Effect of AT1 receptor blockade on cardiovascular outcome after cardiac arrest: an experimental study in rats.

Angiotensin II receptor 1(AT1) antagonists are beneficial in focal ischemia/reperfusion (I/R). However, in cases of global I/R, such as cardiac arrest (CA), AT1 blocker's potential benefits are still unknown. Wistar male rats were allocated into four groups: Control group (CG)-animals submitted to CA by ventricular fibrillation induced by direct electrical stimulation for 3 min, and anoxia for 5 min; Group AT1 (GAT1)-animals subjected to CA and treated with 0.2 mg/kg of candesartan diluted in dimethylsulfoxide (DMSO) (0.1%); Vehicle Group (VG): animals subjected to CA and treated with 0.2 ml/kg of DMSO and Sham group (SG)-animals submitted to surgical interventions, without CA. Cardiopulmonary resuscitation consisted of group medications, chest compressions, ventilation, epinephrine (20 mcg/kg) and defibrillation. The animals were observed up to 4 h after spontaneous circulation (ROSC) return, and survival rates, hemodynamic variables, histopathology, and markers of tissue injury were analyzed. GAT1 group had a higher rate of ROSC (62.5% vs. 42.1%, p < 0.0001), survival (100% vs. 62.5%, p = 0.027), lower incidence of arrhythmia after 10 min of ROSC (10% vs. 62.5%, p = 0.000), and lower neuronal and cardiac injury scores on histology evaluation (p = 0.025 and p = 0.0052, respectively) than GC group. The groups did not differ regarding CA duration, number of adrenaline doses, or number of defibrillations. AT1 receptor blockade with candesartan yielded higher rates of ROSC and survival, in addition to neuronal and myocardial protection.

Improvement in Olfaction in Patients With CRSwNP and Severe Asthma Taking Anti-IgE and Anti-IL-5 Biologics: A Real-Life Study.

BACKGROUND AND OBJECTIVES: Chronic rhinosinusitis with nasal polyps (CRSwNP), which is characterized by partial loss of smell (hyposmia) or total loss of smell (anosmia), is commonly associated with asthma and/or nonsteroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD). CRSwNP worsens disease severity and quality of life. The objective of this real-world study was to determine whether biological treatments prescribed for severe asthma can improve olfaction in patients with CRSwNP. A further objective was to compare the improvement in in olfaction in N-ERD and non-N-ERD subgroups. METHODS: We performed a multicenter, noninterventional, retrospective, observational study of 206 patients with severe asthma and CRSwNP undergoing biological treatment (omalizumab, mepolizumab, benralizumab, or reslizumab). RESULTS: Olfaction improved after treatment with all 4 monoclonal antibodies (omalizumab [35.8%], mepolizumab [35.4%], reslizumab [35.7%], and benralizumab [39.1%]), with no differences between the groups. Olfaction was more likely to improve in patients with atopy, more frequent use of short-course systemic corticosteroids, and larger polyp size. The proportion of patients whose olfaction improved was similar between the N-ERD (37%) and non-N-ERD (35.7%) groups. CONCLUSIONS: This is the first real-world study to compare improvement in olfaction among patients undergoing long-term treatment with omalizumab, mepolizumab, reslizumab, or benralizumab for severe asthma and associated CRSwNP. Approximately 4 out of 10 patients reported a subjective improvement in olfaction (with nonsignificant differences between biologic drugs). No differences were found for improved olfaction between the N-ERD and non-N-ERD groups.

Kidney Transplantation After Hematopoietic Cell Transplantation in Plasma Cell Dyscrasias: Case Reports.

The plasma cell dyscrasias (PCDs) include a number of entities such as multiple myeloma, primary amyloidosis, and monoclonal immunoglobulin deposition disease. Hematopoietic cell transplant (HCT) is the only cure for a variety of hematologic and oncologic diseases. Clinically significant renal impairment is a common feature in plasma cell myeloma, affecting 20% to 55% of patients at initial diagnosis; 2% to 3% of patients present with failure sufficiently severe to require hemodialysis. This circumstance is associated with a high early mortality. The necessity for immunosuppression after HCT could complicate its management and may precipitate the development of complications. In some patients an effective alternative could be kidney transplant (KT); however, the presence of 2 transplants will require optimal adjustment of immunosuppression and management of complications. At present, there are few published cases of KT after HCT, and the experience of managing 2 transplants is limited. We would like to describe our experience with 4 patients who had a PCD and initially received HCT and received subsequent KT. In our experience the progress and outcome of KT after HCT were optimal. We would like to address that a higher incidence of cytopenia associated with the combination of immunosuppression (lenalidomide, tacrolimus, mycophenolate, etc.) and other drugs (ie, valganciclovir) should be considered together with an increased risk of opportunistic infections and PCD relapse.

Recomendaciones sobre el diagnóstico y manejo de la enfermedad pleural y pulmonar por asbesto / Recommendations for the diagnosis and management of asbestos-related pleural and pulmonary disease

Asbesto, también conocido en España como amianto, es el término utilizado para nombrar a un conjunto de silicatos minerales que suelen romperse en fibras. Su uso ha comportado la aparición de numerosas enfermedades, especialmente pleuropulmonares, todas ellas caracterizadas por su prolongada latencia. El asbesto es, además, un carcinógeno del grupo IA reconocido por la OMS desde 1987. En España está prohibido desde 2002. La publicación en 2013 de la 3.ª edición del protocolo de vigilancia sanitaria específica del amianto junto con la aparición de nuevas técnicas diagnósticas han motivado al grupo EROM de SEPAR a promover la elaboración de esta normativa que revisa aspectos clínicos, radiológicos y funcionales de las diferentes enfermedades relacionadas. También establece recomendaciones para el diagnóstico y seguimiento de los pacientes expuestos. Dichas recomendaciones han sido establecidas mediante sistema GRADE.(AU)

Asbestos is the term used for a set of mineral silicates that tend to break up into fibers. Its use has been associated with numerous diseases affecting the lung and pleura in particular, all of which are characterized by their long period of latency. Asbestos, moreover, has been recognized by the WHO as a Group IA carcinogen since 1987 and its use was banned in Spain in 2002. The publication in 2013 of the 3rd edition of the specific asbestos health monitoring protocol, together with the development of new diagnostic techniques, prompted the SEPAR EROM group to sponsor publication of guidelines, which review the clinical, radiological and functional aspects of the different asbestos-related diseases. Recommendations have also been made for the diagnosis and follow-up of exposed patients. These recommendations were drawn up in accordance with the GRADE classification system.(AU)

Pharmacokinetic assessment of sufentanil in cardiac surgery.

Plasma monitoring and pharmacokinetic assessment are important tools used in therapeutic control. Sufentanil is responsible for the hemodynamic stabilization of patients, providing better suppression of the neuroendocrine response compared to its analogue fentanyl. This study aims to use the plasma monitoring of sufentanil in patients undergoing cardiac surgery with extracorporeal circulation (ECC, group 1) or without ECC (group 2) to assess the pharmacokinetics of the compound.The 42 patients in this study received 0.5 µg/kg of sufentanil through bolus injection followed by a maintenance infusion of 0.5 µg/kg.h. Serial blood samples were collected during the post induction intraoperative period and during the postoperative period until 36 h after sufentanil administration. The plasma concentrations were determined by a validated method utilizing liquid chromatography coupled to mass spectrometry. The pharmacokinetic modeling was performed using a 3-compartment model fit.The surgical patients included in the protocol were adults of both genders, with 30 patients in the ECC group and 12 in the group without ECC. The plasma concentrations obtained were significantly different between the 2 groups. During the extracorporeal circulation procedure, intense fluctuations were observed in the sufentanil plasma concentrations. Compared with the results of group 2, the ECC procedure reduced the terminal or gamma half-life from 36.35 ± 6.37 h to 23.25 ± 2.75 h in group 1. In addition, the ECC procedure promoted higher fluctuations in the sufentanil plasma concentrations without causing alterations in the area under the curve, distribution volume, clearance or the distributional (alpha) and rapid elimination (beta) half-lives (t1/2α and t1/2ß, respectively).

Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass

Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31 percent postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19 percent (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27 percent, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27 percent, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46 percent. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.

Computed tomography assessment of lung structure in patients undergoing cardiac surgery with cardiopulmonary bypass.

Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated postoperative pulmonary alterations and their impact on blood oxygenation. Eighteen non-hypoxemic patients (15 men and 3 women) with normal cardiac function scheduled for CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at admission to the intensive care unit, and 12, 24, and 48 h after surgery. Pre- and postoperative volumetric thoracic CT scans were acquired under apnea conditions after a spontaneous expiration. Data were analyzed by the paired Student t-test and one-way repeated measures analysis of variance. Mean age was 63 ± 9 years. The PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially improving 12 h after surgery. Compared to preoperative CT, there was a 31% postoperative reduction in pulmonary gas volume (P < 0.001) while tissue volume increased by 19% (P < 0.001). Non-aerated lung increased by 253 ± 97 g (P < 0.001), from 3 to 27%, after surgery and poorly aerated lung by 72 ± 68 g (P < 0.001), from 24 to 27%, while normally aerated lung was reduced by 147 ± 119 g (P < 0.001), from 72 to 46%. No correlations (Pearson) were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. The data show that lung structure is profoundly modified after CABG with CPB. Taken together, multiple changes occurring in the lungs contribute to postoperative hypoxemia rather than atelectasis alone.

Annular erythematous papules in the neckline.

A 45-year-old woman with personal history of hypertension presented with an erythematous lesion in the neckline for a year and with a progressive growth. A physical examination revealed an annular lesion with erythematous papules in the edge. Histological exam showed phagocytosis of elastic fibers by multinucleated cells compatible with annular elastolytic giant-cell granuloma. The patient did not present any other associated systemic manifestation. Treatment with tacrolimus 0.1 percent ointment was prescribed with a very good response after two months.

Inducción de esputo en niños: desarrollo técnico / Sputum induction in children: technical development

Objetivos: Comparar el rendimiento (total de muestras obtenidas) de nebulizadores ultrasónicos de flujo bajo y alto en la inducción de esputo en niños asmáticos, y valorar los efectos adversos asociados. Pacientes y métodos: Se nebulizó suero salino hipertónico a concentraciones crecientes (3%, 4%, 5%) utilizando nebulizadores ultrasónicos de bajo flujo (Omron NE-U07(R); flujo 1ml/min) y de alto flujo (Omron NE-U12(R); flujo 3 ml/min, y DeVilbiss Ultraneb 3000(R); flujo 2,5ml/min). Resultados: Se realizaron 49 inducciones en 49 pacientes entre 7 y 15 años de edad (en 15 niños se utilizó un nebulizador de bajo flujo y en 34 niños un nebulizador de alto flujo (Omron NEU12(R): 6 casos, DeVilbiss Ultraneb 3000(R): 28 casos). Se obtuvieron 37 muestras. Treinta y seis presentaban<20% de células escamosas y 26 tenían una viabilidad ≥60%. El rendimiento de la prueba fue mayor con los nebulizadores de alto flujo (85,3% de muestras), frente al 53% (p=0,04). El 69% de las muestras obtenidas con los nebulizadores de alto flujo fueron válidas, frente al 62,5% con el de bajo flujo (p=0,7). Con los nebulizadores de alto flujo disminuyó la incidencia de tos (17,6%, p=0,08) y de picor de ojos (0%, p=0,02), respecto al nebulizador de bajo flujo (47% y 20% respectivamente), aunque aumentó el sabor desagradable (82,3%, p<0,001) y la sialorrea (14,7%, p=0,3). Conclusiones: Con los nebulizadores ultrasónicos de alto flujo se consigue un mayor rendimiento de la técnica sin que se observe un aumento de efectos adversos significativos (AU)

Objective: To compare low and high flow nebulizers performance (total of samples) and its side effects on sputum induction in asthmatic children. Patients and methods: Sputum induction was performed by inhalation of a hypertonic saline solution at increasing concentrations (3%, 4% and 5%) using low flow (OMRON NE-U07(R); flow rate 1ml/min), or high flow (OMRON NE-U12(R); flow rate 3ml/min, and DeVilbiss Ultraneb 3000(R); flow rate 2.5ml/min) ultrasonic nebulizers. Results: We performed 49 inductions in 49 patients from 7 to 15 years old (in 15 children we used a low flow nebulizer (Omron NE-U07(R)) and in 34 children a high flow nebulizer (OMRON NEU12(R), 6 patients, and DeVilbiss Ultraneb 3000(R), 28 patients). We obtained 37 samples of which 36 had less than 20% of squamous cells, and 26 had a viability ≥60%. The test performance was higher with high-flow nebulizers, obtaining 85.3% of samples compared to 53% (p=0.04). A total of 69% of samples obtained with the high flow nebulizer were valid, compared to 62.5% (p=0.7) with the low flow nebulizers. With high flow rate nebulizers the incidence of cough (17.6%, p=0.08) and itchy eyes (0%, p=0.02) decreased with the low flow nebulizer (47% and 20% respectively), but bad taste (82.3%, p <0.001) and salivation (14.7%, p=0.3) increased. Conclusions: With high flow rate ultrasonic nebulizers we obtain a higher performance of the technique without an increase in significant side effects (AU)

[Sputum induction in children: Technical development]. / Inducción de esputo en niños: desarrollo técnico.

OBJECTIVE: To compare low and high flow nebulizers performance (total of samples) and its side effects on sputum induction in asthmatic children. PATIENTS AND METHODS: Sputum induction was performed by inhalation of a hypertonic saline solution at increasing concentrations (3%, 4% and 5%) using low flow (OMRON NE-U07; flow rate 1ml/min), or high flow (OMRON NE-U12; flow rate 3ml/min, and DeVilbiss Ultraneb 3000; flow rate 2.5ml/min) ultrasonic nebulizers. RESULTS: We performed 49 inductions in 49 patients from 7 to 15 years old (in 15 children we used a low flow nebulizer (Omron NE-U07) and in 34 children a high flow nebulizer (OMRON NEU12, 6 patients, and DeVilbiss Ultraneb 3000, 28 patients). We obtained 37 samples of which 36 had less than 20% of squamous cells, and 26 had a viability > or =60%. The test performance was higher with high-flow nebulizers, obtaining 85.3% of samples compared to 53% (p=0.04). A total of 69% of samples obtained with the high flow nebulizer were valid, compared to 62.5% (p=0.7) with the low flow nebulizers. With high flow rate nebulizers the incidence of cough (17.6%, p=0.08) and itchy eyes (0%, p=0.02) decreased with the low flow nebulizer (47% and 20% respectively), but bad taste (82.3%, p <0.001) and salivation (14.7%, p=0.3) increased. CONCLUSIONS: With high flow rate ultrasonic nebulizers we obtain a higher performance of the technique without an increase in significant side effects.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 ± 1.2 years, BMI: 23.8 ± 3.6 kg/m²). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH2O steps up to 20 cmH2O every 5 breaths. At CPAP 20 cmH2O, an inspiratory pressure of 20 cmH2O above CPAP was applied, reaching an airway pressure of 40 cmH2O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-á, IL-1â, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-á: 1.2 ± 3.8 vs 6.4 ± 8.6 pg/mL; IL-1â: 4.9 ± 15.6 vs 22.4 ± 28.4 pg/mL; IL-6: 1.4 ± 3.3 vs 6.5 ± 5.6 pg/mL; IL-8: 13.2 ± 8.8 vs 33.4 ± 26.4 pg/mL; IL-10: 3.3 ± 3.3 vs 7.7 ± 6.5 pg/mL, and IL-12: 3.1 ± 7.9 vs 9 ± 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Lung hyperinflation stimulates the release of inflammatory mediators in spontaneously breathing subjects.

Lung hyperinflation up to vital capacity is used to re-expand collapsed lung areas and to improve gas exchange during general anesthesia. However, it may induce inflammation in normal lungs. The objective of this study was to evaluate the effects of a lung hyperinflation maneuver (LHM) on plasma cytokine release in 10 healthy subjects (age: 26.1 +/- 1.2 years, BMI: 23.8 +/- 3.6 kg/m(2)). LHM was performed applying continuous positive airway pressure (CPAP) with a face mask, increased by 3-cmH(2)O steps up to 20 cmH(2)O every 5 breaths. At CPAP 20 cmH(2)O, an inspiratory pressure of 20 cmH(2)O above CPAP was applied, reaching an airway pressure of 40 cmH(2)O for 10 breaths. CPAP was then decreased stepwise. Blood samples were collected before and 2 and 12 h after LHM. TNF-alpha, IL-1beta, IL-6, IL-8, IL-10, and IL-12 were measured by flow cytometry. Lung hyperinflation significantly increased (P < 0.05) all measured cytokines (TNF-alpha: 1.2 +/- 3.8 vs 6.4 +/- 8.6 pg/mL; IL-1beta: 4.9 +/- 15.6 vs 22.4 +/- 28.4 pg/mL; IL-6: 1.4 +/- 3.3 vs 6.5 +/- 5.6 pg/mL; IL-8: 13.2 +/- 8.8 vs 33.4 +/- 26.4 pg/mL; IL-10: 3.3 +/- 3.3 vs 7.7 +/- 6.5 pg/mL, and IL-12: 3.1 +/- 7.9 vs 9 +/- 11.4 pg/mL), which returned to basal levels 12 h later. A significant correlation was found between changes in pro- (IL-6) and anti-inflammatory (IL-10) cytokines (r = 0.89, P = 0.004). LHM-induced lung stretching was associated with an early inflammatory response in healthy spontaneously breathing subjects.

Selection on life-history traits and genetic population divergence in rotifers.

A combination of founder effects and local adaptation - the Monopolization hypothesis - has been proposed to reconcile the strong population differentiation of zooplankton dwelling in ponds and lakes and their high dispersal abilities. The role genetic drift plays in genetic differentiation of zooplankton is well documented, but the impact of natural selection has received less attention. Here, we compare differentiation in neutral genetic markers (F(ST)) and in quantitative traits (Q(ST)) in six natural populations of the rotifer Brachionus plicatilis to assess the importance of natural selection in explaining genetic differentiation of life-history traits. Five life-history traits were measured in four temperature x salinity combinations in common-garden experiments. Population differentiation for neutral genetic markers - 11 microsatellite loci - was very high (F(ST) = 0.482). Differentiation in life-history traits was higher in traits related to sexual reproduction than in those related to asexual reproduction. Q(ST) values for diapausing egg production (a trait related to sexual reproduction) were higher than their corresponding F(ST) in some pairs of populations. Our results indicate the importance of divergent natural selection in these populations and suggest local adaptation to the unpredictability of B. plicatilis habitats.

Selection of low investment in sex in a cyclically parthenogenetic rotifer.

Cyclical parthenogens, which combine asexual and sexual reproduction, are good models for research into the ecological and population processes affecting the evolutionary maintenance of sex. Sex in cyclically parthenogenetic rotifers is necessary for diapausing egg production, which is essential to survive adverse conditions between planktonic growing seasons. However, within a planktonic season sexual reproduction prevents clonal proliferation. Hence, clones with a low propensity for sex should be selected, becoming dominant in the population as the growing season progresses. In this context, we studied the dynamics of the heritable variation in propensity for sexual reproduction among clones of a Brachionus plicatilis rotifer population in a temporary Mediterranean pond during the period the species occurred in plankton. Clonal isolates displayed high heritable variation in their propensity for sex. Moreover, the frequency of clones with low propensity for sex increased during the growing season, which supports the hypothesized short-term selection for low investment in sex within a growing season. These results demonstrate (1) the inherent instability of the cyclical parthenogenetic life cycle, (2) the cost of sexual reproduction in cyclical parthenogens where sex produces diapausing eggs and (3) the role of the association between sexual reproduction and diapause in maintaining sex in these cyclical parthenogens.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol.

The pharmacokinetics of some beta-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32 degrees C). On the day before and on the first day after surgery, blood samples were collected before beta-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 +/- 0.75 to 11.46 +/- 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 +/- 2.83 to 19.33 +/- 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 +/- 1.60 to 11.44 +/- 2.89 h) or atenolol volume of distribution (from 2.90 +/- 0.36 to 3.83 +/- 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.