The effect of a nitroxide antioxidant on ischemia-reperfusion injury in the rat in vivo hind limb model

Department of Plastic Surgery, Hebrew University-Hadasah Medical School, Jerusalem, Israel.
Free Radical Research (Impact Factor: 2.98). 03/2008; 42(2):114-23. DOI: 10.1080/10715760701834545
Source: PubMed


Microsurgical procedures such as free tissue transfer or replantations of amputated digits involve an obligatory ischemic period leading to regional tissue oedema, rhabdomyolysis, systemic acidosis, hypercalcemia and multiple organ dysfunction syndrome reflecting ischemia-reperfusion (I/R) injury. Since nitroxide stable radicals act as antioxidants their potential protective effects were tested. Anaesthetized Sabra rats were subjected to regional ischemia of the hind limb for 2 h using a tourniquet. Upon reperfusion rats were injected with 4-OH-2,2,6,6-tetramethylpiperidine-1-oxyl (TPL). Systemic I/R-induced damage was assessed by sampling blood for differential count, lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) serum levels. Regional injury was evaluated by analysing excised muscle samples for oedema (tissue water content) and inflammatory infiltrate (number of cell nuclei in histomorphometric analysis). I/R-induced changes of biomarkers reflecting systemic damage peaked about 8 h following the start of reperfusion and fully disappeared as the biomarkers relaxed to their pre-ischemic values after 24 h. TPL facilitated the recovery of some of these parameters and partially affected release of cellular CPK and LDH. The parameters of I/R-induced regional tissue injury did not demonstrate any recovery and were not inhibited by TPL.

1 Follower
8 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The use of a pneumatic tourniquet to provide a bloodless field in orthopedic surgery is often complicated by tourniquet pain. The mechanism of this pain remains incompletely understood, but it is probably multifactorial. Nerve compression is a common etiologic feature. The use of local anaesthetics may be considered the best choice for avoiding tourniquet pain. Superficial (skin) compression and deep components compression like blood vessels and muscles can both induce tourniquet pain. Central nervous system can also interfere. Release of tourniquet can increase the pain by post-ischaemic oedema due to ischaemia and reperfusion injury.
    Cahiers d'anesthésiologie 02/1995; 43(6):573-8.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model. Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159+/-44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65+/-13% (P=0.016) and 45+/-34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132+/-16% versus 185+/-42%; P=0.011) and muscle viability (74+/-11% versus 57+/-9%; P=0.004) and contraction force (68+/-40% versus 26+/-7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027). Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.
    Circulation 11/2008; 118(19):1920-8. DOI:10.1161/CIRCULATIONAHA.108.787754 · 14.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Piperidine and pyrrolidine nitroxyl radicals (nitroxide) contain unpaired electrons and have been widely recognized as antioxidants, contrast agents, spin probes, radiation protective agents and polymerization mediators. Nitroxyl radicals can react with free radicals and reductants and their reactivities depend on the basic structure of the nitroxyl radicals themselves. However, reductants easily reduce these radicals and they lose their paramagnetic nature and function. Therefore, the aim of this study was to develop various functional nitroxyl radicals, particularly focusing on stability towards AsA through the improvement of the synthetic route for a series of 2,6-substituted nitroxyl radicals. Tetraethyl-substituted piperidine nitroxyl radical 8 exhibited resistance to AsA reduction and 2,6-dispiro-4',4''-dipyrane-piperidin-4-one-N-oxyl 5 had a second-order rate constant 10-times greater than those of hydroxyl-TEMPO and oxo-TEMPO. The 2,6-substituted compound offers various reactivities towards AsA and the possibility to be used as a new antioxidant, contrast agent and radical polymerizer.
    Free Radical Research 05/2009; 43(6):565-71. DOI:10.1080/10715760902914575 · 2.98 Impact Factor
Show more

Similar Publications