Blood perfusion

Traumatic brain injury is the most common cause of death in subjects under the age of 40, and an important risk factor for AD. Loss of hippocampal cells and depletion of ACh and of muscarinic receptors can be attenuated in injured experimental animals, improve blood perfusion in ischemic areas and increase cholinergic transmission in cortex and hippocampus the same mechanism invoked for treatment of VD. 

In PBPK models tissue blood perfusion and tissue composition can be characterized independently of the drug thus such a model can be created once and reused for many different drugs. Furthermore, because physical laws (mass conservation, diffusion, or facilitated transport mechanisms) are incor-... 

Curcumin possesses strong antioxidant capacities, which may explain its effects against degenerative diseases in which oxidative stress plays a major role. As previously described for flavonoids, it is unlikely that curcumin acts as a direct antioxidant outside the digestive tract since its concentration in peripheral blood and organs is very low (near or below 1 pM, even after acute or long-term supplementation). Indeed, it has been shown that the intestinal epithelium limits its entry into the body, as reflected by absorption studies in various models (portal blood perfusion, everted bags). ... 

Figure 4.2 Epicardial ECG recorded from an isolated blood-perfused rat heart at the moment of reperfusion. The heart was made regionally ischaemic by occluding a snare around the left anterior descending coronary artery and, after 10 min, reperfused by releasing the snare. Note the rapid onset of ventricular tachycardia (VT) and its subsequent degeneration into ventricular fibrillation (VF). Reproduced with permission from Lawson (1993).

Monitor for adequate perfusion of vital organs through assessment of mental status, creatinine clearance, liver function tests, and a stable HR between 50 and 100 beats per minute. Additionally, adequate skin and muscle blood perfusion and normal pH is desirable. 

The fact that the GIT is so well perfused by the bloodstream permits efficient delivery of absorbed materials to the body. As a result of this rapid blood perfusion, the blood at the site of absorption represents a virtual sink for absorbed material. Under normal conditions, then, there is never a buildup in drug concentration in the blood at the site of absorption. Therefore, the concentration gradient will favor further unidirectional transfer of drug from the gut to the blood. Usually, then, blood flow is not an important consideration in drug absorption. Generally, the properties of the dosage form (especially dissolution rate) or the compound s inherent absorbability will be the limiting factors in absorption. 

The rate-limiting step in the absorption of those compounds that readily penetrate the intestinal membrane (i.e., have a large permeability coefficient) may be the rate at which blood perfuses the intestine. However, absorption will be independent of blood flow for those compounds that are poorly permeable. Extensive studies have illustrated this concept in rats [106,107]. The absorption rate of tritiated water, which is rapidly absorbed from the intestine, is dependent on intestinal blood flow, but a poorly absorbed compound, such as ribitol, penetrates the intestine at a rate independent of blood flow. In between these two extremes are a variety of intermediate compounds whose absorption rate is dependent on blood flow at low flow rates but independent of blood flow at higher flow rates. By altering blood flow to the intestine of the dog, as blood flow decreased the rate of sulfaethidole absorption also decreased [108]. These relationships are illustrated in Fig. 16. 

Temperature influences skin permeability in both physical and physiological ways. For instance, activation energies for diffusion of small nonelectrolytes across the stratum corneum have been shown to lie between 8 and 15 kcal/mole [4,32]. Thus thermal activation alone can double the rate skin permeability when there is a 10°C change in the surface temperature of the skin [33], Additionally, blood perfusion through the skin in terms of amount and closeness of approach to the skin s surface is regulated by its temperature and also by an individual s need to maintain the body s 37° C isothermal state. Since clearance of percuta-neously absorbed drug to the systemic circulation is sensitive to blood flow, a fluctuation in blood flow might be expected to alter the uptake of chemicals. No clear-cut evidence exists that this is so, however, which seems to teach us that even the reduced blood flow of chilled skin is adequate to efficiently clear compounds from the underside of the epidermis. 

There has been great interest in Cu(II) as a result of its role in biology, and the versatility in its available radioactive isotopes. The chemistry of bis(thiosemicarbazonato) metal complexes has received much interest over the last decade with particular interest in the copper complexes that are known blood perfusion tracers and also display hypoxic selectivity. Biomedical applications revolve around its redox chemistry (12,83-88,98-104). 

The absorption rate of drugs administered as intramuscular or subcutaneous injections may be affected in elderly because of reduced tissue blood perfusion. This is also true for transdermal administration, e.g. patches and gels, of drugs (Turnheim 2003). 

The distribution of a chemical in tissue depends on the binding/par-titioning between circulatory blood and tissues, the transfer across biological membranes and the tissue-blood perfusion. After incorporation, contaminants are distributed from blood to high perfusion tissues (e.g. liver, kidney), then to low perfusion ones (skin, muscle) and finally to lipoidal tissues [2], establishing kinetically different compartments (internal organs > liver > head skin) and different times to equilibrium [18]. Surfactants (LAS, AS, AES, AEO and APEO) have been... 

Bilirubin is the waste product derived from haem catabolism. In order to be eliminated from the body, mainly via the gut, bilirubin must be processed through the liver (see Section 6.4). Bilirubin is, however, insoluble in water, so to reach the liver from the spleen where a substantial amount of red cell destruction occurs, bilirubin must first be bound to albumin. As blood perfuses the liver, bilirubin is transported into the hepatocyte where it is conjugated with glucuronic acid prior to excretion. 

The maximum pressure of the blood perfusing the coronary arteries (mmHg). or... 

Nyhlen K, Rippe B, Hultkvist-Bengtsson U (1997) An isolated blood-perfused guinea-pig lung model for simultaneous registration of haemodunamic, microvas-cular and respiratory variables. Acta Physiol Scand 159 293-302. 

The integrated function of the vasculature and heart, as a closed circulatory system, supplies nutrients and oxygen to critical organs and removes metabolic wastes and carbon dioxide. This integrated system results from the careful control of cardiac output, arterial blood pressure (systolic and diastolic pressures integrated to derive mean arterial pressure), and systemic vascular resistance, thereby maintaining blood perfusion through... 

Sugiyama, A., Kobayashi, M., Tsujimoto, G., Motomura, S., and Hashimoto, K., The first demonstration of CGRP-immunoreactive fibers in canine hearts coronary vasodilator, inotropic and chronotropic effects of CGRP in canine isolated, blood-perfused heart preparations, Jpn. J. Pharmacol, 50, 421-427, 1989. 

Ting LL. Sarcoma blood perfusion change after x-irradiation. Int J Radiat Oncol Biol Phys 1991 60 335-339. 

TABLE 3.2 Blood Perfusion Rates in Adult Humans... 

Allopurinol also inhibits reperfusion injury. This injury occurs when organs that either have been transplanted or have had their usual blood perfusion blocked are reperfused with blood or an appropriate buffer solution. The cause of this injury is local formation of free radicals, such as the superoxide anion, the hydroxyl free radical, or peroxynitrite. These substances are strong oxidants and are quite damaging to tissues. 

C. Thomas, C. Counsell, P. Wood, G.E. Adams, Use of F-19 nuclear-magnetic-resonance spectroscopy and hydralazine for measuring dynamic changes in blood perfusion volume in tumors in mice, J. Natl. Cancer Inst. 84 (1992) 174-180. 

The experience of application of various efferent methods of endotoxin elimination has led to the idea of creating selective anti-LPS hemosorbents with Polymyxin B as the bioUgand. The covalently immobilized Polymyxin B does not cause side effects characteristic of free Polymyxin B and keeps its therapeutic effects. G.W. Duff in 1982 demonstrated for the first time the sorption efficiency of Polymyxin B-immobilized sorbent in vitro [9]. In 1984 K. Hanasawa with co-workers developed PMX-F - a fibrous polystyrene based hemosorbent with immobilized Polymyxin B that could be used directly for blood perfusion [10]. In 1994 PMX-F sorbent was officially approved for patient treatment in Japan. Currently, there are several polymyxin immobilized (PMX-F) sorbents produced commercially for clinical use, such as Alteca - LPS Absorber (Sweden), Toray Industries hic. (Japan), etc. However these sorbents have poor hemocompatibility and are very expensive. 

Blood perfusion through a column with a biospecific hemosorbent at a flow rate of 50-70 ml min" after 30 min achieved a significant decrease in LPS level from 66.7 3.1 to 30.5 2.2 pgmL" (P<0.01). By the end of hemoperfusion sessions stabilization of systemic hemodynamics was observed (Table 28.2), which permitted... 

Figure 29.11 presents the kineties of bilirubin removal from blood plasma of eirrhotie patients with hepato-renal syndrome. In this ease, blood perfusion was... 

Figure 9 shows the results of two coronary bypass patients studied with Rb-82 and PET. The uptake of Rb-82 is shown in three 1 cm sections of the myocardium. Each section was imaged with a single bolus infusion of 20 mCi Rb-82. Patient A had blood perfusion defects in the mid and lower sections of the myocardium. 

In human as well as in some experimental models, such as the canine (Mentzer et al. 1975) and feline (Neely et al. 1989), adenosine has been demonstrated to act as a vasodilator in the lungs during conditions of elevated tone. However, the contribution of A3AR to this effect is not clear. Earlier studies have postulated A2 receptors to mediate adenosine-induced vasodilatation (Berne 1963 Phillis et al. 1987 McCormack et al. 1989). In the pulmonary circulation of rabbits and rats, adenosine has been reported to produce vasodilation via A2aAR or A2BAR, respectively (El-Kashef et al. 1999 Haynes et al. 1995,1999). Accordingly, in an isolated blood-perfused rat lung, adenosine-induced vasodilatation was shown to be... 

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