THE EFFECTS OF HYPERTHERMIA ON HUMAN ENDOTHELIAL MONOLAYERS - MODULATION OF THROMBOTIC POTENTIAL AND PERMEABILITY

The effects of hyperthermia on potentially prothrombotic endothelial f unction were investigated by measuring levels of von Willebrand factor , thrombospondin, tissue plasminogen activator and plasminogen activat or inhibitor-1 secreted by unstimulated human umbilical vein endotheli al cells cultured at 37 degrees C, 39 degrees C, 41 degrees C and 43 d egrees C for 24 h. Endothelial barrier function at 43 degrees C was co mpared with that at 37 degrees C by measuring permeability to radiolab elled human serum albumin and low density lipoprotein. Thrombospondin levels were unaffected by a temperature of 39 degrees C; they increase d after 3 h at 41 degrees C and subsequently declined to values signif icantly below the 37 degrees C control. At 43 degrees C, secretion exh ibited a time-dependent decrease. Secretion of von Willebrand factor w as not discernibly affected by exposure to 39 degrees C or 41 degrees C. Its response to 43 degrees C resembled that of thrombospondin to 41 degrees C. In contrast, elevated temperatures markedly increased plas minogen activator inhibitor-1 while decreasing t-PA secretion, though after prolonged exposure to 43 degrees C the levels of both returned t o control values. After 12-24 h at 43 degrees C, endothelial permeabil ity to both albumin and low density lipoprotein increased markedly. Va scular endothelium may contribute to the thrombotic tendency associate d with heat stroke by increasing access to the prothrombotic subendoth elium and reducing fibrinolysis.