Journal of Applied Physiology, Vol 77, Issue 4 1850-1857, Copyright © 1994 by American Physiological Society
Acute lung injury isolated to an in situ lung preparation causes sustained reflex cardiovascular depression in dogs
D. A. Allen, E. R. Schertel, S. E. Weisbrode and P. D. Myerowitz
Division of Thoracic and Cardiovascular Surgery, College of Medicine, Ohio State University, Columbus 42310.
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.
