Blood flow-limited structures

A complete or global tissue distribution model consists of individual tissue compartments connected by the blood circulation. In any global model, individual tissues may be blood flow-limited, membrane-limited, or more complicated structures. The venous and arterial blood circulations can be connected in a number of ways depending on whether separate venous and arterial blood compartments are used or whether right and left heart compartments are separated. The two most common methods are illustrated in Figure 3 for blood flow-limited tissue compartments. The associated mass balance equations for Figure 3A are... 

The alkylglycoside vector is a kidney-specific delivery system that has recently been established [23-25].This vector is efficiently taken up from the basal side of the renal epithelium in a blood flow-limited manner and it can be used with several types of therapeutic molecules. The following sections summarize and discuss, first, how the novel kidney-specific alkylglycoside vector was identified, second, its structural and size requirements and third, the potential limitations of delivery to the kidney and the characterization of its binding sites on kidney cell membranes. 

The obvious need to improve blood flow to the affected lower extremities in LEAD patients, and the well known local vasodilatory effects of physical work prompted early investigators to assess the possible therapeutic effects of structured exercise programs for these patients. Scientific assessment in patients with mild and moderate claudication began in the 1960s (18-21). In a pioneering study, Hillestad (18) assessed calf muscle blood flow at different workloads. He described the different effects speed and distance had on time to claudication. He also suggested that not only blood flow limitations, but additional fac-... 

Fig. 17.5 Schematic representation of a physiological based model. Left figure shows the physiological structure, upper right figure shows a model for a perfusion rate limited tissue, and lower right figure shows a model for a permeability rate-limited tissue. Q denotes the blood flow, CL the excretion rate, KP the tissuerplasma distribution coefficient, and PS the permeability surface area coefficient.

The graph provides a simple description of the topological structure of the model. For simplicity, we assume that the model is flow-limited and that the tissue total concentration is combined with the equilibrium blood total concentration. Because we are mainly concerned with the modeling methodology and the generalization of the method to more complicated models is straightforward, the discussion of this simplified case is sufficient. 

Breast-on-a-chip and splenon-on-a-chip systems have also utilized microfluidic technology. However, their capacities are limited. The breast-on-a-chip devices only mimic the distribution of anatomical vessels of a breast rather than the whole microenvironment containing glandular, fatty, and vascular tissues. The device can be integrated with other tumor-on-a-chip devices to further mimic tumor development in the breast. The splenon-on-a-chip system just simulates the blood filtering function of in vivo splenon using a microfluidic two-phase flow structure. Those chips still lack of accuracy to mimic tissue and cellular level. 

For Doppler a different type of signal processing is used to assess the movement of blood. By comparing the signals from a series of perhaps ten pulses sent along the same direction, changes caused by a moving structure (typically red blood cells) can be extracted. The slower the flow the more pulses must be transmitted and this, as well as the fact that solid tissues also move, sets a limit to the sensitivity of Doppler. The... 

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