Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic ratsReportar como inadecuado

Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic rats - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Critical Care

, 13:R109

First Online: 06 July 2009Received: 13 March 2009Accepted: 06 July 2009


IntroductionIncreasing evidence indicates that epidural anesthesia improves postoperative pulmonary function. The underlying mechanisms, however, remain to be determined. Because pulmonary nitric oxide has been identified to play a critical role in pulmonary dysfunction in sepsis, we hypothesized that thoracic epidural anesthesia TEA modulates endothelial dysfunction via a nitric oxide-dependent pathway.

MethodsThirty-six Sprague-Dawley rats underwent sham laparotomy or induction of peritoneal sepsis caused by cecal ligation and puncture CLP. Septic animals were then treated with either bupivacaine 0.5% or normal saline epidurally 15 μl-h for 6 hours or 24 hours after injury. Previous experiments demonstrated that these time points correspond with a hyperdynamic at 6 hours and hypodynamic circulation at 24 hours, respectively. In addition, two sham control groups received either bupivacaine 0.5% or normal saline epidurally 15 μl-h. Six and 24 hours after injury, hemodynamic measurements and arterial blood gas analyses were performed in awake, spontaneously breathing rats. Exhaled nitric oxide, bradykinin-induced pulmonary vasoconstriction a surrogate marker of endothelial dysfunction, pulmonary wet-dry-weight ratio an estimate of pulmonary edema, and myeloperoxidase activity MPO, a surrogate marker of neutrophil infiltration into lung tisssue were investigated at 6 and 24 hours by using an established model of isolated and perfused lungs.

ResultsIn hyperdynamic sepsis, treatment with TEA resulted in reduced bradykinin-induced pulmonary vasoconstriction P < 0.05 and lower levels of exhaled NO as compared with those in untreated septic rats P < 0.05. However, the development of pulmonary edema or MPO activity in the lungs was not alleviated by sympathetic blockade in this phase of sepsis. Conversely, TEA led to an increased bradykinin-induced pulmonary vasoconstriction and pulmonary edema despite reduced exNO levels and pulmonary MPO activity in hypodynamic sepsis each P < 0.05 versus CLP 24 h. Pulmonary gas exchange was only marginally affected under the influence of TEA in hypodynamic sepsis. Mean arterial pressure and heart rate were not affected beyond the changes caused by sepsis itself.

ConclusionsThe results of the present study suggest that TEA modulates the NO pathway and exerts positive effects on pulmonary endothelial integrity only in hyperdynamic sepsis. Whether the negative effects on endothelial function in hypodynamic sepsis have an impact on overall morbidity and mortality remains to be determined in future studies.

AbbreviationsABEactual base excess


CLPcecal ligation and puncture

exNOexhaled nitric oxide

iNOSinducible nitric oxide synthase

MACminimum alveolar concentration

MPOmyeloperoxidase activity

NOnitric oxide

ODouter diameter

TEAthoracic epidural anesthesia

VSMCvascular smooth muscle cell.

Electronic supplementary materialThe online version of this article doi:10.1186-cc7950 contains supplementary material, which is available to authorized users.

Download fulltext PDF

Autor: Stefan Lauer - Hendrik Freise - Martin Westphal - Alexander Zarbock - Manfred Fobker - Hugo K Van Aken - Andreas W Sielen


Documentos relacionados