Eduardo Antunes

LmrTX, a basic PLA2 (D49) purified from Lachesis muta rhombeata snake venom with enzymatic-related antithrombotic and anticoagulant activity

A basic phospholipase A₂ (LmrTX) isoform was isolated from Lachesis muta rhombeata snake venom and partially characterized. The venom was fractionated by molecular exclusion chromatography in ammonium bicarbonate buffer followed by reverse-phase HPLC on a C-5 Discovery® Bio Wide column. From liquid chromatography-electrospray ionization/mass spectrometry, the molecular mass of LmrTX was measured as 14.277.50 Da. The amino acid sequence showed a high degree of homology between PLA₂ LmrTX from L. muta rhombeata and other PLA₂ from snake venoms, like CB1 and CB2 from Crotalus durissus terrificus; LmTX-I and LmTX-II from Lachesis muta muta. LmrTX had PLA₂ activity in the presence of a synthetic substrate and alkylation of histidine residues significantly inhibited (P < 0.05) the enzymatic activity of LmrTX and its anticoagulant and antithrombotic activity. In this study, we examined the ability of the LmrTX in altering thrombus formation in living mouse, using a photochemically induced arterial thrombosis model. The control animals that did not receive protein injection showed a normal occlusion time, which was around 57 ± 7.8 min. LmrTX, the PLA₂ from L. muta rhombeata venom, caused a change in the occlusion time to 99 ± 10 min with doses of 7.5 μg/mice. Additionally, LmrTX showed the anticoagulant activity in vitro and ex vivo and prolonging the time aggregation in wash platelet induced by ADP and Thrombin.

Head-up tilt testing with different nitroglycerin dosages: experience in elderly patients with unexplained syncope

AIMS Protocols using sublingual nitrates have been increasingly used to improve diagnostic accuracy of head-up tilt testing (HUT). Nevertheless, exaggerated responses to nitrates have been frequently described, particularly in elderly patients. The aim of this article is to evaluate, in an elderly population with unexplained syncope, whether the impact of sublingual nitroglycerin (NTG) used as a provocative agent is dose-dependent. METHODS AND RESULTS One hundred and twenty consecutive elderly patients submitted to HUT using NTG after an asymptomatic drug-free phase were studied. Patients were divided into three groups according to the NTG dosage: 500, 375 and 250 microg. The test was considered positive when there was reproduction of symptoms with bradycardia and/or arterial hypotension. A gradual decrease in the blood pressure after NTG was considered an exaggerated response to nitrates. There were no differences in the clinical characteristics of the different subgroups. A positive test was obtained in 50% of the patients in each group. The rate of exaggerated responses was identical in all groups and ranged between 15 and 17%. CONCLUSION In an elderly population with syncope of unknown origin submitted to HUT, the response to NTG is not dose-dependent, and no difference was found in the rate of exaggerated responses to nitrates with different NTG dosages.

Causa Inesperada de Disfunção Sistólica em Octogenária

Mulher de 82 anos, com antecedentes de hipertensão arterial ligeira, referia cansaço para grandes esforços desde a adolescência, não investigado. O cansaço agravou-se progressivamente, passando a ser desencadeado por pequenos esforços no último ano. Um ecocardiograma efetuado noutro centro revelou ventrículo esquerdo dilatado, com paredes não hipertrofiadas, disfunção sistólica global (fração de ejeção 37%) sem alterações da contratilidade segmentar, insuficiência mitral ligeira e dilatação auricular esquerda; apresentava ainda insuficiência tricúspide moderada, hipertensão pulmonar moderada (estimada em 49 mmHg) e dilatação acentuada da artéria pulmonar (47 mm). Foi referenciada ao nosso serviço para exclusão de etiologia isquémica e o cateterismo cardíaco não revelou doença coronária aparente. Auscultava-se sopro sistodiastólico de grau ii/vi no bordo esternal esquerdo superior não explicado pela investigação prévia. Repetiu ecocardiograma transtorácico (Figura 1) que confirmou os achados do ecocardiograma inicial. Visualizava-se, porém, um fluxo turbulento, contínuo, ao nível da bifurcação da artéria pulmonar, dirigido da aorta para o tronco e ramo direito da artéria

Bloqueio aurículo-ventricular de alto grau induzido por angina de Prinzmetal

We present the case of a 46-year-old woman with episodes of chest pain with ST-T segment elevation and paroxysmal high-degree atrioventricular block and syncopal episodes. Coronary angiography revealed no significant atheromatous lesions. The patient was treated with nitrates and calcium channel blockers but syncopal episodes with atrioventricular block persisted. A DDD-R pacemaker was implanted and four-month follow-up was uneventful.