Effect of astaxanthin in extenders on sperm quality and functional variables of frozen-thawed boar semen.

The aim of the study was to determine whether the presence of astaxanthin (ASX) protects boar spermatozoa against damage related to cryopreservation. Pooled ejaculates extended in Beltsville Thawing Solution (BTS) were used. Three experiments were conducted: 1) sperm samples were pre-incubated overnight (17 °C) with ASX (0, 0.5, 5, 15 µM) prior to freezing and then frozen using cooling and thawing extenders supplemented with ASX (0, 0.5, 5, 15 µM); 2) sperm samples were treated with ASX (0, 0.5, 5, 15 µM) only during overnight pre-incubation (17 °C) prior to cryopreservation; and 3) a thawing extender was supplemented with ASX (0, 0.5, 5, 15 µM). The groups were as follows: control (C; no treatment), ASX 1 (0.5 µM), ASX 2 (5 µM) and ASX 3 (15 µM). Total (TM) and progressive (PM) motility was analyzed using CASA, while sperm viability, reactive oxygen species generation, lipid peroxidation and apoptoticlike changes were analyzed using flow cytometry. Sperm variables were evaluated prior to freezing as well as 30 and 150 min after thawing. In Experiment 1, the values of TM and sperm viability post-thaw were less in the ASX 3 than C group. In Experiment 2, there was no effect of ASX on any of the sperm variables evaluated, while in Experiment 3, apoptotic-like changes were less in the ASX 1 than C group. In conclusion, there was a subtle beneficial effect on cryopreserved boar spermatozoa after addition of ASX to thawing media.

Exogenous ascorbic acid enhances vitrification survival of porcine in vitro-developed blastocysts but fails to improve the in vitro embryo production outcomes.

In this study, the effects of addition of the antioxidant ascorbic acid (AsA) were evaluated during porcine in vitro embryo production (IVP) and vitrification. In experiment 1, the effects of AsA supplementation during IVM, IVF and IVC were evaluated, using a total of 2744 oocytes in six replicates. The IVM, IVF and embryo IVC media were supplemented or not (control) with 50 µg/mL AsA in all possible combinations. No significant effects of AsA were detected in any of the maturation, fertilization or embryo development parameters assessed. In experiment 2, we evaluated the effects of adding AsA to vitrification-warming media on the post-warming survival and quality of blastocysts. Day-6 in vitro-produced blastocysts (N = 588) from six replicates were randomly divided in two groups, with vitrification and warming media either supplemented with 50 µg/mL AsA (VW + group) or un-supplemented (VW- control). Addition of AsA increased (P < 0.05) blastocyst survival rate after vitrification compared with that of VW- control embryos. Vitrification and warming increased (P < 0.05) the production of oxygen species (ROS) and reduced (P < 0.05) the glutathione levels in blastocysts. Although VW + blastocysts displayed higher (P < 0.05) ROS levels than those of fresh control blastocysts, the levels were lower (P < 0.05) than those found in VW- control blastocysts. In conclusion, under the experimental conditions, supplementation of IVM/IVF/IVC media with AsA did not improve the embryo production in vitro. By contrast, the addition of AsA to chemically defined vitrification and warming media increased the survival of in vitro-produced porcine blastocysts by decreasing ROS production.

Tai Chi for Posttraumatic Stress Disorder and Chronic Musculoskeletal Pain: A Pilot Study.

PURPOSE: Explore the feasibility of a Tai Chi intervention to improve musculoskeletal pain, emotion, cognition, and physical function in individuals with posttraumatic stress disorder. DESIGN: Two-phase, one-arm quasi-experimental design. METHOD: Phase 1: 11 participants completed one Tai Chi session, feasibility questionnaire, and were offered participation in Phase 2, a 12-week Tai Chi intervention. Ten participants participated in Phase 2. Pain intensity, interference, physical function scales, an emotional battery, and cognition tests were used for pre- and postintervention outcome measures. Paired t tests and thematic analysis were used for analysis. FINDINGS: In Phase 1, most felt Tai Chi would benefit health (90.9%) and expressed interest in continuing Tai Chi (6.73 out of 7). Phase 2 results showed improvement in fear-affect (raw t = -2.64, p = .03; age adjusted t = -2.90, p = .02), fear-somatic arousal (raw t = -2.53, p = .035), List Sorting Working Memory (raw t = 2.62, p = .031; age adjusted t = 2.96, p = .018), 6-Minute Walk Test ( t = 3.541, p = .008), and current level of Pain Intensity ( t = -4.00, p = .004). CONCLUSIONS: Tai Chi is an acceptable, holistic treatment to individuals with musculoskeletal pain and posttraumatic stress disorder. It may reduce pain, improve emotion, memory, and physical function.

[Autologous blood pleurodesis for treatment of spontaneous pneumothorax and persistent air leak in pediatric patients]. / Pleurodesis con sangre autóloga en el tratamiento del neumotórax en pacientes pediátricos.

AIM OF THE STUDY: Recurrent spontaneous pneumothorax (SP) and persistent air leak (PAL) are a therapeutic challenge in some patients. Autologous blood pleurodesis (ABP) is an alternative treatment, but its usefulness in pediatric patients has not been determined yet. MATERIAL AND METHODS: Retrospective study of pediatric patients treated with ABP at our institution between 2010 and 2014, with special assessment of its indications, description of the technique, volume of blood used, complications and outcomes. RESULTS: During this period, 29 patients were treated for SP. 5 of them (17.2%) received ABP. Indications were: 2 patients with recurrent SP after thoracoscopic bullae resection and pleurodesis and 3 patients with PAL (1 after thoracoscopic bullae resection and 2 in lung transplantation candidates who were not suitable for surgery). Median age was 14.3 years (11.9-16.6) and volume of blood used was 50 ml (26-60). The air leak stopped in a median of 2.6 days (1-7). One patient needed a second ABP for PAL and another one presented an ipsilateral recurrence of SP after ABP. Follow up time was 2.21 years (0.49-3.42). No complications were observed. CONCLUSIONS: ABP is a cheap, safe and easy to perform procedure and may be considered as a therapeutic option in some pediatric patients with SP or PAL.

OBJETTIVOS: Los neumotórax recurrentes y la fuga aérea persistente (FAP) plantean dificultades terapéuticas en determinados pacientes. La pleurodesis con sangre autóloga (PSA) constituye una alternativa en su tratamiento, aunque su utilidad en pacientes pediátricos no ha sido determinada. MATERIAL Y METODOS: Estudio retrospectivo de los pacientes pediátricos tratados con PSA en nuestro centro entre los años 2010 y 2014, centrado en las indicaciones, descripción de la técnica de administración, cantidad de sangre empleada, complicaciones y resultados. RESULTADOS: Durante este periodo, 29 pacientes presentaron neumotórax espontáneos. En 5 de ellos (17,2%) se realizó PSA como método de rescate. Las indicaciones fueron: 2 recidivas de neumotórax tras resección de bullas y pleurodesis y 3 casos de fuga aérea persistente (1 tras resección toracoscópica de bullas subpleurales y en 2 candidatos a trasplante pulmonar con bullas en los que se descartó la cirugía). La mediana de edad fue de 14,3 años (11,9-16,6) y la cantidad de sangre empleada 50 ml (26-60). La fuga aérea se resolvió en una media de 2,6 días (1-7). Un paciente requirió una nueva PSA por persistencia de fuga aérea tras la primera administración y otro presentó una recurrencia posterior del neumotórax. El tiempo de seguimiento fue de 2.21 años (0,49-3,42). No se describieron otras complicaciones. CONCLUSIONES: La PSA es un método de fácil aplicación, seguro y económico que puede ser considerado como opción terapéutica de rescate en determinados pacientes pediátricos con neumotórax o fuga aérea persistente.

Pleurodesis con sangre autóloga en el tratamiento del neumotórax en pacientes pediátricos / Autologous blood pleurodesis for treatment of spontaneous pneumothorax and persistent air leak in pediatric patients

Objetivos. Los neumotórax recurrentes y la fuga aérea persistente (FAP) plantean dificultades terapéuticas en determinados pacientes. La pleurodesis con sangre autóloga (PSA) constituye una alternativa en su tratamiento, aunque su utilidad en pacientes pediátricos no ha sido determinada. Material y métodos. Estudio retrospectivo de los pacientes pediátricos tratados con PSA en nuestro centro entre los años 2010 y 2014, centrado en las indicaciones, descripción de la técnica de administración, cantidad de sangre empleada, complicaciones y resultados. Resultados. Durante este periodo, 29 pacientes presentaron neumotórax espontáneos. En 5 de ellos (17,2%) se realizó PSA como método de rescate. Las indicaciones fueron: 2 recidivas de neumotórax tras resección de bullas y pleurodesis y 3 casos de fuga aérea persistente (1 tras resección toracoscópica de bullas subpleurales y en 2 candidatos a trasplante pulmonar con bullas en los que se descartó la cirugía). La mediana de edad fue de 14,3 años (11,9-16,6) y la cantidad de sangre empleada 50 ml (26-60). La fuga aérea se resolvió en una media de 2,6 días (1-7). Un paciente requirió una nueva PSA por persistencia de fuga aérea tras la primera administración y otro presentó una recurrencia posterior del neumotórax. El tiempo de seguimiento fue de 2.21 años (0,49-3,42). No se describieron otras complicaciones. Conclusiones. La PSA es un método de fácil aplicación, seguro y económico que puede ser considerado como opción terapéutica de rescate en determinados pacientes pediátricos con neumotórax o fuga aérea persistente

Aim of the study. Recurrent spontaneous pneumothorax (SP) and persistent air leak (PAL) are a therapeutic challenge in some patients. Autologous blood pleurodesis (ABP) is an alternative treatment, but its usefulness in pediatric patients has not been determined yet. Material and methods. Retrospective study of pediatric patients treated with ABP at our institution between 2010 and 2014, with special assessment of its indications, description of the technique, volume of blood used, complications and outcomes. Results. During this period, 29 patients were treated for SP. 5 of them (17.2%) received ABP. Indications were: 2 patients with recurrent SP after thoracoscopic bullae resection and pleurodesis and 3 patients with PAL (1 after thoracoscopic bullae resection and 2 in lung transplantation candidates who were not suitable for surgery). Median age was 14.3 years (11.9-16.6) and volume of blood used was 50 ml (26-60). The air leak stopped in a median of 2.6 days (1-7). One patient needed a second ABP for PAL and another one presented an ipsilateral recurrence of SP after ABP. Follow up time was 2.21 years (0.49-3.42). No complications were observed. Conclusions. ABP is a cheap, safe and easy to perform procedure and may be considered as a therapeutic option in some pediatric patients with SP or PAL

Normativa SEPAR sobre disfunción muscular de los pacientes con enfermedad pulmonar obstructiva crónica / Guidelines for the evaluation and treatment of muscle dysfunction in patients with chronic obstructive pulmonary disease

La disfunción muscular de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) constituye una de las comorbilidades más importantes, con repercusiones negativas en su capacidad de ejercicio y calidad de vida. En la presente normativa se ha resumido la literatura publicada más recientemente sobre los diferentes aspectos del tema y se ha utilizado también la escala Grading of Recommendations Assessment, Development, and Evaluation (GRADE) de recomendaciones sobre el grado de evidencia de las diferentes propuestas de la normativa. Respecto a una población control, se estima que en un tercio de los pacientes EPOC la fuerza del cuádriceps es un 25% inferior incluso en estadios precoces de su enfermedad. Aunque tanto los músculos respiratorios como los de las extremidades están alterados, estos últimos suelen verse mayormente afectados. Diversos factores y mecanismos biológicos están involucrados en la disfunción muscular de los pacientes. Se proponen diversas pruebas para evaluar y diagnosticar el grado de afectación de los músculos respiratorios y de las extremidades (periféricos), así como identificar la capacidad de esfuerzo de los pacientes (prueba de marcha de 6min y cicloergometría). Se describen también las posibles estrategias terapéuticas vigentes que incluyen las diversas modalidades de entrenamiento y de soporte farmacológico y nutricional.(AU)

In patients with chronic obstructive pulmonary disease (COPD), skeletal muscle dysfunction is a major comorbidity that negatively impacts their exercise capacity and quality of life. In the current guidelines, the most recent literature on the various aspects of COPD muscle dysfunction has been included. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) scale has been used to make evidence-based recommendations on the different features. Compared to a control population, one third of COPD patients exhibited a 25% decline in quadriceps muscle strength, even at early stages of their disease. Although both respiratory and limb muscles are altered, the latter are usually more severely affected. Numerous factors and biological mechanisms are involved in the etiology of COPD muscle dysfunction. Several tests are proposed in order to diagnose and evaluate the degree of muscle dysfunction of both respiratory and limb muscles (peripheral), as well as to identify the patients' exercise capacity (six-minute walking test and cycloergometry). Currently available therapeutic strategies including the different training modalities and pharmacological and nutritional support are also described.(AU)

Effects and barriers to deployment of telehealth wellness programs for chronic patients across 3 European countries.

BACKGROUND: Benefits of cardiopulmonary rehabilitation (CPR) in patients with chronic obstructive pulmonary disease (COPD) are well established, but long-term sustainability of training-induced effects and its translation into healthy lifestyles are unsolved issues. It is hypothesized that Integrated Care Services supported by Information and Communication Technologies (ICS-ICT) can overcome such limitations. In the current study, we explored 3 ICS-ICT deployment experiences conducted in Barcelona, Trondheim and Athens. METHODS: In the 3 sites, a total of 154 patients completed an 8-week supervised CPR program. Thereafter, they were allocated either to an ICS-ICT group or to usual care (CPR + UC) during a follow-up period of at least 12 months with assessment of 6-min walking test (6MWT) as main outcome variable at all time points in the 3 sites. Because real deployment was prioritized, the interventions were adapted to site heterogeneities. RESULTS: In the ICS-ICT group from Barcelona (n = 77), the use of the personal health folder (PHF) was the cornerstone technological tool to empower COPD patients for self-management showing high applicability and user-acceptance. Long-term sustainability of training-induced increase in exercise capacity was observed in ICS-ICT compared to the control group (p = 0.01). Likewise, ICS-ICT enhanced the activities domain of the SGRQ (p < 0.01) and daily physical activity (p = 0.03), not seen in controls. No effects of ICS-ICT were observed in Trondheim (n = 37), nor in Athens (n = 40), due to technological and/or organizational limitations. CONCLUSIONS: The study results suggest the potential of the ICS-ICT Barcelona's approach to enhance COPD management. Moreover, it allowed identification of the factors limiting transferability to the other sites. The research prompts the need for large multicenter trials specifically designed to assess effectiveness, efficiencies and transferability of this type of intervention.

Effect of MEM vitamins and forskolin on embryo development and vitrification tolerance of in vitro-produced pig embryos.

The aims of this study were (1) to determine the effect of in vitro maturation (IVM) medium supplementation with MEM vitamins on in vitro embryo development and sensitivity to vitrification of Day 6 blastocysts and (2) to evaluate whether the addition of forskolin to in vitro culture (IVC) medium enhances blastocyst survival following Super Open Pulled Straw (SOPS) vitrification. Cumulus-oocyte complexes (COCs; n=4000) were matured with 0.0% or 0.05% (v/v) MEM vitamins. After 44h of IVM, the oocytes were in vitro fertilized, and presumptive zygotes were cultured. At Day 5 of IVC, embryos from both experimental groups were cultured for 24h with 0 or 10µM forskolin, achieving a 2×2 factorial design. The blastocyst formation rate was assessed on Day 6, and subsets of samples from the four experimental groups were vitrified (n=469) or kept fresh (n=546). Fresh and vitrified-warmed blastocysts were cultured for 24h prior to embryo survival and total blastocyst cell number assessment. The MEM vitamins increased (P<0.001) the blastocyst formation rate at Day 6, but they did not affect embryo survival after vitrification. In contrast, the addition of forskolin to the culture medium enhanced (P<0.05) the blastocyst vitrification tolerance. The total blastocyst cell number was similar among the groups. In conclusion, supplementation with 0.05% MEM vitamins improved the blastocyst formation rate, and the addition of 10µM forskolin to the culture medium increased survival in Day 6 in vitro-produced blastocysts after SOPS vitrification.

Electroestimulación y feedback neuromuscular en la fase inicial de rehabilitación de la artroplastia total de la rodilla / Feedback and neuromuscular electrical stimulation during an early phase of a rehabilitation programe after total knee arthroplasty

Objetivo: Estudiar el efecto de la electroestimulación con feedback del cuádriceps (EENM-feedback) en un programa estándar de rehabilitación de artroplastia total de rodilla. Material y métodos: ensayo clínico en 83 pacientes intervenidos de artroplastia de rodilla por gonartrosis primaria. El protocolo postoperatorio se aleatorizó en un grupo de rehabilitación estándar con EENM-feedback y otro grupo control de rehabilitación estándar. Se valoró el balance articular (BA), el test «timed up and go» (TUG) y el cuestionario funcional WOMAC, antes de la artroplastia, al alta del hospital, al mes y a los 3 meses. Resultados: El BA y el WOMAC evolucionaron igual en ambos grupos. Al tercer mes, el TUG mejoró siginificativamente en el grupo de EENM-feedback (p<0,001), mientras que en el grupo estándar fue similar al previo (p = 0,1). Conclusión: La aplicación de EENM-feedback en el postoperatorio de la artroplastia total de rodilla puede ayudar a mejorar la capacidad de deambulación a corto-medio plazo (AU)

Background: The aim of this study was to study the effect of feedback and neuromuscular electrical stimulation (feedback-NMS) on an standard rehabilitation protocol after total knee arthroplasty (TKA). Methods: Clinical trial in 83 patients undergoing TKA for primary knee osteoarthritis. After surgery, patients were randomized in feedback-NMS rehabilitation program or standard rehabilitation. Range of movement (ROM), timed up and go test (TUG) and the Western Ontario and MacMaster Universities (WOMAC osteoarthritis index) were tested previous surgery, at hospital discharge, one month and three moths after. Results: Changes in ROM and WOMAC values were similar in both groups. At three months TUG values were better than previous in feedback-NMS group (p<0,001) but not in control group (p = 0,1). Conclusion: Feedback and NMS as a immediate therapy after TKA can help to improve walking capacity in short-mid term (AU)

Evaluation of l-glutamine for cryopreservation of boar spermatozoa.

The aim of the present study was to evaluate the protective effect of L-glutamine (L-Gln) against cryopreservation injuries on boar sperm. In Experiment 1, L-Gln from 20 to 80 mM was evaluated as a supplement for a standard freezing extender (egg yolk - EY - 20%, and glycerol 3%). No significant improvement (P>0.05) was obtained for any post-thaw sperm parameter assessed (objective sperm motility - CASA system - and flow cytometric analysis of plasma and acrosomal membrane integrity -SYBR14/PI/PE-PNA- and plasma membrane stability -M540/YoPro1-). In Experiment 2, L-Gln was evaluated as a partial glycerol substitute in the freezing extender. Significant (P<0.05) enhancement of post-thaw sperm motion parameters was achieved in sperm frozen in the presence of 2% glycerol and 80 mM L-Gln compared to control (3% glycerol). In Experiment 3, L-Gln was evaluated as an EY substitute in the freezing extender, and no functional sperm were recovered after thawing sperm frozen in the presence of L-Gln and the absence of EY. In conclusion, L-Gln has the ability to cryoprotect boar sperm when it is used as a partial glycerol substitute in the freezing extender.

Integrated care prevents hospitalisations for exacerbations in COPD patients.

Hospital admissions due to chronic obstructive pulmonary disease (COPD) exacerbations have a major impact on the disease evolution and costs. The current authors postulated that a simple and well-standardised, low-intensity integrated care intervention can be effective to prevent such hospitalisations. Therefore, 155 exacerbated COPD patients (17% females) were recruited after hospital discharge from centres in Barcelona (Spain) and Leuven (Belgium). They were randomly assigned to either integrated care (IC; n = 65; age mean+/-sd 70+/-9 yrs; forced expiratory volume in one second (FEV(1)) 1.1+/-0.5 L, 43% predicted) or usual care (UC; n = 90; age 72+/-9 yrs; FEV(1) 1.1+/-0.05 L, 41% pred). The IC intervention consisted of an individually tailored care plan upon discharge shared with the primary care team, as well as accessibility to a specialised nurse case manager through a web-based call centre. After 12 months' follow-up, IC showed a lower hospitalisation rate (1.5+/-2.6 versus 2.1+/-3.1) and a higher percentage of patients without re-admissions (49 versus 31%) than UC without differences in mortality (19 versus 16%, respectively). In conclusion, this trial demonstrates that a standardised integrated care intervention, based on shared care arrangements among different levels of the system with support of information technologies, effectively prevents hospitalisations for exacerbations in chronic obstructive pulmonary disease patients.

[The neurobiology of sleep: Cajal and present-day neuroscience]. / Neurobiología del sueño: Ramón y Cajal y la neurociencia actual.

AIMS: We briefly describe the most significant findings obtained recently concerning the sleep-waking cycle in comparison to the studies conducted by Cajal on the same subject. DEVELOPMENT: This paper includes a short biographical sketch of Santiago Ramón y Cajal, with special emphasis on his importance within the framework of neuroscience. Cajal represents the decisive turning point in neurobiological studies, with the discovery of the synapse and his law of dynamic polarization. We conduct a short survey of the current knowledge about the phases of sleep and oneiric phenomena, based on their anatomo-physiological foundations. We present a summary of the history of the subject and analyze the contributions made by Cajal to this field, i.e. his study of the associative cortices, which are essential in memory processes and related to the mechanisms governing the sleep-waking cycle. For Cajal the fine anatomy of the thalamus must be considered in relation to the specificity of its connections an idea that is still completely valid today. He did not observe any projections of the thalamic reticular nucleus towards the cerebral cortex, a fact that has been corroborated using modern-day techniques. He spoke of the involvement of neuroglia in the attentional and sleep processes, which is so, although not quite in the way Cajal thought. He considered the production of dreams to be based on intimate neural mechanisms, which is still so. He also studied other brain structures related with the regulation of the sleep waking cycle, although avoiding any specific mention of the mechanisms controlling such a cycle. Furthermore, he conducted self-observation studies with a high degree of insight. CONCLUSIONS: Cajal studied the phenomena of attention and sleep in an objective manner and contributed a number of significant interpretations, some of which are now somewhat outdated while others are still wholly valid today.

Ocular iontophoretic supplementation of intravenous foscarnet therapy.

PURPOSE: Reactivation of cytomegalovirus retinopathy during intravenous antiviral therapy is usually treated with higher doses of drug. We sought to determine whether ocular iontophoresis increases the intravitreal foscarnet concentration attained by intravenous injection. METHODS: We injected foscarnet (120 mg/kg or 180 mg/kg) intravenously into 24 rabbits and determined the time of maximal concentrations in serum and vitreous humor. We injected the same doses into 24 additional rabbits and administered ocular foscarnet iontophoresis one hour later. Vitreous humor concentrations were assayed at one, four, eight, 24, 60, and 120 hours after iontophoresis and compared with those from injection alone. RESULTS: Maximum serum and vitreous humor concentrations were achieved one hour after each intravenous dose. Maximum vitreous humor concentrations were achieved four hours after 120 mg/kg intravenous doses plus iontophoresis and eight hours after 180-mg/kg intravenous doses plus iontophoresis. Vitreous humor levels were significantly higher in eyes receiving intravenous foscarnet (120 mg/kg, P < .0001; 180 mg/kg, P < .0001) plus ocular Foscarnet iontophoresis than in those receiving intravenous foscarnet alone. Vitreous humor foscarnet levels in eyes receiving 120 mg/kg intravenously did not differ significantly from those in the group receiving 180 mg/kg intravenously (P < .1). The intravenous dose did not significantly affect vitreous humor levels after iontophoresis (P < .1). Vitreous concentrations fell below therapeutic levels (25 microM) in all eyes 60 hours after intravenous foscarnet and ocular foscarnet iontophoresis. CONCLUSIONS: Ocular iontophoresis significantly increased intravitreous foscarnet concentrations above those attained by intravenous injection alone and may be an effective alternative to increasing the intravenous drug dose in patients with reactivated cytomegalovirus retinopathy.

Cellular bioenergetics after erythropoietin therapy in chronic renal failure.

After erythropoietin (rHuEPO) therapy, patients with chronic renal failure (CRF) do not improve peak O2 uptake (VO2 peak) as much as expected from the rise in hemoglobin concentration ([Hb]). In a companion study, we explain this phenomenon by the concurrent effects of fall in muscle blood flow after rHuEPO and abnormal capillary O2 conductance observed in CRF patients. The latter is likely associated with a poor muscle microcirculatory network and capillary-myofiber dissociation due to uremic myopathy. Herein, cellular bioenergetics and its relationships with muscle O2 transport, before and after rHuEPO therapy, were examined in eight CRF patients (27 +/- 7.3 [SD] yr) studied pre- and post-rHuEPO ([Hb] = 7.8 +/- 0.7 vs. 11.7 +/- 0.7 g x dl-1) during an incremental cycling exercise protocol. Eight healthy sedentary subjects (26 +/- 3.1 yr) served as controls. We hypothesize that uremic myopathy provokes a cytosolic dysfunction but mitochondrial oxidative capacity is not abnormal. 31P-nuclear magnetic resonance spectra (31P-MRS) from the vastus medialis were obtained throughout the exercise protocol consisting of periods of 2 min exercise (at 1.67 Hz) at increasing work-loads interspersed by resting periods of 2.5 min. On a different day, after an identical exercise protocol, arterial and femoral venous blood gas data were obtained together with simultaneous measurements of femoral venous blood flow (Qleg) to calculate O2 delivery (QO2leg) and O2 uptake (VO2leg). Baseline resting [phosphocreatine] to [inorganic phosphate] ratio ([PCr]/[Pi]) did not change after rHuEPO (8.9 +/- 1.2 vs. 8.8 +/- 1.2, respectively), but it was significantly lower than in controls (10.9 +/- 1.5) (P = 0.01 each). At a given submaximal or peak VO2leg, no effects of rHuEPO were seen on cellular bioenergetics ([PCr]/[Pi] ratio, %[PCr] consumption halftime of [PCr] recovery after exercise), nor in intracellular pH (pHi). The post-rHuEPO bioenergetic status and pHi, at a given VO2leg, were below those observed in the control group. However, at a given pHi, no differences in 31P-MRS data were detected between post-rHuEPO and controls. After rHuEPO, at peak VO2, Qleg fell 20% (P < 0.04), limiting the change in QO2leg to 17%, a value that did not reach statistical significance. The corresponding O2 extraction ratio decreased from 73 +/- 4% to 68 +/- 8.2% (P < 0.03). These changes indicate that maximal O2 flow from microcirculation to mitochondria did not increase despite the 50% increase in [Hb] and explain how peak VO2leg and cellular bioenergetics (31P-MRS) did not change after rHuEPO. Differences in pHi, possibly due to lactate differences, between post-rHeEPO and controls appear to be a key factor in the abnormal muscle cell bioenergetics during exercise observed in CRF patients.