CircMAP3K5 promotes cardiomyocyte apoptosis in diabetic cardiomyopathy by regulating miR-22-3p/DAPK2 Axis.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of the serious complications of the accumulated cardiovascular system in the long course of diabetes. To date, there is no effective treatment available for DCM. Circular RNA (circRNA) is a novel r2egulatory RNA that participates in a variety of cardiac pathological processes. However, the regulatory role of circular RNA MAP3K5 (circMAP3K5) in DCM is largely unclear. METHODS AND RESULTS: Microarray analysis of DCM rats' heart circular RNAs was performed and the highly species-conserved circRNA mitogen-activated protein kinase kinase kinase 5 (circMAP3K5) was identified, which participates in DCM processes. High glucose-provoked cardiotoxicity leads to the up-regulation of circMAP3K5, which mechanistically contributes to cardiomyocyte cell death. Also, in high glucose-induced H9c2 cardiomyocytes, the level of apoptosis was significantly increased, as well as the expression of circMAP3K5. In contrast, the depletion of circMAP3K5 could reduce high glucose-induced apoptosis in cardiomyocytes. In terms of mechanism, circMAP3K5 acts as a miR-22-3p sponge and miR-22-3p directly target death-associated protein kinase 2 (DAPK2) in H9c2 cardiomyocytes, where in circMAP3K5 upregulates DAPK2 expression by targeting miR-22-3p. Moreover, we also found that miR-22-3p inhibitor and pcDNA DAPK2 could antagonize the protective effects brought by the depletion of circMAP3K5. CONCLUSION: CircMAP3K5 is a highly conserved noncoding RNA that is upregulated during DCM process. We concluded that circMAP3K5 promotes high glucose-induced cardiomyocyte apoptosis by regulating the miR-22-3p/DAPK2 axis. The results of this study highlight a novel and translationally important circMAP3K5-based therapeutic approach for DCM.

Efficacy, safety, and economy of shensongyangxin capsules for the treatment of coronary heart disease arrhythmia: a meta-analysis of randomized controlled trials.

Background: Shensong Yangxin Capsules (SSYX) is a proprietary Chinese medicine commonly, used in the treatment of arrhythmia. In recent years, a flurry of randomized controlled trials of SSYX was reported in the treatment of Coronary heart disease arrhythmia in China. However, these experiments have not been systematically evaluated by economics. The purpose of this study was to assess the efficacy, safety, and economy of the SSYX in the treatment of arrhythmia in patients with coronary heart disease. Methods: With "Shensong Yangxin Capsules" "Coronary Heart Disease" "Coronary Atherosclerotic Heart Disease"and "Arrhythmia" as the subject words, the relevant journals and conference papers were searched manually in China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP, PubMed, Web Of Science, CBM, Embase and The Cochrane Library. The literature of randomized controlled trials of SSYX in the treatment of coronary heart disease arrhythmia was searched until November 2022. All data were analyzed using RevMan 5.3 Sotware and combined with cost-effectiveness for economic evaluation. Results: Twenty randomized controlled trials were included in this study, with a total of 2011 cases. The meta-analysis showed that the therapeutic effect of SSYX-metoprolol is superior to that of metoprolol alone. SSYX is superior to amiodarone in improving the total clinical effective rate, reducing the incidence of adverse reactions, and reducing the junction premature beats. There was no significant difference between the SSYX and amiodarone in the curative effect of ECG, ventricular premature complexes, and atrial premature beats. The results of pharmacoeconomics show that SSYX has a cost-effectiveness advantage in treating coronary heart disease arrhythmia. Single-factor sensitivity analysis also confirmed the stability of the results. In summary, SSYX has a curative effect, safety, and economy in treating coronary heart disease arrhythmia.

A Model of Long-Term Ventricular Fibrillation in Isolated Rat Hearts.

Ventricular fibrillation (VF) is a fatal arrhythmia with a high incidence in cardiac patients, but VF arrest under perfusion is a neglected method of intraoperative arrest in the field of cardiac surgery. With recent advances in cardiac surgery, the demand for prolonged VF studies under perfusion has increased. However, the field lacks simple, reliable, and reproducible animal models of chronic ventricular fibrillation. This protocol induces long-term VF through alternating current (AC) electrical stimulation of the epicardium. Different conditions were used to induce VF, including continuous stimulation with a low or high voltage to induce long-term VF and stimulation for 5 min with a low or high voltage to induce spontaneous long-term VF. The success rates of the different conditions, as well as the rates of myocardial injury and recovery of cardiac function, were compared. The results showed that continuous low-voltage stimulation induced long-term VF and that 5 min of low-voltage stimulation induced spontaneous long-term VF with mild myocardial injury and a high rate of recovery of cardiac function. However, the low-voltage, continuously stimulated long-term VF model had a higher success rate. High-voltage stimulation provided a higher rate of VF induction but showed a low defibrillation success rate, poor recovery of cardiac function, and severe myocardial injury. On the basis of these results, continuous low-voltage epicardial AC stimulation is recommended for its high success rate, stability, reliability, reproducibility, low impact on cardiac function, and mild myocardial injury.

[Long non-coding RNA in spermatogenesis regulation and male infertility: Progress in research].

Long non-coding RNA (lncRNA) is an RNA molecule transcribed by RNA polymerase II, longer than 200 nt, and not translated into proteins. During gonadal development and spermatogenesis, lncRNAs are involved in epigenetic mechanisms, including DNA methylation, chromatin remodeling, and histone tail modification, which play important regulatory roles at the transcriptional or post-transcriptional level. Epigenomics including lncRNA is considered to be the second dimension of DNA sequence that can be adapted to environmental factors to specifically regulate gene expressions in some cells. Based on the functional action mechanism of lncRNAs, we reviewed the advances in the studies of lncRNAs in the direction of spermatogenesis and male infertility and analyzed the potential of lncRNAs as a biomarker of male infertility. The potential application of lncRNA in the treatment of male infertility diseases can be further explored based on the lncRNA target, RNA interference, competitive binding closed target and structural disruption of lncRNAs.

Human umbilical cord-derived stem cell sheets improve left ventricular function in rat models of ischemic heart failure.

INTRODUCTION: Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are among the most promising cell therapy sources used to treat ischemic heart disease. Cell sheet engineering has been used to transplant stem cells and improve their therapeutic effectiveness. We aimed to evaluate the effectiveness of UC-MSC sheets in the treatment of chronic ischemic heart failure. METHODS AND RESULTS: Flow cytometric analysis showed that UC-MSCs were positive for CD73, CD90, and CD105. UC-MSC sheets were produced from UC-MSCs using temperature-responsive culture dishes. Afterward, these sheets were transplanted onto the epicardial surface at the infarct heart in rat models of chronic ischemic heart failure. At four weeks after the transplantation, echocardiography analysis revealed that the cardiac function of the UC-MSC sheets group was significantly better than that of the suspension and myocardial infarction (MI) only groups. Furthermore, histological examinations revealed that the left ventricular remodeling was attenuated compared with the suspension and MI-only groups. In the UC-MSC slice group, the neovascular den and cell size in the infarct margin region were was significantly improved than in the suspension and MI-only groups. Also, the UC-MSC sheets inhibited the PI3K/AKT/mTOR signaling pathway in chronic ischemic heart failure. CONCLUSIONS: UC-MSC sheets can maintain cardiac function and attenuate ventricular remodeling in chronic ischemic heart failure, indicating that this strategy would be a promising therapeutic option in the clinical scenario.

Toxic element (As and Hg) content and health risk assessment of commercially available rice for residents in Beijing based on their dietary consumption.

Arsenic (As) and mercury (Hg) are toxic elements that are often classified as heavy metals, much like cadmium (Cd) and lead (Pb) and others. In this study, we determined the As and Hg contents in rice samples obtained from commercially available rice in Beijing and the health risks associated with daily dietary exposure to As and Hg by the consumption of this rice. Furthermore, the pollution levels of the rice were evaluated based on the Nemerow index. For this purpose, we collected 353 rice samples from 16 municipal districts in Beijing and determined the As and Hg contents in these samples by microwave digestion and inductively coupled plasma mass spectrometry (ICP-MS). The results were as follows: (i) the average content of As in the collected rice samples was 154.91 µg/kg (95% confidence interval (CI) of 139.90-169.92 µg/kg), and the average content of Hg was 2.02 µg/kg (95% CI of 1.25-2.79 µg/kg), which did not exceed the limits established by China's National Standard; (ii) the Nemerow index indicated that the As and Hg contents in these rice samples were safe; (iii) the dietary exposure to As and Hg by rice consumption was, respectively, 15.35 µg/day and 0.20 µg/day, which accounted for 12.91% and 3.35% of the total dietary exposure, respectively; (iv) the hazard quotients (HQs) of As and Hg by the dietary consumption of rice were, respectively, 0.77 and 0.03, and both the HQ and hazard index (HI is 0.8) were less than one. These results indicate that dietary exposure to As and Hg would have no detrimental effect on the health of the residents in the study area; however, the possible carcinogenesis by As in these residents warrants serious attention.

Epidemiological and clinical characteristics of 3327 cases of traffic trauma deaths in Beijing from 2008 to 2017: a retrospective analysis.

We investigated the epidemiological and clinical characteristics deaths from road traffic injury (RTI) in Beijing, and provided evidence useful for the prevention of fatal traffic trauma and for the treatment of traffic-related injuries.We retrospectively reviewed death cases provided by the Beijing Red Cross Emergency Center on road traffic injury deaths from 2008 to 2017. We analyzed population characteristics, time distribution, distribution of transportation modes, intervals to death, locations and injured body parts.From 2008 to 2017, there were 3327 deaths from RTI recorded by the Beijing Red Cross Emergency Center, with mainly males among these deaths. The average age at death was 46.19 ±â€Š17.43 years old (46.19, 0.43-100.24). In accidents with more detail recorded, pedestrians and people using nonmotorized transportation modes suffered the most fatalities (664/968, 68.60%). The most commonly injured body parts were the head (2569/3327, 77.22%), followed by the chest (180/3327, 5.41%), abdomen (130/3327, 3.91%), lower extremities (68/3327, 2.04%), pelvis (67/3327, 2.01%), spinal cord (31/3327, 0.93%), and upper extremities (26/3327, 0.78%). Burns accounted for 0.96% (32/3327), and unknown body parts were affected in 11.28% (365/3327). The average time interval from injury to death was 36.90 ±â€Š89.57 h (36.90, 0-720); 46.7% (1554/3327) died within 10 minutes after injury; 9.02% (300/3327) died between 10 min and 1 hour; 30.33% (1009/3327) died between 1 hour and 3 days; 13.95% (464/3327) died between 3 and 30 days.In Beijing, RTI is a significant cause of preventable death, particularly among pedestrians and users of non-motorized vehicles. Head trauma was the most lethal cause of RTI deaths. Our findings suggested that interventions to prevent collisions and reduce injuries, and improved trauma treatment process and trauma rescue system could address a certain proportion of avoidable RTI deaths.

Information Diffusion on Social Media During Natural Disasters.

Social media analytics has drawn new quantitative insights of human activity patterns. Many applications of social media analytics, from pandemic prediction to earthquake response, require an in-depth understanding of how these patterns change when human encounter unfamiliar conditions. In this paper, we select two earthquakes in China as the social context in Sina-Weibo (or Weibo for short), the largest Chinese microblog site. After proposing a formalized Weibo information flow model to represent the information spread on Weibo, we study the information spread from three main perspectives: individual characteristics, the types of social relationships between interactive participants, and the topology of real interaction networks. The quantitative analyses draw the following conclusions. First, the shadow of Dunbar's number is evident in the "declared friends/followers" distributions, and the number of each participant's friends/followers who also participated in the earthquake information dissemination show the typical power-law distribution, indicating a rich-gets-richer phenomenon. Second, an individual's number of followers is the most critical factor in user influence. Strangers are very important forces for disseminating real-time news after an earthquake. Third, two types of real interaction networks share the scale-free and small-world property, but with a looser organizational structure. In addition, correlations between different influence groups indicate that when compared with other online social media, the discussion on Weibo is mainly dominated and influenced by verified users.

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

Differential effects of lysophosphatidylcholine and ACh on muscarinic K(+),non-selective cation and Ca(2+) currents in guinea-pig atrial cells.

We compared the effects of lysophosphatidylcholine (LPC) and acetylcholine (ACh) on IK(ACh), ICa and a non-selective cation current (INSC) in guinea-pig atrial myocytes to clarify whether LPC and ACh activate similar Gi/o-coupled effector systems.　IK(ACh), ICa and INSC were analyzed in single atrial myocytes by the whole cell patch-clamp.　LPC induced INSC in a concentration-dependent manner in atrial cells.　ACh activated IK(ACh), but failed to evoke INSC.　LPC also activated IK(ACh) but with significantly less potency than ACh.　The effects of both ligands on IK(ACh) were inhibited by intracellular loading of pre-activated PTX.　This treatment also inhibited LPC-induced INSC, indicating that IK(ACh) and INSC induced by LPC are both mediated by Gi/o.　LPC and ACh had similar potencies in inhibiting ICa, which was pre-augmented by forskolin, indicating that LPC and ACh activate similar amounts of α-subunits of Gi/o.　The different effects of LPC and ACh on IK(ACh) and INSC may suggest that LPC and ACh activate Gi/o having different types of ßγ subunits, and that LPC-induced INSC may be mediated by ßγ subunits of Gi/o, which are less effective in inducing IK(ACh).

Establishment of a chronic left ventricular aneurysm model in rabbit.

OBJECTIVES: To establish a cost-effective and reproducible procedure for induction of chronic left ventricular aneurysm (LVA) in rabbits. METHODS: Acute myocardial infarction (AMI) was induced in 35 rabbits via concomitant ligation of the left anterior descending (LAD) coronary artery and the circumflex (Cx) branch at the middle portion. Development of AMI was confirmed by ST segment elevation and akinesis of the occluded area. Echocardiography, pathological evaluation, and agar intra-chamber casting were utilized to validate the formation of LVA four weeks after the surgery. Left ventricular end systolic pressure (LVESP) and diastolic pressure (LVEDP) were measured before, immediately after and four weeks after ligation. Dimensions of the ventricular chamber, thickness of the interventricular septum (IVS) and the left ventricular posterior wall (LVPW) left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), and ejection fraction (EF) were recorded by echocardiogram. RESULTS: Thirty one (88.6%) rabbits survived myocardial infarction and 26 of them developed aneurysm (83.9%). The mean area of aneurysm was 33.4% ± 2.4% of the left ventricle. LVEF markedly decreased after LVA formation, whereas LVEDV, LVESV and the thickness of IVS as well as the dimension of ventricular chamber from apex to mitral valve annulus significantly increased. LVESP immediately dropped after ligation and recovered to a small extent after LVA formation. LVEDP progressively increased after ligation till LVA formation. Areas in the LV that underwent fibrosis included the apex, anterior wall and lateral wall but not IVS. Agar intra-chamber cast showed that the bulging of LV wall was prominent in the area of aneurysm. CONCLUSIONS: Ligation of LAD and Cx at the middle portion could induce development of LVA at a mean area ratio of 33.4% ± 2.4% which involves the apex, anterior wall and lateral wall of the left ventricle.

Combined treatment of ulinastatin and tranexamic acid provides beneficial effects by inhibiting inflammatory and fibrinolytic response in patients undergoing heart valve replacement surgery.

OBJECTIVE: To investigate the effect of ulinastatin and tranexamic acid administered alone or in combination on inflammatory cytokines and fibrinolytic system in patients undergoing heart valve replacement surgery during cardiopulmonary bypass (CPB). BACKGROUND: CPB-induced fibrinolytic hyperfunction and systemic inflammatory response syndrome (SIRS) are the leading causes responsible for the occurrence of postsurgical complications such as postsurgical cardiac insufficiency and lung injury, which may lead to an increase in postsurgical bleeding, prolongation of hospital stay, and increased costs. METHODS: One hundred twenty patients undergoing heart valve replacement surgery during CPB were randomly assigned into 4 groups of 30 patients each: blank control group (Group C), tranexamic acid group (Group T), ulinastatin group (Group U), and tranexamic acid-ulinastatin combination group (Group D). Physiological saline, tranexamic acid, ulinastatin, and a combination of tranexamic acid and ulinastatin were given to each group, respectively. Arterial blood was collected from the radial artery at 4 time points: after induction of anesthesia (T1), unclamping the ascending aorta (T2), and at 1 hour (T3) and 24 hours (T4) after CPB. The levels of plasma tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), neutrophil elastase (NE), and the concentrations of tissue plasminogen activator (t-PA) and α2-antiplasmin (α2-AP) were detected. The changes in the volume of pericardial mediastinal drainage after surgery were observed and recorded. RESULTS: The plasma TNF-α, IL-6, and NE levels significantly increased in patients from all 4 groups at time points of T2, T3, and T4 in comparison to those before CPB (P < .05), and the plasma TNF-α and IL-6 levels in groups U and D were significantly lower than those in the other 2 groups (P < .05). The plasma t-PA, α2-AP, and D-dimer concentrations significantly increased in patients from all 4 groups at T2 and T3 compared with those before CPB (P < .05), and the plasma t-PA and D-dimer concentrations were significantly lower in groups T and D than those in groups U and C (P < .05) at T2 and T3. The plasma α2-AP concentrations in groups T and D were significantly higher than those in Group C at T3 (P < .05). The volumes of pericardial mediastinal drainage per body surface area were significantly lower in groups T and D than those in Group C 6 hours after the surgery (P < .05). CONCLUSIONS: Ulinastatin inhibits the release of inflammatory medium and reduces the inflammatory response during CPB. Tranexamic acid can effectively inhibit the fibrinolytic hyperfunction caused by CPB and thus decreases postsurgical bleeding. In addition, it exhibits a minor anti-inflammatory response. As a consequence, a combined treatment of ulinastatin and tranexamic acid reduces postsurgical bleeding and shortens postoperative hospital stay in patients undergoing heart valve replacement surgery.

[Inhibitory effect of fluvastatin on lysophosphatidylcholine-induced ventricular arrhythmias in rats].

OBJECTIVE: To investigate the effect of fluvastatin on lysophosphatidylcholine (LPC)-induced ventricular arrhythmias and its mechanism. METHODS: Twenty male SD rats were randomly allocated into two equal groups, namely LPC treatment group and fluvastatin pretreatment group. Langendorff apparatus was used for cardiac perfusion ex vivo with 5 µmol/L LPC for 5 min followed by washing for 30 min in LPC treatment group, and in fluvastatin pretreatment group, a 30-min perfusion with 10 µmol/L fluvastatin was administered before LPC perfusion. The LPC-induced nonselective cation current (I(NSC)) in the ventricular myocytes was recorded using the whole-cell voltage-clamp method. RESULTS: Fluvastatin significantly inhibited LPC-induced ventricular tachyarrhythmia/fibrillation and I(NSC). The small G-protein Rho inhibitor (C3) and Rho-kinase inhibitor (Y-27632) in the pipette solution also suppressed LPC-induced I(NSC). CONCLUSION: Fluvastatin offers cardiac protection against LPC by inhibiting LPC-induced I(NSC). LPC induces fatal arrhythmia via a Rho/Rho-kinase-mediated pathway.

[Promoting effect of granulocyto-colony stimulating factor on neovascularization in rats with myocardial infarction].

OBJECTIVE: To investigate the effects of granulocyto-colony stimulating factor (G-CSF) on the mobilization of endothelial progenitor cells (EPCs) in the rats with myocardial infarction (MI), to observe the density of neovascularization and the mRNA expressions of vascular endothelial growth factor (VEGF) and its receptor (Flk-1) in the border area of MI. METHODS: Thirty-six adult male rats (weighing 250-280 g) were divided randomly into control group, MI group, and G-CSF group. In MI group and G-CSF group, the models of MI were established by left anterior descending coronary artery ligation and were treated with intraperitoneal injection of saline (0.3 mL/d) or G-CSF [30 microg/(kg x d)] for 5 days. In control group, after open chest operation, chest was closed without treatment. The level of EPCs was surveyed and the plasma concentrations of VEGF and C-reaction protein (CRP) were measured at 7 days. The mRNA expressions of VEGF and its receptor Flk-1 in the border area of infarct myocardium were determined through RT-PCR. RESULTS: Compared with control group, the number of circulating white blood cell (WBC) and EPCs levels, and the serum concentrations of VEGF and CRP were all significantly increased in MI group and G-CSF group (P < 0.05); when compared with MI group, the number of circulating WBC and EPCs levels, and the serum concentrations of VEGF were increased and the concentration of CRP was decreased in G-CSF group (P < 0.05). Compared with control group, the mRNA expressions of VEGF and Flk-1, and the density of neovascularization in the border area of infarct myocardium were increased in MI group and G-CSF group, whereas those in G-CSF group were significantly augmented compared with MI group (P < 0.05). CONCLUSION: In the rats with MI, G-CSF could promote EPCs mobilization, increase the mRNA expressions of VEGF and Flk-1, and augment the density of neovascularization in the border area of infarct myocardium.

[Establishment of a rabbit model of congestive heart failure].

OBJECTIVE: To study the feasibility of establishing a rabbit model of congestive heart failure model by abdominal aortic coarctation combined with intravenous epinephrine infusion. METHODS: Twenty rabbits were randomized into the study group (n=10) and control group (n=10). Congestive heart failure was induced in the study group by abdominal aortic coarctation combined with intravenous epinephrine infusion. The diameter of the abdominal aorta was reduced by 50%-60%, and epinephrine was infused at 2 weeks (5 mg.kg(-1).min(-1) for 60 min), 4 weeks (4 mg.kg(-1).min(-1) for 60 min) and 6 weeks (4 mg.kg(-1).min(-1) for 60 min) after the operation. The changes in the systolic and diastolic functions of the rabbits were assessed by echocardiography and catheterization during the progression of left hypertrophy. RESULTS: The diameter of the abdominal aorta at the coarctation region was 4.87-/+0.53 mm before the operation, reduced to 2.26-/+0.47 mm after the operation. At 8 weeks after the operation, the hearts of the rabbits in the study group showed obvious abnormalities in echocardiography, while the hearts in the control group remained normal. CONCLUSION: Abdominal aortic coarctation combined with intravenous epinephrine infusion allows rapid establishment of a reliable rabbit model of chronic congestive heart failure.

Pravastatin attenuates cardiac dysfunction induced by lysophosphatidylcholine in isolated rat hearts.

Lysophosphatidylcholine (LPC), which accumulates in the ischemic myocardium, is responsible for mechanical and metabolic derangements of hearts, and also contributes to the development of ventricular arrhythmias. We examined the effects of pravastatin on the LPC-induced cardiac dysfunction in isolated rat hearts. Rat hearts were randomly divided into four groups. The groups comprised a control group (n=10), a group treated with LPC (5 microM) (n=20), a group treated with pravastatin (400 ng/ml) (n=10) and a group treated with both LPC and pravastatin (n=20). Our data suggest that, pravastatin possesses some protective profiles against LPC, as manifested by better recovery of cardiac function (improvement in heart rate, left ventricular developed pressure, maximal and minimal first derivatives of left ventricular developed pressure, coronary flow and coronary resistance, less release of biomarkers of cardiac injury (lactate dehydrogenase, creatine kinase-MB and endothelin-1), and attenuation of ventricular arrhythmias (ventricular tachyarrhythmia and ventricular fibrillation).

[The empirical study on paracrine communication of bone marrow mesenchymal stem cells].

OBJECTIVE: To study the influence of (60)Co gamma exposure on paracrine effect of marrow mesenchymal stem cells (MSC). To evaluate the function and construction after early stage of acute myocardial infarction (AMI) by injection of supernatant liquid. To discuss the mechanism of prarcrine communication initially. METHODS: MSC were radiated by (60)Co gamma with different dosage. The culture solution was collected peri-irradiation. The changes of Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Interleuki-1beta (IL-1beta) in supernatant liquid were checked by ELISA. Using a rat model of AMI, the supernatant liquid and control medium were injected intramyocardially and intraperitoneally according to the project. After 4 weeks, the cardiac dimension and functions were assessed, the microvessel density were detected. RESULTS: Three cytokines decreased significantly after irradiation, with the increasing in dosage of irradiation, the secretory volume of cytokines decreased greatly. When compared with the control group (group A 6.6 +/- 0.6) and medium group (group C 5.7 +/- 0.7), the microvessel density in supernatant liquid group (group B 10.8 +/- 2.9) increased obviously, contributing to improvement in cardiac function and dimension. (Left ventricular internal dimension in diastolic (LVDd) postoperation: A 8.1 mm +/- 1.5 mm, B 7.0 mm +/- 1.5 mm, C 7.7 mm +/- 1.1 mm; Eject fraction (EF) postoperation: A 43.8% +/- 8.9%, B 51.5% +/- 7.8%, C 45.6% +/- 8.1%. CONCLUSIONS: (60)Co gamma radiation exposure can degrade MSC' ability of paracrine communication. The paracrine effect which should take important role in improving the cardiac function after AMI. The mechanism of prarcrine is complex, neovascularization is the important link.

[Study of the three-dimensional structure of the ventricular myocardial fiber in human heart].

OBJECTIVE: To study the three-dimensional structure of ventricular myocardial fiber in human heart. METHODS: Eight human heart were obtained from male donors aged 81.9-/+7.2 years with a heart weight of 455.6-/+65.7 g. Each sample was immersed in water and scanned by diffusion tensor magnetic resonance imaging (DT-MRI) using a 3 Tesla Exicte HD by an eight-channel head coils. The duration was 18.6-/+5.2 h from heart arresting to the scanning. The data were obtained using the protocol of single shot echo planar imaging (sshEPI) and sensitivity encoding (SENSE). The SENSE-sshEPI-scans (TE/TRZ86.4/2000 ms) of the whole heart were carried out (b=1000 s/mm(2), voxels 128x128, resolution 1.1 mmx1.1 mmx(3) mm, and FOV 14 cmx14 cm). Fiber tracking and reconstruction were performed using GE Advantage Windows Workstation. The three-dimensional structure of the ventricular myocardial fiber was observed. RESULTS: The left ventricular myocardial fibers showed two layers with different directions of alignment in such regions as the anterior, septum, and posterior walls and the free left ventricular wall. The subendocardial layer ran obliquely from the base to the apex, and the middle layer ran obliquely upward from the base to the apex. The two layers were linked together and aligned in the pattern of helical coils near the apex. CONCLUSIONS: The three-dimensional structure of the myocardial fibers in human heart conforms to Torrent's hypothesis of helical ventricular myocardial band (HVMB).

Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of radical oxygen species, extracellular signal-related kinases 1/2 and mitochondrial permeability transition pore.

The roles of reactive oxygen species (ROS), extracellular signal-regulated kinase 1/2 (ERK 1/2) and mitochondrial permeability transition pore (mPTP) in sevoflurane postconditioning induced cardioprotection against ischemia-reperfusion injury in Langendorff rat hearts were investigated. When compared with the unprotected hearts subjected to 30 min of ischemia followed by 1 h of reperfusion, exposure of 3% sevoflurane during the first 15 min of reperfusion significantly improved functional recovery, decreased infarct size, reduced lactate dehydrogenase and creatine kinase-MB release, and reduced myocardial malondialdehyde production. However, these protective effects were abolished in the presence of either ROS scavenger N-acetylcysteine or ERK 1/2 inhibitor PD98059, and accompanied by prevention of ERK 1/2 phosphorylation and elimination of inhibitory effect on mPTP opening. These findings suggested that sevoflurane postconditioning protected isolated rat hearts against ischemia-reperfusion injury via the recruitment of the ROS-ERK 1/2-mPTP signaling cascade.

Effects of adenovirus-mediated delivery of the human hepatocyte growth factor gene in experimental radiation-induced heart disease.

PURPOSE: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. METHODS AND MATERIALS: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. RESULTS: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +/- 9.01 vs. 41.94 +/- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +/- 1303 vs. 1667 +/- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +/- 1084 vs. 1566 +/- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. CONCLUSION: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.