Combined drug therapy in porcine endotoxemia. Hemodynamic and proteolytic effects of antagonists against histamine, serotonin and endorphin.
In order to investigate the importance of potential mediators of pathophysiologic derangements in endotoxemia, we have examined the effects of the combined administration of antagonists against histamine, serotonin and endorphins in a porcine model of endotoxemia. The treatment regimen significantly reduced the increase in pulmonary artery pressure, pulmonary vascular resistance and systemic arterial pressure seen in the early stages of endotoxemia. Also, cardiac output was better maintained. However, the hemodynamic performance after an observation period of 5 h was not statistically different from untreated animals. The treatment regimen did not hinder the activation of the kallikreinkinin and fibrinolytic systems of plasma, which was evident in both treated and untreated animals, and could not counteract the increase in hematocrit or leukopenia seen in this model. This study shows that the combined blocking of histamine, serotonin and endorphines is not enough to abrogate the detrimental effects of endotoxin in a porcine model.
Naess
F
F
Department of Surgery, Ullevål Hospital, University of Oslo, Norway.
Roeise
O
O
Stadaas
J O
JO
Aasen
A O
AO
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004723:Endorphins / Q000037:antagonists & inhibitors*; D004731:Endotoxins / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects*; D006633:Histamine Antagonists / Q000494:pharmacology*; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000097:blood; D011480:Protease Inhibitors / Q000494:pharmacology*; D011516:Prothrombin / Q000032:analysis; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013552:Swine
D004723:Endorphins; D004731:Endotoxins; D006633:Histamine Antagonists; D011480:Protease Inhibitors; D012702:Serotonin Antagonists; D011516:Prothrombin; D007610:Kallikreins