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.

Although the main function of an arterial graft is to restore distal blood flow, there is evidence that certain local parameters of blood flow, particularly wall shear stresses, are important in determining the graft's long-term patency. Wall shear stresses were associated with intimal hyperplasia, intimal proliferation, and endothelial cell development, morphology, and attachment. Here we present a detailed method which permits the investigation of the wall shear stress acting on arteries and prostheses in dogs. The theory takes into account the nonlinear terms of the Navier-Stokes equations as well as the nonlinear behaviour and large deformation of the arterial wall. It is based on the numerical resolution of the nonlinear equations by the Crank-Nicolson method which was selected for its unconditional stability. Through the locally measured values of the pressure, pressure gradient, radius and flow rate, the velocity distribution and wall shear stress at a given location along the artery or the prosthesis, can be determined. Complete results on the same dog are presented for the distal aorta and for the middle of a chemically processed prosthesis, implanted as substitute in the thoracic aorta.

Many anticancer drugs require oxygen to be cytotoxic, or are selectively cytotoxic toward cells under oxygenated conditions. The effects of the dilute perfluorochemical emulsion Fluosol-DA with a wide variety of chemotherapeutic agents have been explored; however, it has not been possible to determine the optimal level of circulating perfluorochemical emulsion with anticancer drugs because the volume of Fluosol that may be administered in limited. Using a concentrated 90% Perflubron emulsion, Oxygent, a wide range of perfluorochemical emulsion doses have been examined in combination with melphalan, cyclophosphamide and BCNU in a murine solid tumor model. When Oxygent was administered by injection i.v. just prior to the injection of melphalan (10 mg/kg), the greatest tumor growth delays were obtained with Oxygent levels between 4 and 12 g PFC/kg. With each of these drugs the greatest tumor growth delays were obtained when the drug was prepared in the emulsion and the combination injected i.v. In each case, each dose of drug was followed by 6 h. of breathing carbogen.

Perflubron (perfluoroocytlbromide, PFOB) emulsion concentrations of 100%, 90%, or 60% w/v were administered to mice with and without 3 types of murine malignant tumor implants, and the distribution in blood, tumor, lung, liver and spleen were studied 48 hours after a dose of 10 or 3 g/Kg of PFOB. The most important changes were seen in the blood where the PFOB concentration [PFOB] was decreased in tumor bearing mice (TBM). Blood [PFOB] was also decreased in TBM and normal mice (NM) that received the 60% emulsion. Liver [PFOB] was increased in TBM. Lung [PFOB] was directly proportional to the emulsion concentration with the 10g/Kg dose. No major differences were seen in the biodistribution between the 100% and 90% emulsions using 10g/Kg, in spite of differences in composition and manufacturing history.

We bled 25% of estimated total blood volume, then infused pyridoxalated polymerized human stroma-free hemoglobin solution (PP-SFH) (10 g/dl) to dogs under anesthesia in a volume equal to the blood removed. Central hemodynamics, blood flow distribution to organs, and renal function were studied up to 2-3 hours following the infusion. Mean arterial pressure was reduced from 120 +/- 3 to 86 +/- 7 mmHg at the end of the 30-minute hypovolumic period and the cardiac output was reduced by 27%. Immediately following the PP-SFH infusion we observed a further fall in blood pressure (43%) caused by a fall in cardiac output which lasted for 10 minutes. Blood pressure was restored gradually with the continuation of the infusion and the cardiac output was restored and maintained well. During the hypovolumic period, blood flow to the heart, renal cortex, and liver were reduced, whereas normal flow to the renal medulla and brain were maintained. After the resuscitation, blood flow to the heart, brain, liver, and renal medulla significantly exceeded the normal range, but remained subnormal in the renal cortex. Glomerular filtration rate (GFR), urine flow, and electrolyte excretion were all reduced during the hypovolumic period and were not restored to the pre-bleed levels after the infusion.

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.

Fluosol has been shown to alter the disposition of several drugs immediately after its administration. Investigations in this laboratory established that the disposition of several drug markers requiring the hepatic microsomal cytochrome P-450 isoenzymes was time dependent for 72 hours. It was an additional purpose of the research to determine if the nonmicrosomal sulfation and acetylation pathways were also influenced by Fluosol hemodilution in a time dependent manner. Rats were moderately hemodiluted with Fluosol and received an intravenous dose of a drug marker 24, 48, or 72 hours after hemodilution. The formation clearance (ClF) of specific metabolites was used as the pharmacokinetic measure of a specific enzymatic activity. 3-Hydroxymethyl antipyrine ClF (phenobarbital inducible microsomal cytochrome P-450 isoenzymes) increased 300% only at 48 hours. Acetylsulfamethazine ClF (nonmicrosomal acetylation) increased 287% and 162% at 24 and 48 hours, respectively. Acetaminophen sulfate ClF (nonmicrosomal sulfation) decreased 30% only at 48 hours. Substantial evidence shows that cytochrome P-450 content is induced at 72 hours and remains induced for an unprecedented length of time by the PFCs in Fluosol. Therefore, it was unexpected that 3-hydroxymethyl antipyrine ClF was not increased at 72 hours. Several possible explanations are discussed for the unexpected findings.