HYPERVENTILATION INDUCES RELEASE OF CYTOKINES FROM PERFUSED MOUSE LUNG

Artificial mechanical ventilation represents a major cause of iatrogen ic lung damage in intensive care. It is largely unknown which mediator s, if any, contribute to the onset of such complications. We investiga ted whether stress caused by artificial mechanical ventilation leads t o induction, synthesis, and release of cytokines or eicosanoids from l ung tissue. We used the isolated perfused and ventilated mouse lung wh ere frequent perfusate sampling allows determination of mediator relea se into the perfusate. Hyperventilation was executed with either negat ive (NPV) or positive pressure ventilation (PPV) at a transpulmonary p ressure that was increased 2.5-fold above normal. Both modes of hyperv entilation resulted in an approximately 1.75-fold increased expression of tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) m RNA, but not of cyclooxygenase-2 mRNA. After switching to hyperventila tion, prostacyclin release into the perfusate increased almost instant aneously from 19 +/- 17 pg/min to 230 +/- 160 pg/min (PPV) or 115 +/- 87 pg/min (NPV). The enhancement in TNF alpha and IL-6 production deve loped more slowly. In control lungs after 150 min of perfusion and ven tilation, TNF alpha and IL-6 production was 23 +/- 20 pg/min and 330 /- 210 pg/min, respectively. In lungs hyperventilated for 150 min, TNF alpha and IL-6 production were increased to 287 +/- 180 pg/min and mo re than 1,000 pg/min, respectively. We conclude that artificial ventil ation might cause pulmonary and systemic adverse reactions by inducing the release of mediators into the circulation.