Biomaterials, artificial cells, and immobilization biotechnology : official journal of the International Society for Artificial Cells and Immobilization Biotechnology最新文献

Measurements are reported of the solubility of nonreactive gases, e.g., hydrogen and xenon, in the following liquids: (a) Oxypherol (FC-43 emulsion) blood substitute, (b) blood plasma, (c) mixtures of Oxypherol and blood plasma, and (d) perfluorotributylamine. Typical results for Ostwald solubility at 25 degrees C for Xe gas in various liquids are 0.118 in H2O, 0.12 in blood plasma, and 1.51 in N(C4F9)3. Observed solubilities for the mixtures can be calculated from the relation: L(mixture) = L(emulsion)xv(emulsion) + L (plasma)xv(plasma), in which the v's are the volume fractions in the mixture. This linear relation implies that the gas dissolves independently in each liquid in the mixture. The effect of the emulsifier (Pluronic F-68, 2.6%), on gas solubility in the mixture, is small. Results for the temperature dependence of Ostwald solubility, L(T), in the range 10-37 degrees C are reported.

Several clinical trials have been reported using Fluosol and oxygen breathing as an adjunct to radiation. Theoretical considerations and animal experiments, however, indicate that a combination of perfluorochemicals and hyperbaric oxygen (HBO) increases tumor oxygenation and radiation response to a greater extent than is seen either with a perfluorochemical and normobaric oxygen or with HBO alone. This is the first report of a pilot study of the use of Fluosol and HBO with radiation in humans. Twenty patients with anaplastic astrocytoma or glioblastoma multiforme were treated in a phase I trial of radiation with Fluosol and HBO at three atmospheres. Total Fluosol dose was escalated from 42 ml/kg in six courses to 80 ml/kg in four courses. Patients were irradiated in an HBO chamber with 600 cGy weekly fractions following Fluosol administration. Sixteen patients completed treatment; no interruption was necessitated by treatment toxicity. The addition of Fluosol/HBO did not increase the incidence of HBO related toxicities. No significant chronic toxicities were seen. This pilot study demonstrates that Fluosol and HBO can safely be used as an adjunct to radiation in the treatment of human tumors.

The purpose of this study is to evaluate the newly developed liposome-encapsulated hemoglobin, named Neo Red Cells (NRC), in the treatment of hemorrhagic shock. The particle size of NRC is 180 +/- 88 nm, the hemoglobin concentration is 5.6 g/dl, the viscosity is 2 cp and P50 is 49.5 mmHg. The experiment was carried out on six mongrel dogs suffering hemorrhagic shock. Blood was extracted from the femoral artery and blood pressure became lower than 60 mmHg. NRC in amount equal to the amount of blood extracted was transfused immediately. Inhalating normal room air, the above manipulation was repeated 3-5 times. After 59% to 88% blood exchange using NRC, the total peripheral vascular resistance index (TPRI) was reduced and the cardiac index (CI) was increased, thereby alleviating the burden on the heart. The reduction of TPRI in the presence of hemorrhagic shock is presumed to be due to the small size of the NRC granules and their low viscosity. As the exchange rate increased, the oxygen consumption (VO2) increased remarkably, presumably due to the increase of CI and A-V difference of oxygen content. The conclusion of the study is that NRC is more suitable than natural blood for the treatment of hemorrhagic shock.

The uptake and retention of perfluorochemicals (PFCs) into rat liver and spleen have been measured for up to 28 d following injection of either the commercial PFC emulsion, Fluosol, or a novel perfluorodecalin (FDC)-based emulsion. Both quantitative and qualitative differences in the retention of individual PFCs were observed, depending on composition of emulsion administered. Nevertheless, uptake of PFCs into the spleen was consistently greater than into the liver, irrespective of formulation injected.

We have developed a porcine model of the anticipated military use of oxygen-carrying resuscitation solutions. The objective is to determine whether toxicity under adverse conditions will limit further development of hemoglobin-based products. Splenectomized immature female swine are used because of their extensive use in the evaluation of other resuscitation solutions. Five days prior to each experiment, central vascular catheters and a renal arterial flow probe are surgically placed in the animals. After recovery and weight gain has resumed, animals are placed in metabolic cages and deprived of water for 48 hours to produce hyperosmolar dehydration resulting in loss of approximately 7% of body weight. We remove 38% of estimated blood volume, 25 ml/kg, over one hour by a controlled logarithmic hemorrhage. Resuscitation is by administration of a fixed volume of test solution. Hemodynamic function is observed but not further therapy is given for three hours, a period corresponding to evacuation in the field. After this period, corresponding to arrival at a field hospital, the animals' blood is returned. Swine are then observed in metabolic cages for an additional 7 days while blood and urine are sampled daily. At the end of this period, animals are anesthetized, urinary catheters are implanted, and creatinine clearances are measured. Swine are than euthanized, and their tissues are examined. In a pilot study, resuscitation was performed with either Ringer's lactate, albumin, stroma-free hemoglobin, or cross-linked (alpha alpha Hb) hemoglobin. All animals survived.

New fluorophilic and hydrophilic, cost efficient telomeric surfactants derived from tris(hydroxymethyl)acrylaminomethane were synthesized in 2 steps in 80% yield with respect to the perfluoroalkylated telogen. They demonstrate better ability to emulsify fluorocarbons than Pluronic f-68. The biological tolerance of these new surfactants is remarkable, the perfluorohexyl derivative was tolerated at doses of 4g/kg bw after i.v. injection in mice. None of the perfluoroalkylated THAM derivatives induces hemolysis of human red blood cells at concentrations up to 200g/l in physiological solutions.

FDC/FTPA (7:3) emulsions stabilized by procsanol (Emulsion 1) and by procsanol with yolk phospholipids (Emulsion 2) were incubated with the donor plasma. After the incubation during 6 hours of Emulsions 1 and 2 with plasma the 36% and 50% decrease of the cholesterol content in plasma was found. Analysis of the lipid content of lipoproteins after the Emulsion 2 administration to rats (2.5 ml/100 g of weight) revealed the 50% decrease of the cholesterol amount in the HDL fraction at 3 and 24 hours posttransfusion. The ratio cholesterol/total phospholipids in the erythrocyte membrane diminished up to 50% as well. The equal degree of the cholesterol adsorption by emulsion from plasma, HDL of rats and erythrocyte membrane is an evidence of nonspecific interaction of PFC particles with the blood components containing cholesterol.

The purpose of this study was to compare the cardiopulmonary, hematologic, and immunologic responses of unanesthetized sheep to single, "topload", intravenous infusions of either 10 mL/Kg or 40 mL/Kg of Diaspirin Cross-Linked Hemoglobin, 10 mL/Kg or 40 mL/Kg of a Human Serum Albumin (HSA) solution oncotically adjusted with human serum albumin to approximately match the oncotic pressure of the DCLHb, or 10 mL/Kg of Erythrocyte Hemolysate solution prepared in a manner similar to that commonly described in the literature and referred to as "stroma free hemoglobin". Solutions were infused at a rate of 1 mL/Kg/minute and animals were monitored for 72 hours after infusion. These studies demonstrated that in sheep infusion of either DCLHb or HSA solutions was well tolerated and did not produce a significant increase in plasma C3a levels, an increase in the plasma concentration of thromboxane B2, or unexpected fluid shifts. In contrast, infusion of the Erythrocyte Hemolysate produced a greater than 10-fold increase in plasma C3a concentrations, a greater than 6000-fold increase in plasma TxB2 concentration, significant fluid shifts, and changes in a variety of other parameters consistent with induction of a dramatic inflammatory response. These results indicate that appropriately prepared and purified DCLHb solutions do not elicit an inflammatory reaction in sheep.

The effects of modified hemoglobin (Hb) solutions on the coronary vasculature were studied. Hearts were perfused according to Langendorff with constant flow of Tyrode solution. The solutions studied were stroma- free Hb, prepared by lysis of red blood cells in water (SFHb-lys), or prepared by swelling of red blood cells in hypotonic phosphate buffer (SFHb). The increase in coronary vascular resistance at a dose of 200 mg Hb/dl was 68% for SFHb-lys and 13% for SFHb, respectively. Addition of the modified Hb solutions HbNFPLP and polyHbNFPLP produced an increase in coronary resistance of 11% and 8%, respectively. The left ventricular developed pressure (LVDP) (control value 72 +/- 12 mm Hg) increased by 18 and 12 mm Hg, respectively, for a dose of 250 mg Hb/dl. When HbNFPLP was converted to its met-Hb form the increase in LVDP was reduced to 3 mmHg and the increase in perfusion pressure to 6 mm Hg. We conclude that elimination of stromal contamination from Hb solutions can diminish vasoconstrictor effects. The increase in cardiac pressure development and in coronary vascular resistance found for dilute modified Hb solutions is partly due to an improved oxygen transport to the heart.

We examined effects of perfusion of the kidney with pyridoxalated hemoglobin polyoxyethylene conjugate(PHP) solution on rat renal vascular responsiveness to norepinephrine(NE), angiotensin-II (AN-II), acethylcholine(ACh) and nitroglycerine(NG). The rat kidney was perfused with hydroxyethylstarch(HES) or PHP at a constant flow rate, using a pump. Perfusion pressure was monitored by a pressure transducer. Changes in PP induced by NE, AN-II, ACh and NG was examined. NE and AN-II applied intra-arterially induced a dose-related increase in PP in rat kidney perfused with both HES and PHP perfused groups. ACh and NG produced a dose dependent decrease in PP in both HES and PHP-perfused groups. There was no significant difference in response to ACh and NG between both groups. Results suggests that in rat vascular beds, PHP dose not interfere vascular relaxation caused by release of EDRF induced by ACh.