Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome
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Sociedade Brasileira de Cirurgia Cardiovascular
2017
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| _version_ | 1876455624165818368 |
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| author | Granville G. de Oliveira |
| author_facet | Granville G. de Oliveira |
| contents | Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome Granville G. de Oliveira Samer A. H. de Oliveira Paulo Henrique H. Botelho Marcos Aurelio Barboza de Oliveira Ka Bian Ferid Murad Medicina Nitric Oxide Multiple Organ Failure Phosphodiesterase Inhibitors Systemic Inflammatory Response Syndrome Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS. 2017 artículo científico 0102-7638 https://www.redalyc.org/articulo.oa?id=398952564013 en http://www.redalyc.org/revista.oa?id=3989 Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery application/pdf Sociedade Brasileira de Cirurgia Cardiovascular Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (Brasil) Num.4 Vol.32 |
| format | Artículo científico |
| id | redalyc_398952564013 |
| institution | Redalyc |
| language | en |
| publishDate | 2017 |
| publisher | Sociedade Brasileira de Cirurgia Cardiovascular |
| spellingShingle | Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome Granville G. de Oliveira Medicina Nitric Oxide Multiple Organ Failure Phosphodiesterase Inhibitors Systemic Inflammatory Response Syndrome Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome Granville G. de Oliveira Samer A. H. de Oliveira Paulo Henrique H. Botelho Marcos Aurelio Barboza de Oliveira Ka Bian Ferid Murad Medicina Nitric Oxide Multiple Organ Failure Phosphodiesterase Inhibitors Systemic Inflammatory Response Syndrome Introduction: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. Methods: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. Results: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. Conclusion: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS. 2017 artículo científico 0102-7638 https://www.redalyc.org/articulo.oa?id=398952564013 en http://www.redalyc.org/revista.oa?id=3989 Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery application/pdf Sociedade Brasileira de Cirurgia Cardiovascular Revista Brasileira de Cirurgia Cardiovascular/Brazilian Journal of Cardiovascular Surgery (Brasil) Num.4 Vol.32 |
| title | Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome |
| topic | Medicina Nitric Oxide Multiple Organ Failure Phosphodiesterase Inhibitors Systemic Inflammatory Response Syndrome |
| url | https://www.redalyc.org/articulo.oa?id=398952564013 |