RESUMO
OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.
Assuntos
Fibrilação Atrial/genética , Proteína C-Reativa/genética , Polimorfismo Genético , Regiões Promotoras Genéticas , Fibrilação Atrial/sangue , Proteína C-Reativa/análise , Canais de Cálcio Tipo L/fisiologia , Estudos de Casos e Controles , Estudos de Coortes , Éxons , Feminino , Fibroblastos/fisiologia , Genótipo , Haplótipos , Átrios do Coração/citologia , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de RiscoRESUMO
BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.
Assuntos
Inflamação/fisiopatologia , Interleucina-6/sangue , Diálise Peritoneal Ambulatorial Contínua , Fator de Necrose Tumoral alfa/sangue , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Creatinina/sangue , Ecocardiografia Doppler/métodos , Feminino , Humanos , Inflamação/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Disfunção Ventricular Esquerda/complicaçõesRESUMO
BACKGROUND: Many patients with chordae tendineae rupture (CTR) of the mitral valve have obscure aetiologies. The association between pre-existing hypertension and idiopathic CTR was investigated. METHODS: 494 patients with CTR were identified by searching the computer database. For each patient with idiopathic CTR, three matched controls without CTR who were admitted to the same hospital for bone fractures were included. RESULTS: Among the 494 patients with CTR, 351 patients (71%) had idiopathic CTR, and 143 patients (29%) had secondary CTR. The prevalence of pre-existing hypertension was significantly higher in the idiopathic than in the secondary CTR group (50.9% vs 14.6%, p<0.001). The odds ratio was 6.0 (95% CI 3.6 to 10.1). The percentage of patients without adequate blood pressure control was also higher in the idiopathic than in the secondary CTR group (23.1% vs 4.9%, p<0.001). When compared with the fracture group, patients with idiopathic CTR also had a significantly higher prevalence of hypertension (50.9% vs 14.9%, p<0.001), and the odds ratio was 5.9 (95% CI 4.5 to 7.8). After correction for age, the odds ratio of having hypertension was 3.6 (95% CI 2.1 to 6.3) and 6.6 (p<0.001, 95% CI 5.0 to 8.8) when compared with the secondary CTR group and fracture group respectively. CONCLUSIONS: There is a strong association between pre-existing hypertension and idiopathic CTR. Whether or not this disease can be prevented by controlling hypertension deserves further investigation.
Assuntos
Cordas Tendinosas , Ruptura Cardíaca/etiologia , Hipertensão/complicações , Insuficiência da Valva Mitral/etiologia , Adulto , Fatores Etários , Idoso , Cordas Tendinosas/diagnóstico por imagem , Estudos Transversais , Feminino , Ruptura Cardíaca/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , UltrassonografiaRESUMO
BACKGROUND: Diastolic heart failure (DHF) refers to an abnormality of diastolic distensibility, filling or relaxation of the left ventricle. The genetic study of DHF is scarce in the literature. The association of renin-angiotensin system (RAS) and DHF are well known. We hypothesized that RAS genes might be the susceptible genes for DHF and conducted a case-control study to prove the hypothesis. MATERIALS AND METHODS: A total of 1452 consecutive patients were analysed and 148 patients with a diagnosis of DHF confirmed by echocardiography were recruited. We had two control populations. The first controls consisted of 286 normal subjects while the second were 148 matched controls selected on a 1-to-1 basis by age, sex, hypertension, diabetes and medication use. The angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism; multilocus polymorphisms of the angiotensinogen gene; and the A1166C polymorphisms of the angiotensin II type I receptor (AT(1)R) gene were genotyped. RESULTS: In a single-locus analysis, the odds ratios (ORs) for DHF were significant with the ACE DD genotype and the AT(1)R 1166 CC plus AC genotype. In addition, the concomitant presence of ACE DD and AT(1)R 1166 CC/AC genotypes synergistically increased the predisposition to DHF. CONCLUSIONS: Genetic variants in the RAS genes may determine an individual's risk to develop DHF. There is also a synergistic gene-gene interaction between the RAS genes in the development of DHF.
Assuntos
Angiotensina II/genética , Insuficiência Cardíaca Diastólica/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Sistema Renina-Angiotensina/genética , Idoso , Estudos de Casos e Controles , Ecocardiografia , Feminino , Deleção de Genes , Predisposição Genética para Doença/genética , Genótipo , Insuficiência Cardíaca Diastólica/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional/genéticaRESUMO
BACKGROUND AND PURPOSE: Aminoguanidine (AG), an inhibitor of advanced glycation endproducts, has been identified as a prominent agent that prevents the fructose-induced arterial stiffening in male Wistar rats. Our aims were to examine whether AG produced benefits on the left ventricular (LV)-arterial coupling in fructose-fed (FF) animals in terms of the ventricular and arterial chamber properties. EXPERIMENTAL APPROACH: Rats given 10% fructose in drinking water (FF) were daily treated with AG (50 mg x kg(-1), i.p.) for 2 weeks and compared with the untreated FF group. In anaesthetised rats, LV pressure and ascending aortic flow signals were recorded to calculate LV end-systolic elastance (E(es), an indicator of myocardial contractility) and effective arterial volume elastance (E(a)). The optimal afterload (Q(load)) determined by the ratio of E(a) to E(es) was used to measure the coupling efficiency between the left ventricle and its vasculature. KEY RESULTS: There was a significant interaction between fructose and AG in their effects on E(a). Fructose loading significantly elevated E(a) and AG prevented the fructose-derived deterioration in arterial chamber elastance. Both fructose and AG affected E(es) and Q(load), and there was an interaction between fructose and AG for these two variables. Both E(es) and Q(load) exhibited a decline with fructose feeding but showed a significant rise after AG treatment in the FF rats. CONCLUSIONS AND IMPLICATIONS: AG prevented not only the contractile dysfunction of the heart caused by fructose loading, but also the fructose-induced deterioration in matching left ventricular function to the arterial system.
Assuntos
Pressão Sanguínea/efeitos dos fármacos , Frutose/toxicidade , Guanidinas/farmacologia , Disfunção Ventricular Esquerda/prevenção & controle , Análise de Variância , Animais , Débito Cardíaco/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Frutose/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Masculino , Óxido Nítrico Sintase/antagonistas & inibidores , Ratos , Ratos Wistar , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats. MATERIALS AND METHODS: The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls. RESULTS: After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening. CONCLUSIONS: Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.
Assuntos
Aorta/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores Enzimáticos/administração & dosagem , Guanidinas/administração & dosagem , Animais , Aorta/fisiopatologia , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Frequência Cardíaca/efeitos dos fármacos , Injeções Intraperitoneais , Insulina/sangue , Masculino , Pressão , Fluxo Pulsátil , Ratos , Ratos Wistar , Volume Sistólico/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacosRESUMO
BACKGROUND: We determined the effects of NIDDM on haemodynamic parameters describing arterial wall elasticity and cardiac hypertrophy in rats administered streptozotocin (STZ) and nicotinamide (NA), using the aortic impedance analysis. METHODS: Male Wistar rats at 2 months were administered intraperitoneally 180 mg kg(-1) of NA, 30 min before an intravenous injection of 50 mg kg(-1) STZ, to induce type 2 diabetes. The STZ-NA rats were divided into two groups, 4 weeks and 8 weeks after induction of diabetes, and compared with untreated age-matched controls. Pulsatile aortic pressure and flow signals were measured by a high-fidelity pressure sensor and electromagnetic flow probe, respectively, and were then subjected to Fourier transformation for the analysis of aortic input impedance. RESULTS: In each diabetic group, the experimental syndrome was characterized by a moderate and stable hyperglycaemia and a relative deficiency of insulin secretion. However, the 8-week but not the 4-week STZ-NA diabetic rats showed a decrease in cardiac output in the absence of any significant changes in mean aortic pressure, having increased total peripheral resistance. The diabetic syndrome at 8 weeks also contributed to an increase in aortic characteristic impedance, from 1.49 +/- 0.33 (mean +/- SD) to 1.95 +/- 0.28 mmHg s mL(-1) (P < 0.05), suggesting a detriment to the aortic distensibility in NIDDM. Meanwhile, the STZ-NA diabetic animals after 8 weeks had an increased wave reflection factor (0.46 +/- 0.09 vs. 0.61 +/- 0.13, P < 0.05) and decreased wave transit time (25.8 +/- 3.8 vs. 20.6 +/- 2.8 ms, P < 0.05). Ratio of the left ventricular weight to body weight was also enhanced in the 8-week STZ-NA diabetic rats. CONCLUSION: The heavy intensity with early return of the pulse wave reflection may augment systolic load of the left ventricle coupled to the arterial system, leading to cardiac hypertrophy in the rats at 8 weeks after following STZ and NA administration.
Assuntos
Cardiomegalia/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/fisiopatologia , Resistência Vascular , Animais , Aorta/fisiopatologia , Elasticidade , Eletroforese em Gel de Poliacrilamida , Hemodinâmica , Masculino , Fluxo Pulsátil , Ratos , Ratos WistarRESUMO
The clinical features and microbiological characteristics of 315 patients with definite or possible infective endocarditis (IE) from January 1995 to December 2003 were evaluated. There were 187 males and 128 females with a mean age of 51 years (range, 1 month to 92 years). Ninety-three patients (30%) had a diagnosis of valvular heart disease and 24 (8%) had received prosthetic valve replacement. Blood culture was negative in 62 patients (20%). Staphylococci (91 patients, 32%), including methicillin-susceptible Staphylococcus aureus (15%), methicillin-resistant S. aureus (11%), and coagulase-negative staphylococci (6%), were the most commonly encountered pathogens followed by viridans group streptococci (77 patients, 24%). Eight patients (25%) had various neurological, renal, embolic, and cardiac complications. Patients with neurological complications [odds ratio (OR) 8.175, P<0.001], nosocomial IE (OR 6.661, P<0.001), underlying malignancy (OR 4.993, P<0.001), elevated serum creatinine level (OR 3.132, P=0.001), or elevated WBC count (>15000/mm3) (OR 2.537, P=0.007) were at significantly increased risk of mortality. This study found mortality from IE was associated with several factors, among which neurological complications were the most hazardous. Patients with more than one risk factor had poorer prognosis. These results suggest the need for more aggressive management in patients with IE when multiple risk factors for mortality are identified.
Assuntos
Endocardite Bacteriana/mortalidade , Adulto , Idoso , Bacteriemia/microbiologia , Bactérias/isolamento & purificação , Endocardite Bacteriana/microbiologia , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Taiwan , Fatores de TempoRESUMO
Reports of the association of Chlamydia pneumoniae (C. pneumoniae) infection with coronary artery disease (CAD) are scarce in the Oriental population. We therefore conducted a case-control study to explore this issue in Taiwan. There were 242 consecutive subjects (166 men and 76 women) who underwent cardiac catheterization at the National Taiwan University Hospital Cardiac Catheterization Laboratory. Patients with CAD (n = 156) had > or = 1 coronary artery lesion of > 50% diameter stenosis on angiography. Controls (n = 86) had no demonstrable CAD angiographically. Antibodies to C. pneumoniae were tested by using an enzyme-linked immunosorbent assay. The prevalence of antibodies to C. pneumoniae was as follows: immunoglobulin-G (IgG), 50% (122 of 242 patients); immunoglobulin-A (IgA), 72% (176 of 242 patients); and either IgG or IgA, 79% (192 of 242 patients ). The odds ratio (OR) for CAD with either IgG or IgA was 1.4 (95% confidence interval [CI] 0.7 to 2.7, p = 0.31). After adjusting for the known CAD risk factors, the OR decreased to 0.8 (95% CI 0.3 to 2.1, p = 0.60). The OR for unstable angina or acute myocardial infarction with the presence of either IgG or IgA was 0.5 (95% CI 0.2 to 1.1, p = 0.08) and 0.4 ( 95% CI 0.1 to 1.0, p = 0.049) after adjusting for other risk factors. These results suggest a high prevalence of C. pneumoniae infection in Taiwan. However, C. pneumoniae infection is not associated with angiographically documented CAD, and, in contrast, is a negative predictor for the development of acute coronary syndromes.
Assuntos
Angina Instável/microbiologia , Infecções por Chlamydophila/epidemiologia , Chlamydophila pneumoniae , Doença das Coronárias/microbiologia , Infarto do Miocárdio/microbiologia , Idoso , Angina Instável/epidemiologia , Estudos de Casos e Controles , Angiografia Coronária , Doença das Coronárias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prevalência , Estudos Soroepidemiológicos , TaiwanRESUMO
Cilostazol, a novel oral phosphodiesterase inhibitor, has shown consistent improvement in exercise tolerance in patients with intermittent claudication (IC). In addition to this effect, cilostazol has previously been shown to have beneficial effects on the dyslipidemia, i.e., combination of high triglycerides with low high-density-lipoprotein cholesterol (HDL-C) levels. Interleukin-6 (IL-6) suppresses the activity of lipoprotein lipase, which modulates the metabolism of triglycerides and HDL-C. To determine whether a reduction of IL-6 contributes to the improvement of lipid profiles, we prospectively investigated the effect of cilostazol (n=16, 100 mg, twice daily) on the changes of lipid profiles and on the association with the changes of IL-6 compared with those of pentoxifylline (n=16, 400 mg, bid) in patients with IC. After eight weeks of administration of cilostazol to patients with IC, walking distances were increased, associated with a 29% decrease in plasma triglycerides and a 13% increase in HDL-C. No significant changes of lipid profiles in the pentoxifylline and placebo groups were observed although a similar improvement in walking distances was achieved in the pentoxifylline group. IL-6 levels were significantly reduced in patients receiving cilostazol as compared with those receiving placebo or pentoxifylline. The cilostazol-induced changes in the IL-6 were positively related to those of triglycerides in the cilostazol group (r=0.63, P<0.05) and negatively related to those of HDL-C (r=-0.55, P<0.05). These findings suggest that in addition to consistent improvement of exercise tolerance, cilostazol may improve lipid profiles by reducing IL-6 release. However, pentoxifylline did not affect lipid profiles although a similar improvement of maximal walking distance (MWD) was achieved.
Assuntos
Inibidores Enzimáticos/uso terapêutico , Hipolipemiantes/uso terapêutico , Interleucina-6/sangue , Claudicação Intermitente/sangue , Lipídeos/sangue , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Tetrazóis/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Cilostazol , Método Duplo-Cego , Feminino , Humanos , Interleucina-6/fisiologia , Claudicação Intermitente/tratamento farmacológico , Masculino , Estudos Prospectivos , Triglicerídeos/sangueRESUMO
To evaluate whether or not ultrasonic tissue characterization (UTC) can detect jeopardized or salvageable myocardium in patients having chronic coronary artery disease, we studied 103 patients with sequential UTC, dobutamine stress echocardiography (DSE) and (201)thallium stress-reinjection single-photon emission computed tomography (T1-SPECT). This revealed that the weighted amplitude of the cyclic modulation of integrated backscatter was larger for the myocardium with less ischemia burden or greater viability (p<0.001). The segments with larger ischemia burden or the nonviable myocardium demonstrated the contrary result. Using the receiver-operating characteristic curve analyses to determine the cutoff value of weighted amplitude for various predictions, UTC can detect ischemia in normokinetic myocardium (kappa = 0.34 compared to DSE or T1-SPECT) and viability in dyssynergic myocardium (kappa = 0.57 compared to DSE and 0.45, to T1-SPECT). These observations show that UTC may prove useful in the identification and pathophysiological understanding of myocardial ischemia and viability.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Ecocardiografia/métodos , Cardiotônicos/administração & dosagem , Doença Crônica , Doença das Coronárias/fisiopatologia , Dobutamina/administração & dosagem , Teste de Esforço , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Miocárdio/metabolismo , Curva ROC , Índice de Gravidade de Doença , Radioisótopos de Tálio/administração & dosagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Genes with important functions and rarely expressed would probably more easily be cloned from a modified equalized kidney cDNA library for further investigation. METHODS: A kidney cDNA library of a spontaneously hypertensive rat was synthesized by a modified equalization method. Inserts of random clones were amplified by PCR and sequenced. Sequences were compared against a nonredundant database in GenBank. The cDNA profile was compared with an expression profile of a mouse renal proximal tubule cDNA library. Seven clones were analyzed by Northern blot analysis. The cDNA ends of two novel genes were amplified by PCR, sequenced and analyzed. RESULTS: 336 cDNA clones were analyzed and grouped into 323 species of transcript with 77 species similar to previously reported genes. Northern blot analysis identified one kidney-specific, one rarely expressed and lung-specific, and another relatively testis-specific gene. Two novel genes were cloned. One was 4.1 kb in length and encoded a 390-amino acid zinc-finger protein. Another was 2.5 kb and encoded a 474-amino acid protein of unknown function. Compared with the expression profile of a mouse renal proximal tubule cDNA library, this kidney library had a lower proportion of ribosomal genes and had a greater proportion of genes for signal transduction and DNA or RNA binding. CONCLUSIONS: Rare or novel genes could be more easily isolated from this library for molecular study of hypertension and renal pathophysiology.
Assuntos
DNA Complementar/genética , Hipertensão/genética , Rim/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Primers do DNA/genética , Expressão Gênica , Biblioteca Gênica , Humanos , Masculino , Camundongos , Dados de Sequência Molecular , Ratos , Ratos Endogâmicos SHR , Dedos de Zinco/genéticaRESUMO
BACKGROUND AND PURPOSE: Genetic and environmental factors may contribute to the pathogenesis of essential hypertension. To facilitate genetic studies of hypertension and renal disorders, we sought to clone novel genes from a modified, equalized kidney (MEK) cDNA library of a spontaneously hypertensive rat (SHR). METHODS: A kidney cDNA library of an SHR was synthesized using the modified equalization method. Inserts of 350 random clones were amplified by polymerase chain reaction (PCR) and sequenced, of which 246 were presumably unknown after being compared against a nonredundant database in the GenBank. The cDNA ends of clone 38S were obtained by rapid amplification of cDNA ends, sequenced, and then analyzed with Translate, Prosite, Profile, SignalP, and TMpred programs. RESULTS: The full-length cDNA was 938 bp, and translated into a 182-amino acid protein. The deduced protein had a metallophosphoesterase domain, a signal peptide at its amino end, a protein kinase C phosphorylation site, and a transmembrane domain. Northern blot analysis revealed that this gene was expressed in the heart, brain, spleen, lungs, liver, skeletal muscles, kidneys and testes of Sprague-Dawley rats. A putative protein of Arabidopsis thaliana shares 62% homology with protein 38S, but the two proteins differ in terms of function and structure. CONCLUSIONS: Our results support that protein 38S is a novel membrane metallophosphoesterase, although its function in the kidneys remains to be elucidated. This study also demonstrates the feasibility of using PCR to clone novel genes from our MEK cDNA library.
Assuntos
Fosfatase Ácida/genética , Hipertensão/enzimologia , Rim/enzimologia , Diester Fosfórico Hidrolases/genética , Esfingomielina Fosfodiesterase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Clonagem Molecular , Biblioteca Gênica , Masculino , Dados de Sequência Molecular , Ratos , Ratos Endogâmicos SHRRESUMO
The objective of the present study was to investigate the characteristics of body surface potential map (BSPM) findings during ventricular repolarization in patients with coronary artery disease (CAD). A total of 108 consecutive patients, 99 men and 9 women with angina pectoris and positive treadmill exercise test results as well as angiographically documented CAD underwent BSPM study in a fasting state. Their ages ranged from 30 to 70 years. There were 13 patients with right coronary artery (RCA) lesions, 37 with left anterior descending artery (LAD) lesions, 5 with left circumflex artery (LCX) lesions, 17 with both RCA and LAD lesions, 12 with both LCX and LAD lesions, and 24 with 3-vessel disease. The BSPMs were obtained by using the heart potential map system designed by Toyama et al. There were 59 lead points on the anterior chest wall and 28 on the back. The BSPMs in isopotential distribution were made every one msec throughout the ventricular activation period. The distribution of positive and negative potentials, potential maximum and potential minimum, polarity of potential distribution, and the reversal of potential distribution during ventricular repolarization were analyzed. The following information on BSPMs was obtained: (1) In early ventricular repolarization, the negative potential and the potential minimum appeared abnormally on the anterior thorax. The potential abnormality displayed on the right portion or the inferior portion in patients with RCA lesions, on the middle portion or the left portion in patients with LAD lesions, and on the left-superior portion or the left-middle portion in patients with LCX lesions. In patients with multi-vessel disease, the abnormal potential distribution showed a combined pattern of individual vessel lesions. (2) In some cases, the multipolar potential distribution appeared abnormally during the initial stage and the peak of the T wave. (3) The reversal of potential distribution was observed in about half of the patients. The characteristic findings of the BSPM during ventricular repolarization, including abnormal potential distribution, multipolar potential distribution and reversal of potential distribution, will be of clinical value in patients with CAD.
Assuntos
Mapeamento Potencial de Superfície Corporal , Doença das Coronárias/diagnóstico , Adulto , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/fisiopatologia , Doença das Coronárias/fisiopatologia , Eletrofisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Função VentricularRESUMO
One of the most important intracellular Ca2+ regulatory mechanisms in nonexcitable cells, "capacitative Ca2+ entry" (CCE), has not been adequately studied in astrocytes. We therefore investigated whether CCE exists in cultured rat cerebellar astrocytes and studied the roles of cyclic AMP (cAMP) and protein kinase C (PKC) in CCE. We found that (1) at least two different intracellular Ca2+ stores, the endoplasmic reticulum and mitochondria, are present in cerebellar astrocytes; (2) CCE does exist in these cells and can be inhibited by Ni2+, miconazole, and SKF 96365; (3) CCE can be directly enhanced by an increase in intracellular cAMP, as 8-bromoadenosine 3',5'-cyclic monophosphate (8-brcAMP), forskolin, and isobutylmethylxanthine have stimulatory effects on CCE; and (4) neither of the two potent protein kinase A (PKA) inhibitors, H8 and H89, nor a specific PKA agonist, Sp-adenosine 3',5'-cyclic monophosphothioate, had a significant effect on cAMP-enhanced Ca2+ entry. The [Ca2+]i increase was not due to a release from calcium stores, hyperpolarization of the membrane potential, inhibition of calcium extrusion, or a change in pHi, suggesting that cAMP itself probably acts as a novel messenger to modulate CCE. We also conclude that activation of PKC results in an increase in CCE. cAMP and PKC seem to modulate CCE by different pathways.
Assuntos
Astrócitos/metabolismo , Canais de Cálcio/metabolismo , Cálcio/metabolismo , Cerebelo/metabolismo , AMP Cíclico/fisiologia , Animais , Astrócitos/efeitos dos fármacos , Canais de Cálcio/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , AMP Cíclico/metabolismo , Ativação Enzimática , Feminino , Concentração de Íons de Hidrogênio , Masculino , Potenciais da Membrana , Proteína Quinase C/metabolismo , Proteína Quinase C/fisiologia , Ratos , Ratos WistarRESUMO
During early ventricular depolarization, the normal body surface potential map (BSPM) has a maximal potential that is greater than the absolute value of the minimal potential; this reverses in late depolarization, so that the absolute value of the minimal potential is greater. Nevertheless, an abnormal "early reversal" BSPM pattern has been observed in some patients with cardiovascular disease. To investigate the implications of this abnormal pattern, BSPMs were studied in 100 patients with angiographically proven coronary artery disease (CAD). There were 57 patients (57%; group A) with an abnormal early reversal pattern and 43 (43%; group B) without this early reversal pattern. A significant (> 70% narrowing) CAD lesion was observed in a significantly higher proportion of group A (97%) than group B (77%) patients, although the number of involved coronary arteries was not significantly different between the two groups. The maximal extent of the abnormal negative potential was significantly greater in group A (21.2 +/- 9.6 cm2) than in group B (12.2 +/- 7.5 cm2). The abnormal negative potential lasted significantly longer in group A (22.1 +/- 12.1 msec) than in group B (14.4 +/- 9.2 msec). Similarly, the minimal potential lasted significantly longer in group A (20.1 +/- 11.3 msec) than in group B (11.8 +/- 7.1 msec). These findings suggest that the abnormal early reversal BSPM pattern is a valuable indicator of extensive myocardial lesions and the severity of CAD.
Assuntos
Mapeamento Potencial de Superfície Corporal , Doença das Coronárias/diagnóstico , Doença das Coronárias/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: We report the electrophysiologic study and radiofrequency catheter ablation of isthmus-independent atrial flutter in 2 patients. The isthmus-independent atrial flutter in these 2 patients had similar ECG and electrophysiologic findings. Both were reproducibly induced by rapid atrial pacing. The atrial activation sequence and entrainment study proved that these atrial flutters were not isthmus-dependent. A high-right atrial site was identified as the critical site of the slow conduction zone of the tachycardia in both. This site showed double potentials and mid-diastolic potentials. Radiofrequency catheter ablation at this site successfully eliminated the isthmus-independent atrial flutter in both patients.
Assuntos
Flutter Atrial/cirurgia , Ablação por Cateter , Eletrofisiologia/métodos , Átrios do Coração/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Flutter Atrial/fisiopatologia , Cateterismo Cardíaco , Seguimentos , Sistema de Condução Cardíaco/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos TestesRESUMO
In the presence of a normal atrial systole and optimal AV delay, atrial kick contributes to a significant fraction of the stroke volume. This atrial contribution may be lost during atrial asystole or mismatch in the timing of atrial and ventricular contraction. A patient received atrial compartment operation for his chronic AF. Although the AF was successfully converted to sinus rhythm, the conduction from the right to left atrium was markedly delayed so that the left atrial and ventricular activations occurred almost simultaneously. This delay in left atrial activation resulted in impaired cardiac performance.
Assuntos
Fibrilação Atrial/cirurgia , Função do Átrio Esquerdo/fisiologia , Débito Cardíaco/fisiologia , Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial , Eletrofisiologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
The body surface potential map (BSPM) may reflect regional myocardial electrical activity. This technique can thus provide information regarding the excitation of ventricles. This study is an attempt to evaluate the usefulness of BSPM in determining the sites of the atrioventricular (AV) accessory pathway (AP) in patients with Wolff-Parkinson-White (W-P-W) syndrome. The BSPMs were obtained from 40 consecutive patients with W-P-W syndrome in a fasting state, using the heart potential map system designed by Toyama et al. Unipolar electrocardiograms were recorded simultaneously from 87 lead points on the chest surface, including 59 lead points on the anterior chest and 28 on the back. Wilson's central terminal was used as a voltage reference and BSPMs in an isopotential distribution pattern were made every millisecond throughout ventricular activation from these unipolar ECGs with the use of a microcomputer system. All patients underwent an electrophysiologic study (EPS) at cardiac catheterization. We analyzed the potential distribution during ventricular depolarization and compared the results between EPS and BSPM findings. The following results were obtained: (1) seven types of BSPM pattern were identified in accordance with the sites of the AV AP confirmed by EPS; (2) the location of the potential minimum of ventricular depolarization and the direction of the excitation wavefront during early ventricular depolarization, the reversal pattern of ventricular potential distribution, the epicardial right ventricular breakthrough and the dynamic change of ventricular potential distribution were useful for the detection of the ventricular pre-excitation site; (3) epicardial right ventricular breakthrough occurred in nearly all patients with left ventricular free wall accessory AV connections; (4) the abnormal early reversal pattern of ventricular potential distribution did not occur in patients with left ventricular AV connections but did appear in most patients with right ventricular free wall AV connections. Accordingly, BSPM is a reliable non-invasive procedure to determine the ventricular pre-excitation sites of patients with W-P-W syndrome.