PLASMINOGEN-ACTIVATOR INHIBITOR-1 RISES AFTER HEMORRHAGE IN RATS

Large hemorrhage leads to hypercoagulability, a phenomenon that has ne ver been well explained. Because an elevation of plasminogen activator inhibitor (PAI)-1 increases procoagulant activity, we have determined whether plasma PAI activity and tissue PAI-1 mRNA are elevated after hemorrhage. Sprague-Dawley rats were bled (20 or 15 ml/kg) 4 days afte r cannulation. Plasma PAI activity was determined by the capacity of p lasma to inhibit tissue-type plasminogen activator activity. Changes o f PAI-1 mRNA in various tissues were detected by high-performance liqu id chromatography after reverse transcription and polymerase chain rea ction. Hemorrhage (20 ml/kg) significantly elevated plasma PAI activit y at 0.5, 1, 2, 4, 6, and 8 h after hemorrhage and PAI-1 mRNA in liver at 1, 2, 4, and 6 h after hemorrhage. The PAI-I message was also sign ificantly elevated in lung, heart, and kidney at 4 h after hemorrhage. The increases of PAI-1 mRNA after 20 ml/kg hemorrhage were significan tly greater than those after 15 ml/kg hemorrhage. These findings indic ate that large hemorrhage can induce the increases in PAI activity and PAI-1 message and suggest that induction of PAI-1 may be involved in the thrombogenic responses observed after large hemorrhage.