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.


CONCLUSIONS
Intravenous use of MB, at the investigated dose, did not cause any abnormal hemodynamic responses or impairment of endothelium-dependent relaxation.
Menardi
Antonio Carlos
AC
Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Viaro
Fernanda
F
Vicente
Walter Vilella de Andrade
WV
Rodrigues
Alfredo José
AJ
Evora
Paulo Roberto Barbosa
PR
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D005260:Female; D007262:Infusions, Intravenous; D008163:Luminescent Measurements; D008751:Methylene Blue / Q000008:administration & dosage* / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000097:blood*; D009573:Nitrites / Q000097:blood; D034421:Sus scrofa; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D008751:Methylene Blue