LTB4 mediated hypoxemia in guinea pigs: relationship to pulmonary and cardiovascular pathophysiology.
LTB4 is released in the presence of lung injury and may therefore play a role in the pathophysiology of the lung damage. We therefore, administered LTB4 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. LTB4 airway pressure (AP) rose transiently by 5 +/- 1 mmHg and at five min was back to baseline while PaO2 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 LTB4 raised AP by 4.6 +/- 0.2 mmHg while PaO2 fell from 90 +/- 7 to 52 +/- 5 mmHg. AP recovered by 20 min but PaO2 remained low at least for 1 hour. MAP, RVSP and CI and Cstat were unaffected. Both I.V. and inhaled LTB4 increased neutrophil infiltrate in the lung although the water aerosol control did too, preventing us from showing a significant effect with LTB4 aerosol. Indomethacin blocked the airway effects and the hypoxemia after I.V. or aerosolized LTB4 but not the neutrophil infiltrate or the rise in RVSP. It actually enhanced (p less than .05) the rise in MAP after I.V. LTB4. Thus cyclooxygenase released products likely mediated the rise in airway pressure and the prolonged fall in PaO2 after LTB4 in guinea pigs but not the pulmonary and systemic vasoconstriction.
D000280:Administration, Inhalation; D000818:Animals; D001980:Bronchi / Q000503:physiopathology; D006168:Guinea Pigs; D006321:Heart / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007975:Leukotriene B4 / Q000008:administration & dosage / Q000502:physiology*; D008168:Lung / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D011312:Pressure; D014661:Vasoconstriction
D007975:Leukotriene B4; D007213:Indomethacin