Effect of human hemoglobin on systemic and regional hemodynamics in a porcine model of endotoxemic shock.
OBJECTIVE
Excessive release of nitric oxide has been implicated as being an important factor contributing to systemic arterial hypotension in septic shock. Hemoglobin is an effective nitric oxide scavenger. The purpose of this study was to test the hypothesis that treatment with cross-linked human hemoglobin can ameliorate systemic arterial hypotension and improve organ perfusion in a porcine model of normodynamic endotoxemic shock.


METHODS
Prospective, randomized, controlled trial.


METHODS
Laboratory at a university medical center.


METHODS
Fourteen, male, random-bred swine.


METHODS
All animals were challenged with Escherichia coli lipopolysaccharide (400 microg/kg) infused from t = 0 to 90 mins. Pigs in group 1 (n = 7) were infused with cross-linked human hemoglobin (150 mg/kg) at t = 30 mins. Pigs in group 2 (n = 7) were infused at t = 30 mins with 150 mg/kg of dextran (average molecular weight 70,000 daltons) as a 5% (weight per volume) solution.


RESULTS
After infusion of endotoxin, mean arterial pressure decreased significantly (p < .05) but baseline cardiac index was maintained in both groups. In hemoglobin-treated pigs (group 1), mean arterial pressure was higher than in controls (group 2) from t = 60 to 120 mins (p < .05). There were no significant differences between the two groups in systemic vascular resistance index, renal blood flow, mesenteric blood flow, systemic oxygen delivery, or systemic oxygen extraction. Ileal mucosal blood flow was lower (p < .07) in group 1 than in group 2. Mean pulmonary arterial pressure increased relative to baseline in both groups, but was significantly greater in group 1 as compared with group 2. Compared with controls, infusion of hemoglobin significantly exacerbated endotoxin-induced arterial hypoxemia (p < .05).


CONCLUSIONS
Treatment with hemoglobin improved mean arterial pressure in endotoxemic swine without significantly impairing blood flow to the renal or mesenteric vascular beds. Infusion of hemoglobin, however, significantly exacerbated endotoxin-induced pulmonary hypertension and arterial hypoxemia. Additional pharmacologic strategies may be necessary to ameliorate the potential adverse pulmonary effects of administering hemoglobin solutions to patients with sepsis.
Aranow
J S
JS
Department of Surgery, Beth Israel Hospital and Harvard Medical School, Boston, MA 02215, USA.
Wang
H
H
Zhuang
J
J
Fink
M P
MP
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006454:Hemoglobins / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D011446:Prospective Studies; D011897:Random Allocation; D012772:Shock, Septic / Q000503:physiopathology / Q000628:therapy*; D013552:Swine
D006454:Hemoglobins; D009569:Nitric Oxide