RESUMEN
Testosterone may affect myocardial contractility since its deficiency decreases the contraction and relaxation of the heart. Meanwhile, testosterone replacement therapy has raised concerns because it may worsen cardiac dysfunction and remodeling after myocardial infarction (MI). In this study, we evaluate cardiac contractility 60 days after MI in rats with suppressed testosterone. Male Wistar rats underwent bilateral orchidectomy one week before the ligation of the anterior descending left coronary artery. The animals were divided into orchidectomized (OCT); MI; orchidectomized + MI (OCT + MI); orchidectomized + MI + testosterone (OCT + MI + T) and control (Sham) groups. Eight weeks after MI, papillary muscle contractility was analyzed under increasing calcium (0.62, 1.25, 2.5 and 3.75 mM) and isoproterenol (10-8 to 10-2 M) concentrations. Ventricular myocytes were isolated for intracellular calcium measurements and assessment of Ca2+ handling proteins. Contractility was preserved in the orchidectomized animals after myocardial infarction and was reduced when testosterone was replaced (Ca2+ 3.75 mM: Sham: 608 ± 70 (n = 11); OCT: 590 ± 37 (n = 16); MI: 311 ± 33* (n = 9); OCT + MI: 594 ± 76 (n = 7); OCT + MI + T: 433 ± 38* (n=4), g/g *p < 0.05 vs Sham). Orchidectomy also increased the Ca2+ transient amplitude of the ventricular myocytes and SERCA-2a protein expression levels. PLB phosphorylation levels at Thr17 were not different in the orchidectomized animals compared to the Sham animals but were reduced after testosterone replacement. CAMKII phosphorylation and protein nitrosylation increased in the orchidectomized animals. Our results support the view that testosterone deficiency prevents MI contractility dysfunction by altering the key proteins involved in Ca2+ handling.
Asunto(s)
Contracción Miocárdica , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Testosterona/deficiencia , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatología , Animales , Peso Corporal , Calcio/metabolismo , Hemodinámica , Pulmón/patología , Masculino , Miocardio/patología , Orquiectomía , Tamaño de los Órganos , Peptidil-Dipeptidasa A/metabolismo , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Infarto del Miocardio/fisiopatología , Enfermedad Aguda , Animales , Barorreflejo/fisiología , Determinación de la Presión Sanguínea , Enfermedad Crónica , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas WistarRESUMEN
Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance.