Effect of antibodies to intercellular adhesion molecule type 1 on the protection of distant organs during reperfusion syndrome in rats

Abstract

We investigated kidney and lung alterations caused by intercellular adhesion molecule type 1 (ICAM-1) blockade after ischemia and reperfusion of hind limb skeletal muscles. Rats were submitted to ligature of the infrarenal aorta for 6 h. The animals were randomized into three groups of 6 rats each: group I, sacrificed after ischemia; group II, reperfusion for 24 h, and group III, reperfusion for 24 h after receiving monoclonal anti-ICAM-1 antibodies. At the end of the experiment, blood samples were collected for creatinine, lactate dehydrogenase, creatine phosphokinase, potassium, pH and leukocyte counts. Samples were taken from the muscles of the hind limbs and from the kidneys and lungs for histological analysis and measurement of the neutrophil infiltrate by myeloperoxidase staining. The groups did not differ significantly with regard to the laboratory tests. There were no major histological alterations in the kidneys. An intense neutrophil infiltrate in the lungs, similar in all groups, was detected. Myeloperoxidase determination showed that after reperfusion there was significantly less retention of polymorphonuclear neutrophils in the muscles (352 ± 70 vs 1451 ± 235 × 10 2 neutrophils/mg; P<0.01) and in the kidneys (526 ± 89 vs 852 ± 73 × 10 2 neutrophils/mg; P<0.01) of the animals that received anti-ICAM-1 before perfusion compared to the group that did not. The use of anti-ICAM-1 antibodies in this experimental model minimized neutrophil influx, thus reducing the inflammatory process, in the muscles and kidneys after ischemia and reperfusion of the hind limbs.

Alprostadil attenuates inflammatory aspects and leucocytes adhesion on renal ischemia and reperfusion injury in rats

“…[13][14][15] Some authors have also studied shorter clamping times with similar reperfusion periods with renal pedicle or single limb artery clamping, suggesting questionable benefit of its use. [17][18][19][20][21] We believe that these conflicting results are related to short clamping periods, some of what could even controversially work as preconditioning protective factor. Another major difference is the potential to create significant IRI, which is long known to be When comparing electrolytes, no statistically significant difference between groups on the levels of Sodium (p>0.05) and Calcium (p>0.05) were found.…”

“…Several approaches have been proposed as an attempt to preclude IRI, such as hypothermia, ischemic pre-and postconditioning, as well as several drugs concomitantly and posterior to ischemic insult, 16,17 with studies suggest potential local and distant benefit after flow restoration through leukotactic inhibition, controlled reperfusion, oxygen-free radical removers, prostaglandin analogs or a combination of these. 17,18,19 Alprostadil is a prostaglandin-analog drug (PGE1).…”

Estudo das alterações oxidativas, da capacidade antioxidante total e do óxido nítrico, em ratos submetidos à isquemia e reperfusão de membros posteriores

“…Já em 1941 chamava-se a atenção para a síndrome metabólica complexa que a isquemia e reperfusão de membros inferiores desencadeava principalmente com alterações sofridas pelos rins 30 . Posteriormente, essas alterações foram denominadas de síndrome mionefropática 2,3,12,22,23 . Devido a isso o rim é utilizado como órgão a ser estudado na síndrome de isquemia e reperfusão de membros inferiores.…”

“…As pesquisas básicas mostraram, claramente, os mecanismos fisiopatológicos do envolvimento de radicais livres na genese das lesões teciduais, na síndrome de isquemia e reperfusão 3 . Várias alternativas terapêuticas potenciais surgiram desses conhecimentos direcionadas, fundamentalmente, no bloqueio direto dos radicais livres, na inativação de enzimas ou metais, na interrupção das reações em cadeia de lipoperoxidação e, no bloqueio da chegada e da atividade dos neutrófilos 3,12 . Fundamentalmente, essas alternativas utilizaram vasodilatadores e anticoagulantes 13,14 .…”

Effects of Human Umbilical Cord Mesenchymal Stem Cells on Renal Ischaemia-reperfusion Injury in Rats

“…Numerous experiments indicate that adhesion and activation of neutrophils is the basis of I/R injury, which further causes mechanical obstruction, release of abundant inflammatory substances, activates more inflammatory cells and parenchyma cells and forms inflammatory cascade. Inhibiting leukocyte activation and blood vessel infiltration is the solution to reduce I/R injury, and blocking any link helps to ameliorate the I/R injury (25,26).…”