Ischemic tissue

Shen Q, Ren H, Fisher M, Bouley J, Duong TQ. Dynamic tracking of acute ischemic tissue fates using improved unsupervised isodata analysis of high-resolution quantitative perfusion and diffusion data. J Cereb Blood Flow Metab. 2004 24 887-897. 

Two forms of xanthine oxidoreductase namely XO and XDH are present in many human and animal cells and plasma, XDH and XO are the predominant species in cytoplasma and serum, respectively [39]. Damaging effects of XO-catalyzed superoxide production in post-ischemic tissues were demonstrated by many authors. For example, Chambers et al. [40] and Hearse et al. [41] have shown that the suppression of superoxide production by the administration of XO inhibitor allopurinol or SOD resulted in the reduction of infarct size in the dog and of the incidence of reperfusion-induced arrhythmia in the rat. Similarly, Charlat et al. [42] has also shown that allopurinol improved the recovery of the contractile function of reperfused myocardium in the dog. However, the use of allopurinol as the XO inhibitor has been questioned because this compound may affect oxygen radical formation not only as a XO inhibitor but as well as free radical scavenger [43]. Smith et al. [44] also showed that gastric mucosal injury depends on the oxygen radical production catalyzed by XO and iron. 

It is usually accepted that the augmentation of the XO activity in ischemic tissues undergoing reperfusion is a consequence of the formation of hypoxanthine from degradation of ATP in the presence of dioxygen. It has been confirmed by Xia and Zweier [55] who studied the mechanism of stimulation of the XO-catalyzed superoxide production in postischemic tissues. It was found that an increase in superoxide production in isolated rat hearts after reperfusion was triggered by the enhancement of hypoxanthine and xanthine levels due to the degradation of ATP during ischemia. 

The answer is d. (Hardman, pp 865-867.) Lidocaine usually shortens the duration of the action potential and, thus, allows more time for recovery during diastole. It also blocks both activated and inactivated Na channels. This has the effect of minimizing the action of lidocaine on normal myocardial tissues as contrasted with depolarized ischemic tissues. Thus, lidocaine is particularly suitable for arrhythmias arising during ischemic episodes such as myocardial infarction (Ml). 

Adenosine is not a classical neurotransmitter because it is not stored in neuronal synaptic granules or released in quanta. It is generally thought of as a neuromodulator that gains access to the extracellular space in part from the breakdown of extracellular adenine nucleotides and in part by translocation from the cytoplasm of cells by nucleoside transport proteins, particularly in stressed or ischemic tissues (Fig. 17-2C). Extracellular adenosine is rapidly removed in part by reuptake into cells and conversion to AMP by adenosine kinase and in part by degradation to inosine by adenosine deaminases. Adenosine deaminase is mainly cytosolic but it also occurs as a cell surface ectoenzyme. 

Diffusion is defined as the random translational motion of molecules or ions that is driven by internal thermal energy - the so-called Brownian motion. The mean movement of a water molecule due to diffusion amounts to several tenth of micrometres during 100 ms. Magnetic resonance is capable of monitoring the diffusion processes of molecules and therefore reveals information about microscopic tissue compartments and structural anisotropy. Especially in stroke patients diffusion sensitive imaging has been reported to be a powerful tool for an improved characterization of ischemic tissue. 

Lu E, Wagner WR, Schellenberger U, Abraham JA, Klibanov AL, WouRe SR et al. Targeted in vivo labeling of receptors for vascular endothelial growth factor approach to identification of ischemic tissue. Circulation 2003 108 97-103... 

Lidocaine (Xylocaine) was introduced as a local anesthetic and is still used extensively for that purpose (see Chapter 27). Lidocaine is an effective sodium channel blocker, binding to channels in the inactivated state. Lidocaine, like other IB agents, acts preferentially in diseased (ischemic) tissue, causing conduction block and interrupting reentrant tachycardias. 

Lee HT, Schroeder CA, Shah PM, Babu SC, Thompson Cl, Belloni EL (1996) Preconditioning with ischemia or adenosine protects skeletal muscle from ischemic tissue reperfusion injury. J Surg Res 63 29-34... 

The effects of VEGFs are at least partially mediated by the enhanced production of NO and prostacyclin (Laitinen et al., 1997b Zachary, 1998). Furthermore, in addition to endothelial cell proliferation and inhibition of neointima formation, VEGF-A may also lead to neoangiogenesis in ischemic tissues... 

Phentolamine has been used to reverse the intense local vasoconstriction caused by inadvertent infiltration of d agonists (eg, norepinephrine) into subcutaneous tissue during intended intravenous administration. The antagonist is administered by local infiltration into the ischemic tissue. 

DFO is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischemic tissue (40). It was shown experimentally that DFO reduces the early inflammatory reaction and improves myocardial microcirculation (41). Moreover, Dross et al, (42) showed that DFO s scavenging effect on superoxide anion could play a role in the cellular defense against oxygen radicals during cardiac operation. 

Luttun A, Tjwa M, Moons L, et al. Revascularization of ischemic tissues by PIGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-FIt I. Nat Med 2002 8 831-840. 

In the cardiovascular area, it has been studied for its potential to enhance neovascularization of ischemic tissue, including the myocardium, particularly when delivered locally. By virtue of promoting endothelial cell growth, it is also involved in the recovery of a normal, functional endothelium at the site of vascular injury, for example, after percutaneous coronary intervention. Finally, VEGF appears to have a role in the microvasculature of the atherosclerotic plaque. 

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