Effect of granulocyte depletion on altered lung mechanics after endotoxemia in sheep

Abstract
To examine the role of circulating granulocytes in the airway changes caused by endotoxemia, the response of chronically instrumented unanesthetized sheep to endotoxemia before and after granulocyte depletion with hydroxyurea were measured. Granulocyte depletion did not affect the increases in mean pulmonary arterial pressure caused by endotoxin [peak pressure 59 .+-. 8 cmH2O .+-. (SE) control, 51 .+-. 8 cmH2O granulocyte depleted]. The early (30-60 min after endotoxin) airway response to endotoxemia was markedly attenuated. Without granulocyte depletion, endotoxin caused dynamic compliance (Cdyn) to decrease to 41 .+-. 10% of the base-line value and total lung resistance (RL) to increase to 283 .+-. 61% of base line. When animals were granulocyte depleted, endotoxin decreased Cdyn to 69 .+-. 6% (P < 0.05) of base line and increased RL to 141 .+-. 20% of base line (P < 0.05). Grnaulocyte depletion also attenuated the effect of endotoxin on arterial oxygenation. During the maximum airway response to endotoxin, the alveolar-to-arterial O2 gradient was 47 .+-. 5 Torr in control studies and 32 .+-. 2 Torr in granulocyte depleted studies (P < 0.05). Thus, interaction of granulocytes with the lung contributes to the changes in lung mechanics observed following endotoxemia; the early pulmonary hypertension and the early alterations in lung mechanics caused by endotoxemia are caused by separate processes.

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