Simulation of potassium extraction by continuous haemodiafiltration.

Prediction of potassium extraction rates by continuous haemodiafiltration (CHDF) is useful for safe management of potassium levels in patients with hyperkalaemia. For this purpose, we developed a formula to predict the quantity of potassium extracted by CHDF. We hypothesized that potassium concentration in efflux dialysate was completely saturated by the influx blood, and potassium concentration in efflux blood was calculated based on this hypothesis. To check the accuracy of the calculation, potassium concentration was measured in efflux blood, and values were compared to predicted concentrations. Predicted potassium concentrations demonstrated good correlation to the measured values (95% confidence range, -0.32 to 0.58 mmol/l). These results confirmed that our hypothesis is applicable to clinical use of CHDF. Based on our observations, we created a formula to accurately predict the amount of potassium (dK) extracted by CHDF: dK=(Cb-Cd)xQd+CbxQf-CsxQs (Cb: plasma potassium concentration; Cd: potassium concentration in a dialysate; Cs: potassium concentration in the replacement fluid; Qd: dialysis rate; Qf: filtration rate and Qs: infusion rate of replacement fluid).

Fas/FasL-dependent apoptosis of alveolar cells after lipopolysaccharide-induced lung injury in mice.

To determine the possible contribution of apoptosis in the pathogenesis of acute lung injury (ALI), we investigated Fas antigen (Fas), Fas ligand (FasL), perforin, granzyme A, and granzyme B expressions in a murine model of ALI after intratracheal instillation of Escherichia coli lipopolysaccharide (LPS: 0.3-30 microg) into the left lung. Lung injury, examined by water-to-dry weight ratio and albumin leakage, demonstrated maximal epithelial injury 1 d after 30 microg LPS instillation. Expressions of the proapoptosis molecules' mRNA were dose-dependently up-regulated, with maximal expression in the early phase in the instilled lung and most apparent 1 d after LPS instillation. Negligible mRNA expression of proapoptosis molecules was observed in noninstilled lungs. The terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL) demonstrated positive signals in neutrophils and macrophages as well as in alveolar wall cells of the instilled lung 1 d after LPS instillation. Immunohistochemistry demonstrated that Fas was up-regulated in alveolar and inflammatory cells and FasL-positive inflammatory cells migrated into the air spaces in the LPS-instilled lung. Intratracheal administration of P2 antibody, which is an anti-Fas blocking antibody, attenuated the lung injury after 30 microg LPS instillation without attenuating mRNA expressions of proapoptosis molecules and neutrophil accumulation in the lung. In contrast, concanamycin A, which inhibits the function of perforin, did not alter the outcome after LPS instillation. These results indicate that the Fas/FasL system could be important in the pathogenesis of LPS-induced ALI, and proper regulation of the FasL/Fas system might be important for potential treatment of ARDS.

[Heart rate reduction using edrophonium during coronary artery bypass grafting without cardiopulmonary bypass].

Coronary artery bypass grafting without the use of cardiopulmonary bypass (CPB) is performed with increasing frequency. Performing revascularization on a beating heart is technically more demanding than performing revascularization on the arrested heart, especially in high-risk patients. beta-Blockers and calcium-channel antagonists have been used for the reduction of heart rate (HR) for the local immobilization of the anastomotic site. However, their negative inotropic actions often lead to serious hypotension. Therefore, we investigated the effect of edrophonium on HR reduction in high-risk patients undergoing CABG without CPB. Ten high-risk patients undergoing CABG without CPB were selected. To reduce HR during anastomosis, edrophonium was administered during the procedure. Systemic blood pressure (sBP), HR, and cardiac index (CI) were measured from the induction of anesthesia to the end of surgery. All surgeries were successfully performed without serious complications. To keep the rate under 60 bpm, edrophonium was administered at the time of anastomosis and this decreased the cardiac index from 2.19 to 1.95, while the sPB was maintained easily over 90 mmHg with the infusion of methoxamine. Edrophonium may be useful for the reduction of HR during coronary anastomosis in high-risk patients undergoing CABG without CPB.

Upregulation of two death pathways of perforin/granzyme and FasL/Fas in septic acute respiratory distress syndrome.

Accumulation and activation of inflammatory cells in the lung characterize the acute respiratory distress syndrome (ARDS). However, the precise mechanism for lung epithelial and endothelial cell damage remains unknown. Based on evidence that rapid apoptosis caused by CD8(+) cytolytic T cells can induce pathological cell death, we hypothesized that this mechanism may also participate in the acute lung injury, and attempted to evaluate apoptosis-related factors in bronchoalveolar lavage fluid (BALF) from ARDS patients. Quantitative polymerase chain reaction (PCR) analysis revealed that the messenger ribonucleic acids (mRNAs) for several apoptosis molecules, such as perforin, granzyme A, granzyme B, FasL, and Fas were highly upregulated in the acute phase of ARDS following sepsis. In contrast, low or negligible mRNA expression of these molecules was detected in patients with normal lung function, in septic patients without lung injury (septic non-ARDS), and in patients in the late phase of septic ARDS (late ARDS). While the genes of the classic proinflammatory cytokines interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8, and inducible nitric oxide synthase (iNOS) were upregulated in septic non-ARDS or late ARDS patients, expressions of these genes in the acute phase of septic ARDS were most distinct. The immunofluorescence flow cytometry showed that only the lymphocyte population in BALF from acute phase of septic ARDS patients expressed perforin and granzyme. The level of soluble FasL in the BALF increased only in the acute ARDS patients. These results thus suggested that the dual apoptosis pathway, perforin/granzyme and FasL/Fas system, is likely to be another participant for the pathogenesis of acute lung injury.

[Postoperative hoarseness and sore throat after tracheal intubation: effect of a low intracuff pressure of endotracheal tube and the usefulness of cuff pressure indicator].

Many clinical reports have described postoperative hoarseness and sore throat after general anesthesia. In most cases, these symptoms were attributed to high pressure of the endotracheal tube cuff. The recommended cuff pressure is less than 25 mmHg, as excessive pressure produces ischemia of the tracheal mucosa. However, within the safe pressure range, postoperative hoarseness and sore throat are still often observed. In this study, one hundred and ninety patients of ASA classes I or II were allocated randomly to two groups, low cuff pressure group (< 15 mmHg) or high cuff pressure group (15-25 mmHg), using continuous monitoring with a cuff pressure gauge. We investigated the incidence of postoperative hoarseness and sore throat at 24 hours after intubation and on the seventh postoperative day. The incidence of postoperative hoarseness and sore throat was significantly decreased in the low pressure group at 24 hours after intubation as compared with the high pressure group, but there was no significant difference between the two groups on the seventh postoperative day. These results suggest that keeping the cuff pressure under 15 mmHg can prevent postoperative hoarseness or sore throat at 24 hours after intubation, and that a cuff pressure gauge is thought to be one of the indispensable monitors during anesthesia.

[Simultaneous MIDCAB and subtotal gastrectomy in an elderly patient with severe ischemic heart disease].

An 81 year old man with severe ischemic heart disease and left ventricular dysfunction was scheduled for a subtotal gastrectomy for his advanced gastric cancer. His cardiac function was so poor that we performed minimally invasive coronary artery bypass grafting (MIDCAB; coronary artery bypass grafting without cardiopulmonary bypass for LAD through a small left thoracotomy), just before the abdominal operation. Anesthesia was induced and maintained with fentanyl, vecuronium and sevoflurane. To control heart rate below 60 bpm during local coronary occlusion for bypass grafting, edrophonium 5 mg was administered just before the occlusion. During the bypass grafting procedure, the patient's heart rate was maintained at 50-60 bpm and his hemodynamic profile slightly declined but was permissible. After bypass grafting, his cardiac performance was improved with low dose dobutamine. Subsequently subtotal gastrectomy was carried out. His postoperative course was uneventful. Combined MIDCAB and abdominal operation may be beneficial for selected patients with severe ischemic heart disease.

Expression of inducible nitric oxide synthase and inflammatory cytokines in alveolar macrophages of ARDS following sepsis.

STUDY OBJECTIVE: The objective of this study was to evaluate the role of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines in alveolar macrophages (AMs) in the pathogenesis of ARDS following sepsis. SETTING: ICU in a university hospital. DESIGN: Prospective exploratory, open-labeled study was carried out. PATIENTS: A total of 24 patients were investigated: 8 patients diagnosed as having ARDS following sepsis (ARDS group); 8 patients under general anesthesia in the operating room whose lung functions were normal (control group); and 8 patients who were intubated and artificially ventilated for 1 week in the ICU whose lung functions were not deteriorated without fulfilling the ARDS criteria and whose general state fulfilled the sepsis criteria (long-term ventilation group, or LTV group). MEASUREMENTS AND RESULTS: The expression of iNOS, interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8) in AMs obtained from BAL fluid (BALF) was determined by the immunofluorescent technique. We observed the significant expression of iNOS, IL-6, and IL-8 only in the ARDS group. Meanwhile, NOx (the sum of NO2- + NO3-) was elevated in the BALF supernatant, and IL-6 and IL-8 levels in both the BALF supernatant and the serum were also elevated in the ARDS group. No significant expressions were detected in the control and the LTV group. CONCLUSIONS: The result that iNOS was detected only in ARDS patients following sepsis suggests that iNOS together with proinflammatory cytokines produced by AMs might play a pivotal role in the pathogenesis of acute lung injury and be useful for monitoring disorders in the lung in such conditions.

Role of alveolar macrophages in initiation and regulation of inflammation in Pseudomonas aeruginosa pneumonia.

To evaluate the role of alveolar macrophages (AMs) in acute Pseudomonas aeruginosa pneumonia in mice, AMs were depleted by aerosol inhalation of liposomes containing clodronate disodium. AM-depleted mice were then intratracheally infected with 5 x 10(5) CFU of P. aeruginosa. In addition to monitoring neutrophil recruitment and chemokine releases, lung injury was evaluated soon after infection (8 h) and at a later time (48 h). At 8 h, depletion of AMs reduced neutrophil recruitment, chemokine release, and lung injury. At 48 h, however, depletion of AMs decreased bacterial clearance and resulted in delayed movement of neutrophils from the site of inflammation with aggravated lung injury. With instillation of 5 x 10(7) CFU of bacteria, AM-depleted mice showed low mortality within 24 h of infection but high mortality at a later time, in contrast to non-AM-depleted mice. These results demonstrate that depletion of AMs has beneficial early effects but deleterious late effects on lung injury and survival in cases of P. aeruginosa pneumonia.