RESUMO
OBJECTIVES: To evaluate the performance of the 2016 ACR-EULAR classification Sjögren's syndrome (SS) criteria for classifying patients with secondary SS. METHODS: We randomly selected 300 patients with systemic lupus erythematosus, rheumatoid arthritis and scleroderma, as well as 50 with primary SS. SS diagnosis was established by two independent rheumatologists and was based on the combination of symptoms, signs, diagnostic tests and medical chart review. We evaluated the fulfillment of the 2002 AECG, 2012 ACR and 2016 ACR/EULAR criteria, and their performance using as the gold standard the clinical diagnosis. RESULTS: We identified 154 patients with a clinical (definitive/probable) SS diagnosis, 95 patients (61.7%) fulfilled the AECG, 96 patients (62.3%) the ACR and 90 (58.4%) the 2016 ACR/EULAR criteria. Among the subset with definitive SS clinical diagnosis (n=99), 83 patients (83.8%) fulfilled the AECG, 77 (77.7%) the ACR and 79 (79.7%) the 2016 ACR/EULAR criteria. The concordance rate between the clinical diagnosis (definitive/probable) and the AECG, ACR and 2016 ACR/ EULAR criteria was κ=0.58, κ=0.55 and κ=0.60, respectively. The 2016 ACR/EULAR criteria showed the best AUCs results (0.87 definitive/probable diagnosis, 0.90 definitive diagnosis), followed by the AECG (0.82 definitive/probable diagnosis, 0.85 definitive diagnosis) and ACR (0.80 definitive/probable diagnosis, 0.79 definitive diagnosis) criteria. As a sensitivity analysis, the results were similar when excluding patients with primary SS. CONCLUSIONS: Our study provides further evidence that the 2016 ACR/EULAR criteria are applicable in the setting of secondary SS.
Assuntos
Reumatologia , Esclerodermia Localizada , Síndrome de Sjogren , Área Sob a Curva , Humanos , Satisfação Pessoal , Síndrome de Sjogren/diagnósticoRESUMO
OBJECTIVE: To determine the prevalence of SS in a cohort of recent-onset SLE patients and evaluate the clinical and immunological variables that may identify SLE patients prone to develop SS. METHODS: A total of 103 patients participating in a prospective cohort of recent-onset SLE were assessed for fulfilment of the American European Consensus Group criteria for SS using a three-phase approach: screening (European questionnaire, Schirmer-I test and wafer test), confirmation (fluorescein staining test, non-stimulated whole-salivary flow and anti-Ro/La antibodies) and lip biopsy. Anti-Ro/SSA and anti-La/SSB antibodies and RF were measured at entry into the cohort and at SS assessment. RESULTS: Ninety-three females and 10 males were included. Mean age at lupus diagnosis was 25.9 ± 8.9 years, and lupus duration at SS assessment was 30.9 ± 9.1 years. SS was diagnosed in 19 (18.5%) patients, all female, and the patients were older at SLE diagnosis than patients without SS (30.8 ± 9.3 vs 24 ± 8.8 years, P = 0.004). Anti-Ro/SSA antibody was more common in SLE-SS patients (84% vs 55%, P = 0.02, LR + 1.53, 95% CI 1.14, 2.04). In the multivariate analysis, age ≥25 years and anti-Ro/SSA antibodies at SLE diagnosis were identified as predictors of SLE-SS, while the absence of anti-Ro/SSA, anti-La/SSB and RF seems to be protective (LR- 0.14, 95% CI 0.02, 0.95). CONCLUSION: The overlap of SLE and SS occurs in almost one-fifth of SLE patients and presents early during its evolution. SLE onset at age ≥25 years plus the presence of anti-Ro/SSA antibody at diagnosis are useful predictors, while the absence of anti-Ro/SSA, anti-La/SSB and RF identifies patients at lowest risk.
Assuntos
Anticorpos Antinucleares/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Adulto , Idade de Início , Estudos de Coortes , Intervalos de Confiança , Diagnóstico Precoce , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Análise Multivariada , Valor Preditivo dos Testes , Prevalência , Estudos Prospectivos , Medição de Risco , Síndrome de Sjogren/imunologia , Adulto JovemRESUMO
BACKGROUND: Sildenafil treatment ameliorates progressive renal injury resulting from extensive renal ablation; however, modifications induced by sildenafil in the glomerular hemodynamic pathophysiology of the remnant kidney have not been investigated. AIM: To determine the effects of sildenafil in the glomerular microcirculation and their relation to histological damage in the renal ablation model. METHODS: Micropuncture studies were performed 60 days after 5/6 nephrectomy in rats that received no treatment, sildenafil (5 mg/kg/day) and reserpine, hydralazine and hydrochlorothiazide to maintain the blood pressure within normal levels. Sham-operated rats untreated and treated with sildenafil served as controls. RESULTS: As expected, renal ablation induced systemic and glomerular hypertension, hyperfiltration, proteinuria, glomerulosclerosis and tubulointerstitial inflammatory damage in the remnant kidney. Sildenafil treatment prevented single-nephron hyperfiltration and hypertension, suppressed renal arteriolar remodeling, ameliorated systemic hypertension and proteinuria, increased urinary excretion of cGMP and NO(2)(-)/NO(3)(-), decreased oxidative stress and improved histological damage in the remnant kidney. Normalization blood pressure with reserpine, hydralazine and hydrochlorothiazide did not modify glomerular hemodynamics, proteinuria or histological changes induced by renal ablation. CONCLUSIONS: Beneficial effects of sildenafil in the remnant kidney are associated with a reduction in the arteriolar remodeling, renal inflammatory changes and prevention of changes in the glomerular microcirculation.
Assuntos
Hipertensão/prevenção & controle , Hipertensão/cirurgia , Glomérulos Renais/efeitos dos fármacos , Glomérulos Renais/cirurgia , Nefrectomia , Piperazinas/uso terapêutico , Sulfonas/uso terapêutico , Animais , Hipertensão/patologia , Glomérulos Renais/patologia , Masculino , Piperazinas/farmacologia , Purinas/farmacologia , Purinas/uso terapêutico , Ratos , Ratos Wistar , Citrato de Sildenafila , Sulfonas/farmacologia , Resultado do Tratamento , Vasodilatadores/farmacologia , Vasodilatadores/uso terapêuticoRESUMO
BACKGROUND: Living kidney donation is increasing as a partial solution for wait-listed patients. Despite properly followed guideline criteria for donor selection, current reports identify unsuspected renal pathology at preimplantation or time-zero biopsy (T0-RBx). METHODS: T0-RBx was evaluated for following: interstitial fibrosis (IF), tubular atrophy (TA), arteriolar hyalinosis (AH), mesangial increase (MI), and glomerulosclerosis (GS). Predonation data were demography, body weight, body mass index (BMI), systolic/diastolic blood pressure (BP), serum creatinine (SCr), estimated glomerular filtration rate (eGFR), and proteinuria. RESULTS: Two hundred nineteen T0-RBx were analyzed. Of these 54.4% had abnormal findings, namely, IF in 29%, TA in 13%, MI in 12%, AH in 10%, and GS in 10%. Mean clinical data were as follows: age 35.4+/-10 years, weight 66.27+/-10.14 kg, BMI 25.53+/-2.99, systolic BP 115+/-9 mm Hg, diastolic BP 74+/-7 mm Hg, SCr 0.91+/-0.25 mg/dL, eGFR 96+/-16.65 mL/min, and proteinuria 70.25+/-62.8 mg/24 hr. A total of 56.7% were women. IF correlated to age (r=0.22, P=0.001) and SCr (r=0.19, P=0.005); TA to diastolic BP (r=0.15, P=0.03) and proteinuria (r=0.20, P=0.009); AH to SCr (r=0.15, P=0.02) and eGFR (r=-0.16, P=0.018); MI to BMI (r=0.13, P=0.047). Multivariate analysis failed to sustain the significant associations found on bivariate analysis, most likely due to a low event/parameter relation and sample size. CONCLUSIONS: A significant correlation was established between T0-RBx findings and clinical predonation parameters. Whether these mild histologic findings at the time of kidney donation represent a higher risk for the remaining kidney ought to be evaluated during follow-up. In an era, when living kidney donation is increasing, we advise closer donor surveillance to modify risk factors that participate in kidney damage progression.
Assuntos
Transplante de Rim/fisiologia , Rim/anormalidades , Rim/patologia , Doadores Vivos/estatística & dados numéricos , Listas de Espera , Biópsia , Pressão Sanguínea , Índice de Massa Corporal , Feminino , Humanos , Rim/fisiologia , Nefropatias/epidemiologia , Nefropatias/patologia , Glomérulos Renais/patologia , Transplante de Rim/patologia , Masculino , Seleção de Pacientes , Proteinúria/epidemiologia , Circulação Renal/fisiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Endothelial dysfunction is a characteristic feature during the renal damage induced by mild hyperuricemia. The mechanism by which uric acid reduces the bioavailability of intrarenal nitric oxide is not known. We tested the hypothesis that oxidative stress might contribute to the endothelial dysfunction and glomerular hemodynamic changes that occur with hyperuricemia. Hyperuricemia was induced in Sprague-Dawley rats by administration of the uricase inhibitor, oxonic acid (750 mg/kg per day). The superoxide scavenger, tempol (15 mg/kg per day), or placebo was administered simultaneously with the oxonic acid. All groups were evaluated throughout a 5-wk period. Kidneys were fixed by perfusion and afferent arteriole morphology, and tubulointerstitial 3-nitrotyrosine, 4-hydroxynonenal, NOX-4 subunit of renal NADPH-oxidase, and angiotensin II were quantified. Hyperuricemia induced intrarenal oxidative stress, increased expression of NOX-4 and angiotensin II, and decreased nitric oxide bioavailability, systemic hypertension, renal vasoconstriction, and afferent arteriolopathy. Tempol treatment reversed the systemic and renal alterations induced by hyperuricemia despite equivalent hyperuricemia. Moreover, because tempol prevented the development of preglomerular damage and decreased blood pressure, glomerular pressure was maintained at normal values as well. Mild hyperuricemia induced by uricase inhibition causes intrarenal oxidative stress, which contributes to the development of the systemic hypertension and the renal abnormalities induced by increased uric acid. Scavenging of the superoxide anion in this setting attenuates the adverse effects induced by hyperuricemia.
Assuntos
Hipertensão Renal/metabolismo , Hiperuricemia/metabolismo , Estresse Oxidativo/fisiologia , Superóxidos/metabolismo , Aldeídos/metabolismo , Angiotensina II/metabolismo , Animais , Antioxidantes/farmacologia , Arteríolas/fisiologia , Peso Corporal , Óxidos N-Cíclicos/farmacologia , Modelos Animais de Doenças , Taxa de Filtração Glomerular/fisiologia , Hipertensão Renal/tratamento farmacológico , Hiperuricemia/induzido quimicamente , Hiperuricemia/tratamento farmacológico , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/metabolismo , Masculino , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ácido Oxônico/toxicidade , Ratos , Ratos Sprague-Dawley , Circulação Renal/fisiologia , Marcadores de Spin , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
We evaluated whether the blockade of the proinflammatory transcription factor NF-kappaB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC; 200 mg.kg(-1).day(-1) sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-kappaB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-kappaB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.
Assuntos
Hipertensão Renal/tratamento farmacológico , Glomérulos Renais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Pirrolidinas/farmacologia , Tiocarbamatos/farmacologia , Aldeídos/metabolismo , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Glutationa Redutase/metabolismo , Hipertensão Renal/fisiopatologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Glomérulos Renais/fisiopatologia , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Peroxidases/metabolismo , Proteinúria/fisiopatologia , Pirrolidinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Fluxo Plasmático Renal/efeitos dos fármacos , Fluxo Plasmático Renal/fisiologia , Superóxido Dismutase/metabolismo , Tiocarbamatos/uso terapêutico , Fator de Transcrição RelA/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismoRESUMO
BACKGROUND/AIMS: The effect of febuxostat (Fx), a non-purine and selective xanthine oxidase inhibitor, on glomerular microcirculatory changes in 5/6 nephrectomy (5/6 Nx) Wistar rats with and without oxonic acid (OA)-induced hyperuricemia was evaluated. METHODS: Four groups were studied: 5/6 Nx+vehicle (V)+placebo (P) (n = 7); 5/6 Nx+V+Fx (n = 8); 5/6 Nx+OA+P (n = 6) and 5/6 Nx+OA+Fx (n = 10). OA (750 mg/kg/day, oral gavage) and Fx (3-4 mg/kg/day, drinking water) were administered for 4 weeks. Systolic blood pressure, proteinuria and plasma uric acid were measured at baseline and at the end of 4 weeks. Measurement of glomerular hemodynamics and evaluation of histology were performed at the end of 4 weeks. RESULTS: 5/6 Nx+OA+P rats developed hyperuricemia, renal vasoconstriction and glomerular hypertension in association with further aggravation of afferent arteriolopathy compared to 5/6 Nx+V+P. Fx prevented hyperuricemia in 5/6 Nx+OA+Fx rats and ameliorated proteinuria, preserved renal function and prevented glomerular hypertension in both 5/6 Nx+V+Fx and 5/6 Nx+OA+Fx groups. Functional improvement was accompanied by preservation of afferent arteriolar morphology and reduced tubulointerstitial fibrosis. CONCLUSION: Fx prevented renal injury in 5/6 Nx rats with and without coexisting hyperuricemia. Because Fx helped to preserve preglomerular vessel morphology, normal glomerular pressure was maintained even in the presence of systemic hypertension.
Assuntos
Modelos Animais de Doenças , Hiperuricemia/prevenção & controle , Hiperuricemia/fisiopatologia , Falência Renal Crônica/prevenção & controle , Falência Renal Crônica/fisiopatologia , Microcirculação/efeitos dos fármacos , Tiazóis/administração & dosagem , Animais , Febuxostat , Hiperuricemia/induzido quimicamente , Hiperuricemia/diagnóstico , Rim/irrigação sanguínea , Rim/efeitos dos fármacos , Rim/fisiopatologia , Falência Renal Crônica/diagnóstico , Masculino , Microcirculação/fisiopatologia , Nefrectomia , Ácido Oxônico , Ratos , Ratos Wistar , Recuperação de Função Fisiológica/efeitos dos fármacos , Resultado do TratamentoRESUMO
Increased fructose consumption is associated with hyperuricemia, metabolic syndrome, and renal damage. This study evaluated whether febuxostat (Fx), an investigational nonpurine, and selective xanthine oxidase inhibitor, could alleviate the features of metabolic syndrome as well as the renal hemodynamic alterations and afferent arteriolopathy induced by a high-fructose diet in rats. Two groups of rats were fed a high-fructose diet (60% fructose) for 8 wk, and two groups received a normal diet. For each diet, one group was treated with Fx (5-6 mg.kg(-1).day(-1) in the drinking water) during the last 4 wk (i.e., after the onset of metabolic syndrome), and the other received no treatment (placebo; P). Body weight was measured daily. Systolic blood pressure and fasting plasma uric acid (UA), insulin, and triglycerides were measured at baseline and at 4 and 8 wk. Renal hemodynamics and histomorphology were evaluated at the end of the study. A high-fructose diet was associated with hyperuricemia, hypertension, as well as increased plasma triglycerides and insulin. Compared with fructose+P, fructose+Fx rats showed significantly lowered blood pressure, UA, triglycerides, and insulin (P < 0.05 for all comparisons). Moreover, fructose+Fx rats had significantly reduced glomerular pressure, renal vasoconstriction, and afferent arteriolar area relative to fructose+P rats. Fx treatment in rats on a normal diet had no significant effects. In conclusion, normalization of plasma UA with Fx in rats with metabolic syndrome alleviated both metabolic and glomerular hemodynamic and morphological alterations. These results provide further evidence for a pathogenic role of hyperuricemia in fructose-mediated metabolic syndrome.
Assuntos
Rim/fisiopatologia , Síndrome Metabólica/induzido quimicamente , Tiazóis/farmacologia , Xantina Oxidase/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Energia , Febuxostat , Frutose , Supressores da Gota/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Circulação Renal/efeitos dos fármacosRESUMO
BACKGROUND: Experimentally-induced hyperuricaemia [due to inhibition of uricase with oxonic acid (OA)] in rats causes hypertension and renal alterations which can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an investigational, nonpurine and selective xanthine oxidase inhibitor, is a more effective UA-lowering agent than allopurinol. We therefore tested the hypothesis that Fx might be useful in treating hyperuricemia-induced hypertension and renal damage. METHODS: Four groups of male rats were studied: OA (750 mg/kg by daily gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n = 10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks after initiation of the study. Two groups of normal (N) rats were studied as controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting plasma UA were measured in all animals at baseline and at 4 and 8 weeks. Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks followed by histological evaluation of glomerular and afferent arteriole morphologies. RESULTS: In OA-induced hyperuricaemic rats, Fx lowered UA and ameliorated systemic and glomerular hypertension as well as mesangial matrix expansion and the development of preglomerular arteriolar disease as indicated by a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx tended to lower UA and had no effect on blood pressure, renal hemodynamics and afferent arteriole morphology. CONCLUSION: These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Hipertensão Renal/tratamento farmacológico , Hiperuricemia/complicações , Tiazóis/uso terapêutico , Xantina Oxidase/antagonistas & inibidores , Animais , Febuxostat , Seguimentos , Hipertensão Renal/sangue , Hipertensão Renal/etiologia , Hiperuricemia/sangue , Hiperuricemia/induzido quimicamente , Glomérulos Renais/patologia , Masculino , Ácido Oxônico/toxicidade , Ratos , Ratos Sprague-Dawley , Circulação Renal/efeitos dos fármacos , Ácido ÚricoRESUMO
Experimental hyperuricemia (HU) results in preglomerular arteriolopathy, cortical vasoconstriction, and glomerular hypertension. Recently, uric acid has been shown to induce endothelial dysfunction. We therefore studied the effect of acute and chronic administration of l-arginine (a substrate for endothelial nitric oxide synthase) on the renal hemodynamic and vascular structural alterations induced by HU. To induce HU, oxonic acid (OA; 750 mg.kg(-1).day(-1)) was administered in male Sprague-Dawley rats. To study the acute effect of arginine, nine rats received l-arginine (l-Arg; 15 mg.kg(-1).min(-1)) during micropuncture. To elucidate the chronic effect of l-Arg, OA + 1% l-Arg (n = 8) and OA + 2.5% l-Arg (n = 6; drinking water) were evaluated throughout the 5-wk period. Eight normal control (N), and eight OA, rats were also studied. Kidneys were fixed by perfusion and afferent arteriole morphology was evaluated. HU rats developed the renal functional and structural alterations described and had suppressed urinary excretion of NO(2)(-)/NO(3)(-). Acute stimulation of nitric oxide (NO) synthesis markedly increased urinary NO(2)(-)/NO(3)(-), lowered systemic blood pressure, and relieved cortical vasoconstriction despite a significant increment of glomerular hypertension and afferent arteriole damage. Increasing doses of chronic l-Arg were associated with increasing excretion of urinary NO(2)(-)/NO(3)(-), reduction of systemic hypertension, and prevention of cortical vasoconstriction (2.5% l-Arg). In addition, both doses prevented glomerular hypertension and preglomerular arteriolopathy. Thus an acute relief of renal vasoconstriction in the setting of afferent arteriole damage cannot reverse glomerular hypertension, likely due to impairment in preglomerular autoregulation. On the other hand, chronic l-Arg preserved arteriolar structures probably mediated by the antiproliferative effect of NO on vascular smooth muscle cells.
Assuntos
Arginina/farmacologia , Hipertensão/fisiopatologia , Hiperuricemia/complicações , Glomérulos Renais/fisiologia , Animais , Arginina/administração & dosagem , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Endotélio Vascular/fisiopatologia , Hipertensão/induzido quimicamente , Hiperuricemia/patologia , Glomérulos Renais/efeitos dos fármacos , Masculino , Nitratos/urina , Nitritos/urina , Ácido Oxônico , Ratos , Ratos Sprague-DawleyRESUMO
Fructose intake has been recently linked to the epidemic of metabolic syndrome and, in turn, the metabolic syndrome has been epidemiologically linked with renal progression. The renal hemodynamic effects of fructose intake are unknown, as well as the effects of different routes of administration. Metabolic syndrome was induced in rats over 8 wk by either a high-fructose diet (60%, F60, n = 7) or by adding fructose to drinking water (10%, F10, n = 7). Body weight and food and fluid intake of each rat were measured weekly during the follow-up. At baseline and at the end of wk 8, systolic blood pressure, plasma uric acid, and triglycerides were measured. At the end of week 8 glomerular hemodynamics was evaluated by micropuncture techniques. Wall thickening in outer cortical and juxtamedullary afferent arterioles was assessed by immunohistochemistry and computer image analysis. Fructose administration either in diet or drinking water induced hypertension, hyperuricemia, and hypertriglyceridemia; however, there was a progressive increment in these parameters with higher fructose intake (CAssuntos
Frutose/farmacologia
, Hipertensão Renal/fisiopatologia
, Glomérulos Renais/fisiopatologia
, Síndrome Metabólica/induzido quimicamente
, Síndrome Metabólica/patologia
, Circulação Renal/fisiologia
, Animais
, Peso Corporal/efeitos dos fármacos
, Peso Corporal/fisiologia
, Capilares/patologia
, Ingestão de Líquidos/fisiologia
, Ingestão de Alimentos/fisiologia
, Rim/patologia
, Masculino
, Síndrome Metabólica/fisiopatologia
, Néfrons/patologia
, Tamanho do Órgão/efeitos dos fármacos
, Ratos
, Ratos Sprague-Dawley
, Triglicerídeos/sangue
, Ácido Úrico/metabolismo
RESUMO
Intramyocardial dissecting hematoma is a form of subacute cardiac rupture complicating acute myocardial infarction. Initially contained within the myocardial wall, the hematoma may expand, rupture into adjacent structures, or spontaneously resolve. However, long-term follow-up is unknown because clinical and serial imaging data are lacking. The purpose of this study was to characterize the early and late myocardial wall changes after transmural myocardial infarction using serial ultrasound examinations of the infarct-related segments. Clinical, electrocardiographic, and echocardiographic features of 8 patients (7 men, mean age 59 years) who presented with acute myocardial infarction and echocardiographically documented intramyocardial dissecting hematoma were analyzed. All patients had precordial echocardiography and 6 underwent transesophageal echocardiography. Differentiating hematoma from trabeculations, thrombus, or pseudoaneurysm was done with contrast and color flow Doppler. Seven patients presented with S-T elevation in V1 to V4, and in 3 the elevation extended to V5, V6, I, and aVL. One patient presented with S-T elevation in II, III, aVF, V3R, and V4R. The most striking feature was persistent S-T elevation of more than 72 hours in all patients. Hematoma consisted of a cysticlike, echolucent cavity variable in size, adjacent to severely hypokinetic or dyskinetic infarct-related segments. Hematoma acoustic characteristics depended on time of evolution. Two patients underwent elective revascularization and the rest were medically treated. Two patients died and 6 were alive at the mean follow-up of 12 months. In conclusion, persistent S-T elevation is an important clue in suggesting intramyocardial dissecting hematoma, which is confirmed by its unique ultrasound appearance. Serial echocardiography is useful in determining its evolving nature, and may guide outcome.
Assuntos
Ecocardiografia Transesofagiana , Cardiopatias/complicações , Cardiopatias/diagnóstico por imagem , Hematoma/complicações , Hematoma/diagnóstico por imagem , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico por imagem , Adulto , Idoso , Dissecção Aórtica/complicações , Dissecção Aórtica/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Ventricular septal rupture (VSR), which can complicate an acute myocardial infarction (MI), carries a high mortality rate. Because precordial and transesophageal echocardiography can identify the type of rupture and assess right ventricular (RV) function at the patient's bedside, we examined the prognostic significance of echocardiographic patterns in postinfarct VSR by postulating that complex rupture and RV involvement carry a worse prognosis. Seventeen patients (10 men; mean age 66 years) who had confirmed postinfarct VSR underwent precordial and transesophageal echocardiography followed by coronary angiography. Serial 12-lead and right precordial leads were also available. Type of septal rupture was classified as simple or complex based on autopsy-proved echocardiographic criteria. Three patients had inferior wall MI and 14 had anterior wall MI. ST-segment elevation persisted >72 hours in all 3 patients who had inferior wall MI and in 12 who had anterior wall MI. Segmental wall motion abnormalities helped in detecting the left ventricular entry site, and use of unconventional views superimposed with color flow Doppler provided the RV exit site. RV function was better appreciated with transesophageal echocardiography. Two patients who had inferior wall MI and 7 who had anterior wall MI had complex ruptures. All 3 patients who had inferior wall MI and 7 who had anterior wall MI had electrocardiographic and echocardiographic evidence of RV involvement. Mortality rate was higher in patients who had complex rupture (78% vs 38%, p <0.001) and in those who had RV extension (71% vs 29%, p <0.001). In conclusion, persistent ST elevation is a common finding in patients who have postinfarct VSR. Complex VSR and RV involvement are significant determinants of clinical outcome.
Assuntos
Infarto do Miocárdio/complicações , Ruptura do Septo Ventricular/epidemiologia , Idoso , Angiografia Coronária , Ecocardiografia Transesofagiana , Eletrocardiografia , Feminino , Hospitais de Ensino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Texas/epidemiologia , Ruptura do Septo Ventricular/diagnóstico por imagem , Ruptura do Septo Ventricular/etiologia , Ruptura do Septo Ventricular/mortalidade , Ruptura do Septo Ventricular/patologiaRESUMO
BACKGROUND: Hyperuricemia has been associated with renal disease. Because glomerular hemodynamic alterations critically contribute to initiation and progression of renal disease, we evaluated the effect of mild hyperuricemia in glomerular microcirculatory changes in rats under normal conditions and with renal injury induced by subtotal renal ablation (RK). METHODS: Hyperuricemia was induced in normal and remnant kidney (RK) rats on a normal sodium diet by administration of oxonic acid (OA). To prevent hyperuricemia, allopurinol (AP) was administered concomitantly. Glomerular hemodynamics were evaluated by micropuncture techniques. Systolic blood pressure (SBP), proteinuria, arterial morphology, and serum uric acid were measured. In RK rats, glomerulosclerosis, fibrosis, and inflammatory cell infiltration (CD5+) were also assessed. RESULTS: In normal rats, hyperuricemia resulted in afferent arteriole thickening associated with renal cortical vasoconstriction [single nephron glomerular filtration rate (SNGFR) -35%, P < 0.05) and glomerular hypertension (P < 0.05). Allopurinol treatment prevented structural and functional alterations. In RK rats, hyperuricemia produced more renal vascular damage than control animals coupled with severe cortical vasoconstriction (SNGFR -40%, P < 0.05) and persistent glomerular hypertension. Allopurinol partially prevented cortical vasoconstriction, and fully prevented arteriolopathy and glomerular hypertension associated with significantly less infiltration of CD5+ cells. CONCLUSION: Hyperuricemia induces arteriolopathy of preglomerular vessels, which impairs the autoregulatory response of afferent arterioles, resulting in glomerular hypertension. Lumen obliteration induced by vascular wall thickening produces severe renal hypoperfusion. The resulting ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis, as well as arterial hypertension. These studies provide a potential mechanism by which hyperuricemia can mediate hypertension and renal disease.
Assuntos
Hipertensão Renovascular/fisiopatologia , Hiperuricemia/fisiopatologia , Vasoconstrição/fisiologia , Animais , Arteríolas/patologia , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/patologia , Hiperuricemia/complicações , Hiperuricemia/patologia , Glomérulos Renais/irrigação sanguínea , Glomérulos Renais/patologia , Glomérulos Renais/fisiopatologia , Masculino , Nefrectomia , Ratos , Ratos Sprague-Dawley , Circulação Renal/fisiologia , Sódio na Dieta/administração & dosagemRESUMO
Mildly hyperuricemic rats develop renin-dependent hypertension and interstitial renal disease. Hyperuricemia might also induce changes in glomerular hemodynamics. Micropuncture experiments under deep anesthesia were performed in Sprague-Dawley rats fed a low-salt diet (LS group), fed a low-salt diet and treated with oxonic acid (OA/LS group), and fed a low-salt diet and treated with oxonic acid + allopurinol (OA/LS/AP group) for 5 wk. The OA/LS group developed hyperuricemia and hypertension compared with the LS group: 3.1 +/- 0.2 vs. 1.1 +/- 0.2 mg/dl (P < 0.01) and 143 +/- 4 vs. 126 +/- 2 mmHg (P < 0.01). Hyperuricemic rats developed increased glomerular capillary pressure compared with the LS rats: 56.7 +/- 1.2 vs. 51.9 +/- 1.4 mmHg (P < 0.05). Pre- and postglomerular resistances were not increased. Histology showed afferent arteriolar thickening with increased alpha-smooth muscle actin staining of the media. Allopurinol prevented hyperuricemia (1.14 +/- 0.2 mg/dl), systemic (121.8 +/- 2.8 mmHg) and glomerular hypertension (50.1 +/- 0.8 mmHg), and arteriolopathy in oxonic acid-treated rats. Linear regression analysis showed that glomerular capillary pressure and arteriolar thickening correlated positively with serum uric acid and systolic blood pressure. Glomerular hypertension may be partially mediated by an abnormal vascular response to systemic hypertension due to arteriolopathy of the afferent arteriole.