Estudos hemodinâmicos e da função endotelial em porcas saudáveis após injeção em bolus endovenoso de azul de metileno

Abstract

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.

Effects of methylene blue on microcirculatory alterations following cardiac surgery

“…To the best of our knowledge, the present clinical study is the first one to report data regarding the microcirculatory effects of methylene blue in humans. Two previous animal studies investigated the microcirculation following methylene blue infusion and found, on the one hand, no change in vascular relaxation and nitric oxide plasma levels in anaesthetised pigs, 15 and on the other hand, that the association of methylene blue and norepinephrine increased capillary density of the terminal ileum of rats 14 . We chose to combine several techniques allowing us to investigate different aspects and different territories of microcirculation.…”

“…13 Yet, its microcirculatory and metabolic effects remain poorly documented. 14,15 Microcirculation plays a crucial role in tissue perfusion and might be severely impaired in shock states. 16 The correction of mean arterial pressure (MAP) does not necessarily result in a parallel improvement in microcirculatory perfusion, a phenomenon referred to as loss of haemodynamic coherence.…”

“…A single dose of methylene blue could restore SVR and decrease norepinephrine requirement in refractory vasoplegic syndrome 13 . Yet, its microcirculatory and metabolic effects remain poorly documented 14,15 . Microcirculation plays a crucial role in tissue perfusion and might be severely impaired in shock states 16 .…”

Novel management of methylene blue extravasation: A case report and review of literature

“…Consequently, when cGMP is inhibited, cyclic adenosine monophosphate is released, which is the downstream target of noradrenergic receptors, thus permitting α-adrenergic receptor activation, causing vasoconstriction and subsequently tissue infarction. [ 7 8 ] Moreover, chemical properties of MB may lead to cytotoxicity. Additionally, MB is oxidized to formaldehyde and other deaminized oxide radicals.…”