Am. J. Respir. Crit. Care Med., Vol 155, No. 3, Mar 1997, 978-983.
Thromboxane-mediated alveolar responses to acute obstruction of the pulmonary vasculature
A Mitra, SJ Feinmark and PO Alderson
Department of Radiology, College of Physicians and Surgeons, Columbia- Presbyterian Medical Center, New York, New York 10032, USA.
To investigate the mechanisms responsible for the accelerated radioaerosol
transalveolar clearance rates caused by acute balloon occlusion of the
pulmonary arterial tree in dogs, the effects of vagal tone (n = 5) and
prostaglandins (n = 21) including thromboxane were evaluated. In 15
animals, serial pulmonary arterial and aortic blood samples were acquired
to evaluate pertinent metabolic products. Balloon occlusion of a localized
arterial territory caused significant acceleration of technetium-99m
diethylenetriamine pentaacetic acid (Tc- 99m DTPA) clearance in the zone
immediately distal to the occlusion (baseline clearance half-time 23.1 +/-
0/7 min versus 19.3 +/- 0.4 min, mean +/- SEM, p < 0.05). Vagotomy had
no effect on occlusion- accelerated clearance. However, significant (p <
0.05) normalization did occur in the presence of indomethacin (21.9 +/- 0.4
min) and meclofenamic acid (20.4 +/- 0.5 min). Plasma values of thromboxane
rose dramatically (pulmonary blood baseline 119 pg/ml to > 40,000 pg/ml)
and transiently immediately after pulmonary vascular occlusion, and this
rise was blunted significantly (peak pulmonary thromboxane B2 [TXB2]
concentration = 668 pg/ml, p < 0.05) by meclofenamic acid. Significant
normalization of local DTPA clearance rates also occurred in the presence
of a thromboxane receptor blocker (n = 4), even when blood levels of
thromboxane were elevated. Changes in transalveolar DTPA clearance rates
after balloon occlusion of pulmonary arteries seem to a significant extent
to be thromboxane-mediated.