) and a blunted cortisol response to corticotrophin (403+/-461 vs 1132+/-195 nmol l(-1), P=0.008, [-1163, -2951). Five patients had impaired adrenal function reserve. As compared with controls, septic patients displayed a moderate and non significant decrease in pressor sensitivity to noradrenaline (P=0.112). As compared with patients with adequate adrenal response, patients with impaired adrenal function reserve showed a significant decrease in pressor sensitivity to noradrenaline (P=0.038). In septic patients, hydrocortisone improved pressor response to noradrenaline (P=0.032). This effect was more marked in patients with impaired adrenal function reserve so that, as compared with patients with adequate response, the difference was no longer significant (P=0.123). CONCLUSIONS: In septic shock, impaired adrenal function reserve may partly be accounted for by the depressed pressor sensitivity to noradrenaline. The latter may be substantially improved by physiological doses of hydrocortisone.

Adrenal Gland Diseases↗
PubMed1996

[Iatrogenic air embolism].

The incidence of iatrogenic air embolism can only be estimated since many accidents are not recognized. Clinical manifestations, essentially neurological or cardiovascular disorders vary greatly. Air embolism may occur during coronary or cerebral arteriography, cardiopulmonary bypass, venous catheterism, various types of surgery or blood transfusion among other situations. Once air has entered the arterial circulation, the bubble of gas follows the blood flow until it is blocked by a smaller calibre vessel. The progressive diffusion of the air reduces the size of the embolus which then migrates on to smaller and smaller vessels. Subsequent pathological manifestations of air embolism result from mechanical obstruction leading to ischemia and inflammatory reactions to air acting as a foreign body. The sudden onset signs of neurological impairment with or without a cardiopulmonary component in patients in a high-risk situation leads to clinical diagnosis. Treatment must be started immediately although brain CT scan or echocardiography may help confirm the diagnosis. The source of the air must be immediately identified and removed and the vital functions controlled. Mechanical or facial mask ventilation with pure oxygen is indicated. Hyperbaric oxygen therapy should be instituted. Morbidity and mortality after iatrogenic air embolism is high but major improvements have been achieved with oxygen therapy. Neurological sequellae have been estimated to reach 19 to 50% of the patients. A personal controlled prospective study revealed 14% mortality after hyperbaric oxygen therapy given within 12 hours of the accident.

Embolism, Air↗
PubMed1996

[Respective indications of plasma exchange and high-dose immunoglobulins in polyradiculoneuritis and myasthenia gravis].

The main purpose of plasma exchange is to remove toxic substances. The mechanisms involved appear to be complex. The primary aim of immunoglobulins is to compensate for immunodeficiency, but when given intravenously at high doses, immunoglobulins can also have unexpected immunomodulation effects. Routine therapeutic use of these methods raises the problem of cost and potential morbidity. Two therapeutic trials have demonstrated that plasma exchange in Guillain-Barré syndrome improves outcome when given early. In chronic polyradiculonevritis, plasma exchange and intravenous immunoglobulins have been shown to be equally effective although plasma exchange would give less satisfactory results in patients with polyradiculonevritis and monoclonal IgG. The effect of intravenous immunoglobulins is being evaluated. Plasma exchange has become the gold standard for acute crisis of myasthenia gravis. Recent results suggest that intravenous immunoglobulins could be equally effective in these diseases. Though useful therapeutic tools, the respective indications and optimal doses for these methods remains to be defined.

Humans↗
PubMed1996

Placebo-controlled, randomized, double-blind study of intravenous enalaprilat efficacy and safety in acute cardiogenic pulmonary edema.

BACKGROUND: Converting enzyme inhibitors meet most of the criteria required to be used in acute pulmonary edema. However, they could also induce deleterious effects on renal function and electrolytes. The purpose of this study was to evaluate the efficacy and safety of a single intravenous 2-hour infusion of enalaprilat (1 mg) after an acute pulmonary edema. METHODS AND RESULTS: This was a placebo-controlled, randomized, double-blind study performed in 20 congestive heart failure patients (New York Heart Association class III or IV). Systemic and regional hemodynamic parameters, biological parameters, and blood gases were measured before and repeatedly after the onset of infusion. Compared with placebo, enalaprilat decreased pulmonary capillary wedge pressure (-37% versus -10%, P = .001), diastolic and mean systemic blood pressures (-21% versus 0%, P = .009, and -18% versus -1%, P = .026, respectively), diastolic and mean pulmonary blood pressures (-21% versus -8%, P = .040; -18% versus -9%, P = .046), and brachial and renal resistances (-44% versus -14%, P = .017, and -22% versus -2%, P = .014, respectively); increased brachial and renal blood flows (+77% versus +8%, P = .036, and +12% versus 0%, P = .043, respectively), arterial oxygen tension (+2% versus -16%, P = .041), and arterial oxygen saturation (+1% versus -2%, P = .045); and tended to decrease rate-pressure product (-19% versus -7%, P = .076), increase brachial artery diameter (+13% versus 0%, P = .081), and improve intrapulmonary shunt (-18% versus +16%, P = .080). Enalaprilat did not affect cardiac output or carotid or hepatosplanchnic hemodynamics. CONCLUSIONS: Early administration of enalaprilat is effective and well tolerated in acute pulmonary edema.

Acute Disease↗
PubMed1996

Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon.

BACKGROUND: In myotonic dystrophy (DM), striated muscle is involved in relation to the size of the DNA mutation. Smooth muscle may be similarly impaired at the level of the urinary and digestive apparatus and possibly at the level of small vessels, since microangiopathy has been described in the iris and digital capillaries. Our purpose was to study the function of the myocardial microvasculature in relation to the size of the mutation in DM patients without clinical cardiac involvement and with normal left ventricular dimensions and function and normal large coronary arteries. METHODS AND RESULTS: In 6 control subjects and 10 DM patients, we investigated the coronary blood flow reserve using positron emission tomography with 15O-labeled water. Global and regional flow reserves were obtained from myocardial regions of interest manually drawn on a static FDG image encompassing, respectively, the whole left ventricle and the anterior, septal, and lateral walls. The DNA mutation size was determined on circulating lymphocytes in each DM patient. Compared with control subjects, DM patients had decreased global (2.39 +/- 0.39 versus 4.00 +/- 0.67, P = .00003) and regional (anterior, 2.39 +/- 0.64 versus 3.87 +/- 0.92, P = .002; septal, 2.60 +/- 0.48 versus 4.00 +/- 0.70, P = .0003; lateral, 2.26 +/- 0.58 versus 4.16 +/- 1.11, P = .0005) coronary reserves. In DM patients, the coronary reserve correlated strongly and inversely with the DNA mutation size (r = -.77, P = .009). CONCLUSIONS: The study demonstrated that global and regional coronary reserves are impaired, in relation to the DNA mutation size, in symptom-free DM patients with normal ventricular dimensions and function and normal large coronary vessels. We suggest that a gene-related blunted coronary reserve resulting from an impairment of vascular smooth muscle is an early component of DM cardiomyopathy.

Adult↗
PubMed1996

Systemic, pulmonary, brachial, renal and hepato-splanchnic hemodynamic effects of spirapril in severe congestive heart failure.

The effects of a single oral dose (6 mg) of the angiotensin-I converting enzyme inhibitor, spirapril, on systemic, pulmonary and regional (brachial, renal, hepato-splanchnic) hemodynamics as well as on biological parameters investigating the renin-angiotensin-aldosterone and sympathetic nervous systems were studied over a 24-hour period in eight patients with severe congestive heart failure (CHF). As compared to pretreatment values, spirapril significantly decreased mean arterial (-19%, peak effect), right atrial (-42%), mean pulmonary arterial (-38%) and pulmonary capillary wedge (-46%) pressures. Spirapril significantly decreased heart rate (-14%) and increased stroke volume index (+43%) thus resulting in a slight increase in cardiac index. All these effects were maximal between 2.5 and 4 h. Brachial artery diameter (+12%) and brachial (+41%) and renal (+36%) blood flows increased significantly whereas brachial (-41%) and renal (-36%) vascular resistances decreased significantly. All these effects were usually maximal between 1 and 2.5 h. Hepato-splanchnic hemodynamics were not drug-affected. Spirapril significantly inhibited plasma converting enzyme activity (-96% at 4 h), increased plasma renin activity (+505% at 4 h), and decreased plasma aldosterone (-46% at 24 h), norepinephrine (-31% at 24 h) and atrial natriuretic factor (-33% at 7 h). Thus, in severe CHF, acute administration of spirapril, 6 mg orally, exerts both arterial and venous vasodilating properties and improves both the systemic and regional hemodynamics and the biological status of the patients.

Aged↗