Role of platelet-activating factor antagonism in posthemorrhage septic shock in pigs.
OBJECTIVE
To study the role of platelet-activating factor (PAF) antagonism in posthemorrhage septic shock in pigs.


METHODS
Experimental study.


METHODS
Twelve anesthetized pigs were bled, kept with a mean arterial pressure of 30 mm Hg for 30 minutes, and then resuscitated with 50 mL/kg of isotonic saline. A continuous infusion of Escherichia coli endotoxin 36 micrograms/kg/hour was given intravenously for 3.5 hours starting 30 minutes after resuscitation. The animals were divided into two groups of six each. One group received I mg/kg of BB-882 (a potent specific PAF receptor antagonist) as a bolus during resuscitation, followed by a continuous infusion of BB-882 1 mg/kg/hour. The other group received vehicle alone.


RESULTS
The measured variables were blood temperature, heart rate, intravascular pressures, cardiac output, systemic and pulmonary vascular resistance, lung-thorax compliance, blood gases, hemoglobin oxygen saturation, packed cell volume and blood sugar and serum lactic acid concentrations. The group treated with BB-882 had significantly higher intracardiac pressures and cardiac output, and had less increase in systemic vascular resistance. The BB-882 group had significantly less lactic acidemia than the control group (p < 0.05, analysis of variance appropriate for repeated measurement design). BB-882 had no effect on endotoxin-induced hypoxia or reduced lung-thorax compliance.


CONCLUSIONS
PAF antagonism reduced the increase in systemic vascular resistance, improved cardiac output, and reduced lactic acidemia in posthemorrhage septic shock in pigs, but it did not improve hypoxia or reduced lung-thorax compliance.
Abu-Zidan
F M
FM
Department of Surgery, University Hospital, Linköping. Sweden.
Walther
S
S
Lennquist
S
S
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology*; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
C094498:BB 882; D010972:Platelet Activating Factor; D007930:Leucine