Use of cardiotonic drugs and inhibitors of nitric oxide synthesis to alleviate pathologic hypotension

DETAILED DESCRIPTION The present invention involves a method for prophylaxis or treatment of an animal for systemic hypotension induced by endotoxin and/or a biological response modifier such as the cytokines, IFN, TNF, IL-1 or IL-2 and the like.
Said method involves administering, preferably intravascularly, a therapeutically effective amount of dobutamine and an inhibitor of nitric oxide formation from arginine.
Although preferable administration is intravascular, it is contemplated that other parenteral administration routes such as intraperitoneal, intramuscular or subdermal injection, for example, may prove useful.
Enteral or topical administration of nitric oxide formation inhibitors such as arginine analogs may also prove beneficial under certain clinical conditions.
In one embodiment the preferred NO.
formation inhibitor is N.
sup.
G -substituted-arginine or N.
sup.
G,N.
sup.
G -disubstituted arginine which is administered to an animal possibly developing or experiencing NO.
-induced systemic hypotension.
The arginine analogs of the present invention are preferably of the L configuration and include any pharmaceutically acceptable addition salts as commensurate with planned treatments.
A particular use of the method of the present invention is for prophylaxis or treatment of systemic hypotension induced in a patient by chemotherapeutic treatment with tumor necrosis factor, interleukin-2 or both.
In this aspect, the method involves intravascularly administering to the chemotherapy patient a therapeutically effective amount of a cardiotonic drug such as dobutamine and an arginine analog such as an N.
sup.
G -substituted arginine or an N.
sup.
G,N.
sup.
G -disubstituted arginine.
An important aspect of the present invention is as a method for treatment of an animal for systemic hypotension induced by endotoxin, i.
e.
, septic shock.
Although prophylaxis is less practical here, treatment is essential.
The treatment involves intravascularly administering to such a hypotensive animal a therapeutically effective amount of cardiotonic drug and an inhibitor of NO