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

• Published in: Revista brasileira de cirurgia cardiovascular 2017-01, Vol.32 (4), p.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: Article
• Language: English
• Subjects: Animal research; 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
• ISSN: 0102-7638; 1678-9741; 1678-9741
• DOI: 10.21470/1678-9741-2017-0503

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