Interaction between hemoglobin and glutathione in the regulation of blood flow in normal and septic pigs.
BACKGROUND
Hemoglobin (Hb) induces vasoconstriction by heme group binding nitric oxide in an irreversible fashion. Recent in vitro studies indicate that the thiol groups in Hb reversibly bind nitric oxide and participate in trans-nitrosylation reactions with other thiols. Sepsis is a pathophysiologic state characterized by vasodilation mediated, at least in part, by an excessive release of nitric oxide. The role of nitrosothiols (RSNOs) in these changes is unknown.


OBJECTIVE
We tested the following in a porcine model of sepsis: (i) whether glutathione (GSH) reverses the hemodynamic effects of Hb; (ii) whether GSH induces an increase in blood flow in sepsis; (iii) whether RSNO plasma concentration increases in sepsis and is related to hypotension.


METHODS
Nonrandomized animal controlled study.


METHODS
Animal research facility in a university hospital.


METHODS
Anesthetized pigs were monitored with a pulmonary artery catheter and ultrasonic blood flow probes in the mesenteric artery and the portal vein for measurement of systemic, mesenteric, and portal blood flows (Q(TOT), Q(MES), and Q(POR), respectively). Four groups of pigs were studied: nonseptic, septic, nonseptic treated with Hb (stroma-free purified porcine hemoglobin), and septic treated with Hb (n = 6 in each group).


METHODS
Sepsis was induced at 0 min by the administration of live Escherichia coli. Hb (400 mg/kg/hr) was administered at 240 mins, followed by glutathione (1 g iv).


RESULTS
Hb induced a pressor response and a decrease in Q(TOT), Q(MES), and Q(POR). Glutathione reversed the effects of Hb on Q(MES) and Q(POR). In septic pigs not treated with Hb, GSH induced an increase in Q(POR). RSNO plasma concentration increased after the induction of sepsis and correlated significantly with blood pressure.


CONCLUSIONS
These results indicate the reversibility of the effects of Hb by GSH, probably by interactions between nitric oxide and the reduced sulfhydryl groups in Hb, and suggest a role of RSNOs in the cardiovascular changes of sepsis.
Tejedor
Carmen
C
Servicio de Cuidados Intensivios, Hospital Universitario de Getafe, Madrid, Spain.
Lorente
José A
JA
Delgado
Miguel A
MA
Fernández-Segoviano
Pilar
P
De Paula
Marta
M
Tobalina
Raul
R
Alonso
Maite
M
Moscoso
Amelia
A
Soto
Francisco
F
Blázquez
Javier
J
Esteban
Andrés
A
D000704:Analysis of Variance; D000818:Animals; D005978:Glutathione / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000494:pharmacology*; D007022:Hypotension / Q000097:blood; D016014:Linear Models; D009569:Nitric Oxide / Q000097:blood; D026403:S-Nitrosothiols / Q000097:blood; D018805:Sepsis / Q000188:drug therapy* / Q000503:physiopathology; D013552:Swine
D006454:Hemoglobins; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D005978:Glutathione