Endogenous humoral determinants of vascular endothelial dysfunction as triggers of acute poisoning complications.

The vascular endothelium is not only the semipermeable membrane that separates tissue from blood but also an organ that regulates inflammation, vascular tone, blood clotting, angiogenesis and synthesis of connective tissue proteins. It is susceptible to the direct cytotoxic action of numerous xenobiotics and to the acute hypoxia that accompanies acute poisoning. This damage is superimposed on the preformed state of the vascular endothelium, which, in turn, depends on many humoral factors.

Promotion of the toxic action of cyclophosphamide by digestive tract luminal ammonia in rats.

To estimate the influence of the digestive tract luminal ammonia pool on acute toxic effects of cyclophosphamide, the dynamics of blood ammonia, glutamine and urea level, symptoms of toxic action and the survival time have been studied in rats, intraperitoneally treated with cyclophosphamide, at the background of the gavage with non-lethal dose of ammonium acetate (12 mmol/kg, i.e., 0.

Cyclophosphamide-induced leakage of gastrointestinal ammonia into the common bloodstream in rats.

The kinetics of ammonia of gastrointestinal origin has been studied in rats in hematopoietic or neurovascular forms of acute lethal cyclophosphamide intoxication. Portal and caval blood ammonia, glutamine and urea, and blood markers of cytolysis were determined, and transperitoneal ammonia and glutamine fluxes were estimated after the single high-dose cyclophosphamide intraperitoneal (i.p.

Fulminant hyperammonaemia induced by thiopental coma in rats.

Fulminant hyperammonaemia as a threshold effect of coma-inducing dose of sodium thiopental has been revealed in rats. Blood ammonia content increased progressively after the introduction of 1.0 LD(50) (but not 0.

Succinate and artificial maintenance of normal body temperature synergistically correct lethal disorders in thiopental coma rat.

Under modeling of thiopental coma influence of sodium succinate and (or) external warming for the support of normal body temperature (isothermal regimen) on the gas exchange, blood gas content, acid-base status and survival rate was studied in rats. In the absence of therapy hypothermia was developed (-9.4 degrees C), O(2) consumption decreased by a factor 5, oxygenation of arterial blood (pO(2)) did not change while that of venous blood increased, where with arteriovenous oxygen tension gradient decreased by half.

Intermediates of Krebs cycle correct the depression of the whole body oxygen consumption and lethal cooling in barbiturate poisoning in rat.

Rats poisoned with one LD50 of thiopental or amytal are shown to increase oxygen consumption when intraperitoneally given sucinate, malate, citrate, alpha-ketoglutarate, dimethylsuccinate or glutamate (the Krebs cycle intermediates or their precursors) but not when given glucose, pyruvate, acetate, benzoate or nicotinate (energy substrates of other metabolic stages etc). Survival was increased with succinate or malate from control groups, which ranged from 30-83% to 87-100%. These effects were unrelated to respiratory depression or hypoxia as judged by little or no effect of succinate on ventilation indices and by the lack of effect of oxygen administration.