ABSTRACT
We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.
Subject(s)
Mesenchymal Stem Cell Transplantation , Myocardial Infarction/therapy , Physical Conditioning, Animal , Animals , Calcium/metabolism , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Diastole , Echocardiography , Gene Expression , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Myocardial Contraction/physiology , Myocardial Infarction/genetics , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Myocardium/metabolism , Myocardium/pathology , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Physical Endurance , Rats , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Systole , Ventricular RemodelingABSTRACT
Este estudo investigou os efeitos do treinamento em corrida de baixa intensidade (TCBI) sobre propriedades estruturais e mecânicas da epífise proximal do fêmur de ratas osteopênicas. Ratas Wistar [idade = 20 semanas; massa corporal = 271,42 ± 17,6 g] foram submetidas à ovariectomia (OVX) ou laparotomia (SHAM) e alocadas em quatro grupos: corrida OVX (CO, n = 12), controle OVX (CONO, n = 12), corrida SHAM (CS, n = 12) e controle SHAM (CONS, n = 12). Quinze dias pós-cirurgia, os grupos CO e CS foram submetidos ao TCBI em esteira (16 m/min, 60 min/dia, cinco dias/semana) por 10 semanas. O TCBI não alterou os efeitos deletérios da osteopenia induzida por ovariectomia sobre a densidade mineral do fêmur, a quantidade de osso trabecular no trocanter e colo do fêmur, a tenacidade e a força máxima de fratura do colo do fêmur de ratas.
This study investigated the effects of low-intensity running training (LIRT) on the structural and mechanical properties of the proximal femoral epiphysis in osteopenic female rats. Female Wistar rats [age = 20 weeks, body mass = 271.42 ± 17.6 g] were subjected to ovariectomy (OVX) or laparotomy (SHAM) and divided into four groups: running OVX (RO, n = 12), control OVX (CO, n = 12), running SHAM (RS, n = 12) and control SHAM (CS, n = 12). Two weeks after surgery RO and RS groups were submitted to a progressive LITR on a treadmill (60 min / day, 5 days / week) for 10 weeks. The LIRT did not alter the deleterious effects induced by ovariectomy on the femoral bone mineral density, the quantity of trabecular bone in the femoral great trocanter and neck, and femoral neck tenacity and resistance to fracture in female rats.
Este estudio investigó los efectos del entrenamiento en carera de baja intensidad (ECBI) en las propiedades estructurales y mecánicas de la epífisis proximal femoral de ratas osteopénicas. Ratas Wistar con edad de 20 semanas (peso corporal: 271.42 ± 17,6 g) fueran sometidas a ooforectomía (OVX) o laparotomía (SHAM) y asignados en cuatro grupos: carera OVX (CO, n = 12), control OVX (CONO, n = 12), carera SHAM (CS, n = 12) y control SHAM (CONS, n = 12). Quince días después de la cirugía los grupos CO y CS fueran sometidos al ECBI (16 m/ min; 60 min/día, 5 dias/semana) durante 10 semanas. El ECBI no cambió los efectos deletéreos de la osteopenia inducida por ooforectomía sobre la densidad mineral del fémur, la cantidad de hueso trabecular en el trocánter y cuello del fémur, la tenacidad y la resistencia ósea a la fractura del cuello del fémur de ratas.
ABSTRACT
We tested the effects of low-intensity endurance training (LIET) on the structural and mechanical properties of right (RV) and left ventricular (LV) myocytes. Male Wistar rats (4 mo old) were randomly divided into control (C, n = 7) and trained (T, n = 7, treadmill running at 50-60% of maximal running speed for 8 wk) groups. Isolated ventricular myocyte dimensions, contractility, Ca(2+) transients {intracellular Ca(2+) concentration ([Ca(2+)]i)}, and ventricular [Ca(2+)]i regulatory proteins were measured. LIET augmented cell length (C, 152.5 ± 2.0 µm vs. T, 162.2 ± 2.1 µm; P < 0.05) and volume (C, 5,162 ± 131 µm(3) vs. T, 5,506 ± 132 µm(3); P < 0.05) in the LV but not in the RV. LIET increased cell shortening (C, 7.5 ± 0.3% vs. T, 8.6 ± 0.3%; P < 0.05), the [Ca(2+)]i transient amplitude (C, 2.49 ± 0.06 F/F0 vs. T, 2.82 ± 0.06 F/F0; P < 0.05), the expression of sarcoplasmic reticulum Ca(2+)-ATPase 2a (C, 1.07 ± 0.13 vs. T, 1.59 ± 0.12; P < 0.05), and the levels of phosphorylated phospholamban at serine 16 (C, 0.99 ± 0.11 vs. T, 1.34 ± 0.10; P < 0.05), and reduced the total phospholamban-to-sarcoplasmic reticulum Ca(2+)-ATPase 2a ratio (C, 1.19 ± 0.15 vs. T, 0.40 ± 0.16; P < 0.05) in the LV without changing such parameters in the RV. In conclusion, LIET affected the structure and improved the mechanical properties of LV but not of RV myocytes in rats, helping to characterize the functional and morphological changes that accompany the endurance training-induced cardiac remodeling.
Subject(s)
Myocytes, Cardiac/physiology , Physical Conditioning, Animal/physiology , Physical Endurance/physiology , Animals , Blotting, Western , Calcium Signaling/physiology , Calcium-Binding Proteins/metabolism , Calcium-Transporting ATPases/metabolism , Cell Separation , Heart Ventricles/cytology , In Vitro Techniques , Male , Muscle Contraction/physiology , Myocardial Contraction/physiology , Myocytes, Cardiac/ultrastructure , Rats , Rats, Wistar , Running , Ventricular Function, Right/physiologyABSTRACT
The aim of the present study was to verify the effects of low-intensity endurance training and detraining on the mechanical and molecular properties of cardiomyocytes from spontaneously hypertensive rats (SHRs). Male SHRs and normotensive control Wistar rats at 16-weeks of age were randomly divided into eight groups of eight animals: NC8 and HC8 (normotensive and hypertensive control for 8weeks); NT8 and HT8 (normotensive and hypertensive trained at 50-60% of maximal exercise capacity for 8weeks); NC12 and HC12 (normotensive and hypertensive control for 12weeks); NDT and HDT (normotensive and hypertensive trained for 8weeks and detrained for 4weeks). The total exercise time until fatigue (TTF) was determined by a maximal exercise capacity test. Resting heart rate (RHR) and systolic arterial pressure (SAP) were measured. After the treatments, animals were killed by cervical dislocation and left ventricular myocytes were isolated by enzymatic dispersion. Isolated cells were used to determine intracellular global Ca(2+) ([Ca(2+)]i) transient and cardiomyocyte contractility (1Hz; ~25°C). [Ca(2+)]i regulatory proteins were measured by Western blot, and the markers of pathologic cardiac hypertrophy by quantitative real-time polymerase chain reaction (q-RT-PCR). Exercise training augmented the TTF (NC8, 11.4±1.5min vs. NT8, 22.5±1.4min; HC8, 11.7±1.4min vs. HT8, 24.5±1.3min; P<0.05), reduced RHR (NT8initial, 340±8bpm vs. NT8final, 322±10bpm; HT8initial, 369±8bpm vs. HT8final, 344±10bpm; P<0.05), and SBP in SHR animals (HC8, 178±3mmHg vs. HT8, 161±4mmHg; P<0.05). HC8 rats showed a slower [Ca(2+)]i transient (Tpeak, 83.7±1.8ms vs. 71.7±2.4ms; T50%decay, 284.0±4.3ms vs. 264.0±4.1ms; P<0.05) and cell contractility (Vshortening, 86.1±6.7µm/s vs. 118.6±6.7µm/s; Vrelengthening, 57.5±7.4µm/s vs. 101.3±7.4µm/s; P<0.05), and higher expression of ANF (300%; P<0.05), skeletal α-actin (250%; P<0.05) and a decreased α/ß-MHC ratio (70%; P<0.05) compared to NC8. Exercise training increased [Ca(2+)]i transient (NC8, 2.39±0.06F/F0 vs. NT8, 2.72±0.06F/F0; HC8, 2.28±0.05F/F0 vs. HT8, 2.82±0.05F/F0; P<0.05), and cell contractility (NC8, 7.4±0.3% vs. NT8, 8.4±0.3%; HC8, 6.8±0.3% vs. HT8, 7.8±0.3%; P<0.05). Furthermore, exercise normalized the expression of ANF, skeletal α-actin, and the α/ß-MHC ratio in HT8 rats, augmented the expression of SERCA2a (NC8, 0.93±0.15 vs. NT8, 1.49±0.14; HC8, 0.83±0.13 vs. HT8, 1.32±0.14; P<0.05) and PLBser16 (NC8, 0.89±0.18 vs. NT8, 1.23±0.17; HC8, 0.77±0.17 vs. HT8, 1.32±0.16; P<0.05), and reduced PLBt/SERCA2a (NC8, 1.21±0.19 vs. NT8, 0.50±0.21; HC8, 1.38±0.17 vs. HT8, 0.66±0.21; P<0.05). However, all these adaptations returned to control values within 4weeks of detraining in both SHR and normotensive control animals. In conclusion, low-intensity endurance training induces positive benefits to left ventricular myocyte mechanical and molecular properties, which are reversed within 4weeks of detraining.
Subject(s)
Hypertension/therapy , Myocardial Contraction , Myocytes, Cardiac/physiology , Animals , Atrial Natriuretic Factor/genetics , Atrial Natriuretic Factor/metabolism , Calcium Signaling , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cells, Cultured , Exercise Therapy , Gene Expression , Heart Ventricles/metabolism , Heart Ventricles/physiopathology , Hypertension/metabolism , Hypertension/physiopathology , Hypertrophy, Left Ventricular/metabolism , Hypertrophy, Left Ventricular/pathology , Hypertrophy, Left Ventricular/physiopathology , Male , Myosin Heavy Chains/metabolism , Physical Conditioning, Animal , Physical Endurance , Rats , Rats, Inbred SHR , Rats, Wistar , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolismABSTRACT
FUNDAMENTO: A capacidade aeróbica é fundamental para o desempenho físico, e a baixa capacidade aeróbica está relacionada ao desencadeamento de diversas doenças cardiovasculares. OBJETIVO: Comparar a contratilidade e a morfologia de cardiomiócitos isolados de ratos com baixo desempenho e desempenho padrão para o exercício físico. MÉTODOS: Ratos Wistar, com 10 semanas de idade, foram submetidos a um protocolo de corrida em esteira até a fadiga, e foram divididos em dois grupos: Baixo Desempenho (BD) e Desempenho Padrão (DP). Em seguida, após eutanásia, o coração foi removido rapidamente e, por meio de dissociação enzimática, os cardiomiócitos do ventrículo esquerdo foram isolados. O comprimento celular e dos sarcômeros e a largura dos cardiomiócitos foram medidos usando-se um sistema de detecção de bordas. Os cardiomiócitos isolados foram estimulados eletricamente a 1 e 3 Hz e a contração celular foi medida registrando-se a alteração do seu comprimento. RESULTADOS: O comprimento celular foi menor no grupo BD (157,2 ± 1,3µm; p < 0,05) em relação ao DP (161,4 ± 1,3 µm), sendo o mesmo resultado observado para o volume dos cardiomiócitos (BD, 25,5 ± 0,4 vs. DP, 26,8 ± 0,4 pL; p < 0,05). Os tempos para o pico de contração (BD, 116 ± 1 vs. DP, 111 ± 2ms) e para o relaxamento total (BD, 143 ± 3 vs. DP, 232 ± 3 ms) foram maiores no grupo BD. CONCLUSÃO: Conclui-se que os miócitos do ventrículo esquerdo dos animais de baixo desempenho para o exercício físico apresentam menores dimensões que os dos animais de desempenho padrão, além de apresentarem perdas na capacidade contrátil.
BACKGROUND: Aerobic capacity is essential to physical performance, and low aerobic capacity is related to the triggering of various cardiovascular diseases. OBJECTIVE: To compare the morphology and contractility of isolated rat cardiomyocytes with low performance and standard performance for exercise. METHODS: Wistar rats with 10 weeks of age underwent a protocol of treadmill running to fatigue, and were divided into two groups: Low Performance (LP) and Standard Performance (SP). Then, the animals were sacrificed, the heart was quickly removed and, by means of enzymatic dissociation, left ventricular cardiomyocytes were isolated. The cell and sarcomeres length and width of cardiomyocytes were measured using an edge detection system. The isolated cardiomyocytes were electrically stimulated at 1 and 3 Hz and cell contraction was measured by registering the change of their length. RESULTS: The cell length was shorter in the LP group (157.2 1.3µm; p < 0.05) compared to SP (161.4 1.3µm), and the same result was observed for the volume of cardiomyocytes (LP, 25.5 0.4. vs. SP, 26.8 ± 0.4 pL; p < 0.05). The time to peak contraction (LP, 116 1 vs. SP 111 2ms) and total relaxation (LP, 143 3 vs. SP 232 3ms) were higher in the LP group. CONCLUSION: We conclude that left ventricular myocytes of animals with low performance for exercise are smaller than animals with standard performance. In addition to that, they present losses in contractile capacity.
Subject(s)
Animals , Male , Rats , Exercise Test , Myocardial Contraction/physiology , Myocardium/cytology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/physiology , Body Mass Index , Cell Size , Organ Size , Rats, Wistar , Time Factors , Ventricular Function, Left/physiologyABSTRACT
BACKGROUND: Aerobic capacity is essential to physical performance, and low aerobic capacity is related to the triggering of various cardiovascular diseases. OBJECTIVE: To compare the morphology and contractility of isolated rat cardiomyocytes with low performance and standard performance for exercise. METHODS: Wistar rats with 10 weeks of age underwent a protocol of treadmill running to fatigue, and were divided into two groups: Low Performance (LP) and Standard Performance (SP). Then, the animals were sacrificed, the heart was quickly removed and, by means of enzymatic dissociation, left ventricular cardiomyocytes were isolated. The cell and sarcomeres length and width of cardiomyocytes were measured using an edge detection system. The isolated cardiomyocytes were electrically stimulated at 1 and 3 Hz and cell contraction was measured by registering the change of their length. RESULTS: The cell length was shorter in the LP group (157.2 ± 1.3 µm; p < 0.05) compared to SP (161.4 ± 1.3 µm), and the same result was observed for the volume of cardiomyocytes (LP, 25.5 ± 0.4 vs. SP, 26.8 ± 0.4 pL; p < 0.05). The time to peak contraction (LP, 116 ± 1 vs. SP 111 ± 2 ms) and total relaxation (LP, 143 ± 3 vs. SP 232 ± 3 ms) were higher in the LP group. CONCLUSION: We conclude that left ventricular myocytes of animals with low performance for exercise are smaller than animals with standard performance. In addition to that, they present losses in contractile capacity.
