ABSTRACT
This study examines the effects of prostaglandin I2 (PGI2) on urokinase-type plasminogen activator (uPA) production and wound healing by human fibroblasts. Employing fibrin autography, it was found that beraprost sodium, a stable PGI2 analog, enhanced the fibrinolytic activity in media conditioned by human fibroblasts, TIG-3-20 cells. Fibrin zymography, ELISA, and Northern blot analysis confirmed that the enhanced activity was caused by an increase in uPA synthesis and secretion and a decrease in type-1 plasminogen activator inhibitor. While cycloheximide and 2',5'-dideoxyadenosine, an adenylate cyclase inhibitor, suppressed the effect of PGI2, dibutyryl cyclic AMP increased the fibrinolytic activity and uPA mRNA. These findings indicate that PGI2 promotes uPA production in TIG-3-20 cells via direct stimulation of the cyclic AMP intracellular pathway. A similar effect was observed in two other fibroblast cell lines, TIG-7-20 and TIG-7-30. Although PGI2 itself did not affect cellular proliferation, it promoted in vitro repopulation of the denuded area in a wounded monolayer. These observations suggest that PGI2 can stimulate wound healing through the enhanced production of uPA.
Subject(s)
Epoprostenol/analogs & derivatives , Fibrinolysis/drug effects , Urokinase-Type Plasminogen Activator/biosynthesis , Wound Healing/drug effects , Cell Movement/drug effects , Cells, Cultured , Epoprostenol/pharmacology , Fibroblasts/cytology , Humans , RNA, Messenger/analysis , Urokinase-Type Plasminogen Activator/geneticsABSTRACT
Mechanical right ventricular assistance has never been percutaneously instituted. We invented a new method for administering right ventricular assistance without thoracotomy (RAWT) and evaluated its effects in acute experiments using dogs. To institute RAWT, an outflow cannula was inserted into the pulmonary artery from the femoral vein, and an inflow cannula was inserted into the right atrium from the right jugular vein. A Swan-Ganz catheter inserted into the outflow cannula led it to the pulmonary artery under blood pressure monitoring only. A Sarns' centrifugal pump was used as a blood pump. We applied this system to biventricular failed hearts supported by a left ventricular assist device. We could increase cardiac output from 53.3 +/- 31.8 to 77.8 +/- 31.7 ml/min/kg, and mean aortic pressure from 43.5 +/- 12.3 to 57.5 +/- 11.2 mm Hg with RAWT. The right ventricular unloading effect of RAWT was not disturbed by regurgitation through the pulmonary or tricuspid valve.
