Cardiorespiratory responses, nitric oxide production and inflammatory factors in patients with myocardial infarction after rehabilitation.

There is evidence that myocardial infarction (MI) patients have an inflammatory process that includes skeletal muscles, and exercise has been reported to reduce some inflammatory markers. The aim of this work was to study NO and some inflammatory markers in quadriceps muscle of MI patients before and after cardiac rehabilitation. Muscle biopsy was obtained in 17 MI patients before and after CR and only once in 11 healthy subjects. Several cardiorespiratory and metabolic parameters were evaluated and skeletal muscle levels of nitric oxide synthases, nitrate, nitrite, nitrotyrosine, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), interleukin- 6 (IL-6) and CD154. After CR there was an increase in maximal oxygen consumption (21.2 ±â€¯1.4 vs 25.7 ±â€¯2.5 mL/kg/min, P < 0.0001); work load (116.2 ±â€¯14.9 vs 140 ±â€¯17 W, P < 0.0001); pulmonary ventilation (59.8 ±â€¯7,5 vs 73.8 ±â€¯11.6 L/min, P < 0.0001); anaerobic threshold (53.8% ±â€¯3.5% vs 60.2% ±â€¯3.3% of maximal VO2, P < 0.0001), maximal lactatemia (8.1 ±â€¯1.4 vs 9.3 ±â€¯1.5 mmol/L, P < 0.0001), and oxygen pulse (11.7 ±â€¯1.6 vs 14.0 ±â€¯1.9 mL/pulse, P < 0.0001). CSA of type I fibers increased (4380 ±â€¯1868 vs 5237 ±â€¯1530 µm2, P = 0.02), and nitrate (18.6 ±â€¯3.04 vs 20.7 ±â€¯2.0 ng/mg, P < 0.001). There was a negative correlation between BMI, fat%, waist and hip circumferences and NO synthase, nitrite and nitrate after CR. The inflammatory mediators were higher in patients than in control subjects and did not change with CR. TGF-ß correlated directly with nitrite and nitrate and inversely to other inflammatory factors. In conclusion, there is an increase of nitrate post CR, indicating a more effective NO production. TGF-ß was related to anti-inflammatory processes even before CR.

Myopathy in patients with Hashimoto's disease.

Hashimoto thyroiditis (HT) is an autoimmune disease of the thyroid gland. Patients may present or not a hypothyroid state, and frequently have manifestations of myopathy. The present work was aimed to assess the clinical symptoms and signs of skeletal muscle alterations in HT, describe the muscular pathological changes and relate them to the functional thyroid status and to the autoimmune condition of the patient. Clinical and laboratory studies were performed in ten HT patients and three control subjects (hormonal levels and electromyography). Biopsies from their vastus lateralis of quadriceps femoris muscle were analyzed under light (histochemistry and immunofluorescense) and electron microscopy. All patients showed muscle focal alterations, ranging from moderate to severe atrophy, necrosis, activation of satellite cells, presence of autophagosomes, capillary alterations and macrophage and mast cell infiltration, common to autoimmune diseases. The intensity of clinical signs and symptoms was not related to the morphological muscle findings, the electromyography results, or to the state of the thyroid function. Reactions for immunoglobulin in muscle fibers were positive in 80% of the patients. Fiber type II proportion was increased in all patients, with the exception of those treated with L-thyroxine. In conclusion, autoimmune processes in several of the patients may be associated to the skeletal muscle alterations, independently of the functional state of the thyroid gland; however, fiber II type proportion could have been normalized by L-thyroxine treatment.

Myopathy in patients with Hashimoto´s Disease. / Miopatía en pacientes con enfermedad de Hashimoto

Hashimoto thyroiditis (HT) is an autoimmune disease of the thyroid gland. Patients may present or not a hypothyroid state, and frequently have manifestations of myopathy. The present work was aimed to assess the clinical symptoms and signs of skeletal muscle alterations in HT, describe the muscular pathological changes and relate them to the functional thyroid status and to the autoimmune condition of the patient. Clinical and laboratory studies were performed in ten HT patients and three control subjects (hormonal levels and electromyography). Biopsies from their vastus lateralis of quadriceps femoris muscle were analyzed under light (histochemistry and immunofluorescense) and electron microscopy. All patients showed muscle focal alterations, ranging from moderate to severe atrophy, necrosis, activation of satellite cells, presence of autophagosomes, capillary alterations and macrophage and mast cell infiltration, common to autoimmune diseases. The intensity of clinical signs and symptoms was not related to the morphological muscle findings, the electromyography results, or to the state of the thyroid function. Reactions for immunoglobulin in muscle fibers were positive in 80% of the patients. Fiber type II proportion was increased in all patients, with the exception of those treated with L-thyroxine. In conclusion, autoimmune processes in several of the patients may be associated to the skeletal muscle alterations, independently of the functional state of the thyroid gland; however, fiber II type proportion could have been normalized by L-thyroxine treatment.

La tiroiditis de Hashimoto (TH) es una enfermedad autoinmune de la glándula tiroides. Los pacientes pueden tener o no un estado hipotiroideo y suelen presentar manifestaciones de miopatía. Este trabajo estudia los síntomas y signos clínicos de alteración muscular esquelética que puedan estar presentes en pacientes con TH, describe los cambios patológicos musculares y los relaciona con el estado funcional de la glándula tiroides y la condición autoinmune del paciente. Diez pacientes y tres sujetos controles fueron examinados clínicamente, se midieron los niveles de hormonas tiroideas, se practicó electromiografía y se tomó biopsia del vasto lateral del músculo cuádriceps crural para microscopía de luz (histoquímica e inmunofluorescencia) y microscopía electrónica. Todos los pacientes mostraron alteraciones musculares focales, atrofia moderada a severa, presencia de autofagosomas (glucogenosomas), necrosis, activación de las células satélites, infiltración de macrófagos y mastocitos, así como alteraciones en los capilares, similares a las de las enfermedades autoinmunes. La intensidad de los signos y síntomas no estuvo relacionada con los hallazgos morfológicos en músculo, los resultados de la electromiografía ni con el estado funcional tiroideo. La reacción a las inmunoglobulinas fue positiva en el músculo de 80% de los pacientes. La proporción de fibras musculares tipo II estuvo incrementada en los pacientes excepto en aquellos que recibieron tratamiento con L-tiroxina. En conclusión, el proceso autoinmune hacia el músculo parece asociarse a las alteraciones en éste, independientemente del estado funcional tiroideo, sin embargo, la proporción de las fibras tipo II puede haber sido normalizada por el tratamiento con L-tiroxina.

[Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats]. / Estrés oxidativo en los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas.

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in micromol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-alpha) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 +/- 5.0 vs. 3.3 +/- 0.3, p<0.001; EDL 20.2 +/- 4.3 vs. 4.5 +/- 0.4, p<0.0037), iNOS (soleus 26.6 +/- 3.7 vs. 8.3 +/- 0.9; EDL 21.3 +/- 3.7 vs. 11.0 +/- 0.8, both p<0.0001) and TNF-alpha (soleus 2.2 +/- 0.5 vs. 0.6 +/- 0.1, p<0.05; EDL 1.9 +/- 0.2 vs. 0.6 +/- 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 +/- 1.4 vs. 30.3 +/- 1.2, p<0.00001); of nNOS (soleus 16.8 +/- 1.4 vs. 20.7 +/- 1.8, p< 0.05; EDL 13.6 +/- 1.3 vs. 21.9 +/- 1.8, p<.005) and nitrite in EDL (5.8 +/- 0.3 vs. 7.1 +/- 0.5, p<0.026).There was a positive correlation between TNF-alpha vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-alpha and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-alpha, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.

Estrés oxidativo en los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas / Oxidative stress in soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats

Las enfermedades sistémicas crónicas afectan el músculo esquelético, siendo la inflamación y el estrés oxidativo algunos de los mecanismos involucrados. El efecto de la hipertensión arterial esencial sobre el músculo esquelético no es bien conocido. Se estudiaron los músculos soleo y extensor digitorum longus (EDL) de ratas espontáneamente hipertensas (SHR), comparadas con las controles normotensas Wistar Kyoto (WKY). Se determinaron los niveles de nitritos y nitratos en µmoles/mg-proteína; las sintasas del óxido nítrico: endotelial (eNOS); neuronal (nNOS); e inducible (iNOS), nitrotirosina y el factor de necrosis tumoral-alfa (TNF-α) en ng/mg-proteína. En las SHR, en el soleo y el EDL respectivamente, se incrementó la nitrotirosina (24,4 ± 5,0 vs. 3,3 ± 0,3, p<0,001; 20,2 ± 4,3 vs. 4,5 ± 0,4, p<0,0037), iNOS (26,6 ± 3,7 vs. 8,3 ± 0,9; 21,3 ± 3,7 vs. 11,0 ± 0,8 ambos p<0,0001), y TNF-α (2,2 ± 0,5 vs. 0,6 ± 0,1, p<0,05; 1,9 ± 0,2 vs. 0,6 ± 0,1, p<0,02); hubo disminución de eNOS en el soleo (20,6 ± 1,4 vs. 30,3 ± 1,2, p<0,00001); de nNOS (soleo 16,8 ± 1,4 vs. 20,7 ± 1,8, p< 0,05; EDL 13,6 ± 1,3 vs. 21,9 ± 1,8, p<0,005) y de nitrito en el EDL (5,8 ± 0,3 vs. 7,1 ± 0,5, p<0,026). En las SHR se observó correlación positiva entre TNF-α vs. nitrotirosina: soleo (r=0,798; p<0,031) y tendencia en EDL (r=0,739; p<0,057); iNOS vs. nitrotirosina (soleo: r=0,908 p<0,0001; EDL: r=0,707; p=0,01), tendencia entre TNF-α vs. iNOS en EDL (r=0,736; p=0,059); y correlación negativa entre eNOS vs. nitrotirosina en soleo (r=-0,816; p=0,0012). En conclusión, las SHR presentan un proceso inflamatorio muscular, evidenciado por el incremento de TNF-α, nitrotirosina, e iNOS. La disminución de las sintasas constitutivas, con incremento de la iNOS es evidencia de la disfunción endotelial.

Systemic diseases affect skeletal muscle, and inflammation and oxidative stress are some of the involved mechanisms. There is scarce information about the effects of essential hypertension on skeletal muscle. The soleus and extensor digitorum longus (EDL) muscles of spontaneously hypertensive rats (SHR) were studied compared to control Wistar Kyoto (WKY) rats. The levels of nitrite and nitrate in µmol/mg-protein; endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) nitric oxide synthases, nitrotyrosine and tumour necrosis factor alpha (TNF-α) in ng/mg-protein were determined. Compared with controls, the SHR showed increased levels of nitrotyrosine (soleus 24.4 ± 5.0 vs. 3.3±0.3, p<0.001; EDL 20.2 ± 4.3 vs. 4.5 ± 0.4, p<0.0037), iNOS (soleus 26.6 ± 3.7 vs. 8.3 ± 0.9; EDL 21.3 ± 3.7 vs. 11.0 ± 0.8, both p<0.0001) and TNF-α (soleus 2.2 ± 0.5 vs. 0.6 ± 0.1, p<0.05; EDL 1.9 ± 0.2 vs. 0.6 ± 0.1, p<0.02). A decrease of eNOS was found in soleus muscle (20.6 ± 1.4 vs. 30.3 ± 1.2, p<0.00001); of nNOS (soleus 16.8 ± 1.4 vs. 20.7 ± 1.8, p< 0.05; EDL 13.6 ± 1.3 vs. 21.9 ± 1.8, p<0.005) and nitrite in EDL (5.8 ± 0.3 vs. 7.1 ± 0.5, p<0.026).There was a positive correlation between TNF-α vs. nitrotyrosine in soleus (r=0.798; p<0.031) and a tendency in EDL (r=0.739; p=0.059); iNOS vs. nitrotyrosine (soleus: r=0.908; p<0.0001; EDL: r=0.707; p<0.01), a tendency between TNF-α and iNOS (EDL: r=0.736; p<0.059); and a negative correlation between eNOS vs. nitrotyrosine in soleus muscle (r=-0.816; p<0.0012). In conclusion, in skeletal muscles of SHR an inflammatory process was found evidenced by the increase in TNF-α, nitrotyrosine and iNOS. The decreased levels of constitutive synthases, together with the higher level of iNOS, are indicative of endothelial dysfunction.

Gender and skeletal muscle characteristics in subjects with chronic obstructive pulmonary disease.

BACKGROUND: The influence of gender in the clinical expression of COPD has received important attention. Limited information exists regarding gender differences in the skeletal muscle characteristics in COPD subjects. The present study was aimed to determine the differences in the skeletal muscle characteristics in men and women with and without COPD. METHODS: For comparison we studied 24 female (61 ± 9 years) and 30 male (65 ± 8 years) COPD patients with similar disease severity. In addition healthy subjects, 17 women (58 ± 8 years), and 9 men (57 ± 8 years) were studied. Pulmonary function, health status, six minute walk distance test (6MWD) and vastus lateralis muscle biopsy were assessed. Fiber type proportion, fiber type cross sectional area (CSA), capillary counts, and activity of citrate synthase (CS), 3-hydroxyacyl-CoA-dehydrogenase (HAD) and lactate-dehydrogenase (LDH) were determined. RESULTS: Pulmonary function, health status and 6MWD were similar in male and female COPD patients. Fiber type distribution was similar between women (I = 42 ± 9%, IIA = 39 ± 13%, IIX = 19 ± 7%) and men (I = 39 ± 13%, IIA = 38 ± 9%, IIX = 29 ± 10%) with COPD, as well as CSA, capillarity and enzymes (CS 8.59 ± 1.6 vs.9.74 ± 2.6, HAD 9.03 ± 1.9 vs. 9.84 ± 2.5, LDH 124 ± 48 vs. 151 ± 68 µmol min(-1) g(-1)). In normal subjects a decrease in type IIX fibers CSA was found in women compared with men (3703 ± 1478 vs. 5426 ± 1386 µm(2), respectively). CONCLUSIONS: Female and male with COPD have similar skeletal muscle characteristics; it is possible that the disease blurs the gender differences. On the other hand, there seems to be fewer differences in muscle characteristics between older men and women, perhaps due to lower male testosterone levels and physical inactivity.

Different fibre populations distinguished by their calcium transient characteristics in enzymatically dissociated murine flexor digitorum brevis and soleus muscles.

Enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres from mouse were used to compare the kinetics of electrically elicited Ca2+ transients of slow and fast skeletal muscle fibres, using the fast Ca2+ dye MagFluo4-AM, at 20-22 degrees C. For FDB two Ca2+ transient morphologies, types I (MT-I, 11 fibres, 19%) and II (MT-II, 47 fibres, 81%), were found, the kinetic parameters (amplitude, rise time, half width, decay time, and time constants of decay) being statistically different. For soleus (n = 20) only MT-I was found, with characteristics similar to MT-I from FDB. Correlations with histochemically determined mATPase, reduced nicotinamide adenine dinucleotide diaphorase and alpha-glycerophosphate dehydrogenase activities, as well as immunostaining and myosin heavy chain electrophoretic analysis of both muscles suggest that signals classified as MT-I may correspond to slow type I and fast IIA fibres while those classified as MT-II may correspond to fast IIX/D fibres. The results point to the importance of Ca2+ signaling for characterization of muscle fibres, but also to its possible role in determining fibre function.

[Lactate dehydrogenase isozymes in skeletal muscle of patients with chronic obstructive pulmonary disease]. / Isoenzimas de lactatodeshidrogenasa en el músculo esquelético de pacientes con EPOC.

INTRODUCTION AND OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH(4) and LDH(5) are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. PATIENTS AND METHODS: Eighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. RESULTS: Controls and patients had similar concentrations of total LDH (mean [SE], 130 [30]micromol/min/g vs 152 [50]micromol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH(1), LDH(2), and LDH(3), with decreased LDH(5) levels; these patients were women and had a lower oxygen saturation. The LDH(5) level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH(3) and LDH(4) concentrations whereas type IIX fibers were inversely correlated with LDH(3) concentration. CONCLUSION: Measurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism.

Isoenzimas de lactatodeshidrogenasa en el músculo esquelético de pacientes con EPOC / Lactate Dehydrogenase Isozymes in Skeletal Muscle of Patients With Chronic Obstructive Pulmonary Disease

Introducción y objetivos. En los pacientes con enfermedad pulmonar obstructiva crónica (EPOC), las cifras de la enzima lactatodeshidrogenasa (LDH) en los músculos esqueléticos son normales o tienen cierta tendencia a aumentar; cuando dichos pacientes hacen ejercicio, los valores se elevan más rápidamente que en personas sin la enfermedad. Es probable que las concentraciones de las isoenzimas 4 y 5 de la LDH puedan estar aumentadas en estos pacientes, por lo que se han determinado las isoenzimas de la LDH en el músculo periférico de pacientes con EPOC. Pacientes y métodose ha estudiado a 18 pacientes con EPOC y a 10 personas sanas no fumadoras. Se les realizaron pruebas de función pulmonar, la prueba de la marcha de 6min y biopsia del músculo cuádriceps para medir tanto la LDH total como las isoenzimas de la LDH por electroforesis en gel de agarosa, así como para clasificar los tipos de fibras. Resultadoslas concentraciones de LDH total (media¡Àerror estándar: 130¡À30 frente a 152¡À50¦Ìmol/min/g) y sus isoenzimas fueron similares en controles y pacientes. Un subgrupo de 5 pacientes mostró un aumento de las isoenzimas LDH1, LDH2 y LDH3, con disminución de la LDH5; estos pacientes eran mujeres y tenían menor saturación de oxígeno. El valor de la LDH5 se relacionó directamente con la prueba de la marcha de 6min y la saturación de oxígeno. El porcentaje de fibras IIA mostró una correlación directa con la concentración de LDH3 y LDH4, y las fibras IIX se relacionaron inversamente con la LDH3. Conclusión. A partir de las concentraciones de las isoenzimas de la LDH se pudo identificar a un subgrupo de pacientes con una concentración mayor de las isoenzimas cardíacas y menor de las musculares, lo que eventualmente podría representar una adaptación que favorezca el metabolismo aeróbico(AU)

Introduction and Objectives. In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH4 and LDH5 are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. Patients and MethodsEighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. ResultsControls and patients had similar concentrations of total LDH (mean [SE], 130 [30]¦Ìmol/min/g vs 152 [50]¦Ìmol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH1, LDH2, and LDH3, with decreased LDH5 levels; these patients were women and had a lower oxygen saturation. The LDH5 level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH3 and LDH4 concentrations whereas type IIX fibers were inversely correlated with LDH3 concentration. ConclusionMeasurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism(AU)

Morphological alterations in skeletal muscle of spontaneously hypertensive rats.

The Extensor digitorum longus (EDL) and the soleus muscles of spontaneously hypertensive rats (SHR) were studied in comparison with those of their normal counterparts, the Wistar Kyoto (WKY) rats. Quantitative assessment of capillaries and muscle fibre typing was done with optical microscopy, while the study of capillary abnormalities was performed by ultrastructural observation. There were no differences in fibre type proportion or in capillarity indexes between the SHR and the control rats. A reduction in the area of IIB fibres was found in the EDL muscle of the hypertensive animals. The ultrastructural study showed abnormalities in the capillaries of both muscles in SHR, the cross section of the endothelial cells was enlarged; there was irregular distribution of caveolae and pinocytic vesicles, the capillary basement membrane showed irregular width, with parts engrossed and reduplicated. Some pericytes were prominent. There were macrophages present in the interstitial space. In some muscle fibres there was disorganization of the sarcomere structure, swelling of the sarcotubular system, abundant autophagic vacuoles, and proliferative satellite cells. There were abundant collagen fibrils. The presence of cellular rests, autophagic vacuoles and loss of sarcolemma indicated necrosis. It can be concluded, that in SHR, muscle capillaries showed alterations that may be the substrate of functional rarefaction, although anatomical rarefaction (number reduction) could not be demonstrated. In EDL and soleus muscles of SHR, signs of a mild myopathy with focal fibrosis were present.

La prescripción de ejercicio físico en pacientes cardíacos: características y estructura del programa / The physical exercise prescription in cardiac patients: characteristics and structure of the program

La rehabilitación cardíaca ha demostrado ser uno de los elementos, en términos prospectivos, más eficaces para mejorar la capacidad física del paciente cardíaco, disminuir los factores de riesgo, mejorar la calidad de vida, reducir la dosis o número de medicamentos después de un evento isquémico y facilitar la incorporación más temprana a la actividad laboral en mejores condiciones. Entre los componentes que integran la rehabilitación cardíaca: educación, asesoramiento nutricional, asistencia psicológica, orientación vocacional y/o laboral y ejercicio, este último, adquiere la mayor importancia por ser el componente que de forma más temprana y efectiva aumenta la capacidad física del paciente, proporcionándole seguridad e independencia en sus actividades personales y profesionales, y un mayor grado de responsabilidad y participación en su entorno social y familiar. En esta revisión se presentan las pautas recomendadas por las organizaciones profesionales relacionadas con la rehabilitación cardíaca más prestigiosas y confiables del mundo médico, que proponemos sean consideradas en la planificación, organización y ejecución de los programas de rehabilitación en nuestro país, adaptándolas a las condiciones existentes de cada centro donde se realice.

Cardiac rehabilitation has proven to be prospectively an effective element in heart disease patients to endurance functional capacity, diminish risk factors, improve quality of life, reduce dosing and number of medications after an acute event and facilitate an early incorporation to daily labor activities in the best of conditions. Of the elements that compose cardiac rehabilitation one can mention; education, nutritional counseling, psychological assistance, vocational orientation and exercise, the latter being of great significance as responsible of an early and effective improvement of physical capacity that leads to self insurance and independence for personal and professional duties with a greater degree of responsibility and participation in social and family environments. In the following review, guidelines from the most important and trusted professional organizations in the field of cardiac rehabilitation are presented along with a proposal for their use in the planning, organizing and execution of cardiac rehabilitation programs in our country, adjusting them to the existing conditions where to be implemented.

Morphological alterations in skeletal muscle of spontaneously hypertensive rats

Se estudiaron los músculos Extensor digitorum longus (EDL) y soleus de ratas espontáneamente hipertensas (SHR), comparándolas con ratas normotensas Wistar Kyoto (WKY). La evaluación cuantitativa de los capilares y la clasificación de las fibras musculares se hizo con microscopía de luz, mientras que el estudio ultraestructural permitió visualizar cambios morfológicos. No se encontraron diferencias en la proporción de los tipos de fibras, o en los índices de capilaridad entre las ratas controles y las SHR. Una reducción del área de las fibras IIB se encontró en el músculo EDL de las SHR. El estudio ultraestructural mostró anormalidades en los capilares de ambos músculos en las SHR; en las secciones transversales de células endoteliales se observó engrosamiento del citoplasma, además distribución irregular de caveolas y vesículas pinocíticas, la membrana basal capilar mostró una anchura irregular, con algunas partes engrosadas y reduplicadas. Algunos pericitos fueros prominentes. En el espacio intersticial se encontraron macrófagos. En algunas fibras se hallaron sarcómeros estructuralmente desorganizados, el sistema sarcotubular hinchado, abundantes vacuolas autofágicas, y células satélites proliferativas. Las fibrillas de colágeno fueron abundantes. La presencia de restos celulares, vacuolas autofágicas y la pérdida del sarcolema, indicaron necrosis muscular. Se puede concluir que, aun cuando no se demostró la rarefacción anatómica (disminución numérica) en las SHR, los capilares musculares estaban alterados, lo cual puede ser el sustrato de la rarefacción funcional. En los músculos EDL y soleo de las SHR, los signos de una miopatía leve con fibrosis focal estuvieron presentes.

Peripheral muscle alterations in non-COPD smokers.

BACKGROUND: Although tobacco smoke is the main cause of COPD, relatively little attention has been paid to its potential damage to skeletal muscle. This article addresses the effect of smoking on skeletal muscle. METHODS: The vastus lateralis muscle was studied in 14 non-COPD smokers (FEV(1)/FVC, 78 +/- 5%) and 20 healthy control subjects (FEV(1)/FVC, 80 +/- 3%). Muscular structure, enzyme activity, constitutive and inducible nitric oxide (NO) synthases (endothelial NO oxide synthase [eNOS], neuronal NO synthase [nNOS] and inducible NO synthase [iNOS]), nitrites, nitrates, nitrotyrosine, and the presence of macrophages were analyzed. RESULTS: In smokers, type I muscle fibers cross-sectional area was decreased, and a similar trend was found in type IIa fibers. Lactate dehydrogenase levels and the percentage of fibers with low oxidative and high glycolytic capacity were increased in smokers. nNOS (96.9 +/- 11.7 vs 125.4 +/- 31.9 ng/mg protein; p < 0.01) and eNOS (38.9 +/- 11.0 vs 45.2 +/- 7.7 ng/mg protein [+/- SD]; p < 0.05) were lower in smokers, while fiber type distribution, capillarity measures, beta-hydroxy-acyl-CoA-dehydrogenase levels, iNOS, nitrite, nitrate, and nitrotyrosine levels, and macrophage number in the muscle tissue were similar to the nonsmoker subjects. CONCLUSIONS: Smokers presented some alterations of skeletal muscle such as oxidative fiber atrophy, increased glycolytic capacity, and reduced expression of the constitutive NO synthases (eNOS and nNOS). The findings support some muscular structural and metabolic damage but not the presence of local inflammation in the smokers. In addition, they suggest a possible effect of tobacco smoke impairing the normal process of NO generation.

Carazterísticas musculares y potencia anaeróbica y aeróbica máximas en ciclistas de competición / Muscle characteristics and anaerobic and aerobic maximal power in competence cyclists

Se estudiaron 15 ciclistas de la selección del Estado Lara de Venezuela, 9 del sexo masculino y 5 del femenino, de 20± 2 años. Siete eran fondistas, 4 semifondistas y 4 velocistas. La potencia aeróbica fue evaluada por el consumo máximo de oxígeno (VO2 max), la potencia anaeróbica lactácida por la prueba de Wingate y la potencia anaeróbica alactácida por la prueba del salto vertical. Se practicó biopsia del músculo cuadriceps para la clasificación de los tipos de fibras, evaluación de los capilares y determinación de las enzimas citrato sintetasa (CS), ß-hidroxiacil-CoA-deshidrogenasa(HAD) y deshidrogenasa láctica (LDH). El grupo masculino alcanzó mayores valores en todas las pruebas, excepto en el índice de fatiga en el que no difirió del grupo femenino. El músculo mostró niveles más altos de CS en los hombres y fue similar en área de las fibras y en capilaridad respecto a las mujeres. Los fondistas mostraron mayor proporción de fibras tipo I (63±7 %), mayor nivel de CS (29,2±5,5 μmol/min.gr) y mayor densidad capilar (417±31capilares /mm2). Los mediofondistas presentaron mayor porcentaje de fibras tipo IIa (50±5 %). Se encontró correlación entre la CS y los Watts/kg en la prueba del salto (r=0,55), entre la HAD y la potencia promedio/kg en Wingate (r=0,69)y entre la LDH y los resultados de Wingate (r=0,52 a r=0,60).En conclusión, las potencias aeróbica y anaeróbica de los ciclistas del grupo estudiado parecen estar más relacionadas con los efectos del entrenamiento en el músculo, que con su composición miofibrilar (AU)

A group of Venezuelan cyclists from the Lara State selection, aged 20 ± 2 years, formed by 9 males and 5 females, wasstudied. Seven of them were long-distance cyclists, 4 sprinters and 4 middle-distance cyclists. Maximal aerobic power(VO2 max) was evaluated, as well as lactacid (Wingate test) and alactacid power (vertical jump test). A quadriceps musclebiopsy was taken for muscle fiber classification, assessment of capillaries and determination of the enzymes citrate synthase (CS), ß-hydroxacil-CoA-dehydrogenase (HAD) and lactic dehydrogenase (LDH). The male group showed higher values in all tests, except in fatigue index, which was similar to the female group. CS muscle levels were higherin men, but there were not differences in fiber area and capillarity compared to females. The highest percentage in typeI fibers was found in the long-distance cyclists (63±7 %), also the most elevated CS level (29.2±5.5 μmol/min.gr) and the highest capillary density (417±31 capillaries/mm2). Middle-distance cyclists showed the highest proportion of IIafiber type (50±5 %). There was a direct correlation between CS level and Watts/Kg in the jumping test (r=.55), in the HAD level and mean power/Kg in Wingate test (r=0.69), and between LDH level and the all the results of the Wingatetest (r=0.52 to r=0.60).In conclusion, in this group of cyclist, aerobic and anaerobic power tests seemed to be more related to muscle changes due to training that to muscle fiber type proportions (AU)

Alteraciones musculares periféricas en la enfermedad de Chagas

La enfermedad de Chagas sigue siendo un problema en Venezuela y en varios países de Latinoamérica. Este trabajo presenta datos sobre las alteraciones que esta enfermedad produce en los músculos esqueléticos periféricos, lo cual puede contribuir a la incapacidad funcional que presentan muchos de los pacientes. Fueron estudiados 19 pacientes con enfermedad avanzada, a quienes se les hizo evaluación cardiorrespiratoria, ecocardiograma, prueba de ejercicio y biopsia del músculo cuádriceps. El 42% presentó incapacidad funcional moderada a severa, medida por el consumo máximo de oxígeno, que estuvo relacionada con cambios morfológicos y metabólicos en las fibras musculares. Se hallaron alteraciones en la microvasculatura muscular compatibles con daño autoinmune. En conclusión, los pacientes con enfermedad de Chagas sufren alteraciones en la musculatura periférica que puede contribuir a la incapacidad funcional y al grado de afectación por esta enfermedad. La determinación de la capacidad funcional debería agregarse a la evaluación de la enfermedad

Chagas disease is still a problem in Venezuela and other Latin American countries, in spite of efforts to control the disease. Peripheral muscle alterations that contribute to decreased functional capacity in moderate to advanced Chagas’ disease patients are analyzed in the present work. Nineteen Chagas’ disease patients were studied, including cardio-respiratory evaluation, echocardiogram, exercise test and quadriceps muscle biopsy. The results showed 42% patients with moderate to severe decrease of maximal oxygen consumption. Muscle biopsies presented morphologic and metabolic alterations, some related to functional capacity. Capillary vessel damage in muscle was similar to that found in autoimmune diseases. In conclusion, Chagas’ disease patients showed peripheral muscle alterations related to decreased functional capacity. The functional capacity changes may contribute to the severity of the disease and should be added to the evaluation of the patients

Contribución al conocimiento de una patología (síndrome parapléjico bovino) de la ganadería extensiva de los Llanos de Venezuela: parte II: estudio etiopatogénico y estrategias de control / Contribution to the knowledge of an illness (paraplegic syndrome) of the livestock at the Venezuela’s plains: part II: etiopathogenic study and strategies for control

En los llanos venezolanos, que abarcan unos 12 millones de hectáreas tienen asiento los sistemas de producción cría-levante y vaca-maute. Los animales pastorean en sabanas de suelos ácidos donde predominan comunidades de pastos del género Trachypogon, Axonopus y Andropogon, para sostener a unos 8 millones de cabezas de mestizo cebú x criollo. Las condiciones ambientales y de manejo de estas llanuras no son las más idóneas para sostener una ganadería de carne fuertemente mestizada, debido a que innovaciones tecnológicas no han sido incorporadas para mejorar el manejo cualitativo de los rebaños y, en general, la eficiencia de estos sistemas de producción. Un modelo de investigación integral, que implicó realizar estrategias de investigación: aplicada, básica y operativa, en fincas de los productores afectados por el síndrome parapléjico bovino (SPB) acompañado de un conjunto de estrategias en un paquete de mínimas tecnologías (PMT) para ser adoptado por los ganaderos. Se evaluó prioritariamentela situación nutricional y el manejo integral de los animales, se corrigieron las deficiencias detectadas; reflejándose su eficacia en indicadores bioproductivos del rebaño como: edad al primer parto, índice de preñez, índice de natalidad e índice de mortalidad. Además, fueron realizados estudios etiopatogénicos basados en estudios submicroscópicos e histoquímicas de fibras musculares de animales enfermos comparadas con las de animales sanos. Los resultados confirmaron: 1. El SPB es un trastorno de origen multifactorial estrechamente vinculado a deficiencia de minerales, especialmente fósforo, 2. La elevación del patrón tecnológico con el paquete de mínima tecnología (PMT) en los sistemas de producción extensiva, además de erradicar el SPB, aumenta significativamente su eficiencia.

Peripheral muscle composition and health status in patients with COPD.

STUDY OBJECTIVE: The present study evaluated the relationship between health status (HS) and peripheral muscle histochemical characteristics in chronic obstructive pulmonary disease (COPD), and identified selected independent respiratory and extrapulmonary variables that predicted the HS of these patients. DESIGN: Cross-sectional study. SETTING: Outpatient respiratory clinic of a university hospital. PATIENTS AND METHODS: We studied 29 patients (63+/-10 yrs) with a forced expiratory volume in 1s (FEV1) of 39+/-12%. All patients underwent vastus lateralis muscle biopsies for histochemical analysis. They also had spirometry, arterial blood gas analysis, body mass index (BMI), dyspnea determined with the MMRC scale and responded to the St. George's Respiratory Questionnaire (SGRQ) for HS assessment. RESULTS: SGRQ total score correlated with fiber type distribution. A stepwise multiple regression identified three independent predictors of SGRQ total score: type I fiber proportion, BMI, and FEV1; r = 0.78 and r2 = 0.61. CONCLUSIONS: These results indicate that impaired HS in COPD is related to the peripheral muscle changes characterized by less type I fibers proportion. The findings argue in favor of an important contribution of the systemic consequences on the HS in COPD independently from the airflow limitation severity, and help to explain the observation of the poor correlation between the degree of airflow limitation and SGRQ total score.

Muscle arteriolar and venular reactivity in two models of hypertensive rats.

This study was designed to test if skeletal muscle fiber composition could influence vascular response in hypertensive rats. Muscle vessels were observed by intravital microscopy in anesthetized rats and changes in diameter were measured after local administration of endothelium-dependent and -independent vasodilators. Vascular reactivity was compared in two models of hypertension deoxicorticosterone acetate and salt load (DOCA-s) hypertensive rats and spontaneously hypertensive rats (SHR). The muscles used were: the fast-twitch glycolytic muscle, extensor digitorum longus (EDL), and the slow-twitch oxidative, soleus muscle. Maximal dilation induced by vasoactive drugs was of similar magnitude in EDL and soleus arterioles. Terminal arteriole reactivity to acetylcholine and adenosine was blunted in EDL (35% and 49% reduction, respectively) and soleus muscles (42% and 34% reduction, respectively) of SHR compared with Wistar Kyoto rats. Reactivity of DOCA-s rats to acetylcholine, adenosine, and sodium nitroprusside was reduced by 38%, 50%, 39% in EDL third- and fourth-order arterioles and by 30%, 38%, 38% in soleus fourth-order arterioles, respectively. These studies show that hypertension probably induced similar vascular changes in both muscles studied. Vascular reactivity is blunted for some vasodilator drugs and is more affected in DOCA-s rats. In addition, a preferential action for bradykinin was observed on upstream arterioles but not on venules. This effect was not observed for adenosine.

Capillary damage in skeletal muscle in advanced Chagas' disease patients.

The damage to skeletal muscle capillaries in advanced Chagas' disease (stages II and III) was investigated in the vastus lateralis muscle of six patients and compared to that of six normal subjects. Capillaries were visualized by the PAS-amylase reaction and muscle fibres were classified by the ATPase histochemical method. Transmission electron microscopy was used to look for capillary alterations. The capillary-to-fibre ratio and number of capillaries adjacent to type I and type IIa fibres were decreased in the patient group. At the ultrastructural level, all patients showed capillary abnormalities, mainly basement membrane thickening and reduplication, capillary occlusion, proliferative endothelial cell cytoplasm with dense bodies, large vacuoles, altered mitochondria and prominent rough endoplasmic reticulum, as well as pericyte abnormalities. Capillary alterations are similar to those in patients affected by autoimmune diseases, suggesting an autoimmune component in the chronic phase of this disease. The reduction in capillarity may contribute to altered muscle performance in these patients.

Exercise performance and skeletal muscles in patients with advanced Chagas disease.

STUDY OBJECTIVE: This study was designed to evaluate the peripheral muscle metabolic and structural characteristics in patients with advanced Chagas disease (ChD), and whether they were related with exercise performance. DESIGN: Cross-sectional study. SETTING: Outpatient cardiomyopathy clinic of a university hospital. PATIENTS AND METHODS: We studied 11 stage II patients, 8 stage III patients, and 11 healthy volunteers. All patients underwent exercise testing and peripheral muscle biopsies. The muscles were also studied in control subjects. Muscle biopsy specimens were analyzed for histochemical characteristics. In six patients, the muscle was studied ultrastructurally. RESULTS: The data demonstrate more glycolytic and less oxidative capacity of the peripheral muscle in patients with advanced ChD (increased proportion of type IIb fibers, increased proportion of fibers with low nicotinamide adenine dinucleotide diaphorase activity, high proportion of darkly stained fibers for alpha-glycerophosphate dehydrogenase activity, and lower levels of citrate synthase). Many capillaries in patients with ChD had an abnormal aspect: they were either closed or showed a thicker wall. The ultrastructural study also showed fiber atrophy and abnormal capillaries even in patients with normal functional capacity. Some muscle characteristics (enzyme activity, mean cross-sectional area of the fiber, and capillarity) related with exercise parameters (anaerobic threshold, and peak oxygen pulse). CONCLUSIONS: These findings indicate that patients with advanced ChD have decreased oxidative capacity and a shift to anaerobic metabolism in the skeletal muscle. They also suggest that muscular abnormalities are related to oxygen delivery, which is probably reduced in part by the abnormal muscle microvasculature. Those changes could affect oxygen extraction, and therefore exercise tolerance in these patients.