RESUMO
Transforming growth factor-beta (TGF-beta)-stimulated clone-22 (TSC-22) was originally isolated as a TGF-beta-inducible gene. In this study, we identified TSC-22 as a potential leukemia suppressor. Two types of FMS-like tyrosine kinase-3 (Flt3) mutations are frequently found in acute myeloid leukemia: Flt3-ITD harboring an internal tandem duplication in the juxtamembrane domain associated with poor prognosis and Flt3-TKD harboring a point mutation in the kinase domain. Comparison of gene expression profiles between Flt3-ITD- and Flt3-TKD-transduced Ba/F3 cells revealed that constitutive activation of Flt3 by Flt3-TKD, but not Flt3-ITD, upregulated the expression of TSC-22. Importantly, treatment with an Flt3 inhibitor PKC412 or an Flt3 small interfering RNA decreased the expression level of TSC-22 in Flt3-TKD-transduced cells. Forced expression of TSC-22 suppressed the growth and accelerated the differentiation of several leukemia cell lines into monocytes, in particular, in combination with differentiation-inducing reagents. On the other hand, a dominant-negative form of TSC-22 accelerated the growth of Flt3-TKD-transduced 32Dcl.3 cells. Collectively, these results suggest that TSC-22 is a possible target of leukemia therapy.
Assuntos
Regulação Leucêmica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Leucemia/terapia , Proteínas Repressoras/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/química , Animais , Células HL-60 , Humanos , Leucemia/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Células U937 , Tirosina Quinase 3 Semelhante a fms/imunologiaRESUMO
The objective is to evaluate the efficacy of anthocyanin-rich purple-fleshed sweet potato (PSP) beverage on the serum levels of gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in healthy Caucasians with borderline hepatitis. Forty healthy Caucasians (41-69 years) consumed three bottles of the PSP beverage (177 mg anthocyanins per 125-ml bottle) or placebo (1.3 mg) per day for 8 weeks. Thirty-nine subjects completed the study and two subjects were excluded from statistical analysis. GGT levels in the PSP group on days 15 and 43 were lower (P=0.077 and 0.038, respectively), AST levels in the PSP group on days 29 and 43 were lower (P=0.010 and 0.045, respectively) and ALT level in the PSP group on day 43 was lower (P=0.037) than in the placebo group. The PSP beverage did not induce clinically relevant changes in other blood and clinical chemistry parameters.
Assuntos
Antocianinas/administração & dosagem , Bebidas , Hepatite/sangue , Ipomoea batatas/química , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , População Branca , gama-Glutamiltransferase/sangueRESUMO
Water scarcity is rapidly increasing in many regions. In a novel, multi-model assessment, we examine how human interventions (HI: land use and land cover change, man-made reservoirs and human water use) affected monthly river water availability and water scarcity over the period 1971-2010. Here we show that HI drastically change the critical dimensions of water scarcity, aggravating water scarcity for 8.8% (7.4-16.5%) of the global population but alleviating it for another 8.3% (6.4-15.8%). Positive impacts of HI mostly occur upstream, whereas HI aggravate water scarcity downstream; HI cause water scarcity to travel downstream. Attribution of water scarcity changes to HI components is complex and varies among the hydrological models. Seasonal variation in impacts and dominant HI components is also substantial. A thorough consideration of the spatially and temporally varying interactions among HI components and of uncertainties is therefore crucial for the success of water scarcity adaptation by HI.
RESUMO
The effects of various new anthracycline antibiotics on DNA and RNA synthesis were studied using DNA polymerase I (EC 2.7.7.7), RNA polymerase (EC 2.7.7.6) obtained from Escherichia coli and reverse transcriptase obtained from avian myeloblastosis virus. Aclacinomycin A, its analogues, baumycins A1 and A2, adriamycin and daunomycin showed potent inhibitory effects on these polymerases, with calf thymus DNA as template, with IC50 values of 10-30 microM. With poly(rA) x d(pT)10 as template for reverse transcriptase, aclacinomycin A and daunomycin showed IC50 values higher than 500 microM. Baumycins B1, B2, C1, and C2 showed high IC50 values on three polymerases. Addition of excess template DNA to the reaction mixture reversed the inhibitory effect of anthracyclines. Addition of calf thymus DNA to anthracyclines caused a bathochromic and hypochromic change in the visible spectrum. Apparent binding constant for aclacinomycin A, its analogues, and adriamycin were in the range of (1-2) X 10(6) M-1. Aclacinomycin A and adriamycin also bind to heat denatured DNA, but not strongly to yeast RNA. From these results, the structure-activity relationships of new anthracyclines on DNA binding and polymerase reactions are discussed.
Assuntos
Replicação do DNA/efeitos dos fármacos , DNA/metabolismo , RNA/biossíntese , Animais , Antibióticos Antineoplásicos , Bovinos , RNA Polimerases Dirigidas por DNA/antagonistas & inibidores , Matemática , Naftacenos/metabolismo , Inibidores da Síntese de Ácido Nucleico , Inibidores da Transcriptase Reversa , EspectrofotometriaRESUMO
Purine nucleotide pyrophosphotransferase was purified to apparent homogeneity from a culture filtrate of Streptomyces morookaensis. It is a monomeric protein with a molecular weight of 24 000-25 000, and its isoelectric point is 6.9. The enzyme synthesizes purine nucleoside 5'-phosphate (mono, di, or tri) 3'-diphosphates such as pppApp, ppApp, pApp, pppGpp, ppGpp and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides. The purified enzyme catalysed the formation of 435 mumol of pppApp and 620 mumol of pppGpp from ATP and GTP per min mg protein under the standard conditions. The enzyme requires absolutely a divalent cation for activity, and optimum pH for the enzyme activity lay above 10 for Mg2+, for Co2+ and Zn2+ from 9 to 9.5, and for Fe2+ from 7.5 to 8. The following Michaelis constants were determined: AMP, 2.78 mM; ADP, 3.23 mM; GMP, 0.89 mM; GDP, 0.46 mM and GTP, 1.54 mM, in the case of ATP donor. The enzyme is inhibited by guanine, guanosine, dGDP, dGTP, N-bromosuccinimide, iodacetate, sodium borate and mercuric acetate.
Assuntos
Fosfotransferases/metabolismo , Nucleotídeos de Purina/biossíntese , Streptomyces/enzimologia , Trifosfato de Adenosina/metabolismo , Boratos/farmacologia , Bromosuccinimida/farmacologia , Cátions Bivalentes , Difosfatos/metabolismo , Difosfotransferases , Guanina/farmacologia , Guanosina/farmacologia , Guanosina Trifosfato/metabolismo , Concentração de Íons de Hidrogênio , Iodoacetatos/farmacologia , Cinética , Magnésio/farmacologia , Peso Molecular , Fosfotransferases/isolamento & purificaçãoRESUMO
The behavior of an organic hydroperoxide in the presence of lipid and/or alpha-tocopherol in model membranes has been studied using 14C-labeled cholesterol-5 alpha-hydroperoxide as the organic hydroperoxide. Cholesterol-F alpha-hydroperoxide in saturated phospholipid micelles is rapidly isomerized to cholesterol-7 alpha-hydroperoxide. Such an isomerization is inhibited by alpha-tocopherol, but not by an alpha-tocopheryl analogue with a substituted OH groups, present in the micelles, indicating the formation of hydrogen bonds between OH group in alpha-tocopherol and OOH group in the 5 alpha-hydroperoxide. The double bonds in unsaturated phospholipid can also serve to form a hydrogen bond with OOH in the 5 alpha-hydroperoxide moiety in the micelles. The resulting hydrogen-bonded complex could be decomposed by iron-induced lipid peroxidation, accompanied by isomerization of the 5 alpha-hydroperoxide and the further degradation to the 7-ketocholesterol and 7 alpha-hydroxycholesterol. When three components, such as unsaturated phospholipid, 5 alpha-hydroperoxide and alpha-tocopherol, are present in the same micelles, they form hydrogen bonded complexes. Such complexes could be decomposed by iron in the ferrous state, yielding mainly 5 alpha-hydroxycholesterol without significant change in the structure of alpha-tocopherol and peroxidative cleavage of unsaturated phospholipid.
Assuntos
Colesterol/metabolismo , Peróxidos Lipídicos/metabolismo , Lipossomos , Vitamina E/metabolismo , Animais , Técnicas In Vitro , Lipídeos de Membrana/metabolismo , Microssomos Hepáticos/metabolismo , Fosfolipídeos/metabolismo , RatosRESUMO
OBJECTIVES: The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity immediately after successful primary stenting and the recovery of left ventricular (LV) wall motion in patients with acute myocardial infarction (AMI). BACKGROUND: It is difficult to predict the recovery of LV wall motion immediately after direct angioplasty in AMI. Recent reports indicate that dysfunctional coronary microcirculation is an important determinant of prognosis for AMI patients after successful reperfusion. METHODS: We measured left anterior descending coronary flow velocity variables using a Doppler guide wire immediately after successful primary stenting in 31 patients with their first anterior AMI. The patients were divided into two groups: those with and those without early systolic reverse flow (ESRF). Changes in LV regional wall motion (RWM) and ejection fraction (EF) at admission and at discharge were compared between the two groups. Coronary flow velocity variables immediately after primary stenting were compared with changes in left ventriculographic indexes. RESULTS: The change in RWM was significantly greater in the non-ESRF group than it was in the ESRF group (0.9 +/- 0.7 vs. -0.1 +/- 0.3 standard deviation/chord, respectively, p < 0.001). The change in EF was also significantly greater in the non-ESRF group than it was in the ESRF group (10 +/- 10 vs. 1 +/- 6%, respectively, p < 0.05). In the non-ESRF group (diastolic to systolic velocity ratio [DSVR] <3.0), the DSVR correlated positively with the change in RWM (r = 0.60, p < 0.005, n = 24) and the change in EF (r = 0.52, p < 0.01). CONCLUSIONS: The coronary flow velocity pattern measured immediately after successful primary stenting is predictive of the recovery of regional and global LV function in patients with AMI.
Assuntos
Circulação Coronária , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Stents , Função Ventricular Esquerda/fisiologia , Idoso , Velocidade do Fluxo Sanguíneo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Volume Sistólico , Fatores de TempoRESUMO
OBJECTIVES: This study was designed to elucidate the genesis of the Austin Flint murmur. BACKGROUND: The Austin Flint murmur is an apical diastolic rumble associated with significant aortic regurgitation. The precise mechanism of the murmur remains unclear. METHODS: The relation between the Austin Flint murmur and mitral inflow and aortic regurgitant flow dynamics was evaluated nonivasively in 13 patients with moderate to severe aortic regurgitation and 15 control subjects using phonocardiographic and pulsed and color-coded Doppler echocardiographic techniques. The severity of aortic regurgitation was determined by color-coded Doppler echocardiography on the basis of the maximal distance of the regurgitant signal. RESULTS: The direction of aortic regurgitant flow was unrelated to the presence of the Austin Flint murmur. The severity of aortic regurgitation was greater in patients with than in those without this murmur. The peak mitral inflow velocity during early diastole (E) was significantly increased, and both peak mitral inflow velocity at atrial contraction (A) and the A/E ratio were significantly decreased in patients with the Austin Flint murmur compared with values in those without this murmur or in control subjects. However, the maximal amplitude of the Austin Flint murmur did not coincide temporally with the peak mitral inflow velocity. The murmur continued both after rapid mitral inflow had ended and during diastolic mitral regurgitation. CONCLUSIONS: The increased velocity of early diastolic mitral inflow in patients with the Austin Flint murmur is due to aortic regurgitation, but rapid mitral inflow is not an essential requirement for production of the murmur. In some cases, the Austin Flint murmur may be generated by aortic regurgitant flow alone.
Assuntos
Insuficiência da Valva Aórtica/fisiopatologia , Sopros Cardíacos/fisiopatologia , Valva Mitral/fisiopatologia , Adulto , Idoso , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Ecocardiografia Doppler , Feminino , Sopros Cardíacos/diagnóstico por imagem , Sopros Cardíacos/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , FonocardiografiaRESUMO
The 5'-flanking region of the mouse R-type calcium channel (Cchra1) gene was cloned, and a transcriptional start point (tsp) was determined by rapid amplification of 5'-cDNA end (5'RACE) method. The putative promoter region of the gene contained no obvious TATA or CCAAT element in the expected positions, but multiple putative binding sites for transcriptional factors, such as Sp1, AP-1, AP-2, AP-3, EGR-1, EGR-2, NF-kappaB and HIP1, were detected. We found the existence of a tandem CTT trinucleotide repeat within the 5'-untranslated region (UTR) of the gene, and its polymorphism between C57BL/6J and Mus spretus. Using this polymorphism, the Cchra1 was mapped to the region of chromosome 1 where the synteny to human chromosome 1q was conserved.
Assuntos
Canais de Cálcio/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação/genética , Canais de Cálcio/química , Canais de Cálcio/classificação , Mapeamento Cromossômico , Clonagem Molecular , Primers do DNA/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Muridae , Reação em Cadeia da Polimerase , Polimorfismo Genético , Regiões Promotoras Genéticas , Especificidade da Espécie , Fatores de Transcrição/metabolismo , Repetições de TrinucleotídeosRESUMO
Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the first and rate-limiting enzyme of the hexosamine biosynthesis pathway, which plays an important role in glucose toxicity and cellular insulin resistance. Thus, the mechanisms by which GFAT expression is regulated under physiological and pathological conditions are of interest in connection with diabetes. In this study, we cloned the 5'-flanking region of the mouse GFAT2 gene and characterized its promoter activity. Sequence analysis revealed several putative regulatory elements Sp1, a CCAAT box, AP-1 and AP-2, but no TATA box. Transfection experiments showed that the 5'-flanking region between -2462 to +38 relative to the transcription start site of the GFAT2 gene drives transcription in NIH3T3 cells and that the fragment from -141 to -9 has the highest transcription activity. Reporter assays using deletion and mutant variants suggested that the Sp1 sites at positions -83 to -78 and -22 to -17 both play an important role in the basal promoter activity of the mouse GFAT2 gene. Electrophoretic mobility shift assay showed DNA-protein binding at both Sp1 sites. We also compared the promoter activities of mouse GFAT1 and GFAT2 in several cell lines.
Assuntos
Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Regiões Promotoras Genéticas/genética , Células 3T3 , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Linhagem Celular , Clonagem Molecular , DNA/química , DNA/genética , DNA/metabolismo , Regulação Enzimológica da Expressão Gênica , Humanos , Íntrons , Isoenzimas/genética , Isoenzimas/metabolismo , Camundongos , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Mutação , Ligação Proteica , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Fator de Transcrição Sp1/metabolismo , Células Tumorais CultivadasRESUMO
We show here novel intracellular Ca2+ oscillation in v-K-ras-transformed NIH3T3 cells induced by mitogenic peptide hormones, bradykinin and bombesin, as well as fetal calf serum. Induction of the Ca2+ oscillation is strongly correlated with the malignant properties and inversely with PKC activities in vitro and in vivo. These results suggest that the mitogen-induced Ca2+ oscillation is negatively regulated by PKC, which modulates Ca2+ influx in v-K-ras-transformed NIH3T3 cells.
Assuntos
Bombesina/farmacologia , Bradicinina/farmacologia , Cálcio/metabolismo , Transformação Celular Neoplásica , Genes ras , Proteína Quinase C/metabolismo , Animais , Linhagem Celular , Eletroforese em Gel Bidimensional , Cinética , Camundongos , Fosfoproteínas/isolamento & purificaçãoRESUMO
OBJECTIVE: To investigate the relationship between the angiotensin converting enzyme (ACE) gene polymorphism and the effects of the ACE inhibitor enalapril on left ventricular hypertrophy and impaired diastolic filling. DESIGN AND METHODS: Enalapril (5-10 mg/day) was administered for 12 months to 60 previously untreated patients with essential hypertension. M-mode and pulsed Doppler echocardiography were performed before and after treatment, and changes in various parameters after treatment with enalapril were examined. ACE gene polymorphism was examined by the polymerase chain reaction method and the patients were classified as having the 190 bp deletion homozygous (DD) genotype, the 490 bp insertion homozygous (II) genotype or the 490 bp insertion 190 bp deletion heterozygous (ID) genotype. RESULTS: The DD genotype was observed in 10 patients (17%), the ID genotype in 24 patients (40%) and the II genotype in 26 patients (43%). Plasma ACE activity before treatment with enalapril was significantly higher in seven patients with DD genotype than it was in 18 patients with ID genotype and in 14 patients with II genotype. In all of the 60 patients, the left ventricular mass index, the peak atrial systolic velocity:early diastolic velocity ratio and the deceleration time from the peak of the early diastolic wave to the baseline in transmitral flow velocity were decreased significantly after treatment with enalapril. The changes in left ventricular mass index and atrial systolic velocity:early diastolic velocity ratio after enalapril administration were significantly greater in the DD genotype group than they were in the other two genotype groups. CONCLUSION: Enalapril-induced regression of left ventricular hypertrophy and improvement in left ventricular impaired diastolic filling were significantly greater in the DD genotype group than they were in the ID and II genotype groups, suggesting that the circulating and tissue renin-angiotensin systems, particularly the former system, are most active in hypertensive patients with the DD genotype.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diástole/efeitos dos fármacos , Ecocardiografia Doppler de Pulso , Enalapril/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Peptidil Dipeptidase A/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Hipertensão/genética , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Polimorfismo GenéticoRESUMO
A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed. Compound 18b, BMY 40062, exhibits the most favorable overall properties, considering in vitro and in vivo microbiological activity, its low toxicity, and pharmacokinetic profile, and was selected for clinical evaluation.
Assuntos
Anti-Infecciosos/síntese química , Fluoroquinolonas , Naftiridinas , 4-Quinolonas , Animais , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Fenômenos Químicos , Química , Cães , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Taxa de Depuração Metabólica , Camundongos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
A series of novel 7-piperazinyl-1-substituted-6-fluoroquinolones and naphthyridines have been prepared and their antibacterial activities evaluated. These derivatives are characterized by having alkyl, alkenyl, arylalkyl, cycloalkyl, and cycloalkenyl groups at the 1-position. As a result of this study, derivatives 7 and 26, which are substituted with tert-butyl groups at N-1, were found to possess excellent in vitro and in vivo potency, particularly against Staphylococcus aureus, comparable to that of norfloxacin or ciprofloxacin. Structure-activity relationships of N-1 substituted alkyls and cycloalkyls are also discussed.
Assuntos
Antibacterianos/síntese química , Naftiridinas/síntese química , 4-Quinolonas , Animais , Antibacterianos/farmacologia , Fenômenos Químicos , Química , Cães , Bactérias Gram-Negativas/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftiridinas/farmacologia , Staphylococcus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
We investigated temporary changes in left atrial appendage (LAA) flow velocity patterns in patients undergoing electrical cardioversion for chronic isolated atrial fibrillation, and evaluated the role of active LAA contraction in directing blood flow to the left atrial main chamber and left ventricle. The study consisted of 26 patients with chronic isolated atrial fibrillation treated with electrical cardioversion and 20 normal controls in sinus rhythm. Using transthoracic and transesophageal Doppler echocardiography, we recorded transmitral, pulmonary venous, and LAA flow velocity patterns before, 24 hours, and 1 week after cardioversion in all subjects. In the 15 patients who underwent successful cardioversion, the maximal LAA area 24 hours after cardioversion was smaller than the area before cardioversion, whereas LAA ejection fraction during atrial systole and peak atrial systolic emptying velocity of the LAA flow were lower 24 hours after cardioversion than those in the control group. One week after cardioversion, maximal LAA area and LAA peak atrial systolic emptying velocity were restored to levels approximately equivalent to those in the control group, although LAA ejection fraction was lower than in the control group. Maximal LAA area and LAA peak atrial systolic emptying velocity correlated negatively and positively with LAA ejection fraction, respectively, 24 hours and 1 week after cardioversion. These results suggest that LAA and the left atrial main chamber show stunning 24 hours after cardioversion, and the atrial systolic emptying wave of LAA flow is generated by active LAA contraction.
Assuntos
Fibrilação Atrial/terapia , Função do Átrio Esquerdo , Circulação Coronária , Cardioversão Elétrica , Adulto , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Velocidade do Fluxo Sanguíneo , Débito Cardíaco , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/fisiopatologia , Contração Miocárdica , Miocárdio Atordoado/fisiopatologia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Volume Sistólico , Sístole , Função Ventricular EsquerdaRESUMO
Conventional assessment of left ventricular (LV) relaxation by calculating the time constant of LV pressure decay during the isovolumic diastole requires an invasive approach. Conversely, noninvasive parameters obtained by measuring isovolumic relaxation time and transmitral flow velocity often give inaccurate information. Using LV pressure curve, pulsed Doppler echocardiography, and pulsed Doppler tissue imaging in 38 patients with heart disease and 12 control subjects, we calculated the time constant and recorded transmitral flow velocity and motion velocities at the endocardial portions of the ventricular septum and LV posterior wall. Compared with the controls, patients exhibited a prolonged time constant, a decreased peak early diastolic velocity of the LV posterior wall, and a prolonged time interval from the second heart sound to the peak of the early diastolic wave. The time constant correlated well with the isovolumic relaxation time and various parameters calculated from the transmitral flow velocity, except in patients with elevated LV end-diastolic pressure. In all subjects, the time constant correlated negatively with the peak early diastolic velocity of the posterior wall and positively with the time from the second heart sound to the peak of the early diastolic wave. Thus, early diastolic parameters derived from the motion velocity of the LV posterior wall by pulsed Doppler tissue imaging were closely related to the time constant. This technique may allow noninvasive evaluation of abnormal LV relaxation in patients with various heart diseases.
Assuntos
Ecocardiografia Doppler de Pulso , Contração Miocárdica/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo/fisiologia , Cateterismo Cardíaco , Estudos de Casos e Controles , Angiografia Coronária , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Disfunção Ventricular Esquerda/fisiopatologia , Pressão Ventricular/fisiologiaRESUMO
We evaluated the role of left atrial appendage (LAA) in the left atrial (LA) reservoir function by assessing the changes in LA flow dynamics after LAA clamping during cardiac surgery. The subjects were 8 patients who had undergone coronary artery bypass grafting (CABG) and 7 who had undergone mitral valvular surgery due to mitral regurgitation. We recorded transmitral, pulmonary venous and LAA flow velocity patterns by intraoperative transesophageal pulsed Doppler echocardiography, monitoring LA pressure before and 5 minutes after LAA clamping. The maximal LAA area was significantly greater, and the peak late diastolic LAA emptying flow velocity was significantly lower before LAA clamping in the mitral regurgitation group than in the CABG group. In both groups, the peak early and late diastolic transmitral and pulmonary venous flow velocities significantly increased, and the peak second systolic pulmonary flow velocity significantly decreased during LAA clamping. There were no significant changes in heart rate and systemic systolic blood pressure during LAA clamping, whereas mean LA pressure and maximal LA dimension significantly increased in both the groups. The LA pressure-volume relation during ventricular systole shifted upward and to the left during LAA clamping, and the slope was steeper in the MR group than in the CABG group. We conclude that the LAA is more compliant than the LA main chamber, and plays an important role in LA reservoir function in the presence of LA pressure and/or volume overload.
Assuntos
Função do Átrio Esquerdo/fisiologia , Ponte de Artéria Coronária , Implante de Prótese de Valva Cardíaca , Idoso , Velocidade do Fluxo Sanguíneo , Constrição , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Feminino , Átrios do Coração/diagnóstico por imagem , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Função VentricularRESUMO
To elucidate predisposing factors for severe mitral regurgitation (MR) in idiopathic mitral valve prolapse (MVP), 124 MVP patients were classified into the following categories: 55 with isolated clicks (click group), 35 with a late-systolic murmur (late-SM group), and 34 with a holosystolic murmur (holo-SM group). Their clinical and echocardiographic findings were compared with those of 26 patients with spontaneous chordal rupture (rupture group). In 22 patients in the click group, 24 in the late-SM group, and 22 in the holo-SM group, follow-up studies were performed for a mean of 4.5 years (range 1 to 13.5). The mean age was youngest in the click group and oldest in the rupture group. The click and late-SM groups showed a female predominance, but the holo-SM and rupture groups showed a male predominance. There was no difference in the incidence of systemic hypertension among the 4 groups. Most patients in the click and late-SM groups had anterior leaflet prolapse. In the holo-SM and rupture groups, however, the incidence of posterior leaflet involvement was significantly increased. The incidence of thickened mitral valve increased in order of the click (8%), late-SM (21%), holo-SM (38%), and rupture (50%) groups. Six patients in the holo-SM group developed chordal rupture with severe MR during the follow-up period. In the click and late-SM groups, however, there were no complications and no development into a holo-SM. Thus, aging, male sex, posterior leaflet prolapse, thickened mitral valve, and holo-SM were found to be important predisposing factors for severe MR in idiopathic MVP.
Assuntos
Insuficiência da Valva Mitral/etiologia , Prolapso da Valva Mitral/complicações , Adulto , Fatores Etários , Idoso , Distribuição de Qui-Quadrado , Cordas Tendinosas , Ecocardiografia , Feminino , Sopros Cardíacos/diagnóstico , Sopros Cardíacos/etiologia , Ruptura Cardíaca/complicações , Ruptura Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Prolapso da Valva Mitral/diagnóstico , Fonocardiografia , Fatores de Risco , Fatores SexuaisRESUMO
In conclusion, alterations in venous return are more marked in the right side of the heart than in the left side of the heart in patients with complete absence of the left pericardium.