Splanchnic artery occlusion (SAO)
shock, induced by a transient occlusion of splanchnic arteries for 45 min, was performed in male rats, treated with vehicle or
cloricromene, a
coumarin derivative, 15 min before surgery. Survival rate, plasma levels of
myocardial depressant factor (
MDF), macrophage phagocytosis and killing of Candida albicans, and
thromboxane B2 (TxB2) synthesis by peritoneal macrophages were evaluated. Of the SAO-shocked animals, 10% survived for 6 hr after the release of the occlusion of the splanchnic arteries, whereas none of the
sham-shocked rats died. Peritoneal macrophages of shocked animals exhibited decreased phagocytosis (24.7 +/- 2.7%) and killing (8.0 +/- 2.1%) and increased TxB2 levels (3.23 +/- 0.27 ng/ml) with respect to those collected from
sham-shocked animals (phagocytosis 48.8 +/- 3.0%; killing 16.5 +/- 2.4%; TxB2 0.30 +/- 0.18 ng/ml).
MDF was also increased (114.3 +/- 21.5 U/ml) compared with
sham-shocked animals (31.5 +/- 3.7 U/ml).
Cloricromene, given intravenously (i.v.) at doses of 1, 2, and 4 mg/kg, significantly increased survival rate and lowered
MDF in shocked rats. Lower doses (0.25 and 0.5 mg/kg/i.v.) were without effect. Doses that were able to reduce mortality partially reverted
shock-induced macrophage impairment of phagocytosis, killing of C. albicans, and TxB2 synthesis. In addition,
cloricromene (5, 10, and 25 microM) added in vitro to peritoneal macrophages, collected from shocked rats, significantly enhanced their phagocytic activity depressed by
shock.