The incidence of vein-graft occlusion associated with
myocardial infarction and
thrombosis following the use of the
plasmin inhibitor,
aprotinin, to reduce blood loss during
vascular surgery has prompted the isolation of an alternative kinetically distinct inhibitor of
plasmin from the
venom of Pseudonaja textilis. This inhibitor has been called
textilinin (Txln) and two distinct forms have been isolated from the Brown-
snake venom (molecular weight, 6688 and 6692). A comparison of
plasmin inhibitor constants for
aprotinin and the Txlns 1 and 2 indicated that the former bound very tightly (inhibitor constant, Ki approximately 10(-11) mol/l), while both of the latter bound less tightly (Ki approximately 10(-9) mol/l). Homogeneity of Txlns 1 and 2 was confirmed by
sodium dodecyl sulphate-
polyacrylamide gel electrophoresis and mass spectrometry. A sequence difference of six
amino acids was observed between the two forms of Txln.
Txln 1 and 2 showed, respectively, 45 and 43% homology with
aprotinin, while there was 58 and 55% homology, respectively, with a
plasmin inhibitor from the
venom of eastern Taipan, Oxyuranus scutellatus. Both Txlns have six cysteines, like other inhibitors of this group, and homology was determined by alignment of these cysteines. Both have been shown to reduce blood loss by about 60% in a murine tail vein
bleeding model. It is proposed that the kinetic profiles of
Txln 1 and 2 for
plasmin allow the arrest of haemorrhage without the possible threat of
thrombosis.