prostaglandin-f1 and Respiratory-Distress-Syndrome

We tested the hypothesis that acute lung injury (ALI) isolated to a perfused in situ left lung preparation results in sustained reflex cardiovascular depression. Phorbol myristate acetate (PMA), an agent that activates neutrophils, administered into the isolated lung preparation of chloralose-anesthetized dogs resulted in ALI, as assessed by wet-to-dry weight ratios and histopathology, and significant decreases in heart rate (43%), mean arterial pressure (27%), aortic blood flow (29%) and maximum rate of change in left ventricular pressure (30%). Significant reflex effects occurred by 20 min after PMA administration and were sustained for 40 min (n = 7). Hemodynamic variables recovered when the left lung was denervated 60 min after PMA administration. Indomethacin administered into the isolated circulation before PMA (n = 5) did not significantly influence the ALI or reflex effects. Systemic atropinization (n = 6) prevented only the bradycardia. Left lung denervation before ALI (n = 3) prevented all reflex effects. We conclude that PMA administration into an isolated in situ lung preparation results in ALI and sustained reflex cardiovascular depression that is most likely elicited by pulmonary C-fiber stimulation and mediated by withdrawal of sympathetic efferent nerve activity.

Topics: Animals; Atropine; Blood Gas Analysis; Blood Pressure; Denervation; Disease Models, Animal; Dogs; Heart Rate; Hemodynamics; Hydrogen-Ion Concentration; Indomethacin; Lung; Perfusion; Prostaglandins F; Random Allocation; Reflex; Respiratory Distress Syndrome; Tetradecanoylphorbol Acetate; Ventricular Pressure

The effect of platelet depletion on the unanesthetized sheep's pulmonary response to endotoxemia was studied in eight unanesthetized sheep. Platelets were depleted with rabbit anti-sheep platelet antibodies (APA). Bolus injections of APA alone caused marked pulmonary hypertension (PPA increased from 21 +/- 2 to 62 +/- 5 cm H2O +/- SE) and alterations in lung mechanics (dynamic compliance of the lung [Cdyn] decreased to 38.5 +/- 4.6% and resistance to air flow across the lung [RL] increased to 705 +/- 162% +/- SE of control), which were attenuated by pretreatment with meclofenamate. It was possible to deplete platelets before endotoxemia through a slow continuous infusion of APA without altering base-line values of the measured variables. Platelet depletion did not significantly attenuate the alterations in pulmonary hemodynamics, lung mechanics, lung fluid and solute exchange, or the normal increase in lung lymph concentrations of thromboxane B2 or 6-keto-PGF1 alpha observed following endotoxemia in the sheep. We conclude that normal circulating platelet counts are not required for the full expression of the sheep's response to endotoxemia.

Topics: Animals; Blood Cell Count; Blood Platelets; Disease Models, Animal; Endotoxins; Hemodynamics; Lung; Prostaglandins F; Respiration; Respiratory Distress Syndrome; Sheep; Thromboxane B2