LTB4 mediated hypoxemia in guinea pigs: Relationship to pulmonary and cardiovascular pathophysiology

Abstract LTB 4 is released in the presence of lung injury and may therefore play a role in the pathophysiology of the lung damage. We therefore, administered LTB 4 as an I.V. bolus or as an aerosol to guinea pigs and assessed the physiologic response and the lung histology. After 2 ug of I.V. LTB 4 airway pressure (AP) rose transiently by 5 ± 1 mmHg and at five min was back to baseline while PaO 2 fell from 96±5 mmHg to 78±3 mmHg and remained low at least 45 min. Static compliance (Cstat) was unchanged. Right ventricular systolic pressure (RVSP) and mean aortic pressure (MAP) rose from 9±1 to 16±1 mmHg and 43±4 to 62±5 mmHg respectively while cardiac index (c.I.) fell from 266 to 208 ml/kg/min but all values were baseline again by 10 min. Aerosolized LTB 4 raised AP by 4.6 ± 0.2 mmHg while PaO 2 fell from 90±7 to 52±5 mmHg. AP recovered by 20 min but PaO 2 remained low at least for 1 hour. MAP, RVSP and CI and Cstat were unaffected. Both I.V. and inhaled LTB 4 increased neutrophil infiltrate in the lung although the water aerosol control did too, preventing us from showing a significant effect with LTB 4 aerosol. Indomethacin blocked the airway effects and the hypoxemia after I.V. or aerosolized LTB 4 but not the neutrophil infiltrate or the rise in RVSP. It actually enhanced (p 4 . Thus cyclooxygenase released products likely mediated the rise in airway pressure and the prolonged fall in PaO 2 after LTB 4 in guinea pigs but not the pulmonary and systemic vasoconstriction.