[The physicochemical and biological properties of the bovine hemoglobin polymer]. / Izuchenie fiziko-khimicheskikh i riada biologicheskikh svoistv polimera gemoglobina byka.

A study was made of bovine hemoglobin polymer obtained by a new method: intraerythrocytic polymerization of hemoglobin followed by isolation of hemoglobin polymer. The polymer obtained had weighted mean and numerical average molecular mass of 388 kD and 134 kD, respectively, P 32 mm Hg, arteriovenous difference 5.1 vol%, Hill's coefficient 2.14, oxygen output rate constant 55 sec, and it retained its activity during long-term storage. Its solution in a concentration of 9-10 g/dl has a viscosity of 2.34, and an oncotic pressure of 240 mm water. Bovine hemoglobin polymer is nontoxic and capable of long-term circulation in the blood. Its safety and clinical effectiveness should be studied in an extended biological experiment.

[The transhemenation process of bovine and human hemoglobin polymers under conditions simulating the situation in the circulatory bed]. / Protsess transgemirovaniia polimerov gemoglobinov byka i cheloveka v usloviiakh, modeliruiushchikh situatsiiu v krovenosnom rusle.

It was shown that transhemenation, i.e. the transfer of heme from hemoglobin to human serum albumin may have the great importance in metabolism of hemoglobin. It was noted that precipitation in the case of human pyridoxal-5'-phosphate modified polyhemoglobin met-derived incubation.

[Effect of pyridoxal-5-phosphate-modified polyhemoglobin on mammals' erythrocyte aggregation]. / Vliianie poligemoglobina, modofitsirovannogo piridoksal'-5-fosfatom, na agregatsiiu éritrotsitov mlekopitaiushchukh.

Human red blood cells in vitro are most subjected to aggregating action of pyridoxal-5'-phosphate-modified polyhemoglobin (PPPH) as compared to red blood cells of other mammals--mouse, dog, rabbit, rat. A conclusion has been made that the study of rheologic properties of PPPH in the animals cannot completely reflect the aggregating action of this oxygen-carrier in case of its infusion to humans.

[Hemoglobin polymers during their circulation in the vascular bed of animals]. / Izuchenie polimerov gemoglobina v protsesse ikh tsirkuliatsii v krovenosnom rusle zhivotnykh.

The effect of molecular mass of 1 g/kg hemoglobin (Hb) modified by glutaraldehyde and pyridoxal-5'-phosphate on the duration of Hb presence in the rabbit circulation was studied. Hb concentration and met-form content were measured in plasma samples taken 5 min, 6, 18 and 24 h after the injection. Gel and ion exchange chromatography was performed. Predominant clearance of low-molecular fractions within the first 6 h of circulation was shown, it was followed by a rise in high-molecular fraction (greater than 300,000) content, that might be caused by the interaction of modified Hb with plasma proteins. This corroborates the decrease in the overall charge of the circulating fractions.

[Keto acids as regulators of hemoglobin reversible oxygenation]. / Ketokisloty kak reguliatory obratimoi oksigenatsii gemoglobina.

Several ketocarbonic acids covalently attached to the protein moiety of hemoglobin were tested as reversible oxygenation regulators. Two monocarbonic acids (glycoxylic and piruvic) and bicarbonic--alpha-ketoglutaric-acid were used for remoglobin modification. Functional properties and isoelectrical characteristics of modified hemoglobin were recorded. The binding of these acids to hemoglobin was shown to affect the net charge of hemoglobin molecule and the nature of its interaction with allosteric effectors (O2; CI-; H+). Under the influence of glyoxylic acid, the gas-transporting characteristics of hemoglobin underwent most distinct changes approaching those of the human whole blood.

[Oxygen-dissociation properties and the regulation of the oxygen affinity of a hemoglobin polymer in the bull]. / Kislorodno-dissotsiatsionnye svoistva i reguliatsiia srodstva k kislorodu polimera gemoglobina byka.

Oxygen-dissociation properties and some aspects of allosteric regulation of bovine hemoglobin (Hb) and its polymerized form (HbP) have been examined. It has been shown that bovine HbP as well as bovine Hb does not require the presence of organic phosphates for normal functioning and has gas transport characteristics which are similar to those of the whole human blood. Pyridoxal-5'-phosphate (PP) works as an allosteric regulator of bovine HbP only in the absence of Cl- ions and vice versa. However, in covalent binding of PP to HbP both the effectors (PP and Cl- ions) can work simultaneously and independently. Thus, by varying the Hb/PP ratio it is possible to prepare HbP solutions with preset P50 values within the range 30-55 mm Hg. The results can be used in simulation of gas transport characteristics of artificial oxygen carriers.

[Comparative study of the gas transport characteristics of models of an extraerythrocyte oxygen carrier]. / Sravnitel'noe izuchenie gazotransportnykh kharakteristik modelei vneéritrotsitarnogo perenoschika kisloroda.

It was shown that coupling of the 2,3-DPH functional analog, pyridoxal-5'-phosphate (PP) to hemoglobin (Hb) and its polymer (HbP) enables one to obtain an artificial oxygen carrier with gas transport characteristics similar to those of freshly prepared donor's blood. Coupling of PP to HB and HbP also intensifies their interaction with other physiologically important ligands (H+ and CO2) and changes the pattern of the relationship of P50 to the hemoprotein concentration in a solution.

[Polyhemoglobin-based model of an artificial oxygen carrier with functional properties similar to blood]. / Model' iskusstvennogo perenoschika kisloroda na osnove poligemoglibina s funktsional'nymi svoistvami, blizkimi krovi.

The principal physicochemical and biochemical characteristics are described of a new artificial oxygen carrier model that represents polyhemoglobin (polyHb) with chemically attached pyridoxal-5'-phosphate (PLP), regulator of reversible hemoglobin (Hb) oxygenation. Owing to PLP attachment, the compound obtained (poly Hb-PLP) possesses the oxygen dissociation properties similar to those of blood thereby eliminating one of the main faults of exoerythrocytic Hb and of its high-molecular-weight derivatives, namely high affinity for oxygen. P50 of polyHb-PLP is shown to be 26-28 mm Hg; the oxygen dissociation curve of a mixture of blood and 12% polyHb-PLP (1 : 1) virtually coincides with the blood curve. The data are presented on autooxidation of polyHb-PLP solutions and its mixtures with plasma and blood under physiological conditions. The weight average and number average molecular masses of polyHb-PLP are 172000 +/- 16000 and 120000 +/- 11000, respectively. The width of the polydisperse model amounts to 1.4 +/0 0.3. The relative viscosity of 11-12% polyHb-PLP is about 2. The model is not toxic when injected to mice and rats in a dose of 3 g/kg bw. The evidence presented indicates that polyHb-PLP holds promise as a prospective blood substitute.