In perfused organs

With this in mind, the two major themes of this chapter focus on (1) a comparison of the quahty and usefulness of the data generated in ex vivo isolated blood-perfused organ models with the data obtained from in vivo and in vitro studies, and (2) the advantages of liquid chromatography with tandem mass spectrometry (LC-MS/MS) over other analytical techniques for the measurement of the fate and effects of drugs in perfused organ models. 

Na+ shifts are also less sensitive to Ca + ions than for [Dy(PPP)2] . These properties make it an extremely effective SR for Na NMR studies in perfused organs (e.g., hearts) or in in vivo spectroscopic studies in rat brain, liver, or kidney (Figme 13). ... 

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... 

Studies on in vitro systems of various kinds (including whole perfused organs, tissue slices, cell, tissue and organotypic cultures, and sub cellular fractions). 

Most of the perfusion studies have been carried out on the isolated liver since it is in this organ that the change of fat to carbohydrate presumably takes place. On the basis of some of these studies, carbohydrate formation from fat has been postulated.161-166 In such cases more carbohydrate has been present at the end of the perfusion experiment than could be accounted for on the basis of known carbohydrate precursors. In several cases, a decrease in the fat content of the liver was accompanied by a concomitant increase in carbohydrate. However, Gregg166 has been... 

FIGURE 8.11 II S mediated vasorelaxation. Rat aorta segments suspended in an organ bath containing the miniature PHSS and equilibrated with 40pM 02 are stimulated to constrict with lOOnM phenylephrine (PE). Subsequent addition of H2S causes an immediate relaxation event that gradually recovers as the H2S is oxidized or removed by the gas perfusion stream. Repeated additions of H2S at physiologically relevant concentrations demonstrate a predictable kinetic response. 

Noradrenaline and adrenaline increase blood pressure, although in various organs the perfusion can actually be reduced. Since adrenaline, in contrast to noradrenaline, stimulates a-and jSi-adrenoceptors and the jSi-subtype as well, its vascular effects are more complex than those of noradrenaline. In many vessel beds like the splanchnic area and the skin the O -adrenoceptor-mediated vasoconstriction is dominant. However, in others, like the active skeletal muscles, the jS2-adrenoceptor-mediated vasodilatation increases the blood flow. In the lower concentration range adrenaline induce an increase in blood pressure without elevated diastolic values. Catecholamines reduce the permeability of the vascular endothelium which might be of some importance for their antiallergic properties. 

The initial unequal tissue-drug distribution cannot persist, however, because physicochemical forces tend to require an eventual establishment of concentration equilibria with other less well perfused organs. Therefore, as the drug continues to be removed from the blood by the less richly perfused tissues or eliminated by metabolism and excretion or both, plasma levels will fall, and the concentration of anesthetic in the brain will decline precipitously. 

The decomposition of nitric oxide in oxygenated perfused organ baths is commonly assumed to occur by the third-order reaction of... 

A common reason for diuretic use is for reduction of peripheral or pulmonary edema that has accumulated as a result of cardiac, renal, or vascular diseases that reduce blood delivery to the kidney. This reduction is sensed as insufficient effective arterial blood volume and leads to salt and water retention and edema formation. Judicious use of diuretics can mobilize this interstitial edema without significant reductions in plasma volume. However, excessive diuretic therapy may lead to further compromise of the effective arterial blood volume with reduction in perfusion of vital organs. Therefore, the use of diuretics to mobilize edema requires careful monitoring of the patient s hemodynamic status and an understanding of the pathophysiology of the underlying illness. 

The amide local anesthetics are widely distributed after intravenous bolus administration. There is also evidence that sequestration can occur in lipophilic storage sites (eg, fat). After an initial rapid distribution phase, which consists of uptake into highly perfused organs such as the brain, liver, kidney, and heart, a slower distribution phase occurs with uptake into moderately well-perfused tissues, such as muscle and the gastrointestinal tract. As a result of the extremely short plasma half-lives of the ester type agents, their tissue distribution has not been extensively studied. 

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