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ABSTRACTPhlebopus roseusis described as new based on collections from southwest China. Phylogenetic analyses of nuclear rDNA internal transcribed spacer region ITS1-5.8S-ITS2 (ITS) and portions of nuclear 28S rDNA (28S), translation elongation factor 1-alpha (tef1), and the largest and second largest subunits of RNA polymerase II (rpb1, rpb2) support P. roseusas a novel species in the genus Phlebopus(Boletinellaceae, Boletales). The new species resembles P. portentosusbut differs from it in that mature basidiomata have a bright rose-red-colored stipe and a radiate tubular hymenophore with nested pores. Despite extensive searching, P. roseushas only been found at four sites within a 24-hectare orchard dominated by Eriobotrya japonica, which is agriculturally important given its fruit production (loquats). Therefore, this species appears to be endemic and geographically restricted. The ecology of this bolete is also unique. In line with the trophic behavior of other species in the Boletinellaceae, our observations indicate that P. roseusforms a symbiotic association with the scale insect Coccus hesperidum, identified through sequence analysis of its mitochondrial cytochrome coxidase subunit I (COI) region, to form fungus-insect galls that develop on roots of E. japonicatrees. Phlebopus roseusis an edible mushroom species and is collected from the type location by farmers and sold commercially in limited quantities at local markets alongside P. portentosusand other fungi.

ABSTRACTAberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the screening assay of extracts from the root tuber of Tetrastigma hemsleyanumDiels et Gilg, isoquercitrin inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering. Further analysis revealed that isoquercitrin specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met. We also found that isoquercitrin decreased HGF-induced migration and invasion by parental or HGF/SF-transfected bladder carcinoma cell line NBT-II cells. Furthermore, isoquercitrin inhibited HGF/SF-induced epithelial mesenchymal transition in vitroand the invasion/metastasis of HGF/SF-transfected NBT-II cells in vivo. Our data suggest the possible use of isoquercitrin in human cancers associated with dysregulated HGF/SF-Met signaling.

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Interleukin-10 (IL-10) gene transduction into allogeneic smooth muscle cells (SMCs) was evaluated to improve the long-term benefits of allogeneic cell transplantation into infarcted myocardium. Allogeneic cells, including SMCs, have been demonstrated to restore cardiac function and repair the infarcted myocardium, but late rejection of the transplanted cells by the host immune system may reverse the benefits of cell therapy. In a rat myocardial infarction model, three groups of rats were injected with either unmodified autologous, unmodified allogeneic, or allogeneic + IL-10 SMCs into the infarct region. Three weeks later, most of the allogeneic cells were rejected, whereas autologous cells were engrafted in the myocardium. IL-10 gene transduction of the allogeneic SMCs significantly improved the cell survival. To understand the mechanism of this improved survival, we evaluated the host immune responses against the SMCs. Allogeneic SMCs expressing IL-10 decreased leukocyte-mediated cytotoxicity in coculture, decreased the number of cytotoxic CD8+T-cells, and increased the number of CD4+CD25+regulatory T-cells in vitro and in vivo. Furthermore, IL-10 prevented the production of antidonor antibodies by the recipients against the allogeneic SMCs. Transplantation of unmodified autologous SMCs, but not unmodified allogeneic SMCs, significantly improved fractional shortening and left ventricular dimensions compared to the media-injected control group. However, IL-10 gene-enhanced allogeneic SMCs improved ventricular function, increased wall thickness, and decreased scar length in association with their enhanced survival. We conclude that IL-10 gene-enhanced cell therapy with allogeneic SMCs prevents detrimental alloimmune responses in the recipient, thereby increasing the survival of transplanted allogeneic SMCs and more effectively restoring cardiac function.

A new Diels-Alder Adduct of C60 with 1,1’-biindene (CB) has been synthesized. The Langmuir trough study of this new fullerene derivative indicates that floating film could form monomolecular thick film at the air/water interface at lower concentration, and can be well transferred the floating mixed CB and arachidic acid film onto substrates using the Langmuir-Blodgett (LB) technique. In the case of the mixed film, high quality films with thickness of up to 50 layers could be readily built up. The absorption variation with film thickness at 255nm was measured, indicating good LB deposition up to 50 layers.

Over 163 hypogeous fungi species belonging to 45 genera, 25 families have been found and reported in China. The ecological environment and truffle wild resources are being destroyed rapidly due to over-excavation. Diversity, conservation and utilization of the Chinese hypogeous fungi are discussed in this paper with some suggestion for conservation and sustainable utilization.

Localization is a fundamental and essential issue for wireless sensor networks (WSNs). In this paper, we present a range-free region localization (RFRL) algorithm for static WSNs, in which each unknown node collects the location information of anchors within its two-hop distance, and then some location information of its one-hop anchors and two-hop anchors are chosen to implement a grid-scan algorithm. Analysis and simulation results show that our algorithm outperforms the other Grid-Scan schemes even when the communication radius is irregular.

Lyophyllum P. Karst (1881) is characterized by siderophilous basidia and spore becoming blue in cotton blue solution, which was divided into three divided sections (Lyophyllum, Difformia, and Tephrophana) by Singer in 1986 based on color variations of gills bruised and habitat. To 2012, two hundred and thirty-nine taxa were recorded in Indexfungorum.org; nineteen taxa were reported in this genus in China. Most species of the genus Lyophyllum are very important delicious edible and medicinal fungi. For example, L. decastes and L. semitale have anti-cancer effect. In this paper, the authors dwell on some taxonomic questions of the genus Lyophyllum: (1) the characters of classification, including siderophilous granulation in the basidia and spores becoming blue in cotton blue solution, are not unique; (2) a few species that their specific taxonomic position is still unclear, furthermore, phenomenon of synonym and homonym is presented commonly; (3) the Lyophyllum is not monophyletic group. Finally, the authors put forward a natural taxonomic system need be continually studied and generated using a conjoint methods of morphological and molecular.

Direct formic acid fuel cells are a promising portable power-generating device, and the development of efficient anodic catalysts is essential for such a fuel cell. In this work Pt-Bi nanoparticles supported on micro-fabricated gold wire array substrate were synthesized using an electrochemical deposition method for formic acid oxidation in fuel cells. The surface morphology and element components of the Pt-Bi/Au nanoparticles were characterized, and the catalytic activities of the three Pt-Bi/Au nanoparticle electrodes with different Pt/Bi ratios for formic acid oxidation were evaluated. It was found that Pt4Bi96/Au had a much higher catalytic activity than Pt11Bi89/Au and Pt13Bi87/Au, and Pt4Bi96/Au exhibited a current density of 2.7 mA·cm−2, which was 27-times greater than that of Pt/Au. The electro-catalytic activity of the Pt-Bi/Au electrode for formic acid oxidation increased with the increasing Bi content, suggesting that it would be possible to achieve an efficient formic acid oxidation on the low Pt-loading. Therefore, the Pt-Bi/Au electrode offers a promising catalyst with a high activity for direct oxidation of formic acid in fuel cells.

TiO2-N-methyldiethanolamine(MDEA)-H2O nanofluids were prepared by dispersing TiO2 nanoparticles in the 50wt% (mass fraction) MDEA solution. The stability of nanofluids was studied by the method of absorbance. Only with mechanical agitation, the nanofluids can keep stable at least 48 h without any dispersant. The surface tensions; kinematic viscosities and thermal conductivities of the MDEA solution were measured at the temperature of 20 ℃ when the TiO2 na-noparticles concentration was 0.05wt%, 0.2wt%, 0.4wt% and 0.8wt%. The results show that they all increase with increasing concentration of the nanoparticles. The maximum enhancement of the surface tension, kinematic viscosity and thermal conductivity is 0.6 %, 4.6 % and 5.9 % respectively at the concentration of 0.8 wt%. The influence of nanoparticles on CO2 bubble absorption in the MDEA solution was studied. It can be found that the CO2 absorption rate can be enhanced by 1.95%, 6.53%, 7.79%, 11.54% when the TiO2 nanoparticles concentration is 0.05wt%, 0.2wt%, 0.4wt% and 0.8wt% respectively. The possible mechanisms for the phenomena in experiments and related results are also explained.

Autologous stem cell therapy has not been as effective as forecasted from preclinical studies. Patient age was reported as an important contributing factor. The goal of this study was to uncover age-dependent mechanisms of stem cell dysfunction and to investigate possible means to restore the cellular function. Bone marrow mesenchymal stem cells (MSCs) were isolated from cardiovascular patients. Cell proliferation and number of colonies were inversely correlated with patient age. Myogenic differentiation of MSCs in culture was induced with 5-azacytidine. Differentiation correlated with age, with less differentiation in MSCs from aged patients. We performed real-time PCR to identify genes in the WNT/β-catenin signaling network and found that transcript levels of CTNNB1, LEF1, FZD8, WNT3A, and SFRP4were negatively correlated with age, whereas FOSL1, LRP6,and FZD6were positively correlated with age. Protein evaluation showed that β-catenin nuclear translocation correlated with age and was lower in aged MSCs. Aged MSCs treated with lithium chloride—to increase the bioavailability of β-catenin—recovered their capacity for myogenic differentiation through myocyte enhancer factor 2C but not with the knockdown of β-catenin using small-interfering RNA. This study may be the first to relate reduced nuclear β-catenin bioavailability in MSCs from aged patients. Most important, this abnormality was potentially recoverable, providing a target for improving the function of bone marrow stem cells and their clinical utility in aged patients.

A series of poly(aryleneethynylene)s containing dibenzosilole unit has been synthesized by palladium-catalyzed Sonogashira cross-coupling reactions with 2,7-diethynyl-9,9-dihexyl-3,6-dimethoxy-9H-dibenzosilole (4) as the key monomer. Their photo-physical properties in solution were investigated. All of the polymers showed intense fluorescence with high quantum efficiencies.

The reduction of diphenylacetylene with lithium naphthalenide produced two kinds of intermediates, 1or 2, depending on the ratio of diphenylacetylene to lithium naphthalenide. A series of polyaryl substituted ethylene/diene derivatives were synthesized by reaction of electrophiles with the corresponding intermediates produced in situ. All new compounds were fully characterized, and their single crystal structures were determined.

Capillary absorption is essential to mass migration in cementitious materials. Based on previous studies, capillary rise involving gravity effects is of much greater interest in porous building materials because equilibrium is attained at the wetting front when gravitational force balance the capillary force. In this paper, two different solution forms, semi-analytical and numerical, are presented to account for the gravity effect for realistical prediction of water penetration process. The former is stable against small perturbation proved by Stepanyants [1]. The comparison of predicted results by the two methods confirms the reliability of the technique in estimating water transport.

Stem cells exhibit long-term self-renewal by asymmetric division and multipotent differentiation. During embryonic development, cell fate is determined with predictable orientation, differentiation, and partitioning to form the organism. This includes the formation of a hemangioblast from which 2 derivative cell clusters commit to either a hematopoietic or an endothelial lineage. Frequently, it is not clear whether tissue resident stem cells in the adult originate from the bone marrow. Here, we show that blast colony-forming cells exhibiting bilineage (hematopoietic and vascular) potential and long-term self-renewal originate from the uterus in the mouse. This is the first in vitro and in vivo evidence of an adult hemangioblast retained from development in the uterus. Our findings offer new understanding of uterine cell renewal and turnover and may provide insights and opportunities for the study of stem cell maintenance.

We used surface thermal lensing (STL) to measure the weak absorption of optical films. Different trends of STL phase signals were observed in films with two types of defect, i.e., absorptive defects and heat-resistant defects. Theoretical analysis was made, and it is in good agreement with the experimental results. Therefore, an enhanced STL technique is proposed to deduce both the magnitude of absorption and the type of defect in optical films, by considering signal intensity with its phase status.

To deduce the location of absorptive inclusions in thin films, temperature distributions in pure TiO_2 films and TiO_2 films with high-absorptance inclusions are analyzed based on temperature field theory. According to our theoretic simulations, the surface temperature rise increases when absorptive inclusions are incorporated into thin films and shows different values for different inclusions. With the increase of inclusion thickness, the surface temperature rise varies and has a maximum value. A potential method is presented to deduce the location of absorptive inclusion through calculating the surface temperature rise at two modulated frequencies, if it is possible to know in advance the inclusion material or to prejudge this from a thin-film deposition process.

A method is presented to evaluate optical absorption at a random wavelength by calculating temperature distribution in single-layer TiO_2 films. Temperature distribution in single-layer TiO_2 films was analyzed based on temperature field theory. Through our calculations, optical absorption variation was obtained to be similar to that of surface temperature rise in films. The surface temperature rise depends on film thickness, refractive index, extinction coefficient, specific heat, and thermal conductivity. Furthermore, the optical absorptions of the same single-layer TiO_2 film at different wavelengths were deduced. As an example, the surface temperature rises were calculated for the 19 single-layer TiO_2 films, which had been prepared by 12 different laboratories for the annual meeting of the Optical Society of America in 1986. The results agree well with the measured optical absorptions.

Following myocardial infarction (MI), the resulting fibrotic scar is nonconductive and leads to ventricular dysfunction via electrical uncoupling of the remaining viable cardiomyocytes. The uneven conductive properties between normal myocardium and scar tissue result in arrhythmia, yielding sudden cardiac death/heart failure. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), is able to resynchronize myocardial contractions in vivo. Intravenous PAMB‐G injections into mice show that it does not cause any acute toxicity, up to the maximum tolerated dose (1.6 mL kg−1), which includes the determined therapeutic dose (0.4 mL kg−1). There is also no short‐ or long‐term toxicity when PAMB‐G is injected into the myocardium of MI rats, with no significant changes in body weight, organ–brain ratio, hematologic, and histological parameters for up to 12 months post‐injection. At the therapeutic dose, PAMB‐G restores electrical conduction in infarcted rat hearts, resulting in lowered arrhythmia susceptibility and improved cardiac function. PAMB‐G is also durable, as mass spectrometry detected the biopolymer for up to 12 months post‐injection. PAMB‐G did not impact reproductive organ function or offspring characteristics when given intravenously into healthy adult rats. Thus, PAMB‐G is a nontoxic, durable, and conductive biomaterial that is able to improve cardiac function for up to 1 year post‐implantation. Arrhythmia is associated with blocked electrical conduction pathways stemming from myocardial fibrosis. A conductive biopolymer, poly‐3‐amino‐4‐methoxybenzoic acid‐gelatin (PAMB‐G), restores electrical propagation in rat cardiac scar tissue. Its long‐term functionality and toxicity for potential therapeutic use is assessed. PAMB‐G demonstrates long‐term biocompatibility, arrhythmia reduction, along with electrical propagation and functional improvements, thereby providing a novel treatment for cardiac conduction abnormalities.

Conductive Biopolymers PAMB‐G is a non‐toxic, injectable conductive polymer; it has shown good biocompatibility, as well as long‐term efficacy and stability in alleviating arrhythmia by improving conduction across the fibrotic scar tissue post‐myocardial infarction. This improvement aids in restoring cardiac function and can be found in article number 2101838by Ren‐Ke Li and co‐workers.

Cardiovascular disease is the principal cause of death in end-stage renal disease (ESRD) patients. Endothelial progenitor cells (EPCs) play a critical role in vascular repair, and improving EPC biology represents a novel therapeutic target. Three groups of age- and gender-matched patients were studied: 1) 10 healthy control, 2) 12 conventional hemodialysis (CHD) patients, and 3) 10 nocturnal hemodialysis (NHD) patients. EPC number and migratory function were assessed. Left ventricular mass index (LVMI) was derived, and correlations between EPC biology, uremic clearance, and LVMI were made. Compared with controls, EPC number and function were markedly impaired in CHD patients [(3.48 ± 1.2 vs. 0.86 ± 0.20%/50,000 cells, P< 0.05) and (18.8 ± 2.64 vs. 3.75 ± 0.34 cells/high-power field, P< 0.05), respectively]. In contrast, EPC number and function were normal in NHD patients [(3.48 ± 1.17 vs. 3.83 ± 0.77%/50,000 cells) and (18.8 ± 2.6 vs. 22.2 ± 2.4 cells/high-power field), respectively]. Among ESRD patients, EPC number and function inversely correlated with predialysis urea concentration (r= −0.40; r= −0.57), LVMI (r= −0.41; −0.46) and systolic BP (r= −0.58; r= −0.44). We demonstrate that NHD is associated with restoration of abnormal EPC biology in ESRD. Given the increasing importance of EPCs in the repair and restoration of cardiovascular function, these data have important clinical implications for vascular risk in ESRD patients.

The endothelial layer is a key component of the cardiovascular system. Recent evidence indicates that employing strategies aimed at preserving the endothelium may have important implications in the battle against cardiovascular disease. Nitric oxide remains the critical factor determinant of endothelial function. Understanding the regulatory components involved in nitric oxide production may elucidate novel targets for improving compromised vascular function. The caveolae/caveolin system has recently become of interest due to its ability to regulate endothelial nitric oxide synthase activity. The caveolae/caveolin system is a multifaceted structure in the plasma membrane, which plays an integral role in cellular signaling. Recognizing the potential of this specialized domain may provide the fundamental knowledge to target the endothelium in disease.

Homocysteine is an independent risk factor for atherosclerotic vascular disease. It impairs endothelial function via increasing superoxide production and quenching nitric oxide (NO) release. Tetrahydrobiopterin (BH4) is a critical cofactor that couples nitric oxide synthase and facilitates the production of nitric oxide (vs. superoxide anions). In the first study, the effects of hyperhomocysteinemia (0.1 mM, 3 h) on endothelium-dependent vasorelaxation to ACh and A23187 were examined in isolated segments of rat aortae in the presence or absence of BH4(0.1 mM). In the second study, the effects of hyperhomocysteinemia (24 h) on nitric oxide production and superoxide release (using lucigenin chemiluminescence) were studied in human umbilical vein endothelial cells in the absence or presence of BH4(10 μM). Homocysteine incubation impaired receptor-dependent and -independent endothelial function to ACh and A23187. This effect was attenuated by BH4. Furthermore, homocysteine exposure increased superoxide production and impaired agonist-stimulated nitric oxide release. These effects were attenuated by BH4(p < 0.05). Hyperhomocysteinemia impairs endothelial function, in part due to a diminished bioavailability of BH4with resultant uncoupling of nitric oxide synthase. BH4may represent an important target for strategies aimed at improving endothelial dysfunction secondary to hyperhomocysteinemia.

Objectives:Evidence has accrued to suggest that diabetic patients face an increased risk of ischemic events and low output syndrome and might mount an inordinate response to ischemia and reperfusion. Because hyperglycemia is a potent stimulus for endothelin-1 production, we hypothesized that increased production, action, or both of endothelin-1 in diabetes might represent an important mediator of endothelial dysfunction in patients with that disease. To this aim, we compared the effects of cardioplegic arrest and reperfusion on coronary sinus effluent endothelin-1 levels and atrial arteriolar vascular responses in diabetic and case-matched nondiabetic patients undergoing coronary artery bypass grafting. Methods:In study 1 coronary sinus effluent endothelin-1 levels were assessed at baseline and at 1 and 10 minutes after reperfusion in 13 diabetic and 12 nondiabetic patients matched for age, ejection fraction, Parsonnet score, and crossclamp time. In study 2 vascular responses of atrial arterioles subjected to perioperative ischemia-reperfusion were evaluated with videomicroscopy. Atrial microvessels (from appendages) were obtained before and after removal of the aortic crossclamp, and vascular responses to exogenously administered endothelin-1 (10−10mol/L) and substance P (10−8mol/L) were studied in the presence or absence of BQ-123, an endothelin A receptor antagonist. Results:Diabetic patients elaborated more endothelin-1 at 1 and 10 minutes after reperfusion (P=.01). Endothelin-1-mediated vasoconstriction was similar in diabetic and nondiabetic atrial microvessels before cardioplegic arrest and cardiopulmonary bypass. After cardiopulmonary bypass and reperfusion, endothelin-1-mediated vasoconstriction was enhanced in both groups; however, this response was greater in microvessels from diabetic patients (P=.02). BQ-123, the endothelin A antagonist, attenuated the effects of bypass and reperfusion on endothelin-1-mediated vasoconstriction in both groups (P=.01). Substance P-mediated vasodilatation was similar in diabetic and nondiabetic atrial microvessels before bypass. After bypass and reperfusion, substance P-mediated vasodilatation was diminished in both groups; however, this response was more pronounced in the diabetic group (P=.003). BQ-123 coincubation restored substance P-mediated vasodilatation in both groups. Conclusions:We determined the following: (1) the coronary effluent release of endothelin-1 is higher in diabetic than in nondiabetic patients after cardiopulmonary bypass and reperfusion; (2) diabetic coronary microvessels respond to bypass and reperfusion with greater endothelin-1-mediated vasoconstriction and diminished nitric oxide-mediated vasodilatation; and (3) these effects are attenuated by endothelin antagonism. Endothelin-1 might be an important mediator of ischemia-reperfusion injury in patients with diabetes. Furthermore, use of endothelin receptor antagonists might be a novel strategy for improving the resistance of the diabetic heart to cardioplegic arrest and reperfusion.

Objectives:We have previously demonstrated an importance of endothelin-1 in diabetic patients undergoing bypass surgery. Recent evidence suggests that cardiomyocytes might also produce endothelin-1, which might directly impair myocyte contractility by increasing intracellular calcium levels. Because hyperglycemia is a potent stimulus of endothelin-1 production, we hypothesized that increased production, action, or both of endothelin-1 might be a mediator of direct cardiomyocyte injury in diabetes. Therefore we studied the effects of endothelin receptor blockers (BQ-123 and bosentan) on hyperglycemia-induced endothelin-1 production and cellular injury after ischemia-reperfusion. Methods:Using a human ventricular heart cell model of simulated ischemia-reperfusion, we studied the effects of normoglycemia (5 mmol/L, 48 hours) and hyperglycemia (25 mmol/L, 48 hours) on cellular injury and endothelin-1 production. Furthermore, the effects of selective endothelin-A and mixed endothelin-A/B receptor antagonism (with BQ-123 and bosentan, respectively) were evaluated. Results:Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to hyperglycemia and simulated ischemia-reperfusion injury (P=.01); this effect was prevented with both BQ-123 and bosentan (P=.01). In addition, heart cells from the hyperglycemic group elaborated more endothelin-1 after ischemia-reperfusion (P=.02). Conclusions:Endothelin-1 production and cellular injury were greater in human ventricular heart cells subjected to hyperglycemic conditions and simulated ischemia-reperfusion. These effects are mediated by endothelin-A receptors because both BQ-123 and bosentan exerted similar degrees of protection. Endothelin receptor blockade is a novel strategy to improve the resistance of the diabetic heart to cardioplegic arrest and reperfusion.

Objectives:Contemporary cardioprotective strategies to prevent perioperative ischemia-reperfusion injury have focused on the l-arginine nitric oxide pathway. Tetrahydrobiopterin is an absolute cofactor required for the enzyme nitric oxide synthase and is thus a critical determinant of nitric oxide production. We hypothesized that ischemia-reperfusion results in diminished levels of tetrahydrobiopterin, which might represent a key cellular defect underlying endothelial and myocyte dysfunction after ischemia-reperfusion. To this aim, we examined the effects of tetrahydrobiopterin supplementation in (1) an in vivo experimental model of global ischemia-reperfusion and (2) an in vitro human ventricular heart cell model of simulated ischemia-reperfusion. Measures of endothelial function, oxidant production, cell survival, and cardiac function were used to assess outcome. Methods:In study 1 Wistar rats were divided into one of 2 groups (n = 10 per group). One group received tetrahydrobiopterin (25 mg · kg−1· d−1for 7 days), and the other group served as the control group. Hearts were subjected to 30 minutes of ischemia followed by 30 minutes of reperfusion, and left ventricular developed pressure, left ventricular systolic pressure, and left ventricular end-diastolic pressure were determined by using the modified Langendorff technique. In study 2 we quantitated myocardial malondialdehyde, a marker of lipid peroxidation, in ventricular tissues from both groups of animals using butanol phase extraction and spectrophotometric analysis. In study 3 coronary vascular responses were determined in vascular segments of the left coronary artery in both groups of animals after ischemia-reperfusion. Endothelium-dependent and endothelium-independent vasodilatation to acetylcholine and sodium nitroprusside, respectively, were compared between groups. In study 4, using a human ventricular heart cell model of simulated ischemia-reperfusion, we studied the effects of tetrahydrobiopterin (20 μmol/L) on cellular injury (as assessed by means of trypan blue uptake). Results:After ischemia-reperfusion, myocardial dysfunction was evidenced by a decrease in left ventricular developed pressure and an increase in left ventricular end-diastolic pressure (P=.01 compared with baseline). Hearts from tetrahydrobiopterin-treated rats exhibited protection against ischemia-reperfusion injury (left ventricular developed pressure: 74 ± 4 vs control 42 ± 8 mm Hg, P=.01; left ventricular end-diastolic pressure: 12 ± 3 vs 34 ± 7 mm Hg, P=.01). Furthermore, tetrahydrobiopterin treatment attenuated the rise in malondialdehyde levels after ischemia-reperfusion (P=.01). After reperfusion, coronary endothelial function to acetylcholine was attenuated (P=.003 vs sham-treated mice), whereas responses to sodium nitroprusside remained unchanged. Tetrahydrobiopterin-treated rats exhibited an improvement in acetylcholine-mediated vasorelaxation (P=.01 vs ischemia-reperfusion group). Cellular injury, as assessed by means of trypan blue uptake, was higher in human ventricular heart cells subjected to simulated ischemia-reperfusion; this effect was prevented with tetrahydrobiopterin treatment (P=.001). Conclusions:Supplemental tetrahydrobiopterin provides a novel cardioprotective effect on left ventricular function, endothelial-vascular reactivity, oxidative damage, and cardiomyocyte injury after ischemia-reperfusion injury and might represent an important cellular target for future operative myocardial protection strategies.