Assuntos
Desenho de Fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Humanos , NF-kappa B/fisiologia , Antagonistas dos Receptores de Neurocinina-1 , Receptor CB1 de Canabinoide , Receptores de Glucocorticoides/fisiologia , Receptores da Neurocinina-1/fisiologia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/fisiologia , Regulação para CimaRESUMO
A growing body of evidence suggests that oxygen radicals can mediate myocardial tissue injury during ischaemia and, in particular, during reperfusion. This review focuses on the role of neutrophil as a mediator of myocardial damage. Upon reperfusion, neutrophils accumulate and produce an inflammatory response in the myocardium that is responsible, in part, for the extension of tissue injury associated with reperfusion. It has shown that the inhibition of neutrophil accumulation and adhesion is associated with decreased infarct size. This strongly suggests that myocardial cells at risk region undergo irreversible changes upon reperfusion and accumulation of neutrophils. Several pharmacological agents (ibuprofen, allopurinol, prostacyclin, and prostaglandin E analogues) protect the myocardium from reperfusion injury. In addition, the mechanisms by which these agents act and directions of research that may lead to therapeutically useful approaches are also discussed in this review.
Assuntos
Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Neutrófilos/fisiologia , Alopurinol/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Epoprostenol/farmacologia , Sequestradores de Radicais Livres/farmacologia , Humanos , Ibuprofeno/farmacologia , Iloprosta/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Prostaglandinas E Sintéticas/farmacologia , Espécies Reativas de Oxigênio/farmacologiaRESUMO
Despite the discrepancies observed between the data generated from humans and animals, it is a usual practice that the results obtained from animal models are extrapolated on humans. This review stresses that while animal models are essential for the research and development, a critical caution needs to be practiced in interpreting the results. Uncritical reliance on the results of animal experimentation can be dangerously misleading and has resulted in damages to human health in several cases. This review also discusses the role of certain confounding factors in using animal models due to which appropriate precautions need to be taken while deciding to conduct a study using animal models and caution is warranted in extrapolating the data obtained from pre-clinical studies on humans.