[Middle molecules removal. Beyond beta2-microglobulin]. / Depuración de grandes moléculas. Más allá de la beta2-microglobulina.

The uremic toxin removal capacity mainly depends on dialyzer and hemodialysis modes. The low-flux hemodialysis only removes solutes having molecular weights less than 5.000 Da. High-flux hemodyalisis represents a form of low-volume hemodiafiltration because of the internal filtration and back-filtration that can take place within a dialyzer. Hemodiafiltration with large volumes of replacement fluid seems to be the best technique for removing all small, medium-sized and large molecules. The objective of our study was to evaluate the large molecules removal bigger than beta2-microglobuline on high flux haemodialysis and on-line hemodiafiltration with postdilutional infusion, in patients with three times a week dialysis and on short daily dialysis. We studied 24 patients, 15 males and 9 females stable on haemodialysis programme, twelve on standard four to five hours three times a week dialysis and twelve on 2 to 2 1/2 hours six times a week dialysis. All patients were dialysed with Fresenius 4008 monitor, three sessions on high flux haemodialysis (HD) and three sessions on on-line hemodiafiltration (OL-HDF). Two sessions with each filter were performed (polisulfone HF80, polyethersulfone Arylane H9 and new polisulfone APS 900). Pre and postdialysis concentrations of urea, creatinine, (beta2-microglobulin (beta2-m), myoglobin, prolactin and alpha1 microglobulin (alpha1-m) were measured. There was no difference in urea and creatinine small molecules removal. beta2m removal was 68% on HD and 81% on OL-HDF. Myoglobin and prolactin present a similar removal pattern, a higher removal with new filters (60% with Arylane and 59% with APS) in comparison with clasical polisulfone (22% with HF80). The mean alpha1-m reduction rate on HD was 6% and on OL-HDF 22%. OL-HDF with APS 900 filter was the most remove technique (35.4%), significatively higher than the other modes and filters. We can conclude that the new filters generation reach a better uremic toxins removal, specially in large molecules higher than beta2-m and on HD modality.

[Improvement of nutritional status in patients with short daily on-line hemodiafiltration]. / Mejoría del estado nutricional con hemodiafiltración en línea diaria.

Daily dialysis have showed excellent results because a higher frequency of dialysis is more physiological and it decreases the fluctuation of liquid, solutes and electrolytes. Improvement of certain causes of anorexia such as postdialysis fatigue, reduction in fluid overload, uremic milieu, medium and large-sized molecule removal could be observed with daily dialysis. The aim of this study was to evaluate nutritional parameters when thrice weekly on-line hemodiafiltration (OL-HDF) were switched to daily OL-HDF. 24 patients have been studied. Eight patients, 6 males and 2 females, mean age of 65.9 +/- 14 years, on thrice weekly 4 to 5 hours OL-HDF were switched to 2 to 2.5 hours six times per week. Dialysis parameters were the same in both periods and only frequency and dialysis time were changed. Other sixteen patients, mean age of 68.4 +/- 14 years, were a control group which dialysis parameters were maintained. Clinical and biochemical outcome were carried out over twelve months. Daily OL-HDF group: Dry weight increased from 67.8 +/- 8 kg at baseline to 68.5 +/- 8 kg after three months, 69.3 +/- 8 kg after six months (NS), 69.5 +/- 8 kg after nine months (p < 0.05) and 70.8 +/- 8 (p < 0.01) after one year. Mean nPCR increased from 0.93 +/- 0.2 g/kg/d on baseline to 1.18 +/- 0.3 after three moths (P < 0.0-5), 1.13 +/- 0.2 after six months (NS), 1.06 +/- 0.2 after nine months (NS) and 1.10 +/- 0.2 after twelve months (NS). There were no significant changes in serum protein, albumin, prealbumin, transferrin, total cholesterol, HDL-c, LDL-c and triglycerides (TG). There were no changes in control group. Mean dry weight was 62.3 +/- 9 kg at baseline and 62.1 +/- 10 kg after one year. Mean nPCR was 0.97 +/- 0.2 g/kg/d on baseline and 1.03 +/- 0.2 g/kg/d after one year. Neither there were changes in serum protein, albumin, transferrin, total cholesterol, HDL-c, LDL-c and TG. Improvement in nutrition status has been observed with the change from thrice weekly OL-HDF to short daily OL-HDF. Increased appetite and protein intake was accompanied by a dry body weight increase of three kg after twelve months.

Mejoría del estado nutricional con hemodiafiltración en línea diaria / Improvement of nutritional status in patients with short daily on-line hemodiafiltration

La malnutrición proteico-calórica es uno de los principales factores que afectan la morbi-mortalidad de los pacientes en diálisis. Las causas de anorexia en hemodiálisis incluyen la restricción dietética, diálisis inadecuada, inestabilidad cardiovascular, vómitos, fatiga, sobrehidratación, infección y/o inflamación, las cuales podrían mejorar con diálisis diaria. El objetivo del estudio fue valorar la evolución nutricional tras cambiar de hemodiafiltración (HDF) en línea en régimen de 3 sesiones semanales a HDF en línea diaria.24 pacientes en programa estable de HDF en línea en 3 ses/sem durante 36 ñ 15 meses, se incluyeron en el estudio. Ocho pacientes, 6 hombres y 2 mujeres, tiempo 275 ñ 25 min (4-5 h), Qb 445ñ 59 ml/min, Qd 800 ml/min, y 97 ñ 24 I de reinfusión semanal se pasaron a HDF diaria reduciendo el tiempo a la mitad, 129 ñ 8 min (2-2,5 h). Los 16 pacientes restantes permanecieron en HDF en línea en 3 ses/sem (grupo control) con un tiempo de 259 ñ 31 min, QB 416 ñ 35 ml/min, QD 800 ml/min y 84 ñ 14 l de reinfusión semanal. Se valoró la evolución del peso seco y de marcadores analíticos nutricionales durante un año de seguimiento. Resultados: Los pacientes que pasaron a HDF diaria presentaron un incremento progresivo del peso seco, de 67,8 ñ 8 kg banalmente a 68,5 ñ 8 (NS) a los 3 meses, 69,3 ñ 8 (NS) a los seis, 69,5 _+ 8 (p < 0,05) a los 9 meses y 70,8 ñ 8 (p < 0,01) al año. Se observó un incremento de la ingesta proteica medida por el PCRn de 0,93 ñ 0,2 g/kg/d banal a 1,18 ñ 0,3 (p < 0,05), 1,13 ñ 0,2, 1,06 ñ 0,3 y 1,10 ñ 0,2, a los 3, 6, 9 y 12 meses respectivamente. No se observaron cambios en las proteínas totales, albúmina, prealbúmina, colesterol total, HDL, LDL, triglicéridos y transferrina. En el grupo control no se observaron cambios en el peso seco (62,3 ñ 9 basa/ vs 62,1 ñ 10 al año), PCRn (0,97 ñ 0,2 basa/ vs 1,03 ñ 0,2 al año) ni de los otros parámetros estudiados. Conclusiones: En este estudio, con HDF en línea diaria, hemos observado un incremento del apetito con una ganancia de más de 3 kg en el peso corporal al año de seguimiento. No se ha observado cambios en el grupo control (AU)

Mechanism of free radical production in exhaustive exercise in humans and rats; role of xanthine oxidase and protection by allopurinol.

Exhaustive exercise generates free radicals. However, the source of this oxidative damage remains controversial. The aim of this paper was to study further the mechanism of exercise-induced production of free radicals. Testing the hypothesis that xanthine oxidase contributes to the production of free radicals during exercise, we found not only that exercise caused an increase in blood xanthine oxidase activity in rats but also that inhibiting xanthine oxidase with allopurinol prevented exercise-induced oxidation of glutathione in both rats and in humans. Furthermore, inhibiting xanthine oxidase prevented the increases in the plasma activity of cytosolic enzymes (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase) seen after exhaustive exercise. Our results provide evidence that xanthine oxidase is responsible for the free radical production and tissue damage during exhaustive exercise. These findings also suggest that mitochondria play a minor role as a source of free radicals during exhaustive physical exercise.

[Guidelines of the Spanish Society of Cardiology for clinical practice in exercise testing]. / Guías de práctica clínica de la Sociedad Española de Cardiología en pruebas de esfuerzo.

Most exercise testing is performed in adults with known or suspected ischemic heart disease. In the last few years cardiac imaging techniques have been applied in this field, improving the information obtained with the procedure. However, the exceptions to this rule are emerging rapidly not only in healthy people (asymptomatic individuals, athletes, handicapped people) but also in cardiac patients (advanced congestive heart failure, hypertension, rhythm disorders, congenital heart disease, etc.). All the-se issues justify the need for a multidisciplinary consensus document in Spain. This paper reviews and updates the methodological aspects of the stress test, including those related to oxygen consumption measurements. The main aim of this review was to determine the role of exercise testing in the evaluation of ischemic heart disease as well as the applications of imaging stress testing. The usefulness of this test in other non-ischemic cardiac disorders and in selected subsets of healthy people is also reviewed.

[Interaction of the mechanisms of beta 2-microglobulin convection, diffusion, and adsorption in line hemodiafiltration]. / Interacción de los mecanismos de convección, difusión y adsorción de beta 2-microglobulina en la hemodiafiltración en línea.

The in vivo contribution of diffusion, convection ad adsorption to beta 2-microglobulin (beta 2-m) elimination by hemodiafiltration (HDF) was investigated. 11 patients (8M/3W), with a mean age of 59 +/- 10 years and weighing 62.7 +/- 8.7 kg were studied. A 1.89 m2 polysulphone membrane was used in 180 min postdilution HDF. Samples at blood inlet (bi), blood autlet (bo), dialysate outlet (do) and ultrafiltrate (uf) were taken to determine beta 2-m concentrations at 30 and 150 min. Rates of flow (Q, ml(min) prescribed were: infusion, Qinf = 103.6 +/- 12.3, Quf = 14.6 +/- 4.0 y Qb = 465 +/- 5.0. Effective Qbi was automatically measured by the machine and Qdo = 800 + Quf. The removed beta 2-m mass (M, mg/min) was obtained by multiplying rates of flow (Q, L/min) by beta 2-m concentrations (mg/L) at each sampling point. From mass balance, we calculated the mass of beta 2-m removed (mg/min) by adsorption 0.23 +/- 0.2, by convection 0.7 +/- 0.3 and by diffusion 1.0 +/- 0.4, at 30 min. At 150 min, the beta 2-m mass removed was -0.06 +/- 0.1 by adsorption 0.4 +/- 0.1 by convection and 0.3 +/- 0.1 by diffusion. In HDF, these beta 2-m eliminating mechanisms play a variable role throughout the session. The more significant conclusion is that diffusion of beta 2-m with a synthetic "open" membrane is an important method of removing beta 2-m, comparable to convection over the whole procedure. That result explain the relative efficacy of beta 2-m clearance by HDF convection, and also explain why isolated diffusion is an efficient mechanism for beta 2-m removal by high-flux hemodialysis.

[Changes in the anion gap in patients undergoing hemodiafiltration]. / Variaciones del "anion gap" en pacientes en hemodiafiltración.

The serum anion gap (AG) is a calculated value defined as the difference between the sum of sodium and potassium and the sum of chloride and bicarbonate concentrations. Thus, the anion gap is equal to the unmeasured cations minus the unmeasured anions (UA). To evaluate the AG changes during HDF-on line, we studied 20 patients treated with this technique. Blood pH, HCO3, NA, K, Cl, albumin, phosphorus, urea, creatinine and lactate were determined pre and post-HDF. The AG, negative charger of serum albumin (CAA) and phosphate (CAP) were computed by equations. AG decreased during HDF from 23.1 +/- 3.4 mEq/l to 17.3 +/- 3.6 mEq/l (p < 0.001). The CAA rose from 10.9 +/- 0.8 to 12.3 +/- 1.7 mEq/l (p < 0.001). The CAP and lactate fell significantly during HDF (p < 0.001 and 0.05 respectively). Other unmeasured anions (UA) decreased from 7.9 +/- 3.0 to 2.4 +/- 2.7 mEq/l (p < 0.001). The CAA contributed 47.7 +/- 6.5% and 73.01 +/- 12.7% to the pre and post-HDF serum anion gap respectively. The CAP accounted for 12.4 +/- 3.4% and 8.6 +/- 1.8%, lactate 6.4 +/- 3.9% and 6.0 +/- 3.0% and UA for 33.2 +/- 7.7% and 12.2 +/- 13.6% of the anion gap pre and post-HD respectively. AG and UA correlated significantly with blood urea pre-HDF and urea generation. The increase in serum albumin and pH can mask an decreased concentration of unmeasured anions in patients treated with HDF on-line. An adjusted anion gap without effect of CAA and CAP can be obtained. With the help of this adjustments the changes in some undetermined anions organic and inorganic (sulphate and others in renal failure) can be calculated.

Interacción de los mecanismos de convección, difusión y adsorción de beta2-microglobulina en la hemodiafiltración en línea interacción de los mecanismos de convección, difusión y adsorción de beta2-microglobulina en la hemodiafiltración en línea / Interaction of beta2-microglobulin mechanisms of convection, diffusion and adsorption in on-line hemodiafiltration

El objetivo del estudio fue conocer la contribución relativa in vivo de los mecanismos de difusión, convección y adsorción en la eliminación de beta2-microglobulina (beta2-m) en hemodiafiltración (HDF).Participaron 11 pacientes (8V/3H), con una edad media de 59 ñ 10 años y un peso medio de 62,7 ñ 8,7 kg. Se utilizó una membrana de polisulfona de 1,89 m2 en una sesión de HDF postdilución de 180 minutos de duración. Se obtuvieron muestras en sangre a la entrada (bi) y a la salida (bo) del dializador, en el baño, a la salida del dializado (do) y en el ultrafiltrado (uf), en las que se determinaron las concentraciones de beta2-m, a los 30 y 150 minutos. Los flujos (ml/min) prescritos fueron: de infusión, Qinf= 103,6 ñ 12,3, Quf= 14,6 ñ 4,0 y Q,i teórico = 465 ñ 5,0. El Qbi efectivo fue el determinado por el monitor en cada momento y Q&, = 800 + Quf. Se calculó la masa de beta2-m (M, mglmin) eliminada multiplicando los flujos (Llmin) por las concentraciones (mg/L) de beta2-m en cada punto de muestreo. Aplicando el balance de masas, calculamos la masa de beta2-m eliminada por adsorción 0,23 ñ 0,2, por convección 0,7 ñ 0,3 y por difusión 1,0 ñ 0,4 a los 30 min. A los 150 min, la masa de beta2-m eliminada fue -0,06 ñ 0,1 por adsorción 0,4 ñ 0,1 por convección y 0,3 ñ 0,1 por difusión. Los mecanismos de eliminación de beta2-m juegan un papel variable durante la sesión de HDF. La conclusión más significativa fue que la difusión de beta2-m con una membrana de alta permeabilidad era en todo momento un importante mecanismo depurativo, en competición con la convección. Este resultado explicaría la eficacia relativa del aclaramiento de beta2-m por convección en HDF, y que la difusión aislada es un mecanismo eficaz de depuración de beta2-m en la hemodiálisis de alto flujo (AU)

Variaciones del "anion gap" en pacientes en hemodiafiltración / Effects of HDF on-line on serum anion gap

El anion gap (AG) es un valor calculado que representa la diferencia entre cationes y aniones no medidos por técnicas habituales de laboratorio. Para evaluar los principales componentes del AG y los cambios producidos durante la sesión de hemodiafiltración (HDF) en línea, se estudiaron 20 pacientes en esta técnica. Se recogieron muestras pre y post-HDF para la determinación de pH, HC03, NA, K, Cl, albúmina, P, urea y lactato. Se calculó el AG y la carga aniónica de albúmina (CAA) y de fosfato (CAP).El AG descendió de 23,1 ñ 3,4 a 17,3 ñ 3,6 mEq/I durante la sesión (p < 0,001). La CAA se elevó 10,9 ñ 0,8 a 12,3 ñ 1,7 mEq/I (p < 0,001) y la CAP disminuyó de 2,9 ñ 1 a 1,4 ñ 0,4 mEq/I (p < 0,001) al finalizar la sesión. El lactato descendió de 1,4 ñ 0,7 a 1,0 ñ 0,5 mEq/I (p < 0,05) y el resto de aniones (OA) que componen el AG descendieron igualmente de 7,9 ñ 3,0 a 2,4 ñ 2,7 mEq/I (p < 0,001). El porcentaje de reducción de estos OA (PROA) fue de 68,4 ñ 42,6 por ciento. La mayor parte del AG resultó de la CAA con el 47,7 ñ 6,5 por ciento pre-HDF y 73 ñ 12,7 por ciento post-HDF. La CAP constituyó el 12,4 ñ 3,4 por ciento y el 8,6 ñ 1,8 por ciento, respectivamente. El lactato supuso el 6,4 ñ 3,9 por ciento y el 6,0 ñ 3,0 por ciento pre y post-HDF, respectivamente y los OA constituyeron el 33,2 ñ 7,7 por ciento y el 12,2 ñ 13,6 por ciento. Tanto el AG como los OA se correlacionaron de manera significativa con los niveles de urea pre-HDF y con la generación de urea. Podemos concluir que el incremento en la concentración de albúmina y en el pH puede enmascarar un mayor descenso del AG durante la sesión de HDF en línea. Tanto el lactato como la CAP descienden a lo largo de la sesión, esta última como consecuencia de la pérdida de fósforo por difusión y convección. El cálculo de un nuevo concepto de AG libre de interferencias de la CAA y CAP pueden ayudar a monitorizar el descenso de otros aniones inorgánicos (fundamentalmente el sulfato) derivados del catabolismo proteico (AU)

Exercise causes blood glutathione oxidation in chronic obstructive pulmonary disease: prevention by O2 therapy.

The aim of the present study was to determine whether glutathione oxidation occurs in chronic obstructive pulmonary disease (COPD) patients who perform exercise and whether this could be prevented. Blood glutathione red-ox ratio [oxidized-to-reduced glutathione (GSSG/ GSH)] was significantly increased when patients performed exercise for a short period of time until exhaustion. Their resting blood GSSG/GSH was 0.039 +/- 0.008 (SD) (n = 5), whereas after exercise it increased to 0.085 +/- 0.019, P < 0.01. Glutathione oxidation associated with exercise was partially prevented by oxygen therapy (resting value: 0.037 +/- 0.014, n = 5; after exercise: 0.047 +/- 0.016, n = 5, P < 0.01). We conclude that light exercise causes an oxidation of glutathione in COPD patients, which can be partially prevented by oxygen therapy.

Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L-cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

[Prediction of the tachycardia cycle based on auriculoventricular re-entry. Experimental study in dogs]. / Predicción del ciclo de la taquicardia por reentrada auriculoventricular. Estudio experimental en perros.

Seven anaesthesized mongrel dogs subject to thoracotomy were used in a electronic simile of A-V accessory pathway with retrograde conduction to generate reentrant tachycardias with different ventriculo-atrial delays. This was done both under control conditions and following amiodarone i.v. administration. The ability to predict tachycardia cycle length was studied, using a mathematical model of the circuit, in which the cycle length is obtained from the function of nodal conduction and the time of extranodal conduction of the circuit. An analysis was made of the repercussions in using four different mathematical functions describing nodal conduction: three were non-linear (exponential and hyperbolic A and B) and one linear. In the case of the first three, the consequences of using a direct non-linear data-fitting procedure or an indirect procedure by linear transformations of the functions were studied. The exponential and hyperbolic B functions provide a better prediction of tachycardia cycle length on being used in the model; in the case of these functions, a mean value of the squared differences between the real and estimated values of 19.1 +/- 31.0 ms2 and 19.1 +/- 26.7 ms2, respectively, was obtained.

[Quantification of concealed conduction in the atrioventricular node]. / Cuantificación de la conducción oculta en el nodo aurículo-ventricular.

Twenty-eight anaesthetized open-chest mongrel dogs were used. Programmed atrial pacing was used and Hisian electrograms recorded through endocavitary electro-catheters to study and quantify the concealed conduction of non-transmitted atrial impulses in the A-V node. An exponential model was used in three situations to quantify the nodal conduction during incremental atrial pacing: a) during 1:1 conduction, b) during 2:1 nodal block, and c) during pacing, coupling an atrial impulse delivered at fixed intervals and blocked in the A-V node to each transmitted impulse. The relation between intranodal conduction times was analyzed both with and without the presence of blocked impulses, and the quotient between the obtained functions in situations b, c and situation a was determined. In a subgroup of 13 dogs the study was repeated following pharmacological block of the autonomic nervous system. In dogs with autonomic block, this relation always tended to decrease when the atrial pacing rate increased. The variations in the group of dogs with intact autonomic nervous systems were not homogeneous. During pacing with coupled block impulses, the progressive removal of conduction curves obtained for each coupling interval with respect to those obtained during 1:1 transmission, expresses the interval with respect ot those obtained during 1:1 transmission, expresses the lesser influence of the blocked impulses on decreasing their coupling interval.

Effects of propafenone on induction and maintenance of atrioventricular nodal reentrant tachycardia.

Electrophysiologic studies were performed in 10 patients with atrioventricular (A-V) nodal reentrant paroxysmal supraventricular tachycardias (PSVT), before and after intravenous administration of propafenone (1.5 mg/kg). All patients utilized an A-V nodal slow pathway for anterograde conduction and an A-V nodal fast pathway for retrograde conduction of the reentrant impulse. Propafenone depressed retrograde fast pathway conduction which was manifested by: 1) complete V-A block at all ventricular paced cycle lengths after propafenone in 3 cases; 2) increase in mean +/- SD of ventricular paced cycle length producing V-A block from less than 308 +/- 37 ms to 432 +/- 63 ms in the remaining 7 patients. Nine of the 10 patients had induction of sustained PSVT before propafenone. In 7 of the 9, PSVT could not be induced or sustained after propafenone, reflecting depression of the retrograde fast pathway conduction with either absence of atrial echoes (5 patients) or induction of nonsustained PSVT, with termination occurring after the QRS (2 patients). In 1 patient, single atrial echoes were induced before propafenone but none were noted after the drug. In only 2 patients was a sustained PSVT inducible after propafenone. In conclusion, propafenone inhibited induction of sustained A-V nodal reentrant PSVT in most patients, reflecting depression of retrograde A-V nodal fast pathway conduction.

Function of atrioventricular node conduction: hyperbolic model.

Twenty four patients were subjected to an electrophysiologic clinical procedure. The conventional extrastimulus test was applied to verify the relation between conduction time increase through the atrioventricular node of the extrastimulus beat (delta AH), and its preceding interval (A1A2). Following the least square root method the parameters of the hyperbolic model delta AH.A1A2 = m . delta AH + n were adjusted. The correlation coefficients obtained and tested in all cases were very high and significant. From this hyperbolic equation it was possible to determine the equations for the effective refractory period (ERPe = m) and functional refractory period (FRPe = ERPe + n). The theoretical values for refractoriness approached very closely those of the actually measured ERP and FRP, in all cases. This model proved to be, in respect to adjustments and especially in calculating refractory periods, at least as good as the exponential model proposed previously by other authors.