Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q ̇ $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q ̇ $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q ̇ $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q ̇ $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q ̇ $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q ̇ $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q ̇ $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

Pulmonary vein stump thrombosis and organ infarction after lung lobectomy.

Lung resection surgery, which is performed as a treatment for lung cancer and metastatic lung tumors, is currently conducted via minimally invasive techniques such as video-assisted thoracoscopic surgery and robot-assisted methods. Postoperative complications related to this surgery, such as pulmonary vein thrombosis and cerebral and other organ infarctions, have been increasingly reported. The primary cause of these complications is thrombus formation in the pulmonary vein stump. Statistical data on the site of lung lobectomy have indicated that surgeries involving the left upper lobe are most frequently associated with embolic complications. Although this issue has not received considerable attention in anesthesiology, the importance of prevention and treatment in postoperative management is growing. The role of anesthesiologists in preventing these complications is critical. These roles involve careful fluid management to avoid hypercoagulable states, consideration of early postoperative anticoagulation therapy, assessment of the suitability of epidural anesthesia for postoperative anticoagulation, and improvement of hospital-wide safety systems and monitoring of high-risk patients. Anesthesiologists need to understand the pathology and risk factors involved and play an active role in preventing and treating these complications through effective collaboration with thoracic surgeons and the in-hospital stroke team.

Time-trend analysis of the center frequency of the intrinsic mode function from the Hilbert-Huang transform of electroencephalography during general anesthesia: a retrospective observational study.

BACKGROUND: Anesthesiologists are required to maintain an optimal depth of anesthesia during general anesthesia, and several electroencephalogram (EEG) processing methods have been developed and approved for clinical use to evaluate anesthesia depth. Recently, the Hilbert-Huang transform (HHT) was introduced to analyze nonlinear and nonstationary data. In this study, we assessed whether the changes in EEG characteristics during general anesthesia that are analyzed by the HHT are useful for monitoring the depth of anesthesia. METHODS: This retrospective observational study enrolled patients who underwent propofol anesthesia. Raw EEG signals were obtained from a monitor through a previously developed software application. We developed an HHT analyzer to decompose the EEG signal into six intrinsic mode functions (IMFs) and estimated the instantaneous frequencies (HHT_IF) for each IMF. Changes over time in the raw EEG waves and parameters such as HHT_IF, BIS, spectral edge frequency 95 (SEF95), and electromyogram parameter (EMGlow) were assessed, and a Gaussian process regression model was created to assess the association between BIS and HHT_IF. RESULTS: We analyzed EEG signals from 30 patients. The beta oscillation frequency range (13-25 Hz) was detected in IMF1 and IMF2 during the awake state, then after loss of consciousness, the frequency decreased and alpha oscillation (8-12 Hz) was detected in IMF2. At the emergence phase, the frequency increased and beta oscillations were detected in IMF1, IMF2, and IMF3. BIS and EMGlow changed significantly during the induction and emergence phases, whereas SEF95 showed a wide variability and no significant changes during the induction phase. The root mean square error between the observed BIS values and the values predicted by a Gaussian process regression model ranged from 4.69 to 9.68. CONCLUSIONS: We applied the HHT to EEG analyses during propofol anesthesia. The instantaneous frequency in IMF1 and IMF2 identified changes in EEG characteristics during induction and emergence from general anesthesia. Moreover, the HHT_IF in IMF2 showed strong associations with BIS and was suitable for depicting the alpha oscillation. Our study suggests that the HHT is useful for monitoring the depth of anesthesia.

A vacuolar membrane protein Vsb1p contributes to the vacuolar compartmentalization of basic amino acids in Schizosaccharomyces pombe.

Accumulation levels of Arg, Lys, and His in vacuoles of Schizosaccharomyces pombe cells were drastically decreased by the disruption of SPAC24H6.11c (vsb1+) gene identified by a homology search with the VSB1 gene of Saccharomyces cerevisiae. The Vsb1p fused with green fluorescent protein particularly localized at vacuolar membranes in S. pombe cells. Overexpression of vsb1+ markedly increased vacuolar levels of basic amino acids; however, overexpression of the vsb1D174A mutant did not affect the levels of these amino acids. These results suggest that the vsb1+ contributes to the accumulation of basic amino acids into the vacuoles of S. pombe, and the aspartate residue in the putative first transmembrane domain conserved among fungal homologs is crucial for the function of Vsb1p.

Intraoperative Diagnosis of a Stuck Bioprosthetic Valve Leaflet Due to a Loop of Suture After Mitral Valve Replacement.

A stuck mechanical valve leaflet is a well-known cardiovascular complication; however, a stuck bioprosthetic valve is a rare but potentially fatal complication. Herein a case of stuck bioprosthetic mitral valve caused by a loop of suture, which was detected on intraoperative 3-dimensional (3D) transesophageal echocardiography immediately after cardiopulmonary bypass, is presented. Restricted motion of the 2 leaflets during diastole and incomplete coaptation during systole were observed clearly on 3D imaging. Thus, intraoperative 3D transesophageal echocardiography imaging is useful for detecting such complications immediately after cardiopulmonary bypass.

Secondary in-hospital epidemiological investigation after an outbreak of Pseudomonas aeruginosa ST357.

The secondary in-hospital epidemiological investigation for drug-resistant Pseudomonas aeruginosa infections was conducted to evaluate the in-hospital situation and identify any associations between exoenzyme genotypes and other genotypes and antimicrobial resistance characteristics, at the University Hospital in Kyoto, Japan, following a reported outbreak of antimicrobial-resistant P. aeruginosa ST357 between 2005 and 2014. Twelve of the 546 P. aeruginosa isolates collected during the follow-up period were resistant to more than two classes of antimicrobials. All isolates were resistant to fluoroquinolones and 8 (66.7%) showed carbapenem resistance. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were metallo-ß-lactamase test-negative. Among five exoS (-)exoU (+) isolates, three possessing a class 1 integron with gene cassette aadB + cmlA6 were classified as ST357, and one isolate containing a class 1 integron with aacA31 was ST235. Collectively, the second survey results confirm that the initial outbreak is currently undergoing convergence. By combining data from the first and second surveys, we showed that prevalent STs such as ST357 and ST235 are associated with fluoroquinolone resistance, class 1 integron-associated resistance to ß-lactams and aminoglycosides, and cytotoxic exoU (+) genotypes. With the current worldwide spread of ST357 and ST235 isolates, it is important to evaluate epidemiological trends for high-risk P. aeruginosa isolates by continuous hospital monitoring.

A novel in vivo assessment of fluid dynamics on aortic valve leaflet using epi-aortic echocardiogram.

BACKGROUND: Mechanical stress caused by blood flow, such as wall shear stress (WSS) and its related parameters, is key moderator of endothelial degeneration. However, an in vivo method to measure WSS on heart valves has not been developed. METHODS: We developed a novel approach, based on vector flow mapping using intraoperative epi-aortic echocardiogram, to measure WSS and oscillatory shear index (OSI) on the aortic valve. We prospectively enrolled 15 patients with normal valves, who underwent coronary artery bypass graft. RESULTS: Systolic WSS on the ventricularis (2.40 ± 0.44 Pa [1.45-3.00 Pa]) was higher than systolic WSS on the fibrosa (0.33 ± 0.08 Pa [0.14-0.47 Pa], P < .001) and diastolic WSS on the ventricularis (0.18 ± 0.07 Pa [0.04-0.28 Pa], P < .001). Oscillatory shear index on the fibrosa was higher than on the ventricularis (0.29 ± 0.04 [0.24-0.36] vs 0.05 ± 0.03 [0.01-0.12], P < .001). A pilot study involving two patients with severe aortic regurgitation showed significantly different values in fluid dynamics. CONCLUSION: Vector flow mapping method using intraoperative epi-aortic echocardiogram is an effective way of measuring WSS and OSI on normal aortic leaflet in vivo, allowing for better understanding of the pathophysiology of aortic valve diseases.

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

Band alignment in quantum wells from automatically tuned DFT+U.

Band alignment between two materials is of fundamental importance for a multitude of applications. However, density functional theory (DFT) either underestimates the bandgap - as is the case with the local density approximation (LDA) or generalized gradient approximation (GGA) - or is highly computationally demanding, as is the case with hybrid-functional methods. The latter can become prohibitive in electronic-structure calculations of supercells which describe quantum wells. We propose to apply the DFT+U method, with U for each atomic shell being treated as set of tuning parameters, to automatically fit the bulk bandgap and the lattice constant, and then use the thus obtained U parameters in large supercell calculations to determine the band alignment. We apply this procedure to InP/In0.5Ga0.5As, In0.5Ga0.5As/In0.5Al0.5As and InP/In0.5Al0.5As quantum wells, and obtain good agreement with experimental results. Although this procedure requires some experimental input, it provides both meaningful valence and conduction band offsets while, crucially, lattice relaxation is taken into account. The computational cost of this procedure is comparable to that of LDA. We believe that this is a practical procedure that can be useful for providing accurate estimates of band alignments between more complicated alloys.

Cytotoxicity against HL60 Cells of Ficifolidione Derivatives with Methyl, n-Pentyl, and n-Heptyl Groups.

Ficifolidione, a natural insecticidal compound isolated from the essential oils of Myetaceae species, is a spiro phloroglucinol with an isobutyl group at the C-4 position. We found that ficifolidione showed cytotoxicity against cancer cells via apoptosis. Replacement of the isobutyl group by n-propyl group did not influence the potency, but the effect of the replacement of this group by a shorter or longer alkyl group on the biological activity remains unknown. In this study, ficifolidione derivatives with alkyl groups such as methyl, n-pentyl, and n-heptyl group-instead of the isobutyl group at the C-4 position-were synthesized to evaluate their cytotoxicity against the human promyelocytic leukaemia cell line HL60 and their insecticidal activity against mosquito larvae. The biological activities of their corresponding 4-epimers were also evaluated. As a result, the conversion of the isobutyl group to another alkyl group did not significantly influence the cytotoxicity or insecticidal activity. In HL60 cells treated with the n-heptyl-ficifolidione derivative, the activation of caspase 3/7 and the early stages of apoptosis were detected by using immunofluorescence and flow cytometric techniques, respectively, suggesting that the cytotoxicity should be induced by apoptosis even though the alkyl group was changed.

An outbreak of fluoroquinolone-resistant Pseudomonas aeruginosa ST357 harboring the exoU gene.

Antimicrobial-resistant isolates of Pseudomonas aeruginosa collected from 2005 to 2014 in a university hospital in Kyoto, Japan, were retrospectively analyzed by multilocus sequence typing (MLST), exoenzyme genotype determination, integron characterization, and clinical associations. During the study, 1573 P. aeruginosa isolates were detected, and 41 of these were resistant to more than two classes of antimicrobial agents. Twenty-five (61.0%) isolates were collected from urine. All isolates were resistant to ciprofloxacin, 8 (19.5%) isolates showed resistance to imipenem/cilastatin, and 8 (19.5%) isolates showed resistance to meropenem. None of the isolates fulfilled the clinical criteria for multidrug-resistant P. aeruginosa. All isolates were negative in the metallo-ß lactamase test. Thirty-six (87.8%) isolates were of the exoS-exoU+ genotype and 5 (12.2%) isolates were of the exoS+exoU- genotype. Among 36 exoS-exoU+ isolates, 33 (80.5%) were ST357, and 3 (7.3%) were ST235. Five isolates of exoS+exoU- were ST186, ST244, ST314, ST508, and ST512. Thirty-three isolates were positive for class 1 integrons and four different class 1 integrons were detected: aminoglycoside (2') adenyltransferase and chloramphenicol transporter (AadB+CmlA6), OXA-4 ß-lactamase and aminoglycoside 3'-adenyltransferase (OXA4+AadA2), AadB alone, and aminoglycoside acetyltransferase alone (AacA31). Among the 41 patients from which the isolates originated, the most common underlying disease was cancer in 16 patients (39%), and 9 patients (22.0%) died during the hospitalization period. There was no statistical correlation between MLST, exoenzyme genotype, and patient mortality. The results indicated outbreaks of fluoroquinolone-resistant P. aeruginosa in immunocompromised patients mainly due to the propagation of potentially virulent ST357 isolates possessing the exoU+ genotype.

Syntheses of cytotoxic novel arctigenin derivatives bearing halogen and alkyl groups on aromatic rings.

The new lignano-9,9'-lactones (α,ß-dibenzyl-γ-butyrolactone lignans), which showed the higher cytotoxicity than arctigenin, were synthesized. The well-known cytotoxic arctigenin showed activity against HL-60 cells (EC50=12µM), however, it was inactive against HeLa cells (EC50>100µM). The synthesized (3,4-dichloro, 2'-butoxy)-derivative 55 and (3,4-dichloro, 4'-butyl)-derivative 66 bearing the lignano-9,9'-lactone structures showed the EC50 values of 10µM and 9.4µM against HL-60 cells, respectively. Against HeLa cells, the EC50 value of the derivative 66 was 27µM. By comparing the activities with the corresponding 9,9'-epoxy structure (tetrahydrofuran compounds), the importance of the lactone structure of 55 and 66 for the higher activities was shown. The substituents on the aromatic ring of the lignano-9,9'-lactones affected the cytotoxicity level, observing more than 10-fold difference.

Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia.

Vaccination against the type III secretion system of P. aeruginosa is a potential prophylactic strategy for reducing the incidence and improving the poor prognosis of P. aeruginosa pneumonia. In this study, the efficacies of three different adjuvants, Freund's adjuvant (FA), aluminum hydroxide (alum) and CpG oligodeoxynucleotide (ODN), were examined from the viewpoint of inducing PcrV-specific immunity against virulent P. aeruginosa. Mice that had been immunized intraperitoneally with recombinant PcrV formulated with one of the above adjuvants were challenged intratracheally with a lethal dose of P. aeruginosa. The PcrV-FA immunized group attained a survival rate of 91%, whereas the survival rates of the PcrV-alum and PcrV-CpG groups were 73% and 64%, respectively. In terms of hypothermia recovery after bacterial instillation, PcrV-alum was the most protective, followed by PcrV-FA and PcrV-CpG. The lung edema index was lower in the PcrV-CpG vaccination group than in the other groups. PcrV-alum immunization was associated with the greatest decrease in myeloperoxidase in infected lungs, and also decreased the number of lung bacteria to a similar number as in the PcrV-FA group. There was less neutrophil recruitment in the lungs of mice vaccinated with PcrV-alum or PcrV-CpG than in those of mice vaccinated with PcrV-FA or PcrV alone. Overall, in terms of mouse survival the PcrV-CpG vaccine, which could be a relatively safe next-generation vaccine, showed a comparable effect to the PcrV-alum vaccine.

Vector flow mapping analysis of left ventricular energetic performance in healthy adult volunteers.

BACKGROUND: Vector flow mapping, a novel flow visualization echocardiographic technology, is increasing in popularity. Energy loss reference values for children have been established using vector flow mapping, but those for adults have not yet been provided. We aimed to establish reference values in healthy adults for energy loss, kinetic energy in the left ventricular outflow tract, and the energetic performance index (defined as the ratio of kinetic energy to energy loss over one cardiac cycle). METHODS: Transthoracic echocardiography was performed in fifty healthy volunteers, and the stored images were analyzed to calculate energy loss, kinetic energy, and energetic performance index and obtain ranges of reference values for these. RESULTS: Mean energy loss over one cardiac cycle ranged from 10.1 to 59.1 mW/m (mean ± SD, 27.53 ± 13.46 mW/m), with a reference range of 10.32 ~ 58.63 mW/m. Mean systolic energy loss ranged from 8.5 to 80.1 (23.52 ± 14.53) mW/m, with a reference range of 8.86 ~ 77.30 mW/m. Mean diastolic energy loss ranged from 7.9 to 86 (30.41 ± 16.93) mW/m, with a reference range of 8.31 ~ 80.36 mW/m. Mean kinetic energy in the left ventricular outflow tract over one cardiac cycle ranged from 200 to 851.6 (449.74 ± 177.51) mW/m with a reference range of 203.16 ~ 833.15 mW/m. The energetic performance index ranged from 5.3 to 37.6 (18.48 ± 7.74), with a reference range of 5.80 ~ 36.67. CONCLUSIONS: Energy loss, kinetic energy, and energetic performance index reference values were defined using vector flow mapping. These reference values enable the assessment of various cardiac conditions in any clinical situation.

Energetic performance analysis of staged palliative surgery in tricuspid atresia using vector flow mapping.

BACKGROUND: Staged palliative surgery markedly shifts the balance of volume load on a single ventricle and pulmonary vascular bed. Blalock-Taussig shunt necessitates a single ventricle eject blood to both the systemic and pulmonary circulation. On the contrary, bidirectional cavopulmonary shunt release the single ventricle from pulmonary circulation. CASE PRESENTATION: We report a case of tricuspid atresia patient who underwent first palliative surgery and second palliative surgery. Volume loading condition was assessed by energetic parameters (energy loss, kinetic energy) intraoperatively using vector flow mapping. These energetic parameters can simply indicate the volume loading condition. CONCLUSION: Vector flow mapping was useful tool for monitoring volume loading condition in congenital heart disease surgery.

Effective evaluation of arterial pulse waveform analysis by two-dimensional stroke volume variation-stroke volume index plots.

Arterial pulse waveform analysis (APWA) with a semi-invasive cardiac output monitoring device is popular in perioperative hemodynamic and fluid management. However, in APWA, evaluation of hemodynamic data is not well discussed. In this study, we analyzed how we visually interpret hemodynamic data, including stroke volume variation (SVV) and stroke volume (SV) derived from APWA. We performed arithmetic estimation of the SVV-SV relationship and applied measured values to this estimation. We then collected measured values in six anesthesia cases, including three liver transplantations and three other types of surgeries, to apply them to this SVV-SVI (stroke volume variation index) plot. Arithmetic analysis showed that the relationship between SVV and SV can be drawn as hyperbolic curves. Plotting SVV-SV values in the semi-logarithmic scale showed linear correlations, and the slopes of the linear regression lines theoretically represented average mean cardiac contractility. In clinical measurements in APWA, plotting SVV and SVI values in the linear scale and the semi-logarithmic scale showed the correlations represented by hyperbolic curves and linear regression lines. The plots approximately shifted on the rectangular hyperbolic curves, depending on blood loss and blood transfusion. Arithmetic estimation is close to real measurement of the SVV-SV interaction in hyperbolic curves. In APWA, using SVV as an index of preload and the cardiac index or SVI derived from arterial pressure-based cardiac output as an index of cardiac function, is likely to be appropriate for categorizing hemodynamic stages as a substitute for Forrester subsets.

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

IV Immunoglobulin for Acute Lung Injury and Bacteremia in Pseudomonas aeruginosa Pneumonia.

OBJECTIVES: Virulent and multidrug-resistant Pseudomonas aeruginosa causes a lethal pneumonia, especially in patients who are artificially ventilated. It has been reported that the virulence mechanism used by P. aeruginosa, which is linked to acute lung injury, is strongly associated with the type III secretion system, and specific antibodies targeting this system have shown a protective effect in both experimental and clinical settings. We investigated the effect of administering IV immunoglobulins on P. aeruginosa pneumonia, including its associated bacteremia and mortality, although focusing especially on type III secretion system-associated P. aeruginosa virulence. DESIGN: Prospective randomized and controlled animal study. SETTING: University laboratory. SUBJECTS: Male ICR mice. INTERVENTIONS: Mice were infected intratracheally with a lethal dose of the virulent P. aeruginosa PA103 strain. IV immunoglobulin administration was examined in three different settings: 1) premixed; 2) pre-IV, prophylactic administration before bacterial infection; and 3) post-IV, therapeutic administration after bacterial infection. The effect of specific antigen titer depletion of IV immunoglobulins was also examined. MEASUREMENTS AND MAIN RESULTS: Survival and body temperature were monitored for 24 hours. Bacteremia, cytokine concentration, myeloperoxidase activity, WBC counts in the blood, and lung bacterial load were evaluated. Survival improved significantly in mice that received IV immunoglobulins (p < 0.05). Lung edema, lung bacteriologic load, and bacteremia decreased significantly in the IV immunoglobulin-treated mice (p < 0.05). The mechanism of protection was associated with the presence of antibodies against both PcrV and some bacterial surface antigens in the IV immunoglobulins. CONCLUSIONS: IV immunoglobulin administration had a significantly protective effect against lethal infection from virulent P. aeruginosa. Prophylactic IV immunoglobulin administration at the highest dose was comparable with that achieved by administrating a specific anti-PcrV polyclonal IgG into the mice. The mechanism of protection is likely to involve the synergic action of anti-PcrV titers and antibodies against some surface antigen(s) that block the type III secretion system-associated virulence of P. aeruginosa.