Failure of a protease inhibitor to affect the cardiopulmonary response to endotoxin when combined with a cyclooxygenase inhibitor.
The administration of endotoxin produces an early increase in hydrostatic pressure and pulmonary lymph flow, which is associated with elevated levels of thromboxane A2 in the lymph and can be blocked by the cyclooxygenase inhibitor ibuprofen. Two hours after the administration of endotoxin a secondary response is seen. The pulmonary lymph flow is elevated in association with a change in microvascular permeability to protein, this phase of the response can be reduced by the administration of the proteolytic enzyme inhibitor gabexate mesilate. In the present study we administered both compounds to eight sheep prepared for chronic cardiopulmonary and lung lymph studies to reduce both phases with the drug combination. The phase I response was reduced but the changes in lung lymph flow, associated with the phase II response, were unaffected by treatment. It is concluded that the effect of gabexate mesilate on the secondary response to endotoxin must in some way be related to the release of prostanoids.
D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins / Q000633:toxicity*; D016670:Gabexate; D006146:Guanidines / Q000494:pharmacology; D007052:Ibuprofen / Q000494:pharmacology*; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D006146:Guanidines; D011480:Protease Inhibitors; D016670:Gabexate; D007052:Ibuprofen