Journal of Applied Physiology, Vol 64, Issue 4 1700-1708, Copyright © 1988 by American Physiological Society
Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep
T. Ahmed, J. D'Brot, M. Wasserman, R. Muccitelli, M. Robinson, S. Tucker and B. Marchette
Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Florida 33140.
Leukotrienes have been suggested to play a role in the endotoxin-induced
changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is
necessary for contraction of airway and vascular smooth muscle as well as
for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered
whether the calcium antagonist verapamil would modify the
endotoxin-mediated pulmonary effects as well as the generation of
circulating eicosanoids. In twelve conscious sheep, measurements of
pulmonary vascular resistance (PVR), systemic vascular resistance (SVR),
lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial
thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin
F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at
predetermined intervals after a 10-min infusion of Escherichia coli
endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a
bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed
by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or
20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin
caused a biphasic response with an increase in mean PVR and RL to 326 and
276% of base line during phase I (0-1 h) and lesser increases to 177 and
157% of base line during phase II (1.5-4 h), respectively (P less than
0.05). SVR also showed biphasic increases of 44 and 42% during phase I and
II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased
from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked
increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(ABSTRACT
TRUNCATED AT 250 WORDS)
