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Thrombolytic therapy causes an increase in vascular permeability that is reversed by 1-deamino-8-D-vasopressin.

Abstract：

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. METHODS AND 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.

journal_name

Circulation

journal_title

Circulation

authors

Rudd MA,Johnstone MT,Rabbani LE,George D,Ware JA,Loscalzo J

doi

10.1161/01.cir.84.6.2568

subject

Has Abstract

pub_date

1991-12-01 00:00:00

pages

2568-73

issue

6

eissn

0009-7322

issn

1524-4539

journal_volume

84

pub_type

杂志文章

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