Genome Sequencing Unveils Nomadic Traits of Lactiplantibacillus plantarum in Japanese Post-Fermented Tea.

Post-fermented tea production involving microbial fermentation is limited to a few regions, such as Southeast Asia and Japan, with Japan's Shikoku island being particularly prominent. Lactiplantibacillus plantarum was the dominant species found in tea leaves after anaerobic fermentation of Awa-bancha in Miyoshi City, Tokushima, and Ishizuchi-kurocha in Ehime. Although the draft genome of L. plantarum from Japanese post-fermented tea has been previously reported, its genetic diversity requires further exploration. In this study, whole-genome sequencing was conducted on four L. plantarum strains isolated from Japanese post-fermented tea using nanopore sequencing. These isolates were then compared with other sources to examine their genetic diversity revealing that L. plantarum isolated from Japanese post-fermented tea contained several highly variable gene regions associated with sugar metabolism and transportation. However, no source-specific genes or clusters were identified within accessory or core gene regions. This study indicates that L. plantarum possesses high genetic diversity and that the unique environment of Japanese post-fermented tea does not appear to exert selective pressure on L. plantarum growth.

Changes in lactic acid bacteria and components of Awa-bancha by anaerobic fermentation.

Awa-bancha is a post-fermented tea produced in Naka and Kamikatsu, Tokushima, Japan. We investigated the lactic acid bacteria in each stage of production of Awa-bancha and evaluated the relationships with the components. Lactic acid bacteria were isolated from tea leaves cultured with de Man, Rogosa, and Sharpe (MRS) agar plates, and the species were identified by homology of the 16 S rRNA gene and multiplex polymerase chain reaction (PCR) of the recA gene to distinguish the Lactobacillus plantarum group. As a result, a variety of species were isolated from the raw tea leaves, and Lactobacillus pentosus was isolated most frequently after anaerobic fermentation. Regarding the tea leaf components, organic acids, such as lactic acid, increased, free amino acids decreased, and catechins changed owing to anaerobic fermentation. Our results suggest that the microbial flora mainly composed of L. pentosus is important in the anaerobic fermentation process for flavor formation of Awa-bancha.

π-Electronic Co-crystal Microcavities with Selective Vibronic-Mode Light Amplification: Toward Förster Resonance Energy Transfer Lasing.

π-conjugated organic microcrystals often act as optical resonators in which the generated photons in the crystal are confined by the reflection at the crystalline facets and interfere to gain lasing action. Here, we fabricate microcrystals from a mixture of carbon-bridged oligo- para-phenylenevinylenes (COPVs) with energy-donor (D) and energy-acceptor (A) characters. Upon weak excitation of the single D-A co-crystal, Förster resonance energy transfer (FRET) takes place, exhibiting spontaneous emission from A. In contrast, upon strong pumping, stimulated emission occurs before FRET, generating lasing action from D. Lasing occurs with single- and dual-vibronic levels, and the lasing wavelength can be modulated by the doping amount of A. Time-resolved spectroscopic studies reveal that the rate constant of lasing is more than 20 times greater than that of FRET. Furthermore, microcrystals, vertically grown on a Ag-coated substrate, reduce the lasing threshold by one-fourth. This study proposes possible directions toward organic solid FRET lasers with microcrystalline resonators.

Disodium Benzodipyrrole Sulfonate as Neutral Hole-Transporting Materials for Perovskite Solar Cells.

Hole-transporting material (HTM) is an indispensable constituent in organic electronic devices, generally comprising a donor/dopant combination. We report that a disodium salt of substituted benzo[1,2- b:4,5- b']dipyrrole bearing two racemic alkanediylsulfonate anion side chains (BDPSOs) serves as a neutral, nonhygroscopic, dopant-free HTM for lead perovskite (MAPbI3) solar cells. These organic/inorganic hybrid molecules are useful for tunable orbital level and controllable solubility. A fluorinated BDPSO has an energy level matched with MAPbI3, affording an inverted-structure solar cell that performs with 17.2% efficiency with minimal hysteresis. The solar cell devices fabricated using BDPSOs showed remarkable storage and operational stability.

Associations of sensitive cardiac troponin-I with left ventricular morphology, function and prognosis in end-stage renal disease patients with preserved ejection fraction.

Sensitive cardiac troponin I (cTnI) predicts all-cause and cardiovascular mortality in various clinical settings. However, its clinical significance in hemodialysis (HD) patients with preserved left ventricular ejection fraction (LVEF) has not been fully elucidated. This study investigated the association of cTnI with LV morphology and function, and its long-term outcome in HD patients with preserved LVEF. This prospective study consists of 96 HD patients with preserved LVEF (69 ± 8 years and 63% male) who underwent two-dimensional echocardiographic examination and biomarker tests including cTnI, brain natriuretic peptide, and high-sensitive C-reactive protein. The primary endpoint was all-cause death and secondary endpoint was cardiovascular death. Factors independently associated with cTnI were systolic blood pressure (ß = - 0.239, p = 0.011), heart rate (ß = 0.216, p = 0.021), LV mass index (ß = 0.231, p = 0.020), and E to e' ratio (ß = 0.237, p = 0.016). During a mean follow-up of 3.6 years, primary and secondary endpoints were observed in 23 (24%) and 18 (19%) patients, respectively. In the multivariate Cox proportional hazard analysis, the upper cTnI tertile has significantly increased risk of all-cause mortality [hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.139-6.386; p = 0.024] and that of cardiovascular death (HR, 4.56; 95% CI 2.021-16.968; p = 0.006) independent of echocardiographic measures and other serum biomarkers. In HD patients with preserved LVEF, serum cTnI levels were significantly associated with diastolic function and risk of mortality independent of echocardiographic variables and other biomarkers.

Detailed observation of arterial healing after stent implantation in swine arteries by using optical coherence tomography.

BACKGROUND: Histopathological examination is not suitable for sequential in vivo analysis of arterial healing after stenting because it can be performed only after the animals are killed. Optical coherence tomography (OCT) provides higher resolution than intravascular ultrasound (IVUS). The aim of this study was to compare arterial healing images after stenting on the basis of the findings of histopathological examination, IVUS, and OCT. METHODS: We examined 12 vessels; 12 bare-metal stents were implanted in 6 miniature swine. Histopathological examination, IVUS, and OCT imaging were performed at 1 and 4 weeks after stenting. For quantitative analysis of IVUS and OCT images, we examined cross-sectional frames at 1-mm intervals. For neointimal coverage analysis, the neointimal coverage score was classified into 1 of the 4 categories. A fully covered strut was scored as 3, a partially covered strut was scored as 1 or 2, and an uncovered strut was scored as 0. RESULTS: In IVUS and OCT analyses, the average neointimal thickness increased between 1 and 4 weeks (p < 0.0001). OCT revealed higher scores at 1 and 4 weeks than IVUS did (at week 1, p < 0.0001; at week 4, p < 0.0001). OCT analysis evaluated the neointimal coverage similarly to histopathological examination. CONCLUSIONS: On assessment of arterial healing after stenting, we found that the results of the histological examination were more similar to those of the OCT analysis than to those of the IVUS. An OCT imaging device can be used to precisely and sequentially analyze the arterial healing process after stenting.

Utility of myocardial fractional flow reserve for prediction of restenosis following sirolimus-eluting stent implantation.

Drug-eluting stents reduce restenosis due to neointimal growth suppression. Considering long-term outcomes, it is both difficult and important to predict drug-eluting stent restenosis. Thus, this study was designed to examine the utility of myocardial fractional flow reserve (FFR) as a predictor of sirolimus-eluting stent (SES) restenosis. Thirty-three patients (35 lesions) were enrolled. Upon completion of SES implantation, FFR was obtained under hyperemia. At 8 months of follow-up, coronary angiography revealed that five lesions had restenosis. Percent diameter stenosis (restenosis 68.7 ± 12.8% vs. non-restenosis 68.7 ± 12.4%, p = 0.78) and lesion length (restenosis 15.8 ± 9.4 mm vs. non-restenosis 14.4 ± 9.2 mm, p = 0.60) were similar. At post-intervention, percent diameter stenosis (restenosis 16.4 ± 6.1% vs. non-restenosis 14.0 ± 7.4%, p = 0.48) and minimum stent area (restenosis 6.01 ± 1.08 mm2 vs. non-restenosis 6.27 ± 1.85 mm2, p = 0.92) were also equivalent. However, proximal edge lumen area was smaller (restenosis 4.24 ± 1.40 mm2 vs. non-restenosis 7.73 ± 2.64 mm2, p = 0.004) and FFR was lower in the restenosis group (restenosis 0.81 ± 0.12 vs. non-restenosis 0.92 ± 0.06, p = 0.029). SES patients with restenosis had a lower FFR post stent deployment, suggesting the decreased FFR may be a useful predictor for SES restenosis.

Diversity of Lactic Acid Bacteria Involved in the Fermentation of Awa-bancha.

The lactic acid bacteria involved in fermentation and components in the tea leaves of Awa-bancha, a post-fermented tea produced in Naka, Kamikatsu, and Miyoshi, Tokushima, were investigated in the present study. Lactic acid bacteria were isolated from tea leaves after anaerobic fermentation and identified by multiplex PCR targeting of the recA gene and 16S ribosomal RNA gene homology. Lactiplantibacillus pentosus was the most frequently isolated species in Naka and Kamikatsu and Lactiplantibacillus plantarum in Miyoshi. In the phylogenetic tree based on the dnaK gene, L. pentosus isolated from Awa-bancha was roughly grouped by the production area and producer. The bacterial flora after anaerobic fermentation was dominated by Lactiplantibacillus spp. for most producers, and the compositions of samples from each producer varied. Organic acids, free amino acids, and catechins were analyzed as components related to the flavor of Awa-bancha. These components were unique to each producer. The present results revealed diversity in the lactic acid bacteria and flavor of Awa-bancha that depended on the producer.

Ankle-brachial index, arterial stiffness, and biomarkers in the prediction of mortality and outcomes in patients with end-stage kidney disease.

BACKGROUND: Although ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are significant predictors of major adverse cardiovascular event (MACE), their prognostic value in association with biomarkers has not been fully evaluated in patients with end-stage kidney disease (ESKD). HYPOTHESIS: We hypothesized that ABI/baPWV would provide better prognostic value independent of biomarkers in ESKD patients. METHODS: This study included 104 ESKD patients treated with maintenance hemodialysis who underwent ABI and baPWV examinations and laboratory tests, including brain-natriuretic peptide, high-sensitive cardiac troponin T (hs-cTnT), and high-sensitive C-reactive protein (hs-CRP). MACE was defined as a composite event of all-cause death, acute coronary syndrome, and stroke. RESULTS: During a mean follow-up of 3.6 ± 1.7 years, a total of 51 MACE were observed. The independent factors associated with MACE were age >75 years (adjusted hazard ratio [HR], 2.15; P < .05), abnormal ABI (adjusted HR, 2.01; P < .05), left ventricular ejection fraction (LVEF) <50% (adjusted HR, 3.33; P < .001), the upper tertile of hs-cTnT (adjusted HR, 2.77; P < .05), and hs-CRP (HR, 1.96; P < .05). However, baPWV did not remain as an independent predictor of MACE in the entire cohort and also in patients without abnormal ABI. The combination of predictors improves the predictive value of MACE, providing increased HR with 4.00 for abnormal ABI + hs-CRP, 4.42 for abnormal ABI + hs-cTnT, and 7.04 for abnormal ABI + LVEF <50% (all P < .001). CONCLUSION: Abnormal ABI is a robust predictor of MACE independent of biomarkers and their combination provides better risk stratification compared with a single predictor in ESKD patients.

Impact of body mass index and Framingham risk score on coronary artery plaque.

BACKGROUND: It is still unclear whether traditional risk factors for heart disease and body weight correlate with the progression of left main coronary artery (LMCA) atherosclerosis. Thus, the aim of this study was to evaluate the cross-sectional relation between conventional risk score or metabolic disorder and non-stenotic LMCA atherosclerosis using intravascular ultrasound (IVUS). METHODS: We analyzed procedural and demographic data from 217 consecutive patients undergoing intervention for a left anterior descending or left circumflex coronary artery lesion, including their cardiovascular risk (Framingham risk score) and degree of adiposity. IVUS measurements for subclinical LMCA plaque were obtained in all patients and compared to their risk score (low, intermediate or high risk [< or =10%, 10-20%, and > or =20%, respectively]), with volumetric IVUS analyses being performed for the entire LMCA. Patients were further stratified by body weight (normal vs overweight/obesity [body mass index > or =25 kg/m2]). RESULTS: Plaque volume index was greater in patients with high and intermediate risk groups compared to the low risk group (plaque volume index; 9.8 +/- 2.9 mm3/mm and 10.1 +/- 3.0 mm3/mm vs. 8.3 +/- 2.7 mm3/mm, p=0.017 and p=0.0002, respectively). Plaque volume index was also greater in patients in the overweight/obesity group compared to the normal weight group (plaque volume index; 10.2 +/- 2.9 mm3/mm vs 9.1 +/- 3.0 mm3/mm, p=0.005). Linear regression analysis identified overweight/obesity (p=0.034) and high 10-year CAD risk (p=0.003) as independent predictors of increased LMCA plaque volume index. CONCLUSIONS: Conventional coronary risk factors, as well as adiposity itself, related to the volume of coronary plaque at non-stenotic LMCA.

Acute myocardial infarction: clinical characteristics and plaque morphology between expansive remodeling and constrictive remodeling by intravascular ultrasound.

BACKGROUND: According to recent intravascular ultrasound (IVUS) studies, expansive remodeling (ER) at the culprit lesion has been observed in almost 50% of patients with acute coronary syndrome and constrictive remodeling (CR) in 30%. The purpose of this study is to investigate the difference between ER and CR at the culprit lesion in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Preinterventional IVUS images of 73 patients with AMI were identified. The remodeling index (RI) was defined as the ratio of the external elastic membrane (EEM) areas at the culprit lesion to the EEM areas at the proximal reference site. Expansive remodeling was defined as an RI > 1.05; CR, as an RI < 0.95. In patients with AMI, 40 patients (55%) showed ER on IVUS, whereas CR was observed in 18 patients (25%). Patients with ER were significantly older than those with CR (P < .005). The frequency of the presence of calcifications was higher in patients with ER than in those with CR (P < .0005). In patients with AMI with ER, soft plaque with small calcium was the most frequent (58%). Multivariate analysis revealed that age and the presence of calcifications remained as independent predictors of ER. CONCLUSIONS: These findings suggest that ER relates to old age and calcification, and CR may contribute to early plaque progression than ER in patients with AMI.

The impact of IVUS guided bare metal stent implantation for non-small vessel.

UNLABELLED: Previous studies have shown larger target vessel or greater stent area contribute to reduced restenosis rate. Thus, intravascular ultrasound (IVUS)-guided bare metal stent (BMS) implantation for selected lesions might achieve drug-eluting stent-like outcomes. The aim was to examine the long-term outcomes of BMS using IVUS-guided optimization. METHODS: Consecutive 103 coronary artery lesions suitable for IVUS were enrolled. Using IVUS, final stent balloon size selected was 90 percent of media-to-media diameter at the lesion or distal reference. The balloon size was listed as follows: group A (3.0-3.5 mm, n = 15), group B (3.5-3.75 mm, n = 64), and group C (3.75-4.5 mm, n = 24). RESULTS: At post-intervention, average stent area increased by the balloon size (A: 7.2 +/- 1.4 mm2, B: 8.9 +/- 1.5 mm2, and C: 12.1 +/- 2.0 mm2, respectively p < 0.001). At 6 month follow up, the average lumen area increased by balloon size (A: 4.1 +/- 1.7 mm2, B: 5.7 +/- 1.2 mm2, and C: 8.1 +/- 2.0 mm2, respectively p < 0.001). Accordingly, group B and C revealed lower restenosis, compared to group A (A: 46.7%, B: 10.9%, C: 8.3%, A vs B: p = 0.001; C vs A: p = 0.015). Moreover, target lesion revascularization was less in group B and C than group A (A 26.6%, B 3.1%, C 0%, A vs B: p = 0.011; C vs A: p = 0.017). CONCLUSIONS: For non-small vessels, IVUS-guided BMS implantation showed less restenosis and target lesion revascularization compared to small vessels, mainly due to larger initial gain. These study results suggest that IVUS-guided optimal BMS implantation for selected lesions might result in favorable long-term outcomes similar to those seen using drug-eluting stents. For a decade, coronary stenting has become a standard therapy for coronary artery disease due to favorable long-term outcomes and simple treatment procedure. Furthermore, for the last two years, drug-eluting stents (DES), releasing antiproliferative agents from bare metal backbone, revealed the restenosis rates less than half of those seen using conventional bare metal stents (BMS). While target lesions especially suitable for DES continue to be identified, earlier BMS studies showed that larger target vessel or greater stent area contributed to less restenosis. Thus, optimal IVUS-guided BMS implantation for selected lesions might achieve DES-like long-term outcomes. This study was designed to examine the long-term outcomes of BMS with intravascular ultrasound (IVUS)-guided optimization, using coronary angiography and IVUS data.

Impact of HMG-CoA reductase inhibitors for non-treated coronary segments.

BACKGROUND: HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis. METHODS AND RESULTS: In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n = 22) or the non-prescribed group (control group, n = 26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up. External elastic membrane volume (EEMV), lumen volume (LV) and plaque volume (PV) were measured using Simpson's method. The control group revealed no significant serial change in EEMV, PV, and LV during 6 months. On the other hand, the statin group revealed significant reductions of PV (35.5 +/- 12.7 mm3 vs 30.9 +/- 15.6 mm3, p = 0.001), resulting in increase of LV (47.7 +/- 19.8 mm3 vs 52.5 +/- 22.2 mm3, p = 0.003) without EEMV change (82.8 +/- 21.8 mm3 vs 83.9 +/- 25.7 mm3, p = NS). Although percent EEMV and percent LV changes showed no differences between the two groups, a larger percent PV change was observed in the statin group compared to the control group (control; 5.8 +/- 20.3% vs statin; -20.4 +/- 21.8%, p = 0.02). CONCLUSION: The results of this study suggest that statin administration for 6 months reduces coronary plaque without positive vessel remodeling.

Neuroprotective effect through the cerebral sodium-glucose transporter on the development of ischemic damage in global ischemia.

Diabetes mellitus and impaired glucose metabolism are the most important risk factors for stroke. We recently demonstrated that cerebral ischemic stress causes hyperglycemia (i.e., post-ischemic hyperglycemia) and may worsen ischemic neuronal damage in a mouse model of focal ischemia. However, the detailed mechanisms are still unknown. The sodium-glucose transporter (SGLT) generates inward currents in the process of transporting glucose into cells, resulting in depolarization and increased excitability, which is well known to be caused by cerebral ischemia. Hence, we focused on the role of SGLT on the development of neuronal damage using a global ischemic model. Male ddY mice were subjected to 30min of bilateral carotid artery occlusion (BCAO). The neuronal damage was estimated by histological analysis using HE staining on day 3 after BCAO. Intraperitoneal (i.p.) administration of phlorizin (a specific and competitive inhibitor of SGLT, 200mg/kg immediately after reperfusion) suppressed the development of post-ischemic hyperglycemia on day 1 after BCAO. In contrast, intracerebroventricular (i.c.v.) administration of phlorizin (40µg/mouse immediately and 6h after reperfusion) had no effect on day 1 after BCAO. Interestingly, the development of ischemic neuronal damage was significantly suppressed by i.p. and i.c.v. administration of phlorizin on day 3 after BCAO. In addition, BCAO-induced spasticity was significantly suppressed by PHZ (40µg/mouse, i.c.v.) from using gait analysis. Our results indicated that cerebral SGLT was involved in the development of ischemic neuronal damage in global ischemia.

Kimura disease: diagnostic imaging findings and surgical treatment.

We have encountered 11 cases of Kimura disease, comprising 10 males and 1 female. The ages at presentation ranged from 16 to 48 years, with a mean of 31.5 years. The sites of the subcutaneous masses were bilateral posterior auricular regions in two cases, frontal region in two cases, temporal region in two cases, head region in one case, parotid region in two cases, parotid and temporal regions in one case, and left earlobe in one case. The interval from onset to surgery ranged from 1 to 10 years, with a mean of 4.7 years. For diagnostic imaging, a combination of magnetic resonance imaging (MRI) and ultrasonography had a high diagnostic value. MRI depicted abnormalities at sites in contact with bone, such as posterior auricular regions, and sites with abundant soft tissue, such as parotid and cheek regions. Diffuse atrophy of subcutaneous fat was observed at the sites of the masses. On ultrasonography, the interior of lymph nodes was homogeneous and hyperechoic, whereas the periphery was hyperechoic, and blood vessels entering lymph nodes were clearly depicted. Surgery was performed in all cases. Postoperative adjuvant radiotherapy was conducted in one patient and radiotherapy and steroid therapy in one other patient. There were two relapses, and both were excised by repeated surgery. Surgical excision of the subcutaneous mass in Kimura disease has the advantages that the treatment period is short and precise histopathologic diagnosis can be obtained.

Method analysis for optimal continuous imaging using intravascular optical coherence tomography.

OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments. RESULTS: The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of > 75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.

Cardioprotective effect of SEA0400, a selective inhibitor of the Na(+)/Ca(2+) exchanger, on myocardial ischemia-reperfusion injury in rats.

In this study, we investigated whether the Na(+)/Ca(2+) exchanger (NCX) inhibitor SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy]phenoxy-5-ethoxyaniline) might have a protective effect against myocardial ischemia-reperfusion injury in rats. In particular, we focused on cardiac function using Doppler echocardiography and cardiac gene expression. We intravenously administered either SEA0400 and delivery vehicle or only the vehicle (as a control) to Wistar rats 5 min before ischemia was induced. Reperfusion was performed after 30 min of ischemia. At 1 week after ischemia-reperfusion injury, we assessed hemodynamics by inserting a polyethylene-tubing catheter, cardiac function by Doppler echocardiography, and myocardial mRNA expression was determined by Northern blot analysis. Left ventricular (LV) end-diastolic dimensions (LVDd) and LV end-diastolic volume (LVEDV) were significantly increased in the ischemia-reperfusion rat model group compared to the control group. The SEA0400-treated group had a significantly attenuated LVDd (P<0.05) and LVEDV (P<0.01) increase, compared to the vehicle-treated group. A decrease in the LV ejection fraction (P<0.05) was significantly prevented in the SEA0400-treated group compared to the vehicle-treated group. Moreover, mRNA expression of plasminogen activator inhibitor-1 in the non-infarcted LV of the SEA0400-treated group was significantly lower than in the vehicle-treated group (P<0.05). This study demonstrates that the NCX is an important mechanism for cell death in myocardial ischemia and reperfusion in rats. SEA0400 may prove to be a promising new drug in the clinical treatment of myocardial ischemia and reperfusion.