Biomedical subjects
Alfredo José Rodrigues
Publications and source records attributed to Alfredo José Rodrigues.
Hemodynamic and vascular endothelium function studies in healthy pigs after intravenous bolus infusion of methylene blue.
OBJECTIVE: Clinical benefit of methylene blue (MB) treating NO-induced vasoplegia has been reported in sepsis, systemic inflammatory response syndrome (SIRS) in cardiac surgery and anaphylactic shock, but its safety is sometimes questioned, mainly regarding its hemodynamic effects and the possibility of causing endothelium dysfunction. To examine the nitric oxide plasma levels and cardiovascular effects of the infusion of MB in vivo and its effects on endothelium-dependent and endothelium-independent in vitro vascular relaxation. METHODS: The study protocol included two experimental groups of female pigs: Group I (Control) - the animals (n=6) did not receive MB; Group II (MB)--the animals received 3 mg/kg of MB intravenous bolus infusion. After fifteen minutes of hemodynamic parameter recording the animals were sacrificed by exsanguination, and in vitro studies were conducted using segments of coronary, hepatic, superior mesenteric and renal arteries, to determine the effect of MB on the arterial endothelium function with regard to NO release. Nitric oxide plasma levels (NOx) were measured in each of the experimental groups. RESULTS: The results obtained in the present investigation were: 1) intravenous infusion of MB (3.0 mg/kg) caused no hemodynamic changes; 2) absolute and percent plasma NOx values did not differ between the experimental groups; and 3) in vitro study of vascular relaxation showed no significant difference between groups. These results show that MB intravenous infusion seems to be safe. This finding agrees with data from clinical experiments where MB was used to treat vasoplegic syndrome after cardiopulmonary bypass, systemic inflammatory response syndrome (SIRS) and anaphylaxis. These results were not unexpected because, as in healthy subjects, hemodynamics is only fine tuned and not fully under NO control; therefore, MB inhibiting guanylyl cyclase is not expected to do anything. CONCLUSION: Intravenous use of MB, at the investigated dose, did not cause any abnormal hemodynamic responses or impairment of endothelium-dependent relaxation.
[Amiodarone causes endothelium-dependent vasodilation in canine coronary arteries].
OBJECTIVE: To assess the vasodilating effects of amiodarone on canine coronary arteries by using solutions of amiodarone dissolved in polysorbate 80 or water. METHODS: Rings of coronary arteries, with or without intact endothelium, were immersed in Krebs solution and connected to a transducer for measuring the isometric force promoted by a vascular contraction. The arteries were exposed to increasing concentrations of polysorbate 80, amiodarone dissolved in water, amiodarone dissolved in polysorbate 80, and a commercial presentation of amiodarone (Cordarone). The experiments were conducted in the presence of the following enzymatic blockers: only indomethacin, Nomega-nitro-L-arginine associated with indomethacin, and only Nomega-nitro-L-arginine. RESULTS: Polysorbate 80 caused a small degree of nonendothelium-dependent relaxation. Cordarone, amiodarone dissolved in water, and amiodarone dissolved in polysorbate 80 caused endothelium-dependent relaxation, which was greater for amiodarone dissolved in polysorbate and for Cordarone. Only the association of indomethacin and Nomega-nitro-L-arginine could eliminate the endothelium-dependent relaxation caused by amiodarone dissolved in polysorbate 80. CONCLUSION: The results obtained indicate that vasodilation promoted by amiodarone in canine coronary arteries is mainly caused by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.
Endothelium-dependent relaxation in response to poly-L-arginine in canine coronary arteries: implications about hyperpolarization as a mechanism of vasodilatation.
OBJECTIVE: To study the mechanism by which poly-L-arginine mediates endothelium-dependent relaxation. METHODS: Vascular segments with and without endothelium were suspended in organ chambers filled with control solution maintained at 37 C and bubbled with 95% O2 / 5% CO2. Used drugs: indomethacin, acetycholine, EGTA, glybenclamide, ouabain, poly-L-arginine, methylene blue, N G-nitro-L-arginine, and verapamil and N G-monomethyl-L-arginine. Prostaglandin F2 and potassium chloride were used to contract the vascular rings. RESULTS: Poly-L-arginine (10-11 to 10-7 M) induced concentration-dependent relaxation in coronary artery segments with endothelium. The relaxation to poly-L-arginine was attenuated by ouabain, but was unaffected by glybenclamide. L-NOARG and oxyhemoglobin caused attenuation, but did not abolish this relaxation. Also, the relaxations was unaffected by methylene blue, verapamil, or the presence of a calcium-free bathing medium. The endothelium-dependent to poly-L-arginine relaxation was abolished only in vessels contracted with potassium chloride (40 mM) in the presence of L-NOARG and indomethacin. CONCLUSION: These experiments indicate that poly-L-arginine induces relaxation independent of nitric oxide.