Thoracic epidural anesthesia time-dependently modulates pulmonary endothelial dysfunction in septic rats

Abstract

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-1) 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-1). 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.

Gadolinium chloride modulates bradykinin-induced pulmonary vasoconstriction and hypoxic pulmonary vasoconstriction during polymicrobial abdominal sepsis in rats

“…Interestingly, it was shown in recent studies using the same CLP model that bradykinin-induced pulmonary vasoconstriction was significantly elevated at 6 hours post-induction of peritonitis, indicating a profound endothelial injury. However, in accordance with our current data, the paradoxical bradykinininduced vasoconstriction was not detected 24 hours after induction of CLP-sepsis [18,22]. With the progression of sepsis a recovery from endothelial injury seems highly unlikely.…”

“…Thereafter, sham laparotomy or induction of CLP-sepsis was performed and the second set of measurements were taken 24 hours post-injury and defined as time point "24 hours." As noted in previous studies [18], the induction of CLP-sepsis was associated with the development of profound tachycardia, tachypnea, leucopenia, and increased serum lactate levels (P < .05 vs. SHAM each and vs. 0 hour measurement within the CLP group; Tables 1 and 2). No significant changes in blood gas analyses, hemoglobin, and hematocrit were detected in septic animals (CLP) compared with sham controls (SHAM) (Tables 2 and 3).…”

“…We tested the hypothesis in vivo and ex vivo using a model of polymicrobial abdominal sepsis induced by cecal ligation and puncture (CLP) and an established model of isolated and perfused lungs [10,17,18].…”

Neuraxial Regional Anaesthesia in Patients with Active Infection and Sepsis: A Clinical Narrative Review

“…Subsequent studies reported positive effects of thoracic epidural anaesthesia on pulmonary endothelial capillary integrity in septic rats in the hyperdynamic phase, modulating the production of nitric oxide (effects not found in rats with sepsis in the hypodynamic phase) (26). Authors also reported positive effects on the hepatic microcirculation and inflammatory response in these animals, concluding that in the late phase, cardiac output was not affected, while liver hypoperfusion was reversed (restoring the arterial buffer system mechanisms), and the intrahepatic leukocyte adhesion improved (27).…”

Atherosclerosis aggravates ischemia/reperfusion injury in the gut and remote damage in the liver and the lung

“…As an additional parameter for remote injury in the lung, we determined the lung tissue content of MPO, which is a surrogate parameter for inflammatory infiltration by neutrophils [12,13]. Lung tissue specimens (100 lg) were homogenized in 1 ml of 0.05 M potassium-phosphatebuffer (PPS) and hexadecyltrimethylammoniumbromide (HTAB).…”