Published papers

Objective: Inflammatory responses play major roles in the development of acute lung injury following lung cancer surgery. The authors tested the hypothesis that thoracic epidural anesthesia (TEA) during surgery could attenuate both systemic and local inflammatory cytokine productions in patients undergoing lung cancer surgery. Design: A prospective randomized controlled trial. Setting: At Keio University Hospital, Tokyo, Japan. Participants: Patients scheduled for lung cancer surgery. Interventions: Sixty patients were randomly allocated into two groups (n = 30 each group): the epidural group (group E), in which anesthesia was maintained with propofol, fentanyl, rocuronium, and epidural anesthesia with 0.25% levobupivacaine; or the remifentanil group (group R), in which a remifentanil infusion was used as a potent analgesia instead of epidural anesthesia. Measurements and Main Results: The lung epithelial lining fluid (ELF) and blood sampling were collected prior to one-lung ventilation (OLV) initiation (T1) and at 30 minutes after the end of OLV (T2). The concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the ELF at T2 were increased significantly compared with those at T1 in both groups. The ELF concentration of IL-6 in group E was significantly lower than that in group R at T2 (median [interquartile range]: 39.7 [13.8-80.2] versus 76.1 [44.9-138.2], p = 0.008). Plasma IL-6 concentrations at T2, which increased in comparison to that at T1, were not significantly different between the two groups. The plasma concentrations of TNF-α did not change in both groups. Conclusions: This randomized clinical trial suggested that TEA could attenuate local inflammatory responses in the lungs during lung cancer surgery.

Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. Results: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (−8.1 ± 10.0 vs −2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (−9.1 ± 10.2 vs −2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. Conclusion: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

Individuals with chronic pain not only endure the direct burden of pain but also experience various symptoms, including sleep disturbances and fatigue, which deteriorate their quality of life. Notably, these symptoms closely resemble those observed in "long COVID,"a prolonged health complication that can arise after coronavirus disease 2019 (COVID-19) infection. Because the similarities between chronic pain and long COVID remain unexplored, this study aimed to investigate their relationship using Japanese epidemiological data. Using the Japan COVID-19 and Society Internet Survey in 2022, which included 32,000 participants, we analyzed data on the presence of chronic pain, history of COVID-19 infection, and presence of 17 long COVID-like symptoms, including gastrointestinal upset, back pain, limb/joint pain, headache, chest pain, shortness of breath, dizziness, sleep disorder, hearing disorder, taste disorder, smell disorder, memory impairment, poor concentration, hair loss, decreased libido, fatigue, and cough. Individuals with history of COVID-19 experienced a significantly greater number of long COVID-like symptoms (median: 5) compared with those with neither COVID-19 nor chronic pain (median: 4, P < 0.001). Individuals with chronic pain alone and those with both COVID-19 and chronic pain exhibited an even greater number of symptoms (median: 8 and 9, respectively). In addition, individuals with chronic pain exhibited greater prevalence odds for 15 of the 17 symptoms than those with neither COVID-19 nor chronic pain (P < 0.001). Our findings indicate that long COVID-like symptoms are not specifically associated with COVID-19. Instead, the data suggest that chronic pain contributes as an independent risk factor for these symptoms.

Background: Pulmonary diseases (PD) are frequently associated with impaired cardiac function and the presence of mitral and tricuspid regurgitation (MR and TR). Objectives: The study aimed to clarify the impact of PD on clinical outcomes following mitral transcatheter edge-to-edge repair (M-TEER). Methods: Of the 3,764 patients who underwent M-TEER, 3,666 were included in the analysis and stratified according to the absence or presence of PD before the procedure. The primary endpoint was all-cause mortality, evaluated using Kaplan-Meier analysis. Cardiovascular and non-cardiovascular mortality and HFH (HFH) were also assessed during a 4-year follow-up. Moreover, the prognostic impact of TR improvement after M-TEER was evaluated in patients with and without PD. Results: Of the 3,666 patients, 580 (15.8%) had PD, included fewer women, and exhibited greater frailty compared with those without PD. Within a median follow-up of 432 [314–826] days, all-cause mortality did not differ significantly between patients with PD and those without (150 [25.9%] vs. 682 [22.1%], Log rank P = 0.331). No significant differences were observed in the incidence of cardiovascular mortality, non-cardiovascular mortality, and HFH between the two groups. When stratified by PD status, residual significant TR after M-TEER was significantly associated with HFH both in patients with PD and without PD. Conclusions: The intermediate-term prognosis after M-TEER was comparable between patients with and without PD. In patients with PD, MR was effectively reduced through minimally invasive M-TEER. However, appropriate management of TR after MTEER may be required to improve outcomes in this population. Clinical trials: OCEAN-Mitral registry (UMIN-ID: UMIN000023653).

Background: There is no consensus regarding the choice of anesthetic method for patients with pulmonary hypertension (PH). We report two cases in which neuraxial anesthesia was safely performed without general anesthesia during open abdominal surgery in patients with severe PH. Case presentation: Case 1: A 59-year-old woman had an atrial septal defect and a huge abdominal tumor with a mean pulmonary arterial pressure (PAP) of 39 mmHg and pulmonary vascular resistance (PVR) of 3.5 Wood units. Case 2: A 23-year-old woman who had hereditary pulmonary artery hypertension (mean PAP, 65 mmHg; PVR, 16.45 Wood units). Both patients underwent open abdominal surgery under neuraxial anesthesia without circulatory collapse with intraoperative administration of vasoconstrictors. Conclusion: Although anesthetic care must be personalized depending on the pathology and severity of PH, neuraxial anesthesia may be an option for patients with severe PH undergoing abdominal surgery.

Approximately 30% of patients with depression suffer from treatment-resistant depression (TRD). Ketamine has shown antidepressant efficacy for TRD. While glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) has been demonstrated to play crucial roles in the process of pharmacological action of ketamine in experimental animals, it remains elusive how ketamine exhibits its efficacy through changes in AMPAR dynamics in patients with TRD. In this study, using a positron emission tomography (PET) tracer, [11C]K-2, which depicts AMPAR density in the living human brain, we detected a negative correlation between AMPAR density and illness severity and differences in AMPAR distribution between patients with TRD and healthy participants. Furthermore, we detected brain areas where ketamine administration altered AMPAR density in significant correlations with ketamine-induced antidepressant effect in patients with TRD. AMPAR density alteration in these regions partially rescued AMPAR phenotype in the affected areas. Thus, AMPAR dynamics underlies the antidepressant effect of ketamine in patients with TRD.

Background: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. Methods: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. Results: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). Conclusions: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. Clinical trial registration: UMIN000035350.

An increasing number of patients require precise intraoperative hemodynamic monitoring due to aging and comorbidities. To prevent undesirable outcomes from intraoperative hypotension or hypoperfusion, appropriate threshold settings are required. These setting can vary widely from patient to patient. Goal-directed therapy techniques allow for flow monitoring as the standard for perioperative fluid management. Based on the concept of personalized medicine, individual assessment and treatment are more advantageous than conventional or uniform interventions. The recent development of minimally and noninvasive monitoring devices make it possible to apply detailed control, tracking, and observation of broad patient populations, all while reducing adverse complications. In this manuscript, we review the monitoring features of each device, together with possible advantages and disadvantages of their use in optimizing patient hemodynamic management.

BACKGROUND: Both anesthetic-induced and ischemic preconditioning are protective against hepatic ischemia-reperfusion injury. However, the effects of these preventive methods on the metabolic function remain to be elucidated. We investigated the anesthetic conditioning and ischemic preconditioning on the metabolic function of the rabbit model of hepatic ischemia-reperfusion. METHODS: After approval by the institutional animal care and use committee, 36 Japanese White rabbits underwent partial hepatic ischemia for 90 min either under sevoflurane or propofol anesthesia. All the rabbits underwent 90 min of hepatic ischemia, and half of the rabbits in each group underwent additional 10-min ischemia and 10-min reperfusion before index ischemia. Hepatic microvascular blood flow was intermittently measured during reperfusion period, and galactose clearance, serum aminotransferase activities, and lactate concentrations were determined 180 min after reperfusion. RESULTS: Neither anesthetic conditioning with sevoflurane nor ischemic preconditioning altered hepatic microvascular blood flow during reperfusion and serum transaminase activities after reperfusion. However, galactose clearance of reperfused liver was significantly higher under sevoflurane anesthesia than propofol (0.016 +/- 0.005/min vs. 0.011 +/- 0.004/min). Statistically significant interaction between anesthetic choice and application of ischemic preconditioning suggests that the ischemic preconditioning is selectively protective under propofol anesthesia. Increase of blood lactate concentration was significantly suppressed under sevoflurane anesthesia compared to propofol (1.5 +/- 0.8 vs. 3.9 +/- 1.4 mmol/l) without any statistically significant interaction with the application of ischemic preconditioning. CONCLUSION: Sevoflurane attenuated the decrease of galactose clearance and increase of the blood lactate after reperfusion compared to propofol. Application of ischemic preconditioning was significantly protective under propofol anesthesia.

Hemodynamic monitoring is mandatory for perioperative management of cardiac surgery. Recently, the estimated continuous cardiac output (esCCO) system, which can monitor cardiac output (CO) non-invasively based on pulse wave transit time, has been developed. Patients who underwent cardiovascular surgeries with hemodynamics monitoring using arterial pressure-based CO (APCO) were eligible for this study. Hemodynamic monitoring using esCCO and APCO was initiated immediately after intensive care unit admission. CO values measured using esCCO and APCO were collected every 6 h, and stroke volume variation (SVV) data were obtained every hour while patients were mechanically ventilated. Correlation and Bland-Altman analyses were used to compare APCO and esCCO. Welch's analysis of variance, and four-quadrant plot and polar plot analyses were performed to evaluate the effect of time course, and the trending ability. A p-value < 0.05 was considered statistically significant. Twenty-one patients were included in this study, and 143 and 146 datasets for CO and SVV measurement were analyzed. Regarding CO, the correlation analysis showed that APCO and esCCO were significantly correlated (r = 0.62), and the bias +/- precision and percentage error were 0.14 +/- 1.94 (L/min) and 69%, respectively. The correlation coefficient, bias +/- precision, and percentage error for SVV evaluation were 0.4, - 3.79 +/- 5.08, and 99%, respectively. The time course had no effects on the biases between CO and SVV. Concordance rates were 80.3 and 75.7% respectively. While CO measurement with esCCO can be a reliable monitor after cardiovascular surgeries, SVV measurement with esCCO may require further improvement.

BACKGROUND: Previous work in the field of medical informatics has shown that rules-based algorithms can be created to identify patients with various medical conditions; however, these techniques have not been compared to actual clinician notes nor has the ability to predict complications been tested. We hypothesize that a rules-based algorithm can successfully identify patients with the diseases in the Revised Cardiac Risk Index (RCRI). METHODS: Patients undergoing surgery at the University of California, Los Angeles Health System between April 1, 2013 and July 1, 2016 and who had at least 2 previous office visits were included. For each disease in the RCRI except renal failure-congestive heart failure, ischemic heart disease, cerebrovascular disease, and diabetes mellitus-diagnosis algorithms were created based on diagnostic and standard clinical treatment criteria. For each disease state, the prevalence of the disease as determined by the algorithm, International Classification of Disease (ICD) code, and anesthesiologist's preoperative note were determined. Additionally, 400 American Society of Anesthesiologists classes III and IV cases were randomly chosen for manual review by an anesthesiologist. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve were determined using the manual review as a gold standard. Last, the ability of the RCRI as calculated by each of the methods to predict in-hospital mortality was determined, and the time necessary to run the algorithms was calculated. RESULTS: A total of 64,151 patients met inclusion criteria for the study. In general, the incidence of definite or likely disease determined by the algorithms was higher than that detected by the anesthesiologist. Additionally, in all disease states, the prevalence of disease was always lowest for the ICD codes, followed by the preoperative note, followed by the algorithms. In the subset of patients for whom the records were manually reviewed, the algorithms were generally the most sensitive and the ICD codes the most specific. When computing the modified RCRI using each of the methods, the modified RCRI from the algorithms predicted in-hospital mortality with an area under the receiver operating characteristic curve of 0.70 (0.67-0.73), which compared to 0.70 (0.67-0.72) for ICD codes and 0.64 (0.61-0.67) for the preoperative note. On average, the algorithms took 12.64 +/- 1.20 minutes to run on 1.4 million patients. CONCLUSIONS: Rules-based algorithms for disease in the RCRI can be created that perform with a similar discriminative ability as compared to physician notes and ICD codes but with significantly increased economies of scale.

We describe 2 patients who developed anaphylactic shock after sugammadex administration during anesthesia. Both had no history of prior sugammadex administration. The serum tryptase concentrations were elevated after the allergic reaction. Basophil activation testing 1 month after the events was positive for sugammadex in 1 patient, and negative in the other. However, it was positive for light-exposed sugammadex solution in both patients, suggesting a possible allergic reaction to a denatured compound of sugammadex generated by light exposure of the sugammadex solution.

BACKGROUND: The United States is in the midst of an opioid epidemic, and opioid use disorder often begins with a prescription for acute pain. The perioperative period represents an important opportunity to prevent chronic opioid use, and recently there has been a paradigm shift toward implementation of enhanced recovery after surgery (ERAS) protocols that promote opioid-free and multimodal analgesia. The objective of this study was to assess the impact of an ERAS intervention for colorectal surgery on discharge opioid prescribing practices. METHODS: We conducted a historical-prospective quality improvement study of an ERAS protocol implemented for patients undergoing colorectal surgery with a focus on the opioid-free and multimodal analgesia components of the pathway. We compared patients undergoing colorectal surgery 1 year before implementation (June 15, 2015, to June 14, 2016) and 1 year after implementation (June 15, 2016, to June 14, 2017). RESULTS: Before the ERAS intervention, opioids at discharge were not significantly increasing (1% per month; 95% confidence interval [CI], -1% to 3%; P = .199). Immediately after the ERAS intervention, opioid prescriptions were not significantly lower (13%; 95% CI, -30% to 3%; P = .110). After the intervention, the rate of opioid prescriptions at discharge did not decrease significantly 1% (95% CI, -3% to 1%) compared to the pre-period rate (P = .399). Subgroup analysis showed that in patients with a combination of low discharge pain scores, no preoperative opioid use, and low morphine milligram equivalents consumption before discharge, the rate of discharge opioid prescription was 72% (95% CI, 61%-83%). CONCLUSIONS: This study is the first to report discharge opioid prescribing practices in an ERAS setting. Although an ERAS intervention for colorectal surgery led to an increase in opioid-free anesthesia and multimodal analgesia, we did not observe an impact on discharge opioid prescribing practices. The majority of patients were discharged with an opioid prescription, including those with a combination of low discharge pain scores, no preoperative opioid use, and low morphine milligram equivalents consumption before discharge. This observation in the setting of an ERAS pathway that promotes multimodal analgesia suggests that our findings are very likely to also be observed in non-ERAS settings and offers an opportunity to modify opioid prescribing practices on discharge after surgery. For opioid-free anesthesia and multimodal analgesia to influence the opioid epidemic, the dose and quantity of the opioids prescribed should be modified based on the information gathered by in-hospital pain scores and opioid use as well as pain history before admission.

BACKGROUND: This prospective study was designed to examine the associations of demographic, clinical, psychological and neuroendocrine factors with acute and chronic post-operative pain following partial mastectomy. METHODS: Sixty-four female patients scheduled for partial mastectomy were enrolled. Pre-operative anxiety/depression was assessed, using the Hospital Anxiety and Depression Scale (HADS). Pre-operative 24-h urinary cortisol levels were measured 2 days before surgery. Post-operative pain was examined using a visual analog scale (VAS) for acute pain on 0-2 post-operative day (POD), and a short-form McGill Pain Questionnaire for chronic pain at 6 months after surgery. In the last 29 subjects, post-operative 24-h urinary cortisol levels were also measured on 0 POD and were subjected to correlation analysis. RESULTS: Multivariate logistic regression analysis revealed that lower pre-operative cortisol secretion and greater pre-operative anxiety were significantly associated with an increased risk of moderate to severe acute post-operative pain [Odds Ratio (95% Confidence Interval); 0.96 (0.92-0.98), and 1.24 (1.04-1.54)], and that patients with greater pre-operative anxiety and moderate to severe acute pain were more likely to develop chronic post-operative pain [OR (95% CI); 1.63 (1.23-2.40), and 5.07 (1.30-24.6)]. Correlational analysis demonstrated that the post-operative cortisol level was inversely correlated with pre-operative anxiety and the intensity of acute post-operative pain (r = -0.40, p < 0.05, and r = -0.50, p < 0.01), but not with the intensity of chronic pain. CONCLUSIONS: This study confirms that pre-operative anxiety is associated with both acute and chronic post-operative pain after partial mastectomy. It also suggests that lower perioperative cortisol secretion might be associated with greater acute post-operative pain. SIGNIFICANCE: Although the associations between psychological stress/stress hormone levels and chronic post-operative pain remain to be determined, pre-operative psychological stress and perioperative cortisol levels are correlated with acute post-operative pain.

BACKGROUND AND AIM: Because neutrophil gelatinase-associated lipocalin (NGAL) is known to provide significant bacteriostatic effects during infectious conditions, we tested the hypothesis that this protein is up-regulated and secreted into the intraluminal cavity of the gut under critically ill conditions and is thus responsible for the regulation of bacterial overgrowth. METHODS: With our institutional approval, male C57BL/6J mouse (6-7 weeks) were enrolled and applied for lipopolysaccharide or peritonitis model compared with naive control. We assessed NGAL protein concentrations in intestinal lumen and up-regulation of NGAL expression in intestinal tissues in in vivo as well as ex vivo settings. Simultaneously, we examined the effects of NGAL protein administration on the growth of Escherichia coli (E. coli) in in vivo and in vitro experimental settings. The localization of NGAL in intestinal tissues and lumen was also assessed by immunohistological approach using NGAL antibody. RESULTS: Both lipopolysaccharide and peritonitis insults evoked the marked up-regulation of NGAL mRNA and protein levels in gut tissues such as crypt cells. In addition, the administration of NGAL protein significantly inhibited the outgrowth of enteric E. coli under both in vitro and in vivo conditions, accompanied by histological evidence. CONCLUSION: Neutrophil gelatinase-associated lipocalin protein accompanied by apparent bacteriostatic action accumulated in the intestinal wall and streamed into the mucosal layer during critically ill state, thereby possibly shaping microbiota homeostasis in the gut.

BACKGROUND: Since hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4(+) T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions. METHODS: Male Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysaccharide, LPS 1 mg/kg) with or without hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40 %), while the normoglycemia groups were administered saline. Alterations of the mRNA expressions of inflammatory cytokines and CD4(+) T lymphocyte transcriptional factor expressions in the MLNs, and those of the intestinal microbiota were analyzed at 24 hr. RESULTS: Hyperglycemia was kept approximately 250-350 mg/dL during the 24 hr study period. At the end of 24 hr, hyperglycemia augmented the mRNA expressions of interleukin (IL)-1beta and IL-6 in the MLNs, while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors were simultaneously up-regulated under non-endotoxemic condition. LPS injection significantly modulated the obligate anaerobe bacterial populations of the Bacteroidetes class, and altered the population sizes of the Clostridium perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance these alterations of the microbiota evoked by LPS, although it did modify the bacterial populations of the L. reuteri subgroup and staphylococci in healthy condition without endotoxemia. CONCLUSIONS: The present study indicates that both gut immune function and microbiota are significantly modulated by persistent hyperglycemia.

BACKGROUND: In this randomized controlled trial, we examined whether intra- and postoperative infusion of low-dose ketamine decreased postoperative morphine requirement and morphine-related adverse effects as nausea and vomiting after scoliosis surgery. METHODS: After IRB approval and informed consent, 36 patients, aged 10-19 years, undergoing posterior correction surgery for adolescent idiopathic scoliosis, were randomly allocated into two groups: intra- and postoperative ketamine infusion at a rate of 2 mug/kg/min until 48 h after surgery (ketamine group, n = 17) or infusion of an equal volume of saline (placebo group, n = 19). All patients were administered total intravenous anesthesia with propofol and remifentanil during surgery and intravenous morphine using a patient-controlled analgesia device after surgery. The primary outcome was cumulative morphine consumption in the initial 48 h after surgery. Pain scores (Numerical Rating Scale, NRS, 0-10), sedation scales, incidence of postoperative nausea and vomiting (PONV), and antiemetic consumption were recorded by nurses blinded to the study protocol for 48 h after surgery. RESULTS: Patient characteristics did not differ between the two groups. Cumulative morphine consumption for 48 h after surgery was significantly lower in the ketamine group compared to the placebo group (0.89 +/- 0.08 mg/kg vs. 1.16 +/- 0.07 mg/kg, 95% confidence interval for difference between the means, 0.03-0.48 mg/kg, P = 0.019). NRS pain, sedation scales, and incidence of PONV did not differ between the two groups. Antiemetic consumption was significantly smaller in ketamine group. CONCLUSIONS: Intra- and postoperative infusion of low-dose ketamine reduced cumulative morphine consumption and antiemetic requirement for 48 h after surgery.

BACKGROUND: Neutrophil-derived lipocalin-2 exerts bacteriostatic effects through retardation of iron uptake by the Gram-negative organisms like Escherichia coli. We tested the hypothesis that the expression of lipocalin-2, a bacteriostatic protein, was upregulated by induction of surgical site infection (SSI) with E coli in healthy and diseased rats and that epidural anesthesia modulated its expression. METHODS: Male Wistar rats were randomized into a healthy or disease group, the latter of which was administered lipopolysaccharide. Both groups were further divided into 3 subgroups, the control, saline, and lidocaine groups: group healthy control (n = 10), healthy saline (n = 10), and healthy lidocaine (n = 10) versus group disease control (n = 15), disease saline (n = 18), and disease lidocaine (n = 19), respectively. While saline was epidurally administered to the control and saline groups, lidocaine was administered to the lidocaine groups. Except for the control groups, E coli was injected to the pseudosurgical site to mimic SSI after abdominal surgery. Plasma concentrations of inflammatory cytokine and lipocalin-2 were measured. At 72 hours, the surgical site tissues were obtained to evaluate mRNA expression of lipocalin-2 and E coli DNA expression. RESULTS: All disease subgroups showed markedly increased plasma inflammatory cytokines versus the healthy subgroups. Among the disease subgroups, plasma concentrations of lipocalin-2 and tissue mRNA expression of lipocalin-2 were significantly increased in group disease lidocaine versus the others. Concurrently, E coli DNA expression in the tissue specimens was also significantly lower in group disease lidocaine as compared with group disease saline. CONCLUSIONS: Epidural anesthesia was associated with an increase in the expression lipocalin-2 and a decrease in the expression of E coli DNA at pseudosurgical sites in sick but not healthy rats. These observations suggest a potential mechanism by which epidural anesthesia could reduce the risk of SSI.

PURPOSE: Atrial natriuretic peptide (ANP) has been known to be protective against hepatic ischemia/reperfusion injury. The purpose of this study was to verify the hypothesis that ANP conserves microvascular circulation and reduces ischemia-reperfusion injury in the in vivo rabbit model. METHODS: With IRB approval, 30 male Japanese white rabbits under pentobarbital anesthesia were studied. These animals were randomly assigned to the following three groups (n = 10 each): control, ANP, and sham group. Animals in the ANP group received continuous infusion of ANP at 0.1 mug/kg/min throughout the study period. Animals in control and ANP groups underwent 90 min of partial hepatic ischemia by clamping the right hepatic artery and portal vein. Descending aortic blood flow (AoF) was monitored with a transit-time ultrasound flowmeter. Hepatic tissue microvascular blood flow (HTBF) at both right (ischemic) and left (nonischemic) lobe was intermittently evaluated with the hydrogen clearance method. After 180 min of reperfusion, hepatic injury was determined with serum AST and ALT. Galactose clearance of reperfused right lobe was also measured as an indicator of hepatic metabolic function. Histopathological change and the number of apoptotic hepatocytes were also evaluated. RESULTS: Systemic hemodynamic data including mean arterial pressure, heart rate, and AoF did not differ among the three groups during the study period. ANP attenuated ischemia-induced right HTBF decrease. ANP also suppressed histopathological degeneration, apoptosis, and decline in galactose clearance after reperfusion. CONCLUSIONS: ANP attenuated hepatic microvascular dysfunction and hepatocyte injury after reperfusion without significant hemodynamic change.