TY - JOUR
T1 - Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock
AU - Zingarelli, Basilia
AU - Squadrito, Francesco
AU - Ioculano, Mariapatrizia
AU - Altavilla, Domenica
AU - Bussolino, Federico
AU - Campo, Giuseppe M.
AU - Caputi, Achille P.
PY - 1992/11/3
Y1 - 1992/11/3
N2 - Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the celiac trunk for 45 min, developed a severe shock state (splanchnic artery occlusion shock) resulting in a fatal outcome within 75-90 min after release of the occlusion. Shocked rats, treated with an intravenous bolus of L-659,989, a specific platelet activating factor (PAF) receptor antagonist (12.5, 25 or 50 nmol/kg, 4 min after reperfusion followed, 8 min thereafter, by a continuous infusion of 125, 250 or 500 nmol/kg for 30 min), maintained post-release mean arterial blood pressure at significantly higher values than did rats receiving the vehicle. Treatment with L-659,989 significantly increased survival rate, blunted the rise in plasma myocardial depressant factor activity and lowered serum and macrophage levels of tumor necrosis factor (TNF-a). In addition, the drug completely restored macrophage phagocytosis, improved macrophage killing and significantly inhibited leukopenia. To investigate the interaction between PAF, TNF-a and myocardial depressant factor, the blood levels of these three mediators were evaluated: shocked rats exhibited increased PAF levels with a peak at 30 min. The plasma levels of PAF peaked earlier than did either serum TNF-a or plasma myocardial depressant factor. Both peaks occurred 75 min after the release of occlusion. The results of this study therefore suggest that PAF is a key mediator of splanchnic artery occlusion shock and plays a permissive role in inducing the release of other factors (i.e. TNF-a and myocardial depressant factor) that are relevant to shock.
AB - Anaesthetized rats, subjected to total occlusion of the superior mesenteric artery and the celiac trunk for 45 min, developed a severe shock state (splanchnic artery occlusion shock) resulting in a fatal outcome within 75-90 min after release of the occlusion. Shocked rats, treated with an intravenous bolus of L-659,989, a specific platelet activating factor (PAF) receptor antagonist (12.5, 25 or 50 nmol/kg, 4 min after reperfusion followed, 8 min thereafter, by a continuous infusion of 125, 250 or 500 nmol/kg for 30 min), maintained post-release mean arterial blood pressure at significantly higher values than did rats receiving the vehicle. Treatment with L-659,989 significantly increased survival rate, blunted the rise in plasma myocardial depressant factor activity and lowered serum and macrophage levels of tumor necrosis factor (TNF-a). In addition, the drug completely restored macrophage phagocytosis, improved macrophage killing and significantly inhibited leukopenia. To investigate the interaction between PAF, TNF-a and myocardial depressant factor, the blood levels of these three mediators were evaluated: shocked rats exhibited increased PAF levels with a peak at 30 min. The plasma levels of PAF peaked earlier than did either serum TNF-a or plasma myocardial depressant factor. Both peaks occurred 75 min after the release of occlusion. The results of this study therefore suggest that PAF is a key mediator of splanchnic artery occlusion shock and plays a permissive role in inducing the release of other factors (i.e. TNF-a and myocardial depressant factor) that are relevant to shock.
KW - L-659,989
KW - Myocardial depressant factor
KW - PAF (platelet-activating factor,PAF-acether)
KW - Splanchnic artery occlusion shock
KW - TNF-a (tumor necrosis factor)
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U2 - 10.1016/0014-2999(92)90456-E
DO - 10.1016/0014-2999(92)90456-E
M3 - Article
C2 - 1468489
AN - SCOPUS:0026469160
VL - 222
SP - 13
EP - 19
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 1
ER -