Effects of a NO donor L-arginine and a non-selective NO-synthase inhibitor N(G)-nitro-Larginine methyl ester on BP, microcirculation, acid-base balance, and gas content of blood were examined on rat model of hemorrhagic shock; the substances were administered without infusion media before blood loss. Bloodletting was stopped after manifestation of marked microcirculation disorders. Inhibition of NO synthesis in response to blood loss resulted in pronounced centralization of blood circulation with microcirculation disturbances, which was accompanied by metabolic changes aggravating hemorrhagic shock. Administration of NO donor reduced the degree of circulation centralization, maintained vasodilatatory vascular tone and perfusion of vital organs, improved animal resistance to blood loss, and prolonged their lifespan. Enhanced NO generation after administration of NO donor promoted longer microcirculation maintenance, which suggests that the so-called basal level of NO is essential at early stages of hemorrhagic shock.

In experiments on dogs, which were anesthetized and underwent hemorragic shock, the hemodynamics, oxygen transport and acid-base status were studied. Cardiac function was studied using ultrasound equipment. It was established that administration of Volekam and Polyoxidin corrects hypovolemia with subsequent restoration of arterial pressure in the aorta and cardiac cavities and increase in the myocard contractility and cardiac output. Comparative analysis has shown that Polyoxidin exerts a more prolonged action than Volekam. In addition, Polyoxidin decreases the blood and plasma viscosity, lowers the blood cells aggregation which promotes the restoration of peripheral circulation. The efficiency of Volekam and Polyoxidin is not inferior to that of the well known blood substitute Polyglukin (dextran group) and, in respect of some parameters, is even superior to that of the latter.

Experiments on rats showed that infusion of NO precursor L-arginine before bleeding enhanced their tolerance to hemorrhagic shock. When infused after blood loss as a component of saline solution, L-arginine improved efficiency of infusion therapy for hemorrhagic shock and increased survival rate of the animals.

Selective inhibitors of NO synthesis (derivatives of lysine, ornithine, and isothiourea) increased the efficiency of infusion therapy for experimental hemorrhagic shock in rats. These changes were related to improvement of cardiac function (increase in stroke volume, cardiac output, and left ventricular efficiency). Among the three inhibitors, N5-(1-iminoethyl)-L-ornithine dihydrochloride was most potent on this experimental model. This compound improved cardiac function and microcirculation and provided 100% survival of experimental animals.