RESUMO

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) are widely used for chronic central serous chorioretinopathy (cCSCR), but their effectiveness remains unclear. This research was conducted to evaluate the efficacy of this drugs for cCSCR. METHODS: This is a review of randomized clinical trials (RCT) comparing MRAs to placebo in adults with cCSCR, using the effects of MRAs on best-corrected visual acuity (BCVA) and adverse events as primary outcomes and the effects of MRAs on anatomical parameters as secondary outcomes: central subfield thickness (CST), subretinal fluid height (SFH) and central choroidal thickness (CCT). Our all-language online search included Medline (via PubMed), Central, Embase, Lilacs, Ibecs, and RCT registers platforms, as late as May 2021. We used the Cochrane risk-of-bias tool (version 2) to assess the methodological quality of each study and synthesized the results in meta-analyses using a random-effects model. RESULTS: The search identified 302 records, five of which were eligible, totaling 225 cCSCR patients (aged 45-62 years; M/F ratio 3.1:1) treated for 1 to 12 months with spironolactone (50 mg/day) or eplerenone (50 mg/day) vs. placebo. Moderate-certainty evidence suggests MRAs result in little to no improvement in BCVA compared to placebo (SMD 0.22; 95% CI - 0.04 to 0.48; studies = 5; comparisons = 6; participants = 218; I2 = 0%). Very low-certainty evidence suggests that, when compared to placebo, MRAs have a very uncertain impact on adverse effects (no meta-analysis was performed), and CST (MD 18.1; 95% CI - 113.04 to 76.84; participants = 145; studies = 2; I2 = 68%). MRAs also result in little to no difference in SFH (SMD - 0.35; 95% CI - 0.95 to 0.26; studies = 5; comparisons = 6; participants = 221; I2 = 76%; moderate certainty) and CCT (MD - 21.23; 95% CI - 64.69 to 22.24; participants = 206; studies = 4; comparisons = 5; I2 = 85%; low certainty). CONCLUSION: MRAs have little to no effect on BCVA. Evidence for adverse events and CST is very uncertain. MRAs also have little to no effect on SFH and CCT. These findings should be considered when prescribing MRAs for cCSCR. This research was previous registration in the PROSPERO platform (CRD42020182601).

RESUMO

UNLABELLED: The mechanisms by which exercise affects atherosclerotic plaque stability remain incompletely understood. We evaluated the effects of two training protocols on both atherosclerotic plaque structure and the signaling pathways involved in plaque rupture. METHODS: Male low-density lipoprotein (LDL) receptor knockout mice were fed a high-fat, high-cholesterol diet (HFD). One group was subjected to moderate exercise using a treadmill for 14weeks (preventive protocol). The other group started an exercise regimen after 16weeks of the HFD (therapeutic group). Atherosclerotic plaques within the aorta were evaluated for lipid and collagen contents, as well as for inflammatory markers. Plasma cholesterol and cytokine levels were also determined. RESULTS: The mice receiving a HFD developed hypercholesterolemia and atherosclerotic plaques within the aorta. The aortas from the animals in the preventive protocol exhibited smaller lipid cores and higher collagen content. These animals also exhibited lower CD40 expression within the plaques. The aortas of the mice in the therapeutic group exhibited higher collagen content, but no differences in either lipid core size or plaque size were noted. No differences in blood pressure, plasma cholesterol, cytokine levels, plaque size or metalloproteinase 9 expression were observed in the trained animals compared with the sedentary animals. CONCLUSION: Moderate aerobic exercise modified atherosclerotic plaque characteristics and converted the plaques into a more stable phenotype, increasing the collagen content in response to both exercise programs. Furthermore, moderate aerobic exercise reduced the animals' fat content and decreased the activity of the CD40-CD40L signaling pathway in the preventive group.

Assuntos

Condicionamento Físico Animal , Placa Aterosclerótica/fisiopatologia , Animais , Masculino , Camundongos , Camundongos Knockout

RESUMO

OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 µg/kg (TP50; n = 7), 100 µg/kg (TP100; n = 7) and 150 µg/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine.

Assuntos

Epinefrina/farmacologia , Parada Cardíaca/tratamento farmacológico , Lipressina/análogos & derivados , Modelos Animais , Naloxona/farmacologia , Vasoconstritores/farmacologia , Animais , Pressão Arterial/efeitos dos fármacos , Asfixia/complicações , Reanimação Cardiopulmonar , Epinefrina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Lipressina/metabolismo , Lipressina/farmacologia , Masculino , Naloxona/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Terlipressina , Fatores de Tempo , Vasoconstritores/metabolismo

RESUMO

The experimental model of aortocaval fistula is a useful model of cardiac hypertrophy in response to volume overload. In the present study it has been used to investigate the pathologic subendocardial remodeling associated with the development of heart failure during the early phases (day 1, 3, and 7) following volume overload. Compared with sham treated rats, aortocaval fistula rats showed lower systemic blood pressure and higher left ventricular end-diastolic pressure This resulted in lower coronary driving pressure and left ventricular systolic and diastolic dysfunction. Signs of myocyte necrosis, leukocyte cell infiltration, fibroplasia and collagen deposition appeared sequentially in the subendocardium where remodeling was more prominent than in the non-subendocardium. Accordingly, increased levels of TNF-alpha, IL-1 beta, and IL-6, and enhanced MMP-2 activity were all found in the subendocardium of rats with coronary driving pressure ≤ 60 mmHg. The coronary driving pressure was inversely correlated with MMP-2 activity in subendocardium in all time-points studied, and blood flow in this region showed positive correlation with systolic and diastolic function at day 7. Thus the predominant subendocardial remodeling that occurs in response to low myocardial perfusion pressure during the acute phases of aortocaval fistula contributes to early left ventricular dysfunction.

Assuntos

Aorta Abdominal/fisiopatologia , Fístula Arteriovenosa/fisiopatologia , Pressão Sanguínea/fisiologia , Veia Cava Inferior/fisiopatologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Doença Aguda , Animais , Aorta Abdominal/patologia , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/patologia , Circulação Coronária/fisiologia , Modelos Animais de Doenças , Hemodinâmica/fisiologia , Interleucinas/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Peroxidase/metabolismo , Fluxo Pulsátil/fisiologia , Ratos , Ratos Wistar , Veia Cava Inferior/patologia

RESUMO

OBJECTIVE: To evaluate the hemodynamic and metabolic effects of terlipressin and naloxone in cardiac arrest. METHODS: Cardiac arrest in rats was induced by asphyxia and maintained for 3.5 minutes. Animals were then resuscitated and randomized into one of six groups: placebo (n = 7), epinephrine (0.02 mg/kg; n = 7), naloxone (1 mg/kg; n = 7) or terlipressin, of which three different doses were tested: 50 µg/kg (TP50; n = 7), 100 µg/kg (TP100; n = 7) and 150 µg/kg (TP150; n = 7). Hemodynamic variables were measured at baseline and at 10 (T10), 20 (T20), 30 (T30), 45 (T45) and 60 (T60) minutes after cardiac arrest. Arterial blood samples were collected at T10, T30 and T60. RESULTS: The mean arterial pressure values in the TP50 group were higher than those in the epinephrine group at T10 (165 vs. 112 mmHg), T20 (160 vs. 82 mmHg), T30 (143 vs. 66 mmHg), T45 (119 vs. 67 mmHg) and T60 (96 vs. 66.8 mmHg). The blood lactate level was lower in the naloxone group than in the epinephrine group at T10 (5.15 vs. 10.5 mmol/L), T30 (2.57 vs. 5.24 mmol/L) and T60 (2.1 vs. 4.1 mmol/L). CONCLUSIONS: In this rat model of asphyxia-induced cardiac arrest, terlipressin and naloxone were effective vasopressors in cardiopulmonary resuscitation and presented better metabolic profiles than epinephrine. Terlipressin provided better hemodynamic stability than epinephrine. .

Assuntos

Animais , Masculino , Ratos , Epinefrina/farmacologia , Parada Cardíaca/tratamento farmacológico , Lipressina/análogos & derivados , Modelos Animais , Naloxona/farmacologia , Vasoconstritores/farmacologia , Pressão Arterial/efeitos dos fármacos , Asfixia/complicações , Reanimação Cardiopulmonar , Epinefrina/metabolismo , Parada Cardíaca/etiologia , Parada Cardíaca/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Lipressina/metabolismo , Lipressina/farmacologia , Naloxona/metabolismo , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de Tempo , Vasoconstritores/metabolismo

RESUMO

The development of atherosclerosis and the inflammatory response were investigated in LDLr-KO mice on three high-fat diets (40% energy as fat) for 16 weeks: trans (TRANS), saturated (SAFA) or ω-6 polyunsaturated (PUFA) fats. The following parameters were measured: plasma lipids, aortic root total cholesterol (TC), lesion area (Oil Red-O), ABCA1 content and macrophage infiltration (immunohistochemistry), collagen content (Picrosirius-red) and co-localization of ABCA1 and macrophage (confocal microscopy) besides the plasma inflammatory markers (IL-6, TNF-α) and the macrophage inflammatory response to lipopolysaccharide from Escherichia coli (LPS). As expected, plasma TC and TG concentrations were lower on the PUFA diet than on TRANS or SAFA diets. Aortic intima macrophage infiltration, ABCA1 content, and lesion area on PUFA group were lower compared to TRANS and SAFA groups. Macrophages and ABCA1 markers did not co-localize in the atherosclerotic plaque, suggesting that different cell types were responsible for the ABCA1 expression in plaques. Compared to PUFA, TRANS and SAFA presented higher collagen content and necrotic cores in atherosclerotic plaques. In the artery wall, TC was lower on PUFA compared to TRANS group; free cholesterol was lower on PUFA compared to TRANS and SAFA; cholesteryl ester concentration did not vary amongst the groups. Plasma TNF-α concentration on PUFA and TRANS-fed mice was higher compared to SAFA. No difference was observed in IL-6 concentration amongst groups. Regarding the macrophage inflammatory response to LPS, TRANS and PUFA presented higher culture medium concentrations of IL-6 and TNF-α as compared to SAFA. The PUFA group showed the lowest amount of the anti-inflammatory marker IL-10 compared to TRANS and SAFA groups. In conclusion, PUFA intake prevented atherogenesis, even in a pro-inflammatory condition.

Assuntos

Aterosclerose/prevenção & controle , Ácidos Graxos Ômega-6/uso terapêutico , Transportador 1 de Cassete de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/biossíntese , Animais , Aorta/metabolismo , Aterosclerose/metabolismo , Aterosclerose/patologia , Colesterol/sangue , Colágeno/metabolismo , Dieta Hiperlipídica , Gorduras Insaturadas na Dieta/metabolismo , Gorduras Insaturadas na Dieta/uso terapêutico , Inflamação/metabolismo , Inflamação/prevenção & controle , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Knockout , Receptores de LDL/deficiência , Ácidos Graxos trans/farmacologia , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

BACKGROUND: Exercise training (ET) can reduce blood pressure (BP) and prevent functional disability. However, the effects of low volumes of training have been poorly studied, especially in elderly hypertensive patients. OBJECTIVES: To investigate the effects of a multi-component ET program (aerobic training, strength, flexibility, and balance) on BP, physical fitness, and functional ability of elderly hypertensive patients. METHODS: Thirty-six elderly hypertensive patients with optimal clinical treatment underwent a multi-component ET program: two 60-minute sessions a week for 12 weeks at a Basic Health Unit. RESULTS: Compared to pre-training values, systolic and diastolic BP were reduced by 3.6% and 1.2%, respectively (p<0.001), body mass index was reduced by 1.1% (p<0.001), and peripheral blood glucose was reduced by 2.5% (p=0.002). There were improvements in all physical fitness domains: muscle strength (chair-stand test and elbow flexor test; p<0.001), static balance test (unipedal stance test; p<0.029), aerobic capacity (stationary gait test; p<0.001), except for flexibility (sit and reach test). Moreover, there was a reduction in the time required to perform two functional ability tests: "put on sock" and "sit down, stand up, and move around the house" (p<0.001). CONCLUSIONS: Lower volumes of ET improved BP, metabolic parameters, and physical fitness and reflected in the functional ability of elderly hypertensive patients. Trial Registration RBR-2xgjh3.

Assuntos

Pressão Sanguínea , Terapia por Exercício , Hipertensão/fisiopatologia , Hipertensão/terapia , Aptidão Física , Idoso , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Fatores de Tempo

RESUMO

BACKGROUND: Exercise training (ET) can reduce blood pressure (BP) and prevent functional disability. However, the effects of low volumes of training have been poorly studied, especially in elderly hypertensive patients. OBJECTIVES: To investigate the effects of a multi-component ET program (aerobic training, strength, flexibility, and balance) on BP, physical fitness, and functional ability of elderly hypertensive patients. METHODS: Thirty-six elderly hypertensive patients with optimal clinical treatment underwent a multi-component ET program: two 60-minute sessions a week for 12 weeks at a Basic Health Unit. RESULTS: Compared to pre-training values, systolic and diastolic BP were reduced by 3.6% and 1.2%, respectively (p<0.001), body mass index was reduced by 1.1% (p<0.001), and peripheral blood glucose was reduced by 2.5% (p=0.002). There were improvements in all physical fitness domains: muscle strength (chair-stand test and elbow flexor test; p<0.001), static balance test (unipedal stance test; p<0.029), aerobic capacity (stationary gait test; p<0.001), except for flexibility (sit and reach test). Moreover, there was a reduction in the time required to perform two functional ability tests: "put on sock" and "sit down, stand up, and move around the house" (p<0.001). CONCLUSIONS: Lower volumes of ET improved BP, metabolic parameters, and physical fitness and reflected in the functional ability of elderly hypertensive patients. Trial Registration RBR-2xgjh3.

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CONTEXTUALIZAÇÃO: O treinamento físico (TF) é capaz de reduzir a pressão arterial (PA) e prevenir o declínio da capacidade funcional. Entretanto, pouco tem sido estudado sobre os efeitos de menores volumes de treinamento em idosos com hipertensão arterial (HA). OBJETIVOS: Investigar os efeitos de um programa de TF multicomponente (treinamento aeróbico, força, flexibilidade e equilíbrio) na PA, aptidão física e capacidade funcional de idosos com HA. MÉTODOS: Trinta e seis idosos com HA e tratamento clínico otimizado foram submetidos a um programa de exercícios físicos multicomponente, com duas sessões semanais de 60 minutos cada, durante 12 semanas, em uma Unidade Básica de Saúde (UBS). RESULTADOS: Comparados aos valores antes do TF, observou-se redução de 3,6% da PA sistólica (p<0,001), de 1,2% da PA diastólica (p<0,001), de 1,1% do índice de massa corporal (IMC) (p<0,001) e de 2,5% da glicemia periférica em jejum (p=0,002). Observou-se melhora em todos os domínios da aptidão física, como força muscular (testes de levantar da cadeira e flexão de cotovelos, p<0,001); equilíbrio estático (teste de apoio unipodal, p=0,029), capacidade aeróbica (teste de marcha estacionária, p<0,001), com exceção da flexibilidade (teste de sentar e alcançar). Além disso, houve redução no tempo utilizado para realização de dois testes de avaliação da capacidade funcional, o de "calçar meias" e o de "sentar, levantar-se da cadeira e locomover-se pela casa" (p<0,001). CONCLUSÕES: O TF com duas sessões semanais em idosos hipertensos repercutiu na melhora dos indicadores metabólicos, da aptidão física e da capacidade funcional e atuou como auxiliar no controle da PA. Registro de Ensaios Clínicos RBR-2xgjh3.

Assuntos

Idoso , Feminino , Humanos , Masculino , Pressão Sanguínea , Terapia por Exercício , Hipertensão/fisiopatologia , Hipertensão/terapia , Aptidão Física , Terapia por Exercício/métodos , Fatores de Tempo

RESUMO

BACKGROUND: Cardiac remodeling in uremia is characterized by left ventricular hypertrophy, interstitial fibrosis and microvascular disease. Cardiovascular disease is the leading cause of death in uremic patients, but coronary events alone are not the prevalent cause, sudden death and heart failure are. We studied the cardiac remodeling in experimental uremia, evaluating the isolated effect of parathyroid hormone (PTH) and phosphorus. METHODS: Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx); they also received vehicle (V) and PTH at normal (nPTH) or high (hPTH) doses. They were fed with a poor-phosphorus (pP) or rich-phosphorus (rP) diet and were divided into the following groups: 'Sham': G1 (V+normal-phosphorus diet (np)) and 'Nx+PTx': G2 (nPTH+pP), G3 (nPTH+rP), G4 (hPTH+pP) and G5 (hPTH+rP). After 8 weeks, biochemical analysis, myocardium morphometry and arteriolar morphological analysis were performed. In addition, using immunohistochemical analysis, we evaluated angiotensin II, α-actin, transforming growth factor-beta (TGF-ß) and nitrotyrosine, as well as fibroblast growth factor-23 (FGF-23), fibroblast growth factor receptor-1 (FGFR-1) and runt-related transcription factor-2 (Runx-2) expression. RESULTS: Nx animals presented higher serum creatinine levels as well as arterial hypertension. Higher PTH levels were associated with myocardial hypertrophy and fibrosis as well as a higher coronary lesion score. High PTH animals also presented a higher myocardial expression of TGF-ß, angiotensin II, FGF-23 and nitrotyrosine and a lower expression of α-actin. Phosphorus overload was associated with higher serum FGF-23 levels and Runx-2, as well as myocardial hypertrophy. FGFR-1 was positive in the cardiomyocytes of all groups as well as in calcified coronaries of G4 and G5 whereas Runx-2 was positive in G3, G4 and G5. CONCLUSION: In uremia, PTH and phosphorus overload are both independently associated with major changes related to the cardiac remodeling process, emphasizing the need for a better control of these factors in chronic kidney disease.

Assuntos

Doenças Cardiovasculares/etiologia , Fibrose/etiologia , Hormônio Paratireóideo/metabolismo , Fósforo na Dieta/metabolismo , Uremia/complicações , Uremia/fisiopatologia , Animais , Biomarcadores/metabolismo , Doenças Cardiovasculares/patologia , Fibrose/patologia , Técnicas Imunoenzimáticas , Masculino , Nefrectomia/efeitos adversos , Hormônio Paratireóideo/administração & dosagem , Paratireoidectomia/efeitos adversos , Fósforo na Dieta/administração & dosagem , Ratos , Ratos Wistar

RESUMO

OBJECTIVE: To evaluate the effect of low-intensity chronic exercise training (ExT) on blood pressure (BP), as well as the cardiac alterations associated with hypertension in aging hypertensive rats. METHODS: Male spontaneously hypertensive rats (SHR; 21 months old) and their normotensive control Wistar-Kyoto (WKY) rats were submitted to low-intensity training protocol for 13 weeks. BP, cardiac morphological and morphometric analysis, as well as gene expression of fibrotic and inflammatory factors were analyzed at the end of the training period. RESULTS: ExT reduced BP and heart rate in aged SHR. Left ventricle hypertrophy, collagen volume fraction and wall-to-lumen ratio of myocardium arterioles were also decreased in trained SHR. However, ExT was unable to reverse the either reduced capillary density or the cardiac myocyte hypertrophy observed in SHR as compared with WKY rats. Trained SHR showed higher metalloproteinase-2/tissue inhibitor metalloproteinase-2 (MMP-2/TIMP-2) ratio and lower levels of α-smooth muscle actin, but similar levels of connective tissue growth factor, transforming growth factor beta or IL-1 beta to that of nontrained SHR. CONCLUSION: Low to moderate-intensity chronic ExT reverses the cardiac alterations associated with hypertension: myocardial arteriole, left ventricle hypertrophy, collagen content and tachycardia. These changes could be consequence or cause of the reduction in BP observed in trained SHR. In addition, ExT does not worsen the underlying inflammatory burden associated with hypertension. Therefore, the data support a beneficial effect of ExT in aging SHR similar to that reported in young or middle-aged individuals, confirming that exercise is a healthy habit that induces cardiac improvements independently of age.

Assuntos

Envelhecimento/fisiologia , Coração/fisiopatologia , Hipertensão/fisiopatologia , Condicionamento Físico Animal , Actinas/metabolismo , Animais , Pressão Sanguínea/fisiologia , Colágeno/metabolismo , Vasos Coronários/patologia , Expressão Gênica , Frequência Cardíaca/fisiologia , Hipertensão/patologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo

RESUMO

1. The role of haemodynamic changes in left ventricular remodelling has been poorly investigated, especially in the context of volume overload cardiac hypertrophy. Low diastolic blood pressure and high left ventricular filling pressure are expected to affect coronary driving pressure negatively and thereby put in jeopardy subendocardial perfusion in particular. The consequences to global left ventricular remodelling remain undetermined. The aim of the present study was to investigate the role of coronary driving pressure in the development of subendocardial remodelling and the conceivable effects on cardiac function, using a rat model of aortocaval fistula. 2. Wistar rats, weighing 330-350 g, were submitted to aortocaval fistula (ACF group) or sham (control group) operations. Two haemodynamic measurements were determined following surgery, the initial measurement at week 1 and the final measurement at week 8. Cytokine expression, myeloperoxidase (MPO) activity, metalloproteinase expression and activity and fibrosis were assessed in two distinct left ventricular myocardial layers: the subendocardium (SE) and the non-subendocardium (non-SE). 3. The ACF group showed lower initial and final coronary driving pressure and lower final +dP/dt and -dP/dt compared with the control group. Multivariate analyses disclosed initial coronary driving pressure as the only haemodynamic parameter independently associated with SE fibrosis (R(2) = 0.76; P < 0.0001) and with +dP/dt (R(2) = 0.55; P = 0.0004) and -dP/dt (R(2) = 0.91; P < 0.0001). Matrix metalloproteinase (MMP)-2 expression and activity predominated in the SE of ACF animals, particularly in those with low coronary driving pressure. Increased levels of interleukin (IL)-6 and IL-1beta also predominated in the SE of the ACF group. Otherwise, MPO activity and levels of tumour necrosis factor-alpha and IL-10 were similar in both groups. Final coronary driving pressure correlated with both the expression and activity of MMP-2. 4. Low coronary driving pressure early in the course of ACF determines SE damage and, by this mechanism, interferes negatively in left ventricular function.

Assuntos

Doenças da Aorta/fisiopatologia , Fístula Arteriovenosa/fisiopatologia , Endocárdio/fisiopatologia , Veia Cava Inferior , Disfunção Ventricular Esquerda/etiologia , Pressão Ventricular , Remodelação Ventricular , Animais , Doenças da Aorta/complicações , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/patologia , Pressão Sanguínea , Modelos Animais de Doenças , Ecocardiografia , Endocárdio/enzimologia , Endocárdio/metabolismo , Endocárdio/patologia , Fibrose , Frequência Cardíaca , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Peroxidase/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Veia Cava Inferior/cirurgia , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/fisiopatologia

RESUMO

1. In chronic hypertension, the baroreceptors reset to hypertensive levels with a decrease in gain sensitivity, but only a few studies have evaluated baroreceptor resetting during chronic hypotension and, under these conditions, no consistent information is available concerning changes in baroreceptor gain sensitivity. Therefore, in the present study, the aortic baroreceptor function curve and the baroreflex control of heart rate (HR) were evaluated in chronic hypotension produced by myocardial infarction (MI) with no heart failure. 2. Aortic baroreceptor function curves were studied in anaesthetized three groups of rats: (i) MI-7, six rats 7 days after MI; (ii) MI-30, nine rats 30 days after MI; and (iii) five control animals (SHAM). The pressure-nerve activity relationship was measured during rapid changes in blood pressure by integrating the whole-nerve activity of the baroreceptors in a computerized beat-to-beat analysis. 3. Both long-term periods (7 or 30 days) of hypotension were accompanied by complete resetting of the baroreceptor in rats (the leftward displacement of the baroreceptor curve matched the decrease in blood pressure). Moreover, the resetting of the baroreceptor function curve was not accompanied by changes in gain sensitivity (1.47, 1.64 and 1.67%/mmHg for SHAM, MI-7 and MI-30 groups, respectively) and the baroreflex control of HR was normal comparing SHAM and MI-30 groups (bradycardic 1.62 +/- 0.18 vs 1.99 +/- 0.52 b.p.m./mmHg, respectively; tachycardic 3.6 +/- 0.5 vs 4.1 +/- 0.4 b.p.m./mmHg for, respectively). 4. The data indicate that the resetting of baroreceptors in chronic hypotension is stable and is not accompanied by changes in gain sensitivity, as observed in hypertension. This may account for the normal baroreflex control of HR observed in non-anaesthetized rats.

Assuntos

Aorta/inervação , Barorreflexo , Hipotensão/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Pressorreceptores/fisiologia , Animais , Pressão Sanguínea , Vasos Coronários/cirurgia , Frequência Cardíaca , Hipotensão/etiologia , Ligadura , Masculino , Modelos Animais , Infarto do Miocárdio/complicações , Ratos , Ratos Wistar , Fatores de Tempo

RESUMO

Our objective was to evaluate intestinal ischemia-reperfusion injury in growing rats, modulated by hypothermia (I/RH) and N-acetylcysteine (NAC). We used 30 EPM-1 Wistar male rats, aged around 35 days, weighing 90 g. Rats were randomized into 5 groups with 6 animals in each: I/RH group, intestinal ischemia under hypothermia for 40 min and reperfusion for 30 min; I/RH-NAC group, same procedure but adding NAC (150 mg x kg(-1)), previously with ischemia; S-H group, topic hypothermia for 40 min, and observation for 30 min; I/R H-Ve group; and S-NAC group, NAC administration and observation for 70 min. All animals were heparinized and anesthetized with ketamine (60 mg kg(-1)) and xylazine (10 mg kg(-1)) intramuscularly. Surgical procedures were done under microsurgical technique (augmentation, 10x). After laparotomy, the superior mesenteric artery was dissected and clamped to promote ischemia. Topic hypothermia was obtained by using plastic bags at 4 degrees C, changed every 10 min. Rats were sacrificed by exsanguination, and blood samples were utilized to measure D(-)lactate. Intestinal fragments were removed for morphological study. Statistical analysis was done with nonparametric tests (P

Assuntos

Acetilcisteína/administração & dosagem , Sequestradores de Radicais Livres/administração & dosagem , Hipotermia Induzida/métodos , Intestino Delgado/fisiopatologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Citoproteção/efeitos dos fármacos , Intestino Delgado/irrigação sanguínea , Intestino Delgado/efeitos dos fármacos , Masculino , Modelos Animais , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia