RESUMEN
BACKGROUND: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. METHODS: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. RESULTS: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 µm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and ß-myosin heavy chain did not differ between groups. CONCLUSION: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.
Asunto(s)
Restricción Calórica , Ayuno , Infarto del Miocardio/dietoterapia , Función Ventricular Izquierda , Remodelación Ventricular , Animales , Modelos Animales de Enfermedad , Fibrosis , Preparación de Corazón Aislado , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/metabolismo , Infarto del Miocardio/fisiopatología , Miocardio/metabolismo , Miocardio/patología , Ratas Wistar , Factores de Tiempo , Pérdida de PesoRESUMEN
BACKGROUND: Pulmonary arterial hypertension (PAH) occurs in 35% to 65% of hyperthyroid patients. Despite this high frequency, only a few authors have examined the effects of hyperthyroidism treatment on PAH and the right ventricle. We evaluated the effects of hyperthyroidism and its reversal on cardiovascular structure and function using Doppler echocardiography. METHODS: We prospectively evaluated 32 patients (42.5±11.9years old) with thyrotoxicosis. Exclusion criteria included previous cardiovascular disease. An echocardiogram was performed at the time of hyperthyroidism diagnosis and after normalisation of free thyroxine (T4) levels. Patients were divided into two groups according to the presence or absence of PAH at the diagnosis, or at two moments, before and after T4 normalisation. RESULTS: Graves' disease was the most frequent aetiology (75%) of hyperthyroidism. Pulmonary arterial hypertension was observed in 43.8% of patients. Free T4 concentration was higher in PAH than non-PAH patients. Free T4 normalised after 5 (2.0-10.5; median and percentiles) months of treatment. Cardiac chamber sizes and cardiac output were higher in PAH. Right ventricular (RV) systolic function was impaired in PAH. Cardiac output and free T4 (r=0.42; p<0.05) correlated with pulmonary artery systolic pressure (PASP). Cardiac chamber size, cardiac output, left ventricular ejection fraction, and PASP (34.0±8.6 to 21.7±4.5mmHg) reduced after treatment. Right ventricular myocardial performance index and fractional area change improved after T4 normalisation. CONCLUSIONS: Pulmonary arterial hypertension is highly prevalent in hyperthyroid patients and is combined with increased cardiac chambers size and cardiac output, and impaired RV function. Cardiovascular changes are reversible after T4 normalisation in patients without cardiovascular disease.
Asunto(s)
Presión Arterial , Hipertensión Pulmonar Primaria Familiar , Ventrículos Cardíacos , Hipertiroidismo , Disfunción Ventricular Derecha , Función Ventricular Derecha , Adulto , Hipertensión Pulmonar Primaria Familiar/sangre , Hipertensión Pulmonar Primaria Familiar/diagnóstico por imagen , Hipertensión Pulmonar Primaria Familiar/fisiopatología , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertiroidismo/sangre , Hipertiroidismo/diagnóstico por imagen , Hipertiroidismo/fisiopatología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/fisiopatologíaRESUMEN
BACKGROUND: Increased reactive oxygen species (ROS) generation in diabetes mellitus (DM) is an important mechanism leading to diabetic cardiomyopathy. Apocynin, a drug isolated from the herb Picrorhiza kurroa, is considered an antioxidant agent by inhibiting NADPH oxidase activity and improving ROS scavenging. This study analyzed the influence of apocynin on cardiac remodeling in diabetic rats. METHODS: Six-month-old male Wistar rats were assigned into 4 groups: control (CTL, n = 15), control + apocynin (CTL + APO, n = 20), diabetes (DM, n = 20), and diabetes + apocynin (DM + APO, n = 20). DM was induced by streptozotocin. Seven days later, apocynin (16 mg/kg/day) or vehicle was initiated and maintained for 8 weeks. Left ventricular (LV) histological sections were used to analyze interstitial collagen fraction. NADPH oxidase activity was evaluated in LV samples. Comparisons between groups were performed by ANOVA for a 2 × 2 factorial design followed by the Bonferroni post hoc test. RESULTS: Body weight (BW) was lower and glycemia higher in diabetic animals. Echocardiogram showed increased left atrial diameter, LV diastolic diameter, and LV mass indexed by BW in both diabetic groups; apocynin did not affect these indices. LV systolic function was impaired in DM groups and unchanged by apocynin. Isovolumic relaxation time was increased in DM groups; transmitral E/A ratio was higher in DM + APO compared to DM. Myocardial functional evaluation through papillary muscle preparations showed impaired contractile and relaxation function in both DM groups at baseline conditions. After positive inotropic stimulation, developed tension (DT) was lower in DM than CTL. In DM + APO, DT had values between those in DM and CTL + APO and did not significantly differ from either group. Myocardial interstitial collagen fraction was higher in DM than CTL and did not differ between DM + APO and CTL + APO. Serum activity of antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD), and catalase was lower in DM than CTL; apocynin restored catalase and SOD levels in DM + APO. Myocardial NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin restores serum antioxidant enzyme activity despite unchanged myocardial NADPH oxidase activity in diabetic rats.
Asunto(s)
Acetofenonas/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Cardiomiopatías Diabéticas/prevención & control , Depuradores de Radicales Libres/farmacología , Ventrículos Cardíacos/efectos de los fármacos , Estreptozocina , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Catalasa/sangre , Colágeno , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/complicaciones , Cardiomiopatías Diabéticas/sangre , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/fisiopatología , Glutatión Peroxidasa/sangre , Ventrículos Cardíacos/metabolismo , Ventrículos Cardíacos/fisiopatología , Masculino , NADPH Oxidasas/metabolismo , Ratas Wistar , Superóxido Dismutasa/sangreRESUMEN
PURPOSE: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM). METHODS: Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney. RESULTS: Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups. CONCLUSION: Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
Asunto(s)
Acetofenonas/farmacología , Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Cardiomiopatías Diabéticas/prevención & control , Hipertensión/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/prevención & control , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Catalasa/metabolismo , Colágeno Tipo III/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/fisiopatología , Glutatión Peroxidasa/metabolismo , Hipertensión/complicaciones , Hipertensión/metabolismo , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/etiología , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Peróxidos Lipídicos/metabolismo , Masculino , Contracción Miocárdica/efectos de los fármacos , Miocardio/patología , Ratas Endogámicas SHR , Estreptozocina , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: Myostatin has been shown to regulate skeletal and cardiac muscle growth. However, its status on long-term hypertrophied myocardium has not been addressed. The purpose of this study was to evaluate the expression of myocardial myostatin and its antagonist follistatin in spontaneously hypertensive rats (SHR) with heart failure. METHODS: Eighteen-month-old SHR were evaluated to identify clinical features of heart failure such as tachypnea/labored respiration and weight loss. After heart failure was detected, rats were subjected to echocardiogram and euthanized. Age-matched normotensive Wistar-Kyoto (WKY) rats were used as controls. Myostatin and follistatin protein expression was assessed by Western blotting. Statistical analysis was performed by Student's t test. RESULTS: All SHR (n=8) presented right ventricular hypertrophy and five had lung congestion. SHR had left chambers hypertrophy and dilation (left atrial diameter: WKY 5.73±0.59; SHR 7.28±1.17mm; p=0.004; left ventricular (LV) diastolic diameter/body weight ratio: WKY 19.6±3.1; SHR 27.7±4.7mm/kg; p=0.001), and LV systolic dysfunction (midwall fractional shortening: WKY 34.9±3.31; SHR 24.8±3.20%; p=0.003). Myocyte diameter (WKY 23.1±1.50, SHR 25.5±1.33µm; p=0.004) and myocardial interstitial collagen fraction (WKY 4.86±0.01; SHR 8.36±0.02%; p<0.001) were increased in the SHR. Myostatin (WKY 1.00±0.16; SHR 0.77±0.23 arbitrary units; p=0.035) and follistatin (WKY 1.00±0.35; SHR 0.49±0.18 arbitrary units; p=0.002) expression was lower in SHR. Myostatin and follistatin expression negatively correlated with LV diastolic diameter-to-body weight ratio and LV systolic diameter, and positively correlated with midwall fractional shortening. CONCLUSION: Myostatin and follistatin protein expression is reduced in the long-term hypertrophied myocardium from spontaneously hypertensive rats with heart failure.
Asunto(s)
Insuficiencia Cardíaca/metabolismo , Hipertensión/metabolismo , Miocardio/metabolismo , Miostatina/biosíntesis , Animales , Peso Corporal , Ecocardiografía , Folistatina/biosíntesis , Folistatina/metabolismo , Insuficiencia Cardíaca/diagnóstico por imagen , Masculino , Miocardio/patología , Miostatina/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/metabolismoRESUMEN
UNLABELLED: We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. CONCLUSION: Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.
Asunto(s)
Diabetes Mellitus Experimental/terapia , Miocardio/metabolismo , Estrés Oxidativo/fisiología , Condicionamiento Físico Animal/fisiología , Remodelación Ventricular/fisiología , Animales , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/fisiopatología , Terapia por Ejercicio , Corazón/fisiopatología , Masculino , Ratas , Ratas WistarRESUMEN
BACKGROUND: Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure. METHODS: After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting. STATISTICAL ANALYSIS: Student'st test and Pearson correlation. RESULTS: All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615 ± 412; SHR 2035 ± 224 µm(2); P<0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform. CONCLUSION: Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure.
Asunto(s)
Insuficiencia Cardíaca/patología , Músculo Esquelético/patología , Enfermedades Musculares/metabolismo , Factores Reguladores Miogénicos/antagonistas & inhibidores , Factores Reguladores Miogénicos/biosíntesis , Animales , Proteínas Relacionadas con la Folistatina/antagonistas & inhibidores , Proteínas Relacionadas con la Folistatina/biosíntesis , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Masculino , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Enfermedades Musculares/genética , Enfermedades Musculares/patología , Cadenas Pesadas de Miosina/biosíntesis , Cadenas Pesadas de Miosina/genética , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Especificidad de la EspecieRESUMEN
Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean +/- SD): 58.9 +/- 8.2; FR: 50.8 +/- 4.8%, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 +/- 379; FR: 3555 +/- 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 +/- 16; FR: 149 +/- 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 +/- 9; FR: 150 +/- 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 +/- 1.6; FR: 9.2 +/- 0.9%, N = 9, P < 0.05) and LV compliance (control: 82.6 +/- 16.5; FR: 68.2 +/- 9.1%, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.
Asunto(s)
Contracción Miocárdica , Inanición/complicaciones , Disfunción Ventricular Izquierda/etiología , Animales , Presión Sanguínea , Peso Corporal , Ecocardiografía , Masculino , Ratas , Ratas Endogámicas SHR , Inanición/fisiopatología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean ± SD): 58.9 ± 8.2; FR: 50.8 ± 4.8 percent, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 ± 379; FR: 3555 ± 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 ± 16; FR: 149 ± 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 ± 9; FR: 150 ± 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 ± 1.6; FR: 9.2 ± 0.9 percent, N = 9, P < 0.05) and LV compliance (control: 82.6 ± 16.5; FR: 68.2 ± 9.1 percent, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.
Asunto(s)
Animales , Masculino , Ratas , Contracción Miocárdica , Inanición , Disfunción Ventricular Izquierda , Presión Sanguínea , Peso Corporal , Ecocardiografía , Ratas Endogámicas SHRRESUMEN
Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in the LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86+/-0.17 mg/g; FR, 2.19+/-0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.
Asunto(s)
Colágeno/metabolismo , Privación de Alimentos , Ventrículos Cardíacos/metabolismo , Miocardio/metabolismo , Músculos Papilares/metabolismo , Animales , Presión Sanguínea , Peso Corporal , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hidroxiprolina/metabolismo , Técnicas In Vitro , Microscopía Electrónica , Modelos Animales , Contracción Miocárdica , Miocardio/química , Miocardio/ultraestructura , Músculos Papilares/fisiopatología , Ratas , Ratas Endogámicas WKYRESUMEN
BACKGROUND: The effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. METHODS: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. RESULTS: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. CONCLUSIONS: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.
Asunto(s)
Presión Sanguínea , Hipertrofia Ventricular Izquierda/fisiopatología , Contracción Miocárdica , Músculos Papilares/fisiopatología , Inanición , Animales , Peso Corporal , Femenino , Hipertrofia Ventricular Izquierda/metabolismo , Técnicas In Vitro , Masculino , Tamaño de los Órganos , Músculos Papilares/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Factores de TiempoRESUMEN
OBJECTIVE: To assess the effect of food restriction (FR) on hypertrophied cardiac muscle in spontaneously hypertensive rats (SHR). METHODS: Isolated papillary muscle preparations of the left ventricle (LV) of 60-day-old SHR and of normotensive Wistar-Kyoto (WKY) rats were studied. The rats were fed either an unrestricted diet or FR diet (50% of the intake of the control diet) for 30 days. The mechanical function of the muscles was evaluated through monitoring isometric and isotonic contractions. RESULTS: FR caused: 1) reduction in the body weight and LV weight of SHR and WKY rats; 2) increase in the time to peak shortening and the time to peak developed tension (DT) in the hypertrophied myocardium of the SHR; 3) diverging changes in the mechanical function of the normal cardiac muscles of WKY rats with reduction in maximum velocity of isotonic shortening and of the time for DT to decrease 50% of its maximum value, and increase of the resting tension and of the rate of tension decline. CONCLUSION: Short-term FR causes prolongation of the contraction time of hypertrophied muscles and paradoxal changes in mechanical performance of normal cardiac fibers, with worsening of the shortening indices and of the resting tension, and improvement of the isometric relaxation.
Asunto(s)
Ingestión de Alimentos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/fisiopatología , Músculos Papilares/fisiopatología , Desnutrición Proteico-Calórica , Animales , Peso Corporal , Masculino , Contracción Miocárdica , Tamaño de los Órganos , Ratas , Ratas Endogámicas WKYRESUMEN
-The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.
Asunto(s)
Colchicina/farmacología , Supresores de la Gota/farmacología , Insuficiencia Cardíaca/fisiopatología , Corazón/efectos de los fármacos , Hipertrofia Ventricular Izquierda/fisiopatología , Contracción Miocárdica/efectos de los fármacos , Animales , Western Blotting , Interpretación Estadística de Datos , Técnicas Histológicas , Técnicas In Vitro , Masculino , Modelos Cardiovasculares , Músculos Papilares/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Tubulina (Proteína)/análisisRESUMEN
The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 + 8.1; H1: 142 + 7.9; H2: 166 + 7.7 mmHg; P<0.01), there were no significant differences in heart rate (C: 125 + 13.9; H1: 125 + 13.5; H2: 123 + 14.1 bpm; P>0.05) or LVEDP (C:6.2 + 2.48; H1: 6.3 + 2.43; H2: 6.1 + 2.51 mmHg; P>0.05). The values of dP/dt did not change after each elevation of arterial pressure (C:3,068 + 1,057; H1: 3,112 + 996; H2: 3,086 + 980 mmHg/s; P>0.05). In isolated rat papillary muscle, an afterload corresponding to 50 percent and 75 percent of the maximal developed tension did not alter the values of the maximum rate of tension development (100 percent: 78 + 13; 75 percent: 80 + 13; 50 percent: 79 + 11 g mm-2 s-1, P>0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.
Asunto(s)
Perros , Ratas , Animales , Contracción Miocárdica/fisiología , Miocardio , Músculos Papilares/fisiología , Función Ventricular Izquierda/fisiología , Contracción Isométrica/fisiología , Análisis Multivariante , Ratas Wistar , ToracotomíaRESUMEN
OBJETIVO - Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR). MÉTODOS - Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC) e sem falência (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contraçöes isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca 'elevado a +2', 28 'graus Celsius'). RESULTADOS - Os valores da tensão máxima desenvolvida (TD) e da velocidade máxima de encurtamenton (V máx) foram menores nos SHR-IC e SHR, em relação aos WKY (p<0,05). TD e V máx foram semelhantes nos SHR-IC e SHR (p>0,05). A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p<0,05 vs WKY e SHR); esta variável não diferiu entre WKY e SHR (p>0,05). CONCLUSÄO - Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associado ao aumento da rigidez passiva do miocárdio e näo à piora da funçäo contrátil do músculo cardíaco.
Asunto(s)
Humanos , Animales , Lactante , Ratas , Gasto Cardíaco Bajo , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Técnicas In Vitro , Contracción Miocárdica , Alternativas a las Pruebas en Animales , Peso Corporal , Ratas Endogámicas SHR , Factores de TiempoRESUMEN
The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT 4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 + 19 mmHg and RHT8: 194 + 24 mmHg, P<0.05 vs control: 123 + 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 + 0.38 mug/mg; RHT4: 3,02 + 0.40 mug/mg; RHT8: 3,44 + 0.45 mug/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness.
Asunto(s)
Ratas , Animales , Masculino , Cardiomiopatías/fisiopatología , Modelos Animales de Enfermedad , Fibrosis Endomiocárdica , Hipertensión , Ratas WistarRESUMEN
Objetivo - Avaliar a estrutura e função do ventrículo esquerdo (VE) e a rigidez arterial em portadores de diabetes mellitus tipo II. Métodos - Foram estudados 13 doentes diabéticos de ambos os sexox (55 "mais ou menos" 8 anos) sem outras doenças. A estrutura e funçäo do VE foram avaliadas por meio de ecodopplercardiografia associada à monitorizaçäo näo invasiva da pressäo arterial (PA). Os resultados foram comparados aos obtidos em grupo de indivíduos normais de mesma idade (n=12). Resultados - Näo houve diferenças entre os grupos quanto a PA diastólica, dimensöes das câmaras esquerdas e índices de funçäo sistólica e diastólica. Os pacientes diabéticos apresentaram índice de massa do VE (101 "mais ou menos" 10 vs 80 "mais ou menos" 14 g/m2; p "menor" 0,001) e índice de rigidez arterial sistêmica ( 0,86 "mais ou menos" 0,26 vs 0,69 "mais ou menos" 0,19 mmHg/mL; P "menor" 0,05) significantemente maiores que os controles. Conclusäo - O diabets mellitus está associado a aumento da rigidez arterial sistêmica e esse fator poderia contribuir para seus efeitos adversos sobre o VE.
Asunto(s)
Humanos , Persona de Mediana Edad , Cardiomiopatías , Diabetes Mellitus , Angiopatías Diabéticas , Hipertensión , EcocardiografíaRESUMEN
The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 +/- 19 mmHg and RHT8: 194 +/- 24 mmHg, P < 0.05 vs control: 123 +/- 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 +/- 0.38 micrograms/mg; RHT4: 3.02 +/- 0.40 micrograms/mg; RHT8: 3.44 +/- 0.45 micrograms/mg of dry tissue, P < 0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local, conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed by scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness.
Asunto(s)
Fibrosis Endomiocárdica/etiología , Hipertensión Renovascular/complicaciones , Músculos Papilares/patología , Animales , Masculino , Necrosis , Ratas , Ratas WistarRESUMEN
The aim of the present study was to evaluate the effect of interstitial fibrosis alone or associated with hypertrophy on diastolic myocardial function in renovascular hypertensive rats. Myocardial function was evaluated in isolated papillary muscle from renovascular hypertensive Wistar rats (RHT, n = 14), renovascular hypertensive rats treated with the angiotensin converting enzyme inhibitor (ACEI) ramipril, 20 mg.kg-1.day-1 (RHT RAM, n =14), and age-matched unoperated and untreated Wistar rats (CONT, n = 12). The ACEI treatment for 3 weeks allowed the regression of myocyte mass and the maintenance of interstitial fibrosis. Myocardial passive stiffness was analyzed by the resting tension-length relationship. The myocardial fibrosis was evaluated by measuring myocardial hydroxyproline (Hyp) concentration and by histological studies of the myocardium stained with hematoxylin and eosin or picrosirus red. Left ventricular weight was significantly higher in RHT (0.97 +/- 0.12 g) compared with CONT (0.66 +/- 0.06 g) and RHT RAM (0.69 +/- 0.14 g). The Hyp levels were 2.9 +/- 0.4, 3.4 +/- 0.3, and 3.8 +/- 0.4 micrograms/mg of dry tissue for the CONT, RHT, and RHT RAM, respectively. Perivascular and interstitial fibrosis were observed in RHT and RHT RAM groups. There were lymphononuclear inflammatory exudate and edema around arteries, involving adjacent myocytes in the RHT group. There was an increased passive stiffness in RHT and RHT RAM groups compared with the CONT group. In conclusion, our results indicate that the impaired diastolic function in the renovascular hypertensive rats is related to interstitial fibrosis rather than to myocardial hypertrophy.