Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549.

Epithelial cell injury under hyperinflammatory conditions is critical in the development of septic acute lung injury (ALI). The aim of the present study is to analyze the cytotoxic effects of a mixture of proinflammatory cytokines in the human alveolar epithelial cell line A549. The cytotoxicity of proinflammatory cytokines were assessed in A549 cells by measuring lactate dehydrogenase released into the culture medium and by crystal violet staining of surviving cells. Activation of the caspase-dependent apoptotic pathway was evaluated by monitoring cleavage of cytokeratin 18 by caspases using enzyme-liked immunosorbent assay (ELISA). To estimate the cytotoxic signaling pathways responsible for epithelial injury, agents with antiinflammatory or antioxidative properties were extensively screened for cytoprotective effects in the inflammation-associated epithelial injury model. The present study revealed that inflammatory cytokines exerted cytotoxicity in A549 cells. A mixture of interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), designated as cytomix, augmented cytotoxicity compared with each individual cytokine. Treatment with glucocorticoid (dexamethasone), tetracycline-derived antiinflammatory antibiotics (minocycline or doxycycline), angiotensin II receptor blockers (losartan or telmisartan), or antioxidants (dimethyl sulfoxide, catalase) attenuated cytomix-induced cytotoxicity, including caspase activation. These results implied that inflammatory cytokines alone could cause alveolar epithelial injury in the pathophysiology of septic ALI. Caspase-dependent apoptosis was speculated to be one mechanism responsible for the cytokine-induced cytotoxicity. Agents with antiinflammatory or antioxidative properties such as glucocorticoid, tetracycline-derived antibiotics, angiotensin II receptor blockers, or direct antioxidants showed substantial effect in attenuating cytokine-induced cytotoxicity and may be candidates for treatment options.

[Anesthetic management for emergency laparotomy in an adult patient with Eisenmenger syndrome: a case report].

There are few clinical reports concerning anesthetic management for patients with Eisenmenger syndrome requiring non-cardiac surgery. The risk of morbidity and mortality associated with non-cardiac surgery in patients with Eisenmenger syndrome is considerable. During anesthetic management for these patients, careful circulatory and respiratory managements to avoid several factors related to surgery and anesthesia that can potentially increase right to left shunt flow are required. Therefore, it is very important to maintain cardiac output to prevent a decrease in systemic vascular resistance and an increase in pulmonary vascular resistance. For this purpose, combination of intravenous administration of inotropes such as milrinone and dobutamine, and vasopressors such as norepinephrine, might have clinical efficacy. Here we describe an anesthetic management for a 50-year-old woman with a ventricular septal defect and Eisenmenger syndrome undergoing emergency laparotomy. We considered that sufficient fluid therapy and adequate administration of inotropes and vasopressors, based on strict hemodynamic assessment using direct arterial and central venous pressure monitoring, arterial blood gas analysis, and transesophageal echocardiography during general anesthesia, might have contributed to the uneventful perioperative course of the patient.

[Effects of general anesthesia using ketamine and remifentanil on postoperative pain management for patients undergoing laparotomy].

BACKGROUND: Co-administration of ketamine and remifentanil may offer preemptive analgesia and prevention of opioid-induced hyperalgesia, resulting in reduction of postoperative pain. METHODS: We retrospectively analyzed data concerning anesthetic management and postoperative pain management in 19 adult patients undergoing elective laparotomy with general anesthesia using ketamine and remifentanil. RESULTS: Ketamine and remifentanil were co-administered for both induction and maintenance of general anesthesia. Preoperative and total doses of ketamine were 1.4+/-0.5 and 1.9+/-0.4 mg x kg(-1). Infusion rate of remifentanil at the beginning of surgery was 0.24+/-0.02 microg x kg(-1) x min(-1), and minimal and maximal rate were 0.06+/-0.03 and 0.26+/-0.03 microg x kg(-1) min(-1). Pentazocine and nonsteroidal anti-inflammatory drugs (NSAIDs) were used for postoperative pain management. Consumption of pentazocine was 0.51+/-0.33 mg x kg(-1) on 1st postoperative day (1POD), and NSAIDs were co-administered on 1POD for 3 patients. Most patients could stand up and walk on 1POD. CONCLUSIONS: Results in this study suggest that anesthetic management using ketamine and remifentanil may be useful for postoperative pain management, probably by preemptive analgesic effects of both agents and preventive effects of ketamine against opioid-induced hyperalgesia.