RESUMEN
Experimental studies have reported that aerobic exercise after asthma induction reduces lung inflammation and remodeling. Nevertheless, no experimental study has analyzed whether regular/moderate aerobic training before the induction of allergic asthma may prevent these inflammatory and remodeling processes. For this purpose, BALB/c mice (n = 96) were assigned into non-trained and trained groups. Trained animals ran on a motorized treadmill at moderate intensity, 30 min/day, 3 times/week, for 8 weeks, and were further randomized into subgroups to undergo ovalbumin sensitization and challenge or receive saline using the same protocol. Aerobic training continued until the last challenge. Twenty-four hours after challenge, compared to non-trained animals, trained mice exhibited: (a) increased systolic output and left ventricular mass on echocardiography; (b) improved lung mechanics; (c) decreased smooth muscle actin expression and collagen fiber content in airways and lung parenchyma; (d) decreased transforming growth factor (TGF)-ß levels in bronchoalveolar lavage fluid (BALF) and blood; (e) increased interferon (IFN)-γ in BALF and interleukin (IL)-10 in blood; and (f) decreased IL-4 and IL-13 in BALF. In conclusion, regular/moderate aerobic training prior to allergic asthma induction reduced inflammation and remodeling, perhaps through increased IL-10 and IFN-γ in tandem with decreased Th2 cytokines.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Asma/inmunología , Citocinas/inmunología , Pulmón/inmunología , Condicionamiento Físico Animal , Animales , Asma/inducido químicamente , Líquido del Lavado Bronquioalveolar/inmunología , Inmunohistoquímica , Inflamación , Interferón gamma/inmunología , Interleucina-10/inmunología , Interleucina-13/inmunología , Interleucina-4/inmunología , Pulmón/patología , Pulmón/ultraestructura , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Transmisión , Ovalbúmina/efectos adversos , Neumonía/inducido químicamente , Neumonía/inmunología , Neumonía/patología , Factor de Crecimiento Transformador beta/inmunologíaRESUMEN
The mechanisms underlying the functional improvement after injection of multipotent mesenchymal stromal cells (MSCs) in infarcted hearts remain incompletely understood. The aim of this study was to investigate if soluble factors secreted by MSCs promote cardioprotection. For this purpose, conditioned medium (CM) was obtained after three passages from MSC cultures submitted to 72 h of conditioning in serum-free DMEM under normoxia (NCM) or hypoxia (HCM) conditions. CM was concentrated 25-fold before use (NCM-25X, concentrated normoxia conditioned medium; HCM-25X, concentrated hypoxia conditioned medium). The in vitro cardioprotection was evaluated in neonatal ventricular cardiomyocytes by quantifying apoptosis after 24 h of serum deprivation associated with hypoxia (1% O(2)) in the absence or presence of NCM and HCM (nonconcentrated and 25-fold concentrated). The in vivo cardioprotection of HCM was tested in a model of myocardial infarction (MI) induced in Wistar male rats by permanent left coronary occlusion. Intramyocardial injection of HCM-25X (n = 14) or nonconditioned DMEM (n = 16) was performed 3 h after coronary occlusion and cardiac function was evaluated 19-21 days after medium injection. Cardiac function was evaluated by electro- and echocardiogram, left ventricular catheterization, and treadmill test. The in vitro results showed that HCM was able to decrease cardiomyocyte necrosis. The in vivo results showed that HCM-25X administered 3 h after AMI was able to promote a significant reduction (35%) in left ventricular end-diastolic pressure and improvement of cardiac contractility (15%) and relaxation (12%). These results suggest that soluble factors released in vitro by MSCs are able to promote cardioprotection in vitro and improve cardiac function in vivo.
Asunto(s)
Medios de Cultivo Condicionados/farmacología , Células Madre Mesenquimatosas/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Hipoxia de la Célula , Células Cultivadas , Medio de Cultivo Libre de Suero , Ecocardiografía , Corazón/fisiopatología , Masculino , Células Madre Mesenquimatosas/citología , Contracción Miocárdica/efectos de los fármacos , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Ratas , Ratas Wistar , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Therapy with bone marrow-derived cells has been used in ischemic patients with reported success. The aim of this study was to determine the therapeutic efficacy of fresh and frozen human umbilical cord blood cells (hUCB) in Wistar rats submitted to permanent occlusion of the left coronary artery. Three hours after myocardial infarction, 2 x 10(7) hUCB cells or vehicle were administered by intramyocardial injection. The animals were divided into five groups: control (N = 10), sham operated (N = 10), infarcted that received vehicle (N = 9), infarcted treated with cryopreserved hUCB (N = 7), and infarcted treated with fresh hUCB (N = 5). Cardiac function was evaluated by electrocardiogram (ECG) and echocardiogram (ECHO) before cell therapy, and by ECG, ECHO, cardiopulmonary test, and left ventricular pressure measurements 3 weeks later. After 3 weeks, both groups treated with hUCB still had Q wave present in L1, âQRS >90 degrees and reduced shortening fraction (less than 50%). In addition, cardiac indexes of left ventricular contractility and relaxation were 5484 +/- 875 and -4032 +/- 643 mmHg (cryopreserved hUCB) and 4585 +/- 955 and -2862 +/- 590 mmHg (fresh hUCB), respectively. These values were not statistically different from those of saline-treated animals. Cardiopulmonary exercise test profile was typical of infarcted hearts; exercise time was about 14 min and maximal VO2 was 24.77 +/- 5.00 mL.kg-1.min-1. These data show that hUCB therapy did not improve the cardiac function of infarcted animals or prevent cardiac remodeling.
Asunto(s)
Trasplante de Células Madre de Sangre del Cordón Umbilical , Infarto del Miocardio/cirugía , Animales , Ecocardiografía , Electrocardiografía , Humanos , Infarto del Miocardio/fisiopatología , Ratas , Ratas Wistar , Función Ventricular Izquierda/fisiologíaRESUMEN
After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1â (3.8X) and TNF-á (6.0X). IFN-ã was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.
Asunto(s)
Animales , Femenino , Masculino , Ratones , Citocinas/sangre , Insuficiencia Cardíaca/inmunología , Autoanticuerpos/sangre , Modelos Animales de Enfermedad , Ecocardiografía , Perfilación de la Expresión Génica , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/etiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
After myocardial infarction (MI), activation of the immune system and inflammatory mechanisms, among others, can lead to ventricular remodeling and heart failure (HF). The interaction between these systemic alterations and corresponding changes in the heart has not been extensively examined in the setting of chronic ischemia. The main purpose of this study was to investigate alterations in cardiac gene and systemic cytokine profile in mice with post-ischemic HF. Plasma was tested for IgM and IgG anti-heart reactive repertoire and inflammatory cytokines. Heart samples were assayed for gene expression by analyzing hybridization to AECOM 32k mouse microarrays. Ischemic HF significantly increased the levels of total serum IgM (by 5.2-fold) and total IgG (by 3.6-fold) associated with a relatively high content of anti-heart specificity. A comparable increase was observed in the levels of circulating pro-inflammatory cytokines such as IL-1beta (3.8X) and TNF-alpha (6.0X). IFN-gamma was also increased by 3.1-fold in the MI group. However, IL-4 and IL-10 were not significantly different between the MI and sham-operated groups. Chemokines such as MCP-1 and IL-8 were 1.4- and 13-fold increased, respectively, in the plasma of infarcted mice. We identified 2079 well annotated unigenes that were significantly regulated by post-ischemic HF. Complement activation and immune response were among the most up-regulated processes. Interestingly, 21 of the 101 quantified unigenes involved in the inflammatory response were significantly up-regulated and none were down-regulated. These data indicate that post-ischemic heart remodeling is accompanied by immune-mediated mechanisms that act both systemically and locally.
Asunto(s)
Citocinas/sangre , Insuficiencia Cardíaca/inmunología , Animales , Autoanticuerpos/sangre , Modelos Animales de Enfermedad , Ecocardiografía , Femenino , Perfilación de la Expresión Génica , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/etiología , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/inmunología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Therapy with bone marrow-derived cells has been used in ischemic patients with reported success. The aim of this study was to determine the therapeutic efficacy of fresh and frozen human umbilical cord blood cells (hUCB) in Wistar rats submitted to permanent occlusion of the left coronary artery. Three hours after myocardial infarction, 2 x 10(7) hUCB cells or vehicle were administered by intramyocardial injection. The animals were divided into five groups: control (N = 10), sham operated (N = 10), infarcted that received vehicle (N = 9), infarcted treated with cryopreserved hUCB (N = 7), and infarcted treated with fresh hUCB (N = 5). Cardiac function was evaluated by electrocardiogram (ECG) and echocardiogram (ECHO) before cell therapy, and by ECG, ECHO, cardiopulmonary test, and left ventricular pressure measurements 3 weeks later. After 3 weeks, both groups treated with hUCB still had Q wave present in L1, âQRS >90° and reduced shortening fraction (less than 50 percent). In addition, cardiac indexes of left ventricular contractility and relaxation were 5484 ± 875 and -4032 ± 643 mmHg (cryopreserved hUCB) and 4585 ± 955 and -2862 ± 590 mmHg (fresh hUCB), respectively. These values were not statistically different from those of saline-treated animals. Cardiopulmonary exercise test profile was typical of infarcted hearts; exercise time was about 14 min and maximal VO2 was 24.77 ± 5.00 mL·kg-1·min-1. These data show that hUCB therapy did not improve the cardiac function of infarcted animals or prevent cardiac remodeling.
Asunto(s)
Animales , Humanos , Ratas , Trasplante de Células Madre de Sangre del Cordón Umbilical , Infarto del Miocardio/cirugía , Ecocardiografía , Electrocardiografía , Infarto del Miocardio/fisiopatología , Ratas Wistar , Función Ventricular Izquierda/fisiologíaRESUMEN
We investigated whether liver injury by dual exposure to ethanol and carbon tetrachloride (EtOH + CCl4) for 15 weeks would persist after hepatotoxic agents were removed (EtOH + CCl4/8wR). After 15 weeks of hepatic injury with ethanol (5.5%, m/v) and carbon tetrachloride (0.05, mL/kg, ip), 5 of 11 female Wistar rats were sacrificed. The other 6 rats were maintained for an additional 8 weeks without hepatotoxic agents. Ultrasonography showed increased liver echogenicity and dilation of portal vein caliber in both groups (EtOH + CCl4: 0.22 +/- 0.01 cm, P < 0.001; EtOH + CCl4/8wR: 0.21 +/- 0.02 cm, P < 0.01) vs control (0.16 +/- 0.02 cm). Histopathology showed regenerative nodules in both experimental groups. Histomorphometry revealed increased fibrosis content in both groups (EtOH + CCl4: 12.6 +/- 2.64%, P < 0.001; EtOH + CCl4/8wR: 10.4 +/- 1.36%, P < 0.05) vs control (2.2 +/- 1.21%). Collagen types I and III were increased in groups EtOH + CCl4 (collagen I: 2.5 +/- 1.3%, P < 0.01; collagen III: 1.3 +/- 0.2%, P < 0.05) and EtOH + CCl4/8wR (collagen I: 1.8 +/- 0.06%, P < 0.05; collagen III: 1.5 +/- 0.8%, P < 0.01) vs control (collagen I: 0.38 +/- 0.11%; collagen III: 0.25 +/- 0.06%). Tissue transglutaminase increased in both groups (EtOH + CCl4: 66.4 +/- 8%, P < 0.01; EtOH + CCl4/8wR: 58.8 +/- 21%, P < 0.01) vs control (7.9 +/- 0.8%). Cirrhosis caused by the association of CCl4-EtOH remained for at least 8 weeks after removal of these hepatotoxic agents. Ultrasound images can be a useful tool to evaluate advanced hepatic alterations.
Asunto(s)
Cirrosis Hepática Experimental/diagnóstico por imagen , Cirrosis Hepática Experimental/patología , Animales , Tetracloruro de Carbono/toxicidad , Etanol/toxicidad , Femenino , Técnica del Anticuerpo Fluorescente , Cirrosis Hepática Experimental/inducido químicamente , Ratas , UltrasonografíaRESUMEN
We tested the effect of bone marrow cell (BMC) transplantation in either preventing or reversing cirrhosis on an experimental model of chronic liver disease. Female Wistar rats were fed a liquid alcohol diet and received intraperitoneal injections of carbon tetrachloride (CCl4) over 15 weeks. Ten animals (cell-treated group) received five injections of BMCs during the cirrhosis induction protocol (on the 4th, 6th, 8th, 10th, and 12th weeks) and four animals received the cells after liver injury was established through tail vein. Nine animals (nontreated group) were submitted to the previously described protocols; however, they received vehicle injections. Analyses were performed to verify whether the infusion of cells was effective in preventing the development of cirrhosis in our model of induction, and if the cells could reverse cirrhosis once it was established. Hepatic architecture and fibrotic septa were analyzed in liver slices stained with hematoxilin & eosin and Sirius red, respectively. Fibrosis quantification was measured by Sirius red histomorphometry. Indirect immunofluorescence was performed to detect the amount of tissue transglutaminase 2. Blood analyses were performed to assess liver injury and function by the assessment of alanine aminotransferase and albumin. Ultrasound was performed to analyze the portal vein caliber and presence of ascitis. Cirrhosis features (regenerative nodules and fibrous septa) were observed in histopathology after 15 weeks of continuous hepatic injury in nontreated and cell-treated groups. Collagen content, immunofluorescence analysis, and biochemical and ultrasound parameters were similar in nontreated and cell-treated groups; however, both groups showed significant differences compared to a normal control group. Cell infusions with bone marrow-derived cells seem to be ineffective in improving morphofunctional parameters of the liver when applied to chronic cases either during or after establishment of the hepatic lesion.
Asunto(s)
Trasplante de Médula Ósea/métodos , Cirrosis Hepática Experimental/cirugía , Hígado/cirugía , Albúminas/análisis , Albúminas/metabolismo , Animales , Compuestos Azo , Tetracloruro de Carbono/toxicidad , Depresores del Sistema Nervioso Central/toxicidad , Colágeno/análisis , Colágeno/metabolismo , Colorantes , Modelos Animales de Enfermedad , Enzimas/análisis , Enzimas/metabolismo , Eosina Amarillenta-(YS) , Etanol/toxicidad , Femenino , Hematoxilina , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Cirrosis Hepática/cirugía , Cirrosis Hepática Experimental/patología , Cirrosis Hepática Experimental/fisiopatología , Vena Porta/diagnóstico por imagen , Vena Porta/patología , Vena Porta/fisiopatología , Proteína Glutamina Gamma Glutamiltransferasa 2 , Ratas , Ratas Wistar , Resultado del Tratamiento , UltrasonografíaRESUMEN
We investigated whether liver injury by dual exposure to ethanol and carbon tetrachloride (EtOH + CCl4) for 15 weeks would persist after hepatotoxic agents were removed (EtOH + CCl4/8wR). After 15 weeks of hepatic injury with ethanol (5.5 percent, m/v) and carbon tetrachloride (0.05, mL/kg, ip), 5 of 11 female Wistar rats were sacrificed. The other 6 rats were maintained for an additional 8 weeks without hepatotoxic agents. Ultrasonography showed increased liver echogenicity and dilation of portal vein caliber in both groups (EtOH + CCl4: 0.22 ± 0.01 cm, P < 0.001; EtOH + CCl4/8wR: 0.21 ± 0.02 cm, P < 0.01) vs control (0.16 ± 0.02 cm). Histopathology showed regenerative nodules in both experimental groups. Histomorphometry revealed increased fibrosis content in both groups (EtOH + CCl4: 12.6 ± 2.64 percent, P < 0.001; EtOH + CCl4/8wR: 10.4 ± 1.36 percent, P < 0.05) vs control (2.2 ± 1.21 percent). Collagen types I and III were increased in groups EtOH + CCl4 (collagen I: 2.5 ± 1.3 percent, P < 0.01; collagen III: 1.3 ± 0.2 percent, P < 0.05) and EtOH + CCl4/8wR (collagen I: 1.8 ± 0.06 percent, P < 0.05; collagen III: 1.5 ± 0.8 percent, P < 0.01) vs control (collagen I: 0.38 ± 0.11 percent; collagen III: 0.25 ± 0.06 percent). Tissue transglutaminase increased in both groups (EtOH + CCl4: 66.4 ± 8 percent, P < 0.01; EtOH + CCl4/8wR: 58.8 ± 21 percent, P < 0.01) vs control (7.9 ± 0.8 percent). Cirrhosis caused by the association of CCl4-EtOH remained for at least 8 weeks after removal of these hepatotoxic agents. Ultrasound images can be a useful tool to evaluate advanced hepatic alterations.
Asunto(s)
Animales , Femenino , Ratas , Cirrosis Hepática Experimental/patología , Cirrosis Hepática Experimental , Tetracloruro de Carbono/toxicidad , Etanol/toxicidad , Técnica del Anticuerpo Fluorescente , Cirrosis Hepática Experimental/inducido químicamenteRESUMEN
Thyroid hormones has its main role in controlling metabolism, but it can also modulate extracellular fluid Volume (ECFV) through its action on the expression and activity of Na(+) transporters. Otherwise, chloride is the main anion in the ECFV and the influence of thyroid hormones in the regulation of chloride transporters is not yet understood. In this work, we studied the effect of thyroid hormones in the expression of ClC-2, a cell Volume-, pH- and voltage-sensitive Cl(-) channel, in rat kidney. To analyze the modulation of ClC-2 gene expression by thyroid hormones, we used hypothyroid (Hypo) rats with or without thyroxine (T(4)) replacement and hyperthyroid (Hyper) rats as our experimental models. Total RNA was isolated and the expression of ClC-2 mRNA was evaluated by a ribonuclease protection assay, and/or semi-quantitative RT-PCR. Renal ClC-2 expression decreased in Hypo rats and increased in Hyper rats. In addition, semi-quantitative RT-PCR of different nephron segments showed that these changes were due exclusively to the modulation of ClC-2 mRNA expression by thyroid hormone in convoluted and straight proximal tubules. To investigate whether thyroid hormones action was direct or indirect, renal proximal tubule primary culture cells were prepared and subjected to different T(4) concentrations. ClC-2 mRNA expression was increased by T(4) in a dose-dependent fashion, as analyzed by RT-PCR. Western blotting demonstrated that ClC-2 protein expression followed the same profile of mRNA expression.
Asunto(s)
Canales de Cloruro/genética , Regulación de la Expresión Génica , Hipertiroidismo/metabolismo , Hipotiroidismo/metabolismo , Túbulos Renales Proximales/metabolismo , Hormonas Tiroideas/fisiología , Animales , Western Blotting/métodos , Canales de Cloruro CLC-2 , Células Cultivadas , Canales de Cloruro/análisis , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Modelos Animales , ARN Mensajero/análisis , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tiroxina/farmacologíaRESUMEN
Long-term modulation of intercellular communication via gap junctions was investigated in TM3 Leydig cells, under low and high confluence states, and upon treatment of the cells for different times with activators of protein kinase A (PKA) and protein kinase C (PKC). Cells in low confluence were readily coupled, as determined by transfer of the dye Lucifer Yellow; on reaching confluence, the cells uncoupled. Western blots and RT-PCR revealed that connexin 43 (Cx43) was abundantly expressed in TM3 Leydig cells and its expression was decreased after the cells achieved confluence. Stimulation of PKA or PKC induced a decrease in cell-cell communication. Staurosporin, an inhibitor of protein kinases, increased coupling and was able to prevent and reverse the uncoupling actions of dibutyryl cAMP and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Under modulation by confluence, Cx43 was localized to the appositional membranes when cells were coupled and was mainly in the cytoplasm when they were uncoupled. In addition, cAMP and TPA reduced the surface membrane labeling for Cx43, whereas staurosporin increased it. These data show a strong correlation between functional coupling and the membrane distribution of Cx43, implying that this connexin has an important role in intercellular communication between TM3 cells. Furthermore, increased testosterone secretion in response to luteinizing hormone was accompanied by a decrease in intercellular communication, suggesting that gap junction mediated coupling may be a modulator of hormone secretion in TM3 cells.
Asunto(s)
Uniones Comunicantes/efectos de los fármacos , Células Intersticiales del Testículo/ultraestructura , Animales , Transporte Biológico , Bucladesina/farmacología , Adhesión Celular/efectos de los fármacos , Línea Celular , Membrana Celular/química , Colorantes , Conexina 43/análisis , Conexina 43/genética , Inhibidores Enzimáticos/farmacología , Técnica del Anticuerpo Fluorescente , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Isoquinolinas , Células Intersticiales del Testículo/efectos de los fármacos , Hormona Luteinizante/farmacología , Masculino , Ratones , Proteína Quinasa C/antagonistas & inhibidores , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estaurosporina/farmacología , Testosterona/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Factores de TiempoRESUMEN
We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23% of sera or AV block in 40%. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated.
Asunto(s)
Enfermedad de Chagas/sangre , Sistema de Conducción Cardíaco/fisiopatología , Análisis de Varianza , Animales , Nodo Atrioventricular , Comunicación Celular/fisiología , Cardiomiopatía Chagásica/sangre , Cardiomiopatía Chagásica/metabolismo , Enfermedad de Chagas/fisiopatología , Enfermedad Crónica , Electrocardiografía , Bloqueo Cardíaco , Frecuencia Cardíaca , Humanos , Ratones , Conejos , Factores de TiempoRESUMEN
We report results obtained with sera from 58 chronic chagasic patients that were evaluated for effects on heart rate and atrioventricular (AV) conduction in isolated rabbit hearts and screened for the presence of muscarinic and beta-adrenergic activity. We show that sera from 26 patients decreased heart rate, while 10 increased it and 22 had no effect. Additionally, sera from 20 of the 58 patients blocked AV conduction. Muscarinic activation seems to be involved in both effects, but is not the only mechanism, since atropine did not antagonize the decrease in heart rate in 23 percent of sera or AV block in 40 percent. Sera from patients with complex arrhythmias were significantly more effective in depressing both heart rate and AV conduction. Sera that induce increases in heart rate seem to operate exclusively through beta-adrenergic activation. Two of these sera, evaluated with respect to intercellular communication in primary cultures of embryonic cardiomyocytes were able to block gap junction conductance evaluated by a dye injection technique after 24-h exposure. The mechanisms underlying this uncoupling effect are currently being investigated
Asunto(s)
Animales , Conejos , Ratones , Humanos , Enfermedad de Chagas/sangre , Colinérgicos , Receptores Muscarínicos , Análisis de Varianza , Nodo Atrioventricular , Comunicación Celular , Cardiomiopatía Chagásica , Enfermedad Crónica , Electrocardiografía , Electrofisiología , Estructuras Embrionarias/citología , Bloqueo Cardíaco , Sistema de Conducción Cardíaco , Frecuencia Cardíaca , Factores de TiempoRESUMEN
The protozoan parasite Trypanosoma cruzi causes Chagas' disease, a major cause of cardiac dysfunction in Latin Americans. Chagas' disease exhibits both acute and chronic phases, and each may be characterized by cardiac conduction disturbances. In acutely infected cultures of rodent heart cells, synchronized spontaneous beating becomes less regular, and coupling between cells is reduced. The basis of this decreased conduction is apparently in localization of the gap junction protein (Cx43) inside infected cells. Although total Cx43 is normal in infected cells, little is recognizable at appositional membranes. Electrophysiological properties are also altered by this infection. Action potentials are shortened, resting Ca2+ levels are elevated, and response to alpha-adrenergic agonists was altered, compared to controls. Humoral factors may contribute to the conduction defects in chronic Chagas' disease. Sera from chronically infected rabbits produced ECG abnormalities in Langendorff-perfused rabbit hearts. These findings indicate that chagasic infection may modify ion channel function in the heart, and we suggest that these changes may be manifested in the conduction disturbances that characterize this disease.