Tranexamic acid attenuates oleic-acid-induced pulmonary extravasation.
OBJECTIVE
Activation of fibrinolysis is implicated in the development of vascular injury in certain lung injuries. It has yet to be reported that activation of plasmin is involved in extravasation caused by oleic acid (OA). We examined whether or not plasmin is involved in pulmonary extravasation by OA.


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
A total of 78 guinea pigs (498.9 +/- 10.6 g).


METHODS
Evans blue (EB) was administered to anesthetized guinea pigs. Subsequently four protocols were followed: (1) After 1 min, 60 micro l/kg of OA was injected. Perfusion was performed 30, 60 or 90 min after OA injection to wash out intravascular EB. (2) After 1 min, 15, 30 or 60 micro l/kg of OA was injected. (3) Tranexamic acid (TA) (2 g/kg) or saline was administered 30 min before OA (15 micro l/kg) injection. (4) Diphenhydramine hydrochloride (2.9 mg/kg) or saline was administered 7 min before OA (15 micro l/kg) injection.


RESULTS
Except in protocol 1, the chest cavity was opened 90 min after OA injection. Perfusion was then performed. Airway was separated into four parts from trachea to distal bronchus. EB was extracted from the tissues and measured. OA caused an extravasation throughout airways in a time- and dose-dependent manner. Extravasation was more conspicuous in peripheral tissues. TA significantly attenuated extravasation, while diphenhydramine hydrochloride did not.


CONCLUSIONS
It is suggested that plasmin, but not histamine, is involved in extravasation by OA. Inhibition of plasmin can be an effective strategy for treatment of this kind of lung injury.
Moriuchi
H
H
Department of Pathopharmacology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Arai
I
I
Yuizono
T
T
D000704:Analysis of Variance; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004155:Diphenhydramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005341:Fibrinolysin / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects; D006168:Guinea Pigs; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010313:Partial Pressure; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects*; D011654:Pulmonary Edema / Q000139:chemically induced*; D012128:Respiratory Distress Syndrome / Q000097:blood*; D018709:Statistics, Nonparametric; D014148:Tranexamic Acid / Q000494:pharmacology*
D009829:Oleic Acids; D019301:Oleic Acid; D014148:Tranexamic Acid; D004155:Diphenhydramine; D005341:Fibrinolysin