Perfusion rate

Pulmonary perfusion rate Volumetric flow rate within the pulmonary veins. 

To further investigate the role of the liver in brevetoxin metabolism, PbTx-3 was studied in the isolated perfused rat liver model (27, 28). Radiolabeled PbTx-3 was added to the reservoir of a recirculating system and allowed to mix thoroughly with the perfusate. Steady-state conditions were reached within 20 min. At steady-state, 55-65% of the delivered PbTx-3 was metabolized and/or extracted by the liver 26% remained in the effluent perfusate. Under a constant liver perfusion rate of 4 ml/min, the measured clearance rate was 0.11 ml/min/g liver. The calculated extraction ratio of 0.55 was in excellent agreement with the in vivo data. Radioactivity in the bile accounted for 7% of the total radiolabel perfused through the liver. PbTx-3 was metabolized and eliminated into bile as parent toxin plus four more-polar metabolites (Figure 3). Preliminary results of samples stained with 4-(p-nitrobenzyl)-pyridine (29) indicated the most polar metabolite was an epoxide. 

In perfusion models, as depicted in Fig. 3, it is assumed that distribution into and out of the organ is perfusion rate limited such that drug in the organ is in equilibrium with drug concentration in the emergent blood... 

Another method of predicting human pharmacokinetics is physiologically based pharmacokinetics (PB-PK). The normal pharmacokinetic approach is to try to fit the plasma concentration-time curve to a mathematical function with one, two or three compartments, which are really mathematical constructs necessary for curve fitting, and do not necessarily have any physiological correlates. In PB-PK, the model consists of a series of compartments that are taken to actually represent different tissues [75-77] (Fig. 6.3). In order to build the model it is necessary to know the size and perfusion rate of each tissue, the partition coefficient of the compound between each tissue and blood, and the rate of clearance of the compound in each tissue. Although different sources of errors in the models have been... 

We currently established cultural system (amphycultural diffusion capsules) that allowed for conditions favorable for stem cell expansion in vitro. Many cell types and culture protocols and their combination with cytokines, growth factors, feeder layers can be implemented with ADC. Capsules are characterized by high perfusion rates that ensure that allow dilution of inhibitory autocrine factors and support long-term cell expansion. We have shown that ADC in vitro provides optimal cellular microenvironment that supports long term hematopoiesis (Bilko et al. 2005). 

From an economic point of view, perfusion cultures of animal cells should be operated at high perfusion rates [17]. However, the high cell concentrations achieved in such cases result in several technical constraints, such as oxygen transfer, CO2 removal, medium formulation, and, especially, cell retention efficiency. 

Cell Line Product Reactor Volume (L) Max. Perfusion Rate (d ) Cultivation Time (d) Centrifuge Type g-factor " Feed Flow Rate " (L min ) Max. Viable Cell Cone. (10 mL- ) Separation Efficiency (%) Reference... 

Most of the supernatant was sent back to the reactor, in order to simulate the operation of a 1000 L reactor working at a 1 d perfusion rate. Rotor with a non-conventional design, containing 4 layers of spiral settling zones. 

The terminal settling velocity v, can be obtained by Eq. (1) and, in a perfusion system, the overflow rate Q is equal to the product between the specific perfusion rate D and the bioreactor volume V. Hence ... 

In practice, an area three times larger than is recommended. As Eq. (8) shows, when scaling up perfusion systems, the settling area is directly proportional to the reactor volume, for a constant specific perfusion rate. 

Eq. (9) assumes that the settler is an ideal separator and, consequently, the diameter d. obtained would be the cut size, i. e., all cells with higher diameter would settle and all cells with smaller diameter would escape through the overflow. Therefore, to improve the settler separation efficiency, the diameter given by Eq. (9) should decrease. As this equation shows, for a given reactor-settler system, this could be achieved by decreasing viscosity or perfusion rate or increasing the cell density difference. Since the operational temperature is usually fixed at 37 °C and the cell density difference is not an easy variable to be manipulated. 

Hansen et al. [76] used a siliconized modified 300 mb Erlenmeyer flask as an external settling device, with its undersize at 45° to the vertical. The flask was isolated to maintain the temperature at 37°C. The low separation capacity of this adapted flask limited the perfusion rate to a maximum of 1.0 d otherwise the cells would be washed out. 

Knaack et al. [77] developed an ingenious reactor design that incorporates a conical lamella settler within a conical reactor vessel. Unfortunately, this new design presents a serious scale-up limitation, since the maximum perfusion rate attainable decreases hyperbolically with the reactor working volume. For... 

Thompson and Wilson [78] operated a 21-L air-lift perfusion reactor coupled to an external lamella settler. The sedimentation device bearing an angle of inclination of 30° to the vertical was maintained at 37°C. They found a reasonable agreement between the theoretical and experimental values of breakthrough for viable and nonviable cells in the harvest stream. As expected (see Eq. 8), the maximum perfusion rates increased with an increasing settling area. 

The system used by Stevens et al. [79] consisted of an air-lift reactor with an external lamella settler. They did not need to pump the cell suspension through the settler, since free flow convection was achieved by cooling the cell suspension (20 °C) before entering the sedimentation device. As also found by other authors, they could achieve selective retention of viable cells by varying the perfusion rate. 

Fouling caused by increasing perfusion rates can be partially compensated by increasing the spin-filter rotation speed. However, according to Yabaimavar... 

As a consequence, the perfusion bioreactor can only be operated up to a cell concentration supported by the perfusion rate In this way, spin-filter retention efficiency determines the maximum attainable cell concentration in a given perfusion process. 

Combining these techniques, they carried out cultivations for 250-350 h, and were able to repeatedly use the same cartridge (four times at least) without measurable deterioration in filtration efficiency. However, when perfusion rate and cell concentration in the bioreactor increased, fouling eventually occurred. Van Reis et al. [92] provided backpressure on the filtrate line to control filtrate rates and so to avoid too high initial filtration rates, which can cause rapid fouling. De la Broise et al. [99] compared the filter performance using membranes of different pore sizes (2 and 10 pm). In both cases partial retention of the produced IgM was observed and membranes had to be changed every 5 days, the... 

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