Thrombolytic therapy causes an increase in vascular permeability that is reversed by 1-deamino-8-D-vasopressin.
BACKGROUND
To examine the effect of plasminogen activator therapy on vascular permeability, we used a modified rabbit mesenteric model of extravascular tissue accumulation of radiolabeled albumin.


RESULTS
Albumin deposition was measured after saline, tissue-type plasminogen activator (t-PA; 0.86 mg/kg for 1 hour followed by 0.29 mg/kg for 2 hours), or t-PA plus 1-deamino-8-D-arginine vasopressin (DDAVP; 0.6 mg/kg/hr for 30 minutes) infusion in animals with or without aspirin (ASA; 15-mg/kg bolus) pretreatment. In animals not given ASA, t-PA caused a 240% increase in tissue [125I]albumin accumulation over time (p less than 0.001). DDAVP prevented the rise in albumin accumulation normally seen with t-PA alone (p less than 0.05) in animals not given ASA. In animals pretreated with ASA, t-PA similarly caused an increase in tissue albumin accumulation, but this was significantly attenuated from that of animals not given ASA (p less than 0.03). Interestingly, DDAVP failed to block the response to t-PA in the animals given ASA. Because increases in vascular permeability correlated with increases in bleeding time (r = 0.37, p less than 0.03), these data suggest that the effect of plasmin generation on vascular permeability may contribute to the bleeding tendency seen with thrombolytic therapy. The ability of DDAVP to reverse the bleeding tendency and bleeding time may be due in part to its reversal of the increased vascular permeability induced by the administration of plasminogen activators.


CONCLUSIONS
These data show that plasminogen activation causes an increase in vascular permeability that is inhibited by DDAVP; ASA blunts this action of t-PA and prevents the DDAVP blockade of the increase in permeability induced by t-PA in this rabbit model.
Rudd
M A
MA
Cardiology Division, Brigham and Women's Hospital, Boston, MA 02115.
Johnstone
M T
MT
Rabbani
L E
LE
George
D
D
Ware
J A
JA
Loscalzo
J
J
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D005260:Female; D005341:Fibrinolysin / Q000502:physiology; D011817:Rabbits; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D000418:Albumins; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D003894:Deamino Arginine Vasopressin; D001241:Aspirin