Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome

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 elev...

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Published in:	Revista brasileira de cirurgia cardiovascular Vol. 32; no. 4; pp. 312 - 317
Main Authors:	Oliveira, Granville G de, Oliveira, Samer A H de, Botelho, Paulo Henrique H, Oliveira, Marcos Aurelio Barboza de, Bian, Ka, Murad, Ferid
Format:	Journal Article
Language:	English
Published:	Brazil Sociedade Brasileira de Cirurgia Cardiovascular 01-01-2017
Subjects:	Animals CARDIAC & CARDIOVASCULAR SYSTEMS Cardiology Disease Models, Animal Disease Progression Edema Endothelium Heart surgery Hypothalamus, Anterior - injuries Hypotheses Male Multiple organ dysfunction syndrome Multiple Organ Failure Multiple Organ Failure - classification Multiple Organ Failure - etiology Multiple Organ Failure - prevention & control Nervous system Nitric Oxide Original Pathology Phosphodiesterase 5 Inhibitors - administration & dosage Phosphodiesterase 5 Inhibitors - therapeutic use Phosphodiesterase Inhibitors Preoperative Period Protective Agents - administration & dosage Protective Agents - therapeutic use Rats, Wistar Rodents Sepsis Stereotaxic Techniques SURGERY Systemic Inflammatory Response Syndrome Tadalafil - administration & dosage Tadalafil - therapeutic use Thrombosis Thrombosis - chemically induced Thrombosis - rehabilitation Trauma United States > US Multiple Organ Failure Phosphodiesterase Inhibitors Nitric Oxide Systemic Inflammatory Response Syndrome
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Summary:	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. 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. 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. The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.
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ISSN:	0102-7638 1678-9741 1678-9741
DOI:	10.21470/1678-9741-2017-0503