Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia.

BACKGROUND AND PURPOSE: There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries. EXPERIMENTAL APPROACH: Vascular reactivity to ET-1 and ET(A) and ET(B) receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET(A) and ET(B) receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [(125)I]-ET-1. KEY RESULTS: HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET(A) or ET(B) receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET(A) but not of ET(B) receptors abolished enhancement in HHcy tissues. ET(A) and ET(B) receptor gene expressions were not up-regulated. ET(A) receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A(2) receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO. CONCLUSIONS AND IMPLICATIONS: Increased ET(A) receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET(A) receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.

Oxygen therapy, continuous positive airway pressure, or noninvasive bilevel positive pressure ventilation in the treatment of acute cardiogenic pulmonary edema.

OBJECTIVE: To compare the effects of 3 types of noninvasive respiratory support systems in the treatment of acute pulmonary edema: oxygen therapy (O2), continuous positive airway pressure, and bilevel positive pressure ventilation. METHODS: We studied prospectively 26 patients with acute pulmonary edema, who were randomized into 1 of 3 types of respiratory support groups. Age was 69+/-7 years. Ten patients were treated with oxygen, 9 with continuous positive airway pressure, and 7 with noninvasive bilevel positive pressure ventilation. All patients received medicamentous therapy according to the Advanced Cardiac Life Support protocol. Our primary aim was to assess the need for orotracheal intubation. We also assessed the following: heart and respiration rates, blood pressure, PaO2, PaCO2, and pH at beginning, and at 10 and 60 minutes after starting the protocol. RESULTS: At 10 minutes, the patients in the bilevel positive pressure ventilation group had the highest PaO2 and the lowest respiration rates; the patients in the O2 group had the highest PaCO2 and the lowest pH (p<0.05). Four patients in the O2 group, 3 patients in the continuous positive pressure group, and none in the bilevel positive pressure ventilation group were intubated (p<0.05). CONCLUSION: Noninvasive bilevel positive pressure ventilation was effective in the treatment of acute cardiogenic pulmonary edema, accelerated the recovery of vital signs and blood gas data, and avoided intubation.

[Comparative study between verapamil and adenosine triphosphate in the treatment of paroxysmal supraventricular tachycardia]. / Estudo comparativo entre verapamil e adenosina-trifosfato no tratamento das taquicardias paroxísticas supraventriculares.

PURPOSE: To evaluate the efficacy and safety of intravenous (IV) adenosine-triphosphate (ATP) and verapamil to convert acute episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. METHODS: Fifty patients with PSVT were randomized in two groups: A) 25 treated with IV bolus of ATP (10 or 20mg), and V) 25 treated with IV verapamil, up to 15mg, during 3min. We evaluated the time delay necessary to convert the arrhytmia, doses, and side-effects. Patients with acute ischemic syndromes (< 3 weeks), severe congestive heart failure, and treatment with dipyridamole or methylxanthine were excluded. RESULTS: There were no differences between the two groups regarding to age, sex, and success rate. The average time till reversal were respectively, 30s and 248s for ATP and verapamil. Ventricular ectopy and general discomfort were observed in 33% of patients receiving ATP, whereas no side-effects occurred in group V. CONCLUSION: ATP is a good option to convert rapidly PSVT to sinus rhythm and, probably, could be the first choice to treat PSVT patients with ventricular dysfunction.

Estudo comparativo entre Verapamil e Adenosina-Trifosfato no tratamento das taquicardias paroxísticas supraventriculares / Adenosin-three phosphate compared with Verapamil to treat paroxysmal supraventricular tachycardia

Objetivo - comparar a eficácia e segurança da adenosina-trifosfato (ATP) e verapamil endovenosos na reversäo das taquicardias paroxísticas supraventriculares (TPSV). Métodos - foram analisados 50 pacientes com diagnóstico de TPSV pelo eletrocardiograma convencional. Excluíram-se aqueles com insuficiência cardíaca, quadro isquêmico agudo, uso de dipiridamol e metilxantinas. Os pacientes foram distribuídos por sorteio em dois grupos: A) ATP em bolo de 10 ou 20 mg; V) verapamil em infusäo rápida de at15 mg. Avaliaram-se sucesso, tempo de reversäo, dose empregada e efeitos colaterais. Resultados - Ocorreu sucesso na reversão em 96% do grupo A e em 92 % do grupo V (p= 1,0). O tempo médio de reversão foi de 30s no grupo A e 248s no V. Efeitos colaterais foram encontrados em 33% no grupo A, e não ocorreram no grupo V Conclusão - O ATP é uma opção atraente para a reversão das TPSV, apresentando efeitos colaterais fugazes, podendo ser droga de escolha no tratamento desses episódios na presença de disfunção ventricul

Purpose - To evaluate the efficacy and safety of intravenous (IV) adenosine-triphosphate (ATP) and verapamil to convert acute episodes of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. Methods - Fifty patients with PSVT were randomized in two groups: A) 25 treated with IV bolus of ATP (10 or 20mg), and V) 25 treated with IV verapamil, up to 15mg, during 3min. We evaluated the time delay necessary to convert the arrhytmia, doses, and side-effects. Patients with acute ischemic syndromes (<3 weeks), severe congestive heart failure, and treatment with dipyridamole or methylxanthine were excluded. Results - There were no differences between the two groups regarding to age, sex, and success rate. The average time till reversal were respectively, 30s and 248s for ATP and verapamil. Ventricular ectopy and general disconfort were observed in 33% of patients receiving ATP, where as no side-effects occurred in group V. Conclusion - ATP is a good option to convert rapidly PSVT to sinus rhythm and, probably, could be the first choice to treat PSVT patients with ventricular dysfunction