Pulmonary Insufficiency in the Rat after Intravascular Coagulation and Inhibition of Fibrinolysis

Abstract

Thrombin-induced intravascular coagulation was followed by pulmonary dysfunction in rats treated with the fibrinolysis inhibitor AMCA (trans-4-aminoethyl-cyclohexane carboxylic acid). The pulmonary dysfunction developed after a latency period of about 60 min and led progressively to pulmonary insufficiency with a morphological and functional pattern similar to that in the human delayed microembolism syndrome. Neither activation of the kallikrein-kinin system nor inhibition of converting enzyme activity in the lungs was of major importance in the pathogenesis. Accumulation of fibrin degradation products (FDP) occurred in the lungs and may have played a casual role.

Pulmonary Insufficiency in the Rat after Intravascular Coagulation and Inhibition of Fibrinolysis

“…The findings reported above indicate that pulmonary insufficiency fol lowing pulmonary microembolism of fibrin in the rat [6] is characterized by very distended lymph vessels and profound accumulation of highly proteinrich fluid in the lungs. These features point to an increased lymph transport and enhanced microvascular permeability to macromolecules.…”

“…We have shown previously that in spite of a general fibrinolysis inhibi tion a local increase in FDP occurs in the lung tissue of thrombin-injected rats [6], In other studies it has been found that FDP increase microvascular permeability [5] and it can also be concluded that the mechanical effects of microembolism alone cannot explain the profound pulmonary oedema resulting in this model [9]. We therefore attempted to determine whether locally released FDP could have played a role in the development of the pulmonary oedema.…”

“…The pulmonary dysfunction syndrome was induced as described previously [6] in 15 rats of which 5 were used in studies on oedema formation and 10 were used for morphol ogy. 500 NIH units of bovine thrombin (Topostasine®, Hoffmann-La Roche, Switzerland)/kg body weight, dissolved in 1.0 ml saline, was injected manually intravenously in 5 min with a 1-ml disposable syringe graded in 0.01 ml.…”

“…Thrombin-induced pulmonary microembolism is followed by pro found pulmonary oedema and progressive pulmonary insufficiency both in dogs and rats when fibrinolysis is inhibited [2,6,7], Pulmonary dysfunction develops after a delay of about 3-4 h in dogs and of about 1 h in rats. It has many similarities to lung damage in the clinical delayed microembolism syndrome [11].…”

“…In a previous report on investigations in rats, the experimental scheme was described and basic studies on conceivable intermediate mechanisms were presented [6], The possible role of permeability-increasing, fibrinderived peptides was especially emphasized. In the study reported below, lung fluid and solute compartments in this condition were investigated and compared with microscopic findings.…”