RISING beamline (BL28XU) for rechargeable battery analysis.

The newly installed BL28XU beamline at SPring-8 is dedicated to in situ structural and electronic analysis of rechargeable batteries. It supports the time range (1 ms to 100 s) and spatial range (1 µm to 1 mm) needed for battery analysis. Electrochemical apparatus for battery charging and discharging are available in experimental hutches and in a preparation room. Battery analysis can be carried out efficiently and effectively using X-ray diffraction, X-ray absorption fine-structure analysis and hard X-ray photoelectron spectroscopy. Here, the design and performance of the beamline are described, and preliminary results are presented.

Problems in the regulation of genetic tests in Japan: what can we learn from direct-to-consumer genetic tests?

As one of the countries that have invested greatly in the field of bioscience, Japan is facing difficulties introducing human genetic research to the market. A key issue is how to regulate the quality of genetic testing. Since genetic testing is a part of clinical laboratory tests, the regulatory framework for these tests should cover the regulation of genetic testing. Nevertheless, the quality of clinical laboratory tests has been regulated largely by the authority of medical professionals. The fact that genetic testing can be provided without supervision of medical professionals reveals the necessity for the regulation of quality of genetic testing. While medical geneticists have publicly criticized direct-to-consumer (DTC) genetic testing, a group of industries related to DTC genetic testing have established self-regulatory guidelines on the quality control of genetic analysis, based on the OECD guidelines. This article describes the regulatory framework for clinical laboratory tests including genetic tests, and the gaps in regulation, which are particularly highlighted by the appearance of DTC genetic testing. Furthermore the current initiatives taken by different organizations, especially the self-regulatory initiatives by related industries, will be discussed. To conclude the article, recommendations to improve the situation will be made.

[Pacemaker implantation in a patient with sick sinus syndrome, complicated with persistent left superior vena cava and absent right superior vena cava; report of a case].

A 78-year-old man was referred to our hospital with syncope and palpitation. A Holter electrocardiography (ECG) revealed sick sinus syndrome (SSS), and an enhanced chest computed tomography (CT) scan showed persistent left superior vena cava (PLSVC) and absent right superior vena cava. Myocardial leads and a pacemaker implantation were peformed through left anterior thoracotomy approach. There were only 10 reports of pacemaker implantation in a patient with SSS complicated with PLSVC and absent right superior vena cava in Japan. Open thoracotomy approach was thought to be usuful for these patients.

Effect of hemodilution on the adequacy of cerebral perfusion under hypothermic cardiopulmonary bypass.

OBJECTIVE: Open heart surgery without transfusion has been performed even in children. However, the critical limit of the hemoglobin level has not yet been ascertained. Here, we have assessed experimentally the effect of the hemoglobin level on brain metabolism under hypothermic cardiopulmonary bypass. METHODS: Brain tissue pH was measured in 14 rabbits that were put on bypass with a different degree of hemodilution. Cardiopulmonary bypass was started at 37 degrees C and cooled down to 25 degrees C. After maintaining the bypass at 25 degrees C for 60 minutes, the animal was rewarmed to 37 degrees C for 30 minutes and then kept on-bypass for another 30 minutes. The perfusion flow was maintained as 10 ml/kg/min. RESULTS: The lowest hemoglobin level in each rabbit was from 2.5 through 8.5 g/dl. During hypothermic bypass, brain tissue pH increased from 7.21 +/- 0.16 (mean +/- SD, at the normothermic baseline) to 7.55 +/- 0.27 except 2 cases (6.91 +/- 0.16) whose hemoglobin level was lower than 3.0 g/dl. The brain tissue pH after 60 minutes on hypothermic bypass had a good correlation with the hemoglobin level (r = 0.831). After rewarming for 60 minutes, the brain tissue pH was decreased to 7.18 +/- 0.31. In 4 rabbits with less than 4.0 g/dl of hemoglobin, the brain tissue pH (6.67 +/- 0.24) was lower than the baseline level. In the other 10 rabbits, the brain tissue pH (7.22 +/- 0.16) was almost the same as the baseline level. The correlation coefficient between the brain tissue pH and the hemoglobin level after rewarming for 60 minutes was 0.778. CONCLUSIONS: These results indicated that severe hemodilution in cardiopulmonary bypass promoted acidosis in brain even during hypothermia.

A new X-ray spectrometer for high-resolution Compton profile measurements at SPring-8.

An X-ray spectrometer for high-resolution Compton profile measurements using 90-120 keV X-rays has been designed and constructed at SPring-8. A Cauchois-type triply layered bent-crystal analyzer was employed for the energy analysis. A novel use of a solid-state detector with a large active area was devised as a position-sensitive detector. A resolution of 0.10 atomic units in electron momentum has been achieved at an incident X-ray energy of 115 keV. A Compton profile of a single crystal of Nb was measured with a counting rate of 30 counts s-1 at the Compton peak, which demonstrates that the spectrometer is capable of measuring Compton profiles of heavy-element materials.

Comparison of durability of bioprostheses in tricuspid and mitral positions.

BACKGROUND: Few reports have assessed differences in the durability of mitral and tricuspid bioprostheses after simultaneous implantation of the same bioprosthesis in both positions. We investigated the long-term outcome after simultaneous mitral valve replacement (MVR) and tricuspid valve supraannular implantation (TVSI) with the Carpentier-Edwards bioprostheses in patients with severe tricuspid regurgitation and advanced mitral valve disease. METHODS: Between 1982 and 1998, 37 patients in our hospital underwent MVR and TVSI with Carpentier-Edwards bioprostheses. The mean age of the patients was 55+/-11 years. The average postoperative follow-up was 7.9+/-4.5 years after surgery (range 0 to 14.6 years, 315.1 patient-years). The follow-up rate was 100%. We evaluated the actuarial survival rate, the actuarial freedom from structural valve deterioration (SVD) and reoperation, and postoperative complications. RESULTS: The overall actuarial survival rate at 13 years after the operation was 69%+/-31%. The actuarial freedom from SVD and reoperation in the mitral and tricuspid positions were 78+/-22 and 100% and 70+/-30 and 90%+/-10% (p = 0.03), respectively. No patient had systemic or pulmonary thromboembolism, or complications associated with fatal arrhythmia. CONCLUSIONS: These results suggest that the bioprostheses in the tricuspid position yield significantly better long-term results than those in the mitral position after simultaneous MVR and TVSI.

Tricuspid valve supra-annular implantation in adult patients with Ebstein's anomaly.

BACKGROUND: Tricuspid valve supra-annular implantation (TVSI) has been performed for adult patients with Ebstein's anomaly at our hospital for several decades. TVSI is characterized by reliable reduction of tricuspid annulus size without affecting the conduction system; by prevention of residual tricuspid regurgitation (RTR) through preservation of the native tricuspid valve; and by implantation of the bioprosthesis at a supra-annular site. METHODS: Ten adult patients with Ebstein's anomaly underwent TVSI. The right ventricular diameter and residual tricuspid regurgitation were evaluated by echocardiography preoperatively, at discharge, 1 year after the operation, and over the long term (12.4 +/- 5.5 years). Actuarial survival rate, actuarial freedom from structural valve deterioration rate, and postoperative occurrence of arrhythmia were also evaluated. RESULTS: The actuarial survival rate at 19 years was 76 +/- 15%. Tricuspid regurgitation disappeared in 8 patients just after operation. Right ventricular diameter was significantly smaller at discharge than preoperatively (63 +/- 11 vs 37 +/- 9, p < 0.01), and there were no significant differences between values at discharge and at follow-up. The actuarial freedom from structural valve deterioration rate and the reoperation rate were both 100%. There were no fatal complications related to arrhythmia or thromboembolism. CONCLUSIONS: TVSI is useful for adult patients with Ebstein's anomaly. The absence of complications related to fatal arrhythmia and thromboembolism, good durability of the bioprosthesis, and a simple operative procedure are merits of this therapy.

Acute myocarditis with transient eosinophilia and serum hyper-IgE-emia in a patient with atopic dermatitis.

A 14-year-old girl with acute myocarditis, transient eosinophilia, and hyper-IgE-emia associated with atopic dermatitis is described. The patient was admitted because of severe heart failure and shock, and severe atopic dermatitis was seen. Blood examinations showed moderate eosinophilia (1917/mm3) and hyper-IgE-emia (830IU/ml). The response to treatment with dopamine was excellent, and the congestive heart failure was gradually ameliorated, followed by improvement in her atopic dermatitis. In addition, rapid improvement in eosinophilia and hyper-IgE-emia was observed. Histopathological examination of the right ventricular myocardium obtained by endomyocardial biopsy showed mild interstitial fibrosis and mild infiltrations of inflammatory cells, indicating myocarditis. We speculated that the transient eosinophilia and hyper-IgE-emia in the present case indicated that an allergen induced strong allergic reactions, including type 1 allergy, and caused both acute myocarditis and deterioration of the atopic dermatitis; specifically noteworthy is that the patient's disease rapidly improved without corticosteroid treatment.

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

Surgical strategy for severe tricuspid valve regurgitation complicated by advanced mitral valve disease: long-term outcome of tricuspid valve supra-annular implantation in eighty-eight cases.

OBJECTIVE: Although annuloplasty has been the most commonly performed surgical modality for severe tricuspid regurgitation, tricuspid valve supra-annular implantation has been performed in our hospital for more than a decade. The aim of this study was to assess the long-term outcome of tricuspid valve supra-annular implantation in a subgroup of patients with severe tricuspid regurgitation, those who also had advanced mitral valve disease. METHODS: Mitral valve replacement in conjunction with tricuspid valve supra-annular implantation was performed on 88 patients at our hospital between 1984 and 1998. The patients (mean age 57 +/- 11 years) were followed up for an average of 7.2 +/- 4.5 years after the operation (range 0-14 years); total follow-up was 643.1 patient-years. All patients except 2 (97.6%) were included in the follow-up. We evaluated the mortality, the cause of death, survival, the freedom from structural valve deterioration and reoperation, postoperative complications, and long-term echocardiographic findings. RESULTS: Overall survival at 14 years was 69% +/- 7.7%. Freedom from structural valve deterioration at 14 years was 100% and from reoperation, 88% +/- 9. 4%. There were no instances of pulmonary thromboembolism or of complications associated with fatal arrhythmias. Echocardiography showed little residual tricuspid regurgitation, no atrophic and stenotic change in the native tricuspid valve, and no thrombus formation between native valve and the implanted bioprosthesis. CONCLUSIONS: The procedure's simplicity, the good long-term durability of the bioprosthesis, and the absence of fatal arrhythmias and pulmonary thromboembolism indicate that tricuspid valve supra-annular implantation is a useful procedure for patients with severe tricuspid regurgitation complicated by advanced mitral valve disease.

Difference in structural change in the Carpentier-Edwards pericardial valves implanted in the mitral and tricuspid positions.

We report a 29-year-old patient with prosthetic valve dysfunction with severe calcific stenosis in the mitral position but no structural change in the tricuspid position after mitral valve replacement and tricuspid valve supra-annular implantation with same bioprostheses at the seven years before. The difference in structural change between the mitral position and the tricuspid position might be due mainly to the effect of mechanical stress on the cusps, rather than to any difference in serum calcium levels. However, some hormonal effect other than that of the parathyroid hormone on the systemic and pulmonary circulation might be related to the early progression in cusp calcification in the systemic circulation.

SLC7A7 genomic structure and novel variants in three Japanese lysinuric protein intolerance families.

Lysinuric protein intolerance (LPI) is a rare inherited disease caused by defective transport of the dibasic amino acids at the basolateral membranes of epithelial cells in the renal tubules and small intestine. The metabolic defect leads to brain dysfunction caused by hyperammonemia with a functional impairment of the urea cycle. Recently, mutations in the human SLC7A7 cDNA coding for y(+)LAT-1, which express dibasic amino acid transport activity, were reported to be responsible for LPI. In the present study, we examined the genomic structure of SLC7A7 by DNA sequencing of PCR products, and determined that the gene had 11 exons and 10 introns spanning about 18 kb of genomic DNA. We also identified an alternative RNA splicing at the 5' untranslated region of the SLC7A7 mRNA in human peripheral blood leukocytes, cultured lymphoblasts, and fibroblasts. As a result of mutational analysis of SLC7A7 in three Japanese LPI families, we found a nonsense mutation (R410X), a splicing mutation(911+1G>A) in intron 4, and four silent polymorphisms (201C/T, 445A/G, 784C/T, 946T/C). Identification of the genomic structure of SLC7A7 may provide a molecular basis for a genetic survey for LPI.

Clinical role of blood heparin level monitoring during open heart surgery.

Protamine has been used for neutralizing heparin and its dosage is decided by the initial fixed dose of heparin. Adequate protamine neutralization is very important to reduce complications. To attenuate excess reactions, in particular, whole blood heparin concentration during and after cardiopulmonary bypass was measured using Hepcon, and the efficacy of optimal protamine dose in open heart surgery was evaluated. Twenty patients were randomly divided into two comparable groups, P and C. In the C group, heparin was neutralized with an initial fixed dose of protamine, 1.67 mg protamine per milligram total heparin (n = 8). In the P group, protamine dose was determined for residual heparin concentration (n = 12). In the P group, blood heparin concentrations at 60 minutes after the establishment of cardiopulmonary bypass, just after cardiopulmonary bypass and first protamine administration were 2.35 +/- 0.14, 2.31 +/- 0.17 and 0.13 +/- 0.08 U/ml, respectively. Concentrations reached zero with the second protamine administration. The requirement of transfusion (659 +/- 224 vs. 1559 +/- 323 ml, p = 0.0314), pulmonary vascular resistance index just after the protamine administration (190 +/- 22 vs. 286 +/- 18 dyne.s.cm-5.m2, p = 0.0137) and the IL-8 levels (just after protamine: 26.9 +/- 5.1 vs. 43.5 +/- 5.9 pg/ml, p = 0.0499, 12 hours after cardiopulmonary bypass: 37.1 +/- 12.1 vs. 86.8 +/- 20.0, p = 0.0435) in the P group were significantly lower than those in the C group. These data suggested that heparin level monitoring in whole blood may be useful to determine the optimal dose of protamine resulting in the decrease of a requirement of blood components in open heart surgery and attenuating in transient pulmonary hypertension and excess protamine-induced inflammatory reactions.

Selectin on activated platelets enhances neutrophil endothelial adherence in myocardial reperfusion injury.

OBJECTIVES: The glycoprotein P-selectin is an adhesion molecule that is rapidly expressed on the surface of platelets and endothelium during the inflammatory process. P-selectin on endothelium has been reported to play an important role in reperfusion injury. However, little is known regarding P-selectin on platelets in contributing to the pathophysiology of myocardial reperfusion injury. In this study, we hypothesized that P-selectin on platelets may enhance neutrophil endothelial adherence and this may play a role in neutrophil-mediated reperfusion injury. METHODS: Endothelial cells, cardiomyocytes, platelets and neutrophils were isolated from adult rats. Endothelial cells and cardiomyocytes were cultivated in a co-culture system. After exposure to hypoxia and reoxygenation, neutrophil adherence and migration were examined. RESULTS: After exposure to 6 h of hypoxia, endothelial cells co-incubated with platelets showed significantly greater neutrophil adherence (63.1 +/- 4.0%) and migration (78.2 +/- 6.7%) than endothelial cells alone (adhesion: 44.2 +/- 2.8%, migration: 57.9 +/- 4.9%). These increases were significantly inhibited (adhesion: 42.1 +/- 3.5%, migration: 65.5 +/- 3.8%) by an anti-P-selectin monoclonal antibody. Moreover, the superoxide-anion production was significantly elevated when activated platelets were added to neutrophils. This enhanced production was also inhibited by anti-P-selectin antibody. CONCLUSION: The presence of activated platelets enhanced neutrophil adhesion and migration process after hypoxia reoxygenation. This process may occur following platelet-neutrophil interactions via P-selectin and subsequent neutrophil activation.

Hybrid artificial lung with interleukin-10 and endothelial constitutive nitric oxide synthase gene-transfected endothelial cells attenuates inflammatory reactions induced by cardiopulmonary bypass.

BACKGROUND: Recently, the research on hybrid artificial organs such as heart, liver, and kidney has been reported to yield new possibilities for clinical use. However, there have been few reports on the practical use of a hybrid artificial lung, primarily due to difficulties in the concept for its application and techniques for cell attachment. In this study, we investigated the possibility for developing a novel strategy: a hybrid artificial lung with constitutive nitric oxide synthase (NOS) and interleukin (IL)-10 gene-transfected endothelial cells to attenuate inflammatory reactions induced by cardiopulmonary bypass. METHODS AND RESULTS: First, we performed an in vitro study to confirm the efficacy of our gene transfection into endothelial cells. Constitutive nitric oxide synthase and IL-10 cDNA were transfected into endothelial cells according to the hemagglutinating virus of Japan-liposome method. Levels of nitric oxide released from the endothelial constitutive NOS (ecNOS)-transfected endothelial cells were significantly higher than those of control cells (24 hours after the stimulation by lipopolysaccharide: 284.5 +/- 54.0 versus 95.7 +/- 27.9 mumol/L, P = 0.0001). On the other hand, IL-8 levels in the transfected endothelial cells were significantly lower than those in the control group (48 hours after stimulation by tumor necrosis factor-alpha: 3.1 +/- 2.4 versus 62.1 +/- 1.3 ng/mL, P = 0.0002), and IL-10 was detected in the transfected group but not in the control group. Next, we performed an in vivo study to evaluate the possibility of developing a hybrid artificial lung. One-hour partial cardiopulmonary bypass with this lung was established in rats undergoing femorofemoral bypass. Artificial lungs with no cells (group C; n = 5), that were coated with untreated endothelial cells (group E; n = 5), or that were coated with ecNOS and IL-10 gene-transfected endothelial cells (group T; n = 3) were used. At 45 minutes after the initiation of cardiopulmonary bypass, group T showed higher nitric oxide levels than groups C and E (T versus C versus E: 75.2 +/- 6.8 versus 67.2 +/- 4.3 versus 68.6 +/- 5.2 mumol/L, P = NS). The serum IL-8 levels just after cardiopulmonary bypass in group T were significantly lower than those in group C (1728 +/- 282 versus 4275 +/- 145 pg/mL, P = 0.0151). The Pao2 levels in group T just after weaning from cardiopulmonary bypass were significantly higher than those in group C (271.3 +/- 41.7 versus 136.6 +/- 12.3 mm Hg, P = 0.0362). CONCLUSIONS: These results demonstrate that a hybrid artificial lung with IL-10 and ecNOS gene-transfected endothelial cells inhibited IL-8 release and increased nitric oxide production. This suggests the possibility of developing a hybrid artificial lung capable of preserving native lung function by attenuating cardiopulmonary bypass-induced inflammatory reactions via inhibition of IL-8 release and enhanced nitric oxide production.

Evidence of an increased risk of hearing loss in heterozygous carriers in a Wolfram syndrome family.

Wolfram syndrome (MIM 222300) is characterized by juvenile-onset diabetes mellitus and optic atrophy. Previous linkage analyses in the United States and UK families have indicated that the gene for Wolfram syndrome (WFS) is localized on the short arm of chromosome 4. We herein confirm the linkage of the WFS locus to D4S3023 on 4p with a two-point LOD score of 3.42 in a large Japanese family with Wolfram syndrome. Multipoint linkage analysis revealed the maximum LOD score of 4.82 between D4S3023 and D4S394. We also evaluated putative health risks in carriers by multiple logistic analysis with independent variables, age, gender, and numbers of affected haplotypes and with dependent variables, such as hearing loss, diabetes mellitus, polyuria, incontinence, psychological illness, and visual acuity. The results showed that the putative disease haplotype increased a risk of hearing loss (odds ratio =35.68, 95% confidence interval =4.12-308.95) and diabetes mellitus (odds ratio =7.57, 95% confidence interval =2.03-28.23) independently. This is the first report of an increased health risk of illness in carriers, other than for psychiatric disease.

[Antifungal susceptibility of clinically isolated Candida albicans by broth microdilution method].

In this study we investigated the antifungal susceptibility of 285 strains of Candida albicans isolates at Kinki University Hospital from March 1995 to December 1996. The antifungal agents tested were fluconazole, miconazole, intraconazole, amphotericin B and flucytosine. The susceptibility testing were performed according to the broth microdilution method standardized by National Committee for Clinical Laboratory Standards (M27-T). Most isolates of C. albicans showed relatively a low MIC value and the MIC90S were calculated at 1 microgram/ml; fluconazole, 0.125 microgram/mg; miconazole, 0.06 microgram/ml; itraconazole, 1 microgram/ml; amphotericin B, 0.25 microgram/ml; flucytosine. There was only one strain that showed high resistance against fluconazole and it showed cross-resistance against miconazole and itraconazole. There were two flucytosine resistant strains. The MICs of amphotericin B were tightly clustered and resistant strain were not observed.

Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium.

BACKGROUND: Reperfusion injury in the myocardium has recently been considered to be a type of inflammation, and close attention has been paid to the possible involvement of neutrophils, complement, and cytokines in the onset of this injury. Recently, it has been reported that serum levels of interleukin-6 are elevated significantly after myocardial infarction. The major site of interleukin-6 production and its exact roles are still unknown. In this study, we hypothesized that myocytes may produce interleukin-6 during hypoxia and this may play a role in neutrophil-mediated reperfusion injury. METHODS AND RESULTS: In the clinical study, 20 patients who underwent coronary artery bypass grafting were divided into 2 groups: group F, in which patients were treated with a serine protease inhibitor (FUT-175, 2 mg/kg per hour) during cardiopulmonary bypass, and group C (untreated patients). In group C, myocardial interleukin-6 production, as determined by the difference between the interleukin-6 level in the cardiopulmonary bypass circuit and its level in coronary venous blood, increased significantly after reperfusion (12+/-4 pg/mL) as compared with that before aortic crossclamping (2+/-2 pg/mL). In group F, the increase in the interleukin-6 level was suppressed significantly (before aortic crossclamping, 3+/-2 pg/mL; after reperfusion, 4+/-3 pg/mL). The interleukin-6 production differed significantly between group C and group F. In the in vitro experimental study, the supernatant from myocytes exposed to 2 hours of hypoxia (group 2H) showed significantly higher levels of interleukin-6 (455+/-260 pg/mL) than that from normoxic myocytes (group N) (47+/-15 pg/mL). This interleukin-6 production was suppressed by the addition of FUT-175 (123+/-24 pg/mL). The interleukin-6 production by endothelial cells of coronary vessels did not differ between group 2H (283+/-151 pg/mL) and group N (151+/-86 pg/mL). In a coincubation system with a monolayer of endothelial cells on collagen membrane and myocytes under collagen membrane in a modified Boyden chamber, 2 hours of coincubation showed a significantly higher percent of neutrophil transendothelial migration (group 2H vs N, 78%+/-13% vs 26%+/-11%), value of chemiluminescence (22+/-8 vs 5+/-2 x 10(3) counts/3 minutes), and percent of irreversibly damaged myocytes (48%+/-17% vs 12%+/-8%) than normoxic coincubation. In contrast, anti-interleukin-6 monoclonal antibody significantly attenuated neutrophil transendothelial migration (42%+/-19%) and irreversible damage of myocytes (26%+/-15%) in 2 hours of coincubation. CONCLUSIONS: Interleukin-6 is produced from myocardium during ischemia and reperfusion in patients undergoing coronary bypass grafting. This interleukin-6 may be derived from hypoxic myocytes and play a role in neutrophil-mediated reperfusion injury in myocardium.