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1.
Circulation ; 100(4): 427-36, 1999 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-10421605

RESUMO

BACKGROUND: Determinants of left atrial (LA) reservoir function and its influence on left ventricular (LV) function have not been quantified. METHODS AND RESULTS: In an open-pericardium, paced (70 and 90 bpm) pig model of LV regional ischemia (left anterior descending coronary constriction), with high-fidelity LV, LA, and RV pressure recordings, we obtained the LA area with 2D automated border detection echocardiography, LA pressure-area loops, and Doppler transmitral flow. We calculated LV tau, LA relaxation (a-x pressure difference divided by time, normalized by a pressure), and stiffness (slope between x and v pressure points of v loop). Determinants of total LA reservoir (maximum-minimum area, cm(2)) were identified by multiple regression analysis. Different mean rates of LA area increase identified 2 consecutive (early rapid and late slow) reservoir phases. During ischemia, LV long-axis shortening (LAS, LV base systolic descent) and LA reservoir area change decreased (7.3+/-0.3 [SEM] versus 5.6+/-0.3 cm(2), P<0.001) and LA stiffness increased (1.6+/-0.3 versus 3.1+/-0.3 mm Hg/cm(2), P=0.009). Early reservoir area change depended on LA mean ejection rate (LA area at ECG P wave minus minimum area divided by time; multiple regression coefficient=0.9; P<0.001) and relaxation (coefficient=4.9 cm(2)xms/s; P<0.001). Late reservoir area change depended on LAS (coefficient=8 cm/s; P<0.001). Total reservoir filling depended on LA stiffness (coefficient=-0.31 cm(4)/mm Hg; P=0. 001) and cardiac output (coefficient=0.001 cm(2)xmin/L; P=0.002). The strongest predictor of cardiac output was LA reservoir filling (coefficient=301 L/minxcm(2); P<0.001). The v loop area was determined by cardiac output, LV ejection time, tau, and early transmitral flow. CONCLUSIONS: Two (early and late) reservoir phases are determined by LA contraction and relaxation and LV base descent. Acute LV regional ischemia increases LA stiffness and impairs LA reservoir function by reducing LV base descent.


Assuntos
Função do Átrio Esquerdo/fisiologia , Circulação Coronária/fisiologia , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia , Elasticidade , Frequência Cardíaca/fisiologia , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Pressão , Suínos , Sístole
2.
J Am Coll Cardiol ; 24(1): 165-70, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8006261

RESUMO

OBJECTIVES: We evaluated left atrial dimensions and function, as well as left ventricular structure and filling, in hypertensive patients with paroxysmal atrial fibrillation. BACKGROUND: In hypertensive patients, left atrial dilation and enhanced volume transport may facilitate arrhythmias. METHODS: Left ventricular two-dimensional and M-mode echocardiograms and pulsed Doppler echocardiography of transmitral flow were performed in 17 consecutive primary hypertensive patients with paroxysmal atrial fibrillation (group EHf) and in 34 patients with high blood pressure without this arrhythmia (group EH). Seventeen normal subjects (group N) were also investigated. Groups were matched for age and gender. RESULTS: The EH and EHf groups had similar systolic arterial pressures ([mean +/- SD] group EH 185 +/- 27, group EHf 173 +/- 25 mm Hg, p = NS) and left ventricular mass index (group EH 154 +/- 55, group EHf 131 +/- 57.8 g/m2, p = NS), and their M-mode left ventricular systolic wall stress and fractional shortening were comparable to those of normal subjects. M-mode left atrial maximal (group N 37.8 +/- 6, group EH 37.9 +/- 4.6, group EHf 44.6 +/- 6.7 mm, p < 0.05 for group EHf vs. groups N and EH) and minimal diameters and the diameter preceding atrial contraction (group N 31 +/- 3.6, group EH 34.5 +/- 5, group EHf 40.4 +/- 6.9 mm, p < 0.001 for group EHf vs. group N; p < 0.05 for group EHf vs. group EH) were greater in group EHf than in group EH and group N subjects, whereas only the latter diameter was increased in group EH (p < 0.05 vs. group N), so that left atrial fractional shortening was higher than normal only in group EH (group N 10.8 +/- 4.4%, group EH 14.6 +/- 5.5%, group EHf 9.3 +/- 5.3%; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). The pulsed Doppler ratio of early to late transmitral flow rates (E and A wave velocity/time integrals x mitral annulus area) was lower than normal in group EH (group N 2.9 +/- 2.2, group EH 1.75 +/- 0.8, group EHf 2.8 +/- 0.8; group EH vs. group N, p < 0.05; group EHf vs. group EH, p < 0.001; group EHf vs. group N, p = NS) and was "normalized" in group EHf, early flow being increased in this group (group N 42 +/- 13, group EH 39 +/- 29, group EHf 60 +/- 17 ml; group EHf vs. group N, p < 0.05; group EHf vs. group EH, p < 0.05). CONCLUSIONS: These results suggest that the occurrence of paroxysmal atrial fibrillation in hypertension is associated with enlargement of the left atrium, depression of its contractile function and "normalization" of the pattern of left ventricular filling and is independent of left ventricular hypertrophy and systolic wall stress. The mechanisms linking these variables remain undefined.


Assuntos
Fibrilação Atrial/fisiopatologia , Função do Átrio Esquerdo , Hipertensão/fisiopatologia , Função Ventricular Esquerda , Idoso , Análise de Variância , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Doença Crônica , Diástole , Ecocardiografia/instrumentação , Ecocardiografia/métodos , Ecocardiografia/estatística & dados numéricos , Ecocardiografia Doppler/instrumentação , Ecocardiografia Doppler/métodos , Ecocardiografia Doppler/estatística & dados numéricos , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Sístole
3.
J Am Coll Cardiol ; 33(3): 854-66, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10080491

RESUMO

OBJECTIVES: To define the mechanical determinants of transmitral flow and the effect of heart rate during regional ischemia. BACKGROUND: Myocardial ischemia changes the transmitral flow velocity pattern due to disease-induced changes in the heart's diastolic properties. METHODS: Regional ischemia was produced in 12 pigs by partially occluding the left anterior descending coronary artery until segment-length shortening in the ischemic region fell by 20%. Transmitral flow velocity patterns and their determinants were measured under two conditions, baseline and ischemia, at two heart rates, 70 and 90 beats/min. RESULTS: Regional ischemia had a significant effect on two determinants of filling: relaxation, which was slower, and chamber stiffness, which increased. These changes were associated with reduced contractility and increased myocardial stiffness, resulting in an early transmitral flow pattern that was flatter and narrower, but no change in the late flow pattern. Moderate increases in heart rate accelerated relaxation and decreased atrioventricular pressure gradient but had no effect on contractility or myocardial or chamber stiffness, resulting in an early transmitral flow pattern that was flatter and narrower and an increased late flow velocity. CONCLUSIONS: This model of regional ischemia leads to a flatter and narrower early transmitral flow velocity pattern and no change in late flow due to a combination of slowed left ventricular relaxation and increased chamber stiffness. Reflex increases in heart rate that accompany ischemia tend to mask this effect.


Assuntos
Doença das Coronárias/fisiopatologia , Valva Mitral/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Doença das Coronárias/diagnóstico por imagem , Diástole , Modelos Animais de Doenças , Ecocardiografia Doppler de Pulso , Frequência Cardíaca , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Valva Mitral/diagnóstico por imagem , Suínos
4.
J Am Coll Cardiol ; 35(7): 1947-59, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10841248

RESUMO

OBJECTIVE: To elucidate determinants of pulmonary venous (PV) flow. BACKGROUND: Right ventricular (RV) systolic pressure (vis a tergo), left atrial (LA) relaxation and left ventricular (LV) systole and relaxation (vis a fronte) have been suggested as determinants of the pulmonary venous (PV) anterograde Doppler flow velocities, but their relative contributions to those flow velocities have not been quantified. METHODS: We analyzed, by multiple regression analysis, the determinants of PV anterograde velocities in an open-pericardium, paced (70 and 90 beats/min) pig model in which LA afterload was modified by creating LV regional ischemia (left anterior descending coronary artery constriction). We measured high fidelity LA, LV and RV pressures and Doppler flow velocities (epicardial echocardiography). We calculated LV tau, LA relaxation (a through x pressure difference divided by time, normalized by a pressure), LA peak v through x and RV systolic through LA peak v (RVSP-v) pressure differences, LV ejection fraction, long-axis shortening, stroke volume (LV outflow integral x outflow area) and LA four-chamber dimensions, Doppler transmitral and PV flow velocities and velocity-time integrals. RESULTS: Left ventricular regional ischemia increased mildly LA y trough pressure (8 +/- 1 vs. 6 +/- 1 mm Hg, p = 0.001). Left ventricular stroke volume (coefficient: 0.5 cm/ml, SE: 0.2, p = 0.005) and LA peak v pressure (coefficient: -0.8 cm/mm Hg, SE: 0.3, p = 0.008) determined the PV total systolic integral. Left atrial relaxation determined both PV early systolic peak velocity and integral (coefficient: -0.8 cm/mm Hg, SE: 0.3, p = 0.04). Left atrial maximum area (coefficient: 2 cm(-1) SE: 0.7, p = 0.01) and RVSP-v (coefficient: 0.1 cm/mm Hg, SE: 0.05, p = 0.03) determined the late systolic integral. The PV total systolic integral determined both PV early diastolic peak velocity and integral (coefficient: 1.2, SE: 0.2, p = 0.001). CONCLUSIONS: In an experimental model of LV acute ischemia of limited duration, the main independent predictors of PV systolic anterograde flow velocities are LA relaxation and compliance (LA peak v pressure) and LV systole--all vis a fronte factors. In the setting of mildly increased LA pressures, PV systolic flow (LA reservoir filling) is an independent predictor of PV early diastolic flow (LA early conduit).


Assuntos
Veias Pulmonares/fisiologia , Animais , Diástole , Isquemia Miocárdica/fisiopatologia , Pericárdio , Veias Pulmonares/diagnóstico por imagem , Fluxo Sanguíneo Regional , Análise de Regressão , Suínos , Sístole , Ultrassonografia Doppler
5.
Hypertension ; 7(6 Pt 1): 995-1002, 1985.
Artigo em Inglês | MEDLINE | ID: mdl-4077227

RESUMO

This study was undertaken to test whether the emphasized systemic vasomotion during sympathetic activation in hypertension is shared by the pulmonary circulation. To this end, 10 normotensive and 29 primary hypertensive subjects were investigated during adrenergic stimulation by mental arithmetic and cold pressor test. Both stimuli induced a systemic pressor reaction in both groups, which was mediated through an increase in cardiac output and a mild reduction in vascular resistance during arithmetic and through a predominant rise in systemic vascular resistance during cold. Each of these changes was emphasized in the hypertensive population as compared with the normotensive one. Pressure in the pulmonary artery remained unchanged during cold and was slightly raised (systolic) during arithmetic in normotensive subjects. On the contrary, in hypertensive subjects systolic and diastolic pulmonary pressures were consistently augmented by both stimuli, and pulmonary arteriolar resistance (dyn sec cm-5) rose from 92 in the baseline to 125 (p less than 0.01) during arithmetic and to 124 (p less than 0.01) during the cold test. This reaction is interpreted as reflecting a neurally mediated vasoconstriction and not as the consequence of mechanical or chemical changes, since no difference was observed in pulmonary wedge pressure, pleural pressure, arterial blood gas levels, and pH between controls and hypertensive subjects in the steady state and during either stressful stimulation. Baseline pulmonary arteriolar resistance was also found to correlate positively with systemic vascular resistance in the hypertensive group. When pressure changes occurred, the time course was similar in the two circuits; resistance increased to a proportionally similar degree in the two districts during the cold stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Hipertensão/fisiopatologia , Circulação Pulmonar , Adulto , Pressão Sanguínea , Débito Cardíaco , Temperatura Baixa , Feminino , Humanos , Masculino , Processos Mentais/fisiologia , Pessoa de Meia-Idade , Artéria Pulmonar/fisiopatologia , Resistência Vascular
6.
J Hypertens ; 3(1): 39-45, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2987340

RESUMO

We have examined the mechanisms mediating the release of renin elicited in man by reduction of renal perfusion pressure. Fifteen patients with essential hypertension and six normotensive subjects were investigated during diagnostic renal arteriography. Renal neural receptors were inhibited by propranolol (10 mg i.v.) and activated by a standard cold pressor test. Vascular receptors were stimulated by unilateral reduction of renal perfusion pressure by 50%, using a balloon-tipped catheter. The stimulus caused release of renin. In hypertensives, arterial plasma renin increased by 44, 69 and 73% of control at 5, 15 and 30 min, respectively. Adrenergic activation by cold raised the arterial and the renal venous renin by approximately 50% of control and caused a fourfold rise when it was combined with the arterial obstruction. Following propranolol the renin response to reduction of the renal perfusion pressure was delayed and reduced, and cold stimulation, both alone and in combination with arterial obstruction, failed to stimulate renin release. Findings were qualitatively and quantitatively similar in the normotensive group. This study supports the hypothesis that the renin response to reduction of renal perfusion pressure in man results from an interaction of adrenergic and vascular receptors. It cannot be stated whether the former are synergistic or supplementary to the latter, even though adrenergic activation by cold stimulation provides evidence that a synergism between the two may exist.


Assuntos
Hipertensão/fisiopatologia , Sistema Justaglomerular/metabolismo , Pressorreceptores/fisiologia , Receptores Adrenérgicos beta/fisiologia , Circulação Renal , Renina/metabolismo , Adulto , Temperatura Baixa , Feminino , Humanos , Hipertensão Renovascular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Perfusão , Pressorreceptores/efeitos dos fármacos , Propranolol/farmacologia , Receptores Adrenérgicos beta/efeitos dos fármacos
7.
J Med Chem ; 29(5): 868-71, 1986 May.
Artigo em Inglês | MEDLINE | ID: mdl-3701795

RESUMO

(+/-)-Tulipalin B was prepared in six steps from phenyl sulfide and ethyl 2-bromopropionate. The sensitizing power in the skin of (+/-)-tulipalin A (1a) and B (1b) and of the beta-acetoxy derivatives (1c) was studied. All are able to induce allergic contact dermatitis (ACD) and give cross-reactions. gamma,gamma-Disubstituted analogues (with a -(CH2)5- chain in the gamma-position) were synthesized and used to induce ACD in guinea pigs: they all were sensitizers and cross-reacted. However no cross-reaction was demonstrated between gamma,gamma-unsubstituted and gamma,gamma-substituted compounds showing a great specificity of ACD.


Assuntos
4-Butirolactona/síntese química , Dermatite de Contato/etiologia , Furanos/síntese química , 4-Butirolactona/análogos & derivados , Animais , Feminino , Cobaias
8.
J Med Chem ; 25(8): 943-6, 1982 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-7120282

RESUMO

The enantiomers of gamma-methyl-alpha-methylene-gamma-butyrolactone have been prepared stereospecifically from (R)- and (S)-glutamic acid. Three groups of guinea pigs have been sensitized (Feund complete adjuvant technique) to the (+) isomer, the (-) isomer, and the (+/-) mixture. The animals have been tested with each of the enantiomers and with a mixture of the compounds. Only the (-) enantiomer showed some specificity: guinea pigs sensitized to this enantiomer react weakly to the other compound; in turn, animals sensitized to the (+) enantiomer react similarly to both antipodes. Interestingly, reaction to the (+/-) mixture in each group of guinea pigs was the sum of skin responses to the individual enantiomer. These results should be contrasted with sensitization to (+)- and (-)-frullanolides, sesquiterpene lactones for which strong stereospecificity was observed.


Assuntos
4-Butirolactona/síntese química , Alérgenos/síntese química , Dermatite de Contato/etiologia , Furanos/síntese química , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacologia , Animais , Fenômenos Químicos , Química , Dermatite de Contato/imunologia , Adjuvante de Freund/farmacologia , Cobaias , Conformação Molecular , Estereoisomerismo
9.
Thromb Haemost ; 35(1): 186-90, 1976 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-1085500

RESUMO

According to some authors factor VIII procoagulant activity may be dissociable from carrier protein (MW approximately 2 X 10(6) by agarose gel filtration, e.g. at high ionic strength. We were able to reproduce this phenomenon. However, addition of protease inhibitor (Trasylol) prevented the appearance of low molecular weight peak of factor VIII procoagulant activity both at high ionic strength and elevated temperature (37 degrees C). We conclude from our results that procoagulant activity and carrier protein (von Willebrand factor, factor VIII antigen) are closely associated functional sites of native factor VIII macromolecule. Consequently, proteolytic degradation should be avoided in functional and structural studies on factor VIII and especially in preparing factor VIII concentrate for therapeutic use.


Assuntos
Fator VIII/fisiologia , Antígenos , Aprotinina , Proteínas de Transporte/isolamento & purificação , Fator VIII/antagonistas & inibidores , Fator VIII/isolamento & purificação , Humanos , Hidrólise , Concentração Osmolar , Conformação Proteica , Temperatura , Fator de von Willebrand
11.
Am J Cardiol ; 77(9): 783-7, 1996 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-8651138

RESUMO

We investigated 7 patients with chronic congestive heart failure undergoing dynamic cardiomyoplasty with intraoperative transesophageal echocardiography. Biventricular wrapping acutely modified right or left ventricular geometry, but did not induce acute restriction to left ventricular filling.


Assuntos
Débito Cardíaco , Cardiomioplastia , Ecocardiografia Doppler , Ecocardiografia Transesofagiana , Função Ventricular Esquerda , Idoso , Função do Átrio Direito , Pressão Sanguínea , Feminino , Insuficiência Cardíaca/cirurgia , Ventrículos do Coração/patologia , Humanos , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Pressão Propulsora Pulmonar , Processamento de Sinais Assistido por Computador , Volume Sistólico , Ultrassonografia de Intervenção
12.
J Clin Epidemiol ; 54(8): 857-62, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11470397

RESUMO

At the time of the study no information was available in France about the incidence of Reye's Syndrome (RS) and no warnings about RS and aspirin. The objective was to evaluate the incidence of RS in France by a hospital-based study. For a period of 1 year from November 1995 to November 1996, all French paediatric departments were required to report any child under 15 years with unexplained noninflammatory encephalopathy (i.e., CDC consciousness level stage I or deeper with normal CSF) and a threefold (or greater) increase in serum aminotransferase and/or ammonia. All suspected cases were classified by a panel of experts as probable RS or excluded RS. In 10% of randomly selected paediatric departments we checked that every suspected case had been reported. Forty-six suspected cases were reported during the year of the survey, of which 14 were classified as RS. Five of these 14 cases had a metabolic disorder. Nine children were definitively diagnosed as having RS (i.e., an estimated incidence of RS of 0.79/1,000,000 children, i.e., below 15/year). Eight children had been exposed to aspirin, four to aspirin alone and four to aspirin and acetaminophen. On the basis of these results the incidence of RS in France in 1996-1997 was not substantially different from that of countries where warning labels were already in use, but it was higher than in the US after 1994. This was probably due to the reduction in aspirin prescription in France because of warnings in Europe and the US and also because many cases of RS are now identified as metabolic disease. On the basis of these results and because the relationship between aspirin and RS has already been proved, public and professional warnings concerning RS on aspirin-containing products in cases of varicella and viral febrile illness have been adopted by the French Drugs Agency.


Assuntos
Hospitalização , Síndrome de Reye/epidemiologia , Anti-Inflamatórios não Esteroides/efeitos adversos , Aspirina/efeitos adversos , Criança , Pré-Escolar , Rotulagem de Medicamentos , França/epidemiologia , Humanos , Incidência , Lactente , Testes de Função Hepática , Distribuição de Poisson , Vigilância da População , Síndrome de Reye/induzido quimicamente
13.
Chest ; 109(2): 305-11, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8620697

RESUMO

This study was undertaken to test whether multiplane transesophageal echocardiography (TEE) offers advantages in comparison with biplane TEE in the intraoperative monitoring during cardiac surgery. A diagnostic multiplane TEE was performed in 400 patients in the immediate preoperative and postoperative periods. We systematically acquired cardiac images from the gastric fundus, lower esophagus, and upper esophagus; complete views of the descending aorta were also recorded. Usefulness of the different views in providing essential additional clinical information compared with exclusive transverse (0 to 20 degrees) and longitudinal (70 to 110 degrees) planes of the biplane TTE was assessed assuming that with manipulation of a biplane probe, a 20 degrees are could be added to the conventional horizontal and vertical planes. A high success rate of each view was demonstrated; anatomy and pathologic condition were best visualized in oblique planes. The method proved to be particularly useful in the preoperative and postoperative phases of aortic dissection (27 cases), aortic (65 cases) and mitral (35 cases) valve replacement, mitral valve repair (38 cases), left ventricular aneurysmectomy (25 cases), bleeding from proximal suture of an aortic heterograft (2 cases), and positioning of left ventricular hemopump (2 cases). Additional regional wall motion abnormalities of the right (four cases) and left ventricle (six cases) not appreciated in 0 to 20 degrees or 70 to 110 degrees planes were detected. Multiplane TEE is a useful clinical tool during intraoperative monitoring of cardiac surgery. Most structures of the heart and great vessels lie on oblique planes, while other views are optimized with the aid of slight angle corrections. This method improves the evaluation of anatomy and pathologic condition of the heart and great vessels, of native and prosthetic valves, and of left and right ventricular function.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Ecocardiografia Transesofagiana/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dissecção Aórtica/diagnóstico por imagem , Aneurisma Aórtico/diagnóstico por imagem , Doença das Coronárias/cirurgia , Humanos , Período Intraoperatório , Pessoa de Meia-Idade
14.
Drug Saf ; 7(1): 71-3, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1371390

RESUMO

Epidural analgesia for caesarean section is increasingly used and is gradually replacing general anaesthesia. Hypotension is one of the main risks: preloading of the maternal circulation is used to prevent maternal hypotension and its consequences. For this, various colloid and crystalloid solutions are used. We report a case of maternal anaphylactoid reaction with apparent death in a neonate after dextran administration to the mother. After 100ml of a dextran 40 solution administered intravenously, immediately before an epidural blockade, the mother fainted and developed urticaria and mild respiratory disturbances, without hypotension. At that point dextran infusion was stopped. An apparently dead neonate was rapidly delivered. Immediate and vigorous cardiopulmonary resuscitation was successful. Clonismus appeared 12h later, followed by 3 general epileptic fits treated by phenytoin infusion and subsequently oral phenobarbital. No aetiology was found. After 2 months of treatment, barbiturates were stopped following clinical and electroencephalogram (EEG) improvement. Several similar cases of neonatal disorders resulting from preventive dextran administration during delivery were studied in a national pharmacovigilance survey in France. There were 32 cases reported with moderate maternal anaphylactoid reaction associated with severe acute fetal distress; it is probably advisable to take a cautious approach and avoid preventive fluid preload by dextran administration. Gelatins or crystalloid solutions should be preferred, with intravenous vasopressive amine administered promptly and repeated if necessary should significant maternal hypotension occur during epidural anaesthesia.


Assuntos
Dextranos/efeitos adversos , Feto/efeitos dos fármacos , Anafilaxia/induzido quimicamente , Anestesia Epidural/efeitos adversos , Anestesia Obstétrica/efeitos adversos , Cesárea , Dextranos/uso terapêutico , Feminino , Morte Fetal/induzido quimicamente , Humanos , Hipotensão/prevenção & controle , Recém-Nascido
15.
Brain Res ; 679(1): 184-7, 1995 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-7544223

RESUMO

We investigated whether the severity of convulsions evoked by kainic acid and pilocarpine is modified in nitric oxide synthase inhibitor-treated rats. We found that chronic treatment (4 days) with NW-nitro-L-arginine greatly potentiates seizures induced by both convulsants suggesting a potential role for nitric oxide in mechanisms regulating seizure induction and propagation.


Assuntos
Aminoácido Oxirredutases/antagonistas & inibidores , Arginina/análogos & derivados , Ácido Caínico/farmacologia , Pilocarpina/farmacologia , Convulsões/induzido quimicamente , Animais , Arginina/farmacologia , Sinergismo Farmacológico , Injeções Intraperitoneais , Masculino , Óxido Nítrico Sintase , Nitroarginina , Ratos , Ratos Sprague-Dawley
16.
Eur J Pharmacol ; 268(3): 459-62, 1994 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-7805774

RESUMO

The binding selectivity of the muscarinic antagonist tripitramine has been tested on the five cloned human muscarinic receptor subtypes (Hm1 to Hm5) expressed in chinese hamster ovary (CHO-K1) cells. The results indicate that tripitramine binds to the muscarinic Hm2 receptor with a Ki value of 0.27 +/- 0.02 nM. Tripitramine distinguishes Hm2 vs. Hm4 by a factor of 24 and vs. Hm3 and Hm5 by a factor of 142 and 125, respectively. A lower affinity ratio, about 6-fold, was found between muscarinic Hm2 and Hm1 receptors. A comparative study with the well-known selective muscarinic M2 receptor antagonist methoctramine indicates that tripitramine has gained both potency and selectivity for the muscarinic Hm2 receptor subtype.


Assuntos
Benzodiazepinas/metabolismo , Receptores Muscarínicos/metabolismo , Animais , Células CHO , Cricetinae , DNA Complementar/metabolismo , Diaminas/metabolismo , Humanos , Ligantes , Antagonistas Muscarínicos , N-Metilescopolamina , Parassimpatolíticos/metabolismo , Receptores Muscarínicos/genética , Derivados da Escopolamina/farmacocinética , Termodinâmica
17.
Eur J Pharmacol ; 290(2): 125-32, 1995 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-8575526

RESUMO

The chemical structure corresponding to 1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(diethylamino)-1-methylethyl ester has the classical profile of ester-type antimuscarinic drugs. The presence of three chiral carbons leads to eight stereoisomers and the substitutions on the cyclohexyl ring generate cis-isomers (1, named rociverine) and trans-isomers (2). The aim of this study was to determine the binding pattern of the eight stereoisomers and two derived compounds, (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid 2-(dimethylamino)-1-ethyl ester (3) (1S,2S)-1-hydroxy[1,1'-bicyclohexyl]-2-carboxylic acid (S)-2-(diethylamino)-1-methylethyl ester methyl iodide (4), at the five cloned muscarinic receptors stably expressed in chinese hamster ovary cells, in order to define how stereochemical modifications could affect the affinity. Our data showed that cis-stereoisomers exhibited higher variations in affinity than trans-stereoisomers. Among the cis-stereoisomers, those with the (1R,2R) configuration showed considerably higher affinities (up to 240-fold) than those with the (1S,2S) configuration. The (1S,2S) configuration was important for binding selectivity; this was confirmed also by the use of the two additional compounds.


Assuntos
Ácidos Cicloexanocarboxílicos/farmacologia , Antagonistas Muscarínicos/farmacologia , Parassimpatolíticos/farmacologia , Animais , Células CHO , Cricetinae , Feminino , N-Metilescopolamina , Pirenzepina/metabolismo , Receptores Muscarínicos/classificação , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/metabolismo , Derivados da Escopolamina/metabolismo , Relação Estrutura-Atividade , Transfecção
18.
Eur J Pharmacol ; 355(2-3): 267-74, 1998 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-9760041

RESUMO

Recent evidence suggests that G-protein-coupled receptors can behave as multiple subunit receptors, and can be split into parts, maintaining their binding ability. Transfection of a truncated muscarinic m2 receptor (containing transmembrane domains I-V, named m2-trunc) with a gene fragment coding for the carboxyl-terminal receptor portion of the muscarinic m3 receptor (containing transmembrane domains VI and VII, named m3-tail) results in the formation of a binding site with a high affinity for the muscarinic ligand N-[3H]methylscopolamine. In this paper we analyse the antagonist binding profile of this chimeric m2-trunc/m3-tail receptor in comparison with the wild-type muscarinic m2 and m3 receptors. While many of the substances tested had an intermediate affinity for the chimeric m2-trunc/m3-tail receptor compared with m2 and m3, some compounds were able to distinguish between the chimeric m2-trunc/m3-tail receptor on the one hand and the m2 or the m3 receptor on the other. Among them, tripitramine (a high-affinity M2 receptor antagonist) bound to the m2-trunc/m3-tail receptor with the same affinity as m2, but it bound to the m3 receptor with a 103-fold lower affinity; pirenzepine (a selective muscarinic M1 receptor antagonist) bound to the chimeric receptor with an affinity that was 12- and 3-fold higher than that of m2 and m3, respectively. The results of this study demonstrate that the chimeric m2-trunc/m3-tail receptor has a pharmacological profile distinct from that of the originating muscarinic m2 and m3 receptors.


Assuntos
Antagonistas Muscarínicos/metabolismo , Receptores Muscarínicos/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Sequência de Aminoácidos , Animais , Humanos , Dados de Sequência Molecular , Ratos , Receptor Muscarínico M2 , Receptor Muscarínico M3 , Receptores Muscarínicos/química , Proteínas Recombinantes de Fusão/química , Homologia de Sequência de Aminoácidos
19.
J Am Soc Echocardiogr ; 7(1): 20-6, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8155330

RESUMO

The Doppler formulas currently used for right ventricular systolic pressure (RVSP) evaluation include right ventricular-right atrial (RV-RA) gradient and RA pressure. The former is expressed by the velocity of the trans-tricuspid regurgitant flow; the latter is generally assumed and is different from one formula to another. In 110 patients with cardiac disease with normal or elevated pulmonary pressure, we tested a new echo-Doppler formula for the evaluation of RVSP based on the estimation of RA pressure by means of the inferior vena cava collapsibility index (IVCCI) and compared this method with two traditional formulas (methods A and B) and with cardiac catheterization values. Patients were classified into three groups on the basis of IVCCI (group 1 > 45%, group 2 between 35% and 45%, and group 3 < 35%). RVSP was evaluated by method A (RV-RA gradient + 10), method B (RV-RA gradient x 1.1 + 14), and our new method, method C, which assigns 6, 9, and 16 mmHg to RA pressure in the presence of normal (> 45%), moderately reduced (between 35% and 45%), or markedly reduced (< 35%) IVCCI, respectively. IVCCI correctly identified RA pressure in the three groups (group 1, 6.8 mmHg; group 2, 10.8 mm Hg; and group 3, 13.1 mmHg); a high correlation existed between Doppler-derived and invasively determined RV-RA gradient (r = 0.99). Method C improved noninvasive estimation of RVSP in groups 1 and 3 compared with the other methods; in group 2, Doppler estimation of RVSP by methods A and C were comparable, whereas method B significantly overestimated the actual values.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Ecocardiografia Doppler/métodos , Cardiopatias/diagnóstico por imagem , Insuficiência da Valva Tricúspide/diagnóstico por imagem , Função Ventricular Direita/fisiologia , Pressão Ventricular/fisiologia , Função do Átrio Direito/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sístole/fisiologia , Veia Cava Inferior/diagnóstico por imagem
20.
J Am Soc Echocardiogr ; 11(3): 280-8, 1998 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-9560752

RESUMO

The aims of the study were to evaluate in a population of 288 normal subjects 20 to 80 years old (1) the normal values of the indexes of the mitral flow velocity pattern measured either at the tips of the mitral leaflets or at the annulus; (2) whether there was a significant difference between the values obtained at the tips compared with those measured at the mitral annulus; (3) the correlation with aging between the indexes measured in the two different positions; and (4) whether certain physiological variables have different effects on diastolic function measured in the two different positions. The highest values were always measured at the tips of the mitral leaflets (p < 0.05); only atrial filling fraction, E acceleration time, and E deceleration velocity had higher values when measured at the level of the annulus (p < 0.05). The A-wave peak velocity had the same mean value when measured at both the tips and at the annulus. A significant difference in the correlation between parameters measured at the tips of the mitral leaflets with age and at the annulus (with age) was observed for the following parameters: (1) peak E velocity, E integral, total integral and E acceleration showed better correlation with age when measured at the annulus (p < 0.02); (2) peak A velocity and A integral showed better correlation with age when measured at the tips of the mitral leaflets (p < 0.001). Multivariate analysis showed that age was the variable that had the most influence on diastolic function parameters; heart rate had less influence on the diastolic function indexes.


Assuntos
Ecocardiografia Doppler em Cores/métodos , Ecocardiografia/métodos , Valva Mitral/diagnóstico por imagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Diástole/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/fisiologia , Valores de Referência , Função Ventricular Esquerda/fisiologia
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