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Background: This study tested the hypothesis that early administration of SS31 and entresto (En) was superior to either one alone on preserving the heart function in setting of dilated cardiomyopathy (DCM) induced by doxorubicin (Dox) [accumulated dosage of 12.5 mg/kg/administered by intraperitoneal (IP) at 4 separated time points within 20 days] in rat. Methods and results: Adult-male SD rats (n = 40) were equally categorized into groups 1 (sham-control), 2 (DCM), 3 (DCM + SS31/0.7 mg/kg/day/IP, since day-14 after DCM induction to day-60), 4 [DCM + En (30 mg/kg/day/orally since day-14 after DCM induction to day-60)] and 5 (DCM + combined SS31-En), and animals were euthanized by day 60. By day 60, left-ventricular ejection-fraction (LVEF) was highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3 and 4 (all p

This study tested the hypothesis that extracorporeal shock wave (ECSW) treatment can improve ischemia-induced left ventricular (LV) dysfunction in mini-pig with co-existing chronic kidney disease (CKD). LV ischemia in mini-pigs was induced by applying an ameroid constrictor over mid-left anterior descending artery (LAD), while model of CKD was established by right nephrectomy with partial ligation of left renal arterioles 2 weeks before LAD constriction. Thirty mini-pigs were randomly divided into group 1 (sham-control), group 2 (LV-ischemia), group 3 (LV-ischemia + CKD), Group 4 [LV-ischemia + ECSW (applied 1200 shots at 0.1 mJ/m2/equally to 4-ischemic regions by day-90 after LAD constriction], and group 5 (LV-ischemia-CKD + ECSW). By day-180 after CKD induction, echocardiography showed that LV ejection fraction (LVEF) was highest in group 1, lowest in group 3, significantly lower in group 2 than that in groups 4 and 5, and significantly lower in group 5 than that in group 4, whereas LV-end systolic and diastolic dimensions displayed an opposite pattern (all p

We tested the hypothesis that arteriosclerosis-augmented aortic pulse wave velocity (PWV) and -impaired vasorelaxation were attenuated by rosuvastatin (Rosu) and propylthiouracil (PTU) therapy.Thirty-two New Zealand rabbits were equally divided into group 1 (sham-control), group 2 [high-cholesterol-diet (HCD) for 8weeks], group 3 [HCD-Rosu (20mg/kg/day administration after 4-week HFD for 4weeks)], and group 4 [HCD-PTU (0.1% PTU in drinking water), the treatment course as group 3]. KCl-induced vasoconstriction of carotid artery (CA) was significantly higher in group 2 than in other groups (all p0.01), but showed no differences among groups 1, 3 and 4, whereas acetylcholine-induced vasorelaxation exhibited an opposite pattern of KCl-induced vasoconstriction among the four groups (p0.001). Basic nitric-oxide release from endothelial cells of CA was highest in group 1, lowest in group 2, but showed no difference between groups 3 and 4 (all p0.001). PWV value was highest in group 2, lowest in group 1, and significantly higher in group 4 than in group 3 (all p0.001). Serum levels of total-cholesterol, LDL and TG showed an identical pattern to PWV (all p0.001), whereas the levels of free T4, sugar, and body weight did not differ among the four groups (all p0.4). Aortic inflammatory biomarkers in cellular (CD68+/IL-1β+/CD14+) and protein (TNF-α/NF-κB/IL-1β/MMP-9/MCP-1/ICAM-1/PDGF) levels, and aortic oxidative-stress biomarkers in cellular (8-OHdG) and protein (NOX-1/NOX-2/oxidized protein) levels showed an identical pattern to PWV among the four groups (all p0.001).Rosu-PTU therapy ameliorated aortic stiffness and inflammation/oxidative-stress, and improved endothelial-cell function after HCD challenge in rabbit.

This study tested the therapeutic impact of double-loading dose (i.e., 600 mg) versus standard-loading dose (i.e., 300 mg) of clopidogrel on ST-segment-elevation-myocardial-infarction (STEMI) patients undergoing primary-coronary-intervention (PCI).Between January 2005 and December 2013, a total of 1461 STEMI patients undergoing PCI were consecutively enrolled into the study and categorized into group 1 (600 mg/clopidogrel; n = 508) and group 2 (300 mg/clopidogrel; n = 953). We assessed angiographic thrombolysis-in-myocardial-infarction (TIMI) flow in the infarct-related-artery, 30-day mortality and upper-gastrointestinal-bleeding (UGIB) within 30 days as primary-endpoints and later incidents of UGIB as secondary-endpoints.The results showed that the incidences of advanced Killip score (defined as ≥ score 3) upon presentation (23.8% versus 24.6%) and advanced heart failure (defined as ≥ NYHAFc-3) (10.2% versus 10.4%) did not differ between groups 1 and 2 (all P > 0.4). Primary-endpoints, which were final TIM-3 flow (91.3% versus 91.7%) in the infarct-related-artery, incidences of 30-day mortality (5.8% vs. 7.1%), and UGIB ≤ 30 day (7.8% versus 8.9%) did not differ between group 1 and group 2 (all P > 0.33). The secondary-endpoints which were incidences of ≥ 30-day one-year (8.9% versus 10.1%) UGIB did not differ between groups 1 and 2 (all P > 0.45). One-year mortality did not differ between two groups (10.74% versus 12.9%) (P > 0.25). Multiple-stepwise-logistic-regression analysis showed that age and advanced-Killip score were independently predictive of 30-day mortality (all P < 0.001).Double-loading dose of clopidogrel did not confer an additional benefit to the final angiograph results, 30-day/one-year clinical outcomes; and age and advanced Killip-score were powerful predictors of 30-day mortality.

Background Arterial atherosclerotic occlusive syndrome remains the leading cause of mortality and morbidity worldwide. Peripheral arterial occlusive disease (PAOD) is a manifestation of atherosclerosis in the lower extremities. In our previous preclinical study, hyperbaric oxygen (HBO) therapy improved ischemic PAOD mainly through an increase of vascular wall permeability and recruiting endothelial progenitor cells (EPCs) to enhance the angiogenesis and blood flow in the ischemic area. Purpose This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors and blood flow in ischemic area in patients with peripheral arterial occlusive disease (PAOD). Methods 57 consecutive patients with PAOD undergoing the HBO therapy (3 atm for 2h/each time) were prospectively enrolled into the present study. The venous blood sampling was drawn for assessing the circulating levels of EPCs and soluble angiogenesis factors prior to and during five times of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow at ischemic area, was measured by moorVMS-PRES. Results The results demonstrated that the circulating levels of EPCs (CD34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors (VEGF/SDF-1α/HGF/FGF) were significantly increased in post-HBO therapy than in pre-HBO therapy (all p Conclusions HBO therapy augmented circulating levels of EPCs and angiogenesis factors as well as improved the blood flow in the ischemic area. Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research

Intracerebral hemorrhage (ICH) causes 10%-20% of all strokes and results in higher morbidity compared to other subtypes of cerebral stroke. Although early surgical intervention can clear the expanding hematoma, clinical outcomes following ICH have not significantly improved over the decades. Since ICH elicits neuroinflammation to exacerbate brain edema, damage the blood-brain barrier (BBB), lead to secondary neuronal injury, anti-inflammation may be a critical therapeutic strategy. Mesenchymal stem cell (MSC) therapy processes anti-inflammatory, immunomodulatory and tissue regenerative properties, suggesting that MSC therapy could be an effective therapy for ICH. Therefore, this study tested the hypothesis that human induced pluripotent stem cell-derived mesenchymal stem cell (iPSC-MSC) therapy could effectively reduce brain-infract volume (BIV) and improve neurological function in rat after acute ICH induced by a weight-drop device. Adult-male SD rats (n=40) were equally divided into group 1 (sham-operated control), group 2 (ICH), group 3 (ICH + hyaluronic acid (HA)/intracranial injection/3h after ICH), group 4 [ICH + HA + iPSC-MSC (1.2x106 cells/intracranial injection/3h after ICH)] and euthanized by day 28 after ICH procedure. In vitro study showed that hemorrhagic-brain tissue augmented protein expressions of inflammation (HMGB1/MyD88/TLR-4/TLR-2/NF-κB/TNF-α/iNOS/IL-1β) in cultured neurons that were significantly inhibited by iPSC-MSC treatment (all p Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17&ndash, 25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p &lt, 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p &lt, 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p &lt, 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

We investigated the cardioprotective effect of melatonin (Mel) and exendin-4 (Ex4) treatment in a rat model of cardiorenal syndrome (CRS). Male-adult SD rats (n=48) were randomly and equally divided into sham-control (SC), dilated cardiomyopathy (DCM) (doxorubicin 7 mg/kg i.p. every five days/ 4 doses), CRS (defined as DCM + CKD) only, CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 μg/kg/day) and CRS-Mel-Ex4. In-vitro results showed protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized protein), DNA/mitochondrial-damaged (γ-H2AX/cytosolic cytochrome-C) and apoptotic (cleaved caspase-3/PARP) biomarkers, and senescence (β-galactosidase cells) were upregulated, whereas mitochondrial ATP level was decreased in doxorubicin/ p-Cresol-treated H9C2 cells that were revised by Mel and Ex4 treatments (all p

Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1&minus, /&minus, ) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1&minus, mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1&minus, mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1&minus, mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1&minus, mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

We tested the hypothesis that daily melatonin treatment protects endothelial lineage and functional integrity against the aging process, oxidative stress/endothelial denudation (ED), and toxic environment and restored blood flow in murine critical limb ischemia (CLI). In vitro study using HUVECs, in vivo models (ie, CLI through left femoral artery ligation and ED through carotid artery wire injury), and model of lipopolysaccharide-induced aortic injury in young (3 months old) and aged (8 months old) mice were used to elucidate effects of melatonin treatment on vascular endothelial integrity. In vitro study showed that menadione-induced oxidative stress (NOX-1/NOX-2), inflammation (TNF-α/NF-kB), apoptosis (cleaved caspase-3/PARP), and mitochondrial damage (cytosolic cytochrome c) in HUVECs were suppressed by melatonin but reversed by SIRT3-siRNA (all P

We hypothesized that combined therapy with shock wave (SW) and autologous bone marrow-derived mesenchymal stem cells (BMDMSCs) is superior to either therapy alone for alleviating left ventricular (LV) dysfunction.Male mini-pigs (n=30) equally divided into group 1 (sham control), group 2 [acute myocardial infarction (AMI) by left coronary artery ligation], group 3 (AMI-SW), group 4 (AMI-BMDMSC), and group 5 (AMI-SW-BMDMSC) were sacrificed by day 60 and the hearts were collected for studies. Baseline LV injection fraction [LVEF (%)] and LV chamber size did not differ among the five groups (p0.5). By day 60, LVEF was highest in group 1 and lowest in group 2, significantly higher in group 5 than that in groups 3 and 4, and significantly higher in group 4 than that in group 3 (p0.001). Cellular and protein levels of VEGF, CXCR4, and SDF-1α were significantly increased progressively from groups 1 to 5 (all p0.05). Small vessel number and protein expressions of CD31 and eNOS were highest in groups 1 and 5, lowest in group 2, and significantly higher in group 4 than those in group 3 (p0.001). Protein (MMP-9, TNF-1α and NF-κB) and cellular (CD14+, CD40+) levels of inflammatory biomarkers, protein expressions of oxidative stress (oxidized protein, NOX-1, NOX-2), apoptosis (Bax, caspase-3, PARP), infarct size, and LV dimensions showed a pattern opposite to that of LVEF among all groups (all p0.001).Combined SW-BMDMSC therapy is superior to either therapy alone for improving LVEF, reducing infarct size, and inhibiting LV remodeling.

// Tzu-Hsien Tsai 1, 2 , Cheng-Jei Lin 1, * , Sarah Chua 1 , Sheng-Ying Chung 1 , Cheng-Hsu Yang 1 , Meng-Shen Tong 1 and Chi-Ling Hang 1 1 Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 2 Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan * Indicates equal contribution in this study compared with the first author Correspondence to: Chi-Ling Hang, email: samuelhang@hotmail.com Keywords: brain damage, chronic cerebral hypoperfusion, melatonin Received: January 30, 2017 Accepted: June 19, 2017 Published: August 22, 2017 ABSTRACT Background: Vascular cognitive impairment (VCI) is a spectrum of cognitive impairment caused by various chronic diseases including aging, hypertension, and diabetes mellitus. Oxidative and inflammatory reactions induced by chronic cerebral hypoperfusion (CHP) are believed to cause VCI. Melatonin is reported to possess anti-oxidation and anti-inflammation effects. This study was designed to investigate the effect and mechanisms of melatonin in CHP mice model. Results: The behavioral function results revealed that CHP mice were significantly impaired when compared with the control. Melatonin improved the cognitive function, but the addition of MT2 receptor antagonist reversed the improvement. The IHC staining showed melatonin significantly improved WM lesions and gliosis in CHP mice. Again, the addition of MT2 receptor antagonist to melatonin worsened the WM lesion and gliosis. Similar results were also found for mRNA and protein expressions of oxidative reaction and inflammatory cytokines. Materials and Method: Forty C57BL/6 mice were divided into four groups: Group 1: sham control; Group 2: CHP mice; Group 3: CHP with melatonin treatment; Group 4: CHP-melatonin and MT2 receptor antagonist (all groups n = 10). Working memory was assessed with Y–arm test at day-28 post-BCAS (bilateral carotid artery stenosis). All mice were sacrificed at day-30 post-BCAS. The immunohistochemical (IHC) staining was used for white matter (WM) damage and gliosis. The expression of mRNA and proteins about inflammatory and oxidative reaction were measured and compared between groups. Conclusions: Partially through MT2 receptor, melatonin is effective for CHP-induced brain damage.

We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR. Conversely, the circulating glucagon-like peptide 1 (GLP-1) levels were higher in BIR-KIR-F344 and KIR-DPP4D than KIR-F344 rats after acute KIR. KIR-F344 rats showed greater inflammation, oxidative stress, apoptosis, DNA damage and kidney injury than other rat groups. Damage to the kidney architecture in KIR-F344 rats was greater than in BIR-KIR-F344 or KIR-DPP4D rats. Expression of antioxidant proteins and GLP-1 receptor was higher in kidneys from KIR-DPP4D and BIR-KIR-F344 than KIR-F344 rats, which suggests better intrinsic responses. We therefore suggest that elevated circulating GLP-1 levels due to DPP4 deficiency and BIR preconditioning protect kidney function and architecture during acute IR injury.

Background: This investigation tested the hypothesis that preactivated and disaggregated shape-changed platelets (PreD-SCP) and human embryonic stem cell-derived exosomes (hESC-Exo) treatments can reduce brain-infarct area (BIA) in rat with preservation of neurological function following acute ischemic stroke (AIS) induced by left middle-cerebral artery occlusion. Materials and Methods: Adult-male Sprague-Dawley rats (n=24) were randomly divided into group 1 (sham-control), 2 (AIS), 3 [AIS + PreD-SCP (3.0x108 cells)] and 4 (AIS + hESC-Exo, 100 μg). PreD-SCP and hESC-Exo were administered intravenously at 2/6/24 hours after the AIS procedure for animals in group 3 and 4, respectively. All animals were euthanized by day-28 post-AIS. Results: Brain infarct area (BIA) measured by histopathology was significantly larger in group 2 than that in other groups, and significantly larger in group 3 and 4 than that in group 1 (p

This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery.Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg)] and group 4A [CLI-tPA (intravenously at 3 h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], and group 4B (CLI-tPA).The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p0.05) at 6 h and 18 h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p0.01).tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.

This study tested the hypothesis that combined therapy with nicorandil and colchicine is superior to either alone in attenuating monocrotaline (MCT)-induced rat pulmonary arterial hypertension (PAH). Adult male Sprague-Dawley rats (n=50) were equally randomized into group 1 (sham control), group 2 [MCT (60 mg/kg i.p.)], group 3 [MCT-Nicorandil (5.0 mg/kg/day)], group 4 [MCT-Colchicine (1.0 mg/kg/day)], and group 5 (MCT-Nicorandil-Colchicine). Drugs were given on day 5. All animals were sacrificed on day 90 after MCT administration. Right ventricular systolic blood pressure (RVSBP) and RV weight were increased in group 2 compared to group 1, reduced in groups 3 and 4 compared to group 2, and further reduced in group 5, whereas arterial-oxygen saturation showed an opposite pattern (all p

We tested the hypothesis that sitagliptin is capable of increasing blood flow in the rat critical limb ischemia (CLI) model by enhancement of angiogenesis.Adipose tissue from adult-male Fischer 344 rats (n = 6) were cultured in endothelial progenitor cell culture medium for 14 d with (25 μmol/L) or without sitagliptin. CLI was induced by ligation of the left femoral artery. Rats (n = 32) were equally separated into four groups: untreated controls (group 1), sitagliptin (4 mg/kg per day; group 2), CLI (group 3) and CLI with sitagliptin (group 4).In vitro, 7 and 14 d after cell culture, endothelial progenitor cell biomarkers assessed by flow cytometry (Sca-1/CD31+, CXCR4+, c-kit+ and CD34+ cells) and Western blot (vascular endothelial growth factor, CXCR4 and stromal-derived factor [SDF]-1α) were remarkably higher in group 4 than in the other groups (all P 0.01). In vivo, 2 and 14 d after the CLI procedure, circulating angiogenic cell (Sca-1/CD31+, Sca-1+ and CD31+) numbers were significantly higher in group 4 than in the other groups (all P 0.001). Additionally, the messenger RNA and protein expression of angiogenic biomarkers (CXCR4, SDF-1α and vascular endothelial growth factor), immunofluorescent staining of angiogenic cells (CXCR4+, SDF-1α+, CD31+, von Willebrand factor + cells) and immunohistochemical staining of small vessel numbers in the ischemic area were significantly higher in group 4 than in the other groups (all P 0.01). Furthermore, laser Doppler showed that the ratio of ischemic/normal blood flow was remarkably higher group 4 than in group 3 by days 14 and 28 after the CLI procedure (all P 0.01).Sitagliptin therapy enhances circulating angiogenic cell numbers, angiogenesis and blood flow in the CLI area.

It has been reported that plasmin induces migration of endothelial cells. We hypothesized that tissue plasminogen activator (tPA) enhanced endothelial progenitor cell (EPC) mobilization from bone marrow (BM) into the circulation and angiogenesis in murine critical limb ischemia (CLI).Forty male B6 mice were randomly divided into group 1 (control), group 2 [control+recombinant tPA (intra-venous 4 mg/kg)], group 3 (CLI) and group 4 (CLI+tPA).The results demonstrated higher MMP-9 activity in BM and circulatory SDF-1α level in groups 2 and 3 than in group 1, and highest in group 4 (all p0.01) at 18 h after CLI. Compared with circulation, SDF-1α level in BM showed an opposite trend (all p0.03). The circulating EPC (C-kit/CD31, Sca-1/KDR, CXCR4/CD34) levels at 18 h after CLI were higher in group 2 than in groups 1 and 3, and highest in group 4 (all p0.03). EPC (C-kit/CD31, Sca-1/KDR) levels in BM were lower in group 1 than in groups 2 to 4 (all p0.03), whereas number of CXCR4/CD34-positive EPCs in BM did not differ among the four groups at 18 h after CLI. Protein expressions of SDF-1α, CXCR4, eNOS, and VEGF, numbers of CD31+, CXCR4+, SDF-1α+, and vWF+ cells through immunofluorescent staining, numbers of small vessels (15 μm) and blood flow measured by Laser Doppler in an ischemic area were significantly higher in group 4 than in group 3 (all p0.005) at day 14 after CLI.tPA treatment enhanced number of circulating EPCs, angiogenesis, and blood flow to ischemic tissue in a murine model of limb ischemia.

Background Most studies have investigated the diagnostic accuracy of 64-slice multi-detector computed tomography (MDCT) to detect coronary artery stent patency by using conventional coronary angiography (CCA) as the reference standard. In this study, we compared the diagnostic accuracy of MDCT and CCA by using intravascular ultrasonography (IVUS) as the reference standard. Methods Forty-six patients with previously implanted coronary artery stents (n=87) underwent MDCT followed by CCA and IVUS within 24h. Sensitivities, specificities, positive predictive values (PPV) and negative predictive values (NPV) of MDCT and CCA for detecting or excluding in-stent diameter restenosis (ISDR) by using in-stent area restenosis (ISAR) and minimal luminal area (MLA) ≤4.0mm 2 of IVUS as the reference standard were determined. Results Eight stents (9%) were judged non-evaluable using MDCT for the detection of ISDR. ISDR was detected in 28% (22/79) of the evaluable stents using CCA. When ISAR was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 71%, 96%, 91% and 86%, and the corresponding values for CCA were 64%, 96%, 90% and 83%. When MLA ≤4.0mm 2 was detected using IVUS, the sensitivity, specificity, PPV, and NPV for ISDR detection by using MDCT were 87%, 96%, 91% and 95%, and for CCA were 78%, 96%, 90% and 92%. Conclusions When ISAR with MLA ≤4.0mm 2 was detected on IVUS, CCA and MDCT had similar diagnostic accuracies for ISDR detection. High specificity and NPV make 64-slice MDCT a reliable non-invasive method for excluding ISDR.

The present study reports a case of a 64-year-old man was admitted for sudden collapse. On auscultation, new grade 4/6 continuous murmur were detected and was best heard along the right sternal border. Blood culture yielded Staphylococcus haemolyticus and Escherichia coli. Despite appropriate antibiotic treatment, the patient’s condition deteriorated and he developed multiple organ failure. Transesophageal echocardiography revealed echofree spaces with periannular abscess, and two perforations at the noncoronary sinus of Valsalva aneurysms. This case was about an unusual case of prosthetic aortic valve infectious endocarditis with periannular abscess formation and noncoronary sinus of Valsalva aneurysms rupturing into the right atrium and right ventricle.

OBJECTIVES We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats. METHODS Male Sprague-Dawley rats (n = 9 for laser Doppler study and n = 6 for laboratory examinations in each group) were divided into group 1 (sham control), group 2 (critical limb ischemia treated with culture medium), group 3 (critical limb ischemia treated with intramuscular bone marrow-derived endothelial progenitor cells [2.0 × 10 cells]), group 4 (critical limb ischemia treated with extracorporeal shock wave [280 impulses at 0.1 mJ/mm]), and group 5 (combined bone marrow-derived endothelial progenitor cell-extracorporeal shock wave) after critical limb ischemia induction. RESULTS By day 21, laser Doppler showed substantially lower ratios of ischemic/normal blood flow in group 2 compared with other groups (p < .001). The protein expressions of mitochondrial cytochrome c, stromal cell-derived factor-1, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and endothelial nitric oxide synthase were remarkably higher in group 5 than in groups 2 to 4, and notably higher in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of proinflammatory and apoptotic biomarkers and oxidative stress were reduced in group 5 compared with groups 2 to 4, and notably lower in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of anti-inflammatory and antiapoptotic biomarkers were lower in group 2 than in other groups (all p < .01). Immunofluorescent staining showed higher numbers of CD31+ stromal cell-derived factor-1+, chemokine receptor type 4+, and von Willebrand factor+ cells, and vessels in the ischemic area in group 5 than in groups 2 to 4, and in groups 3 and 4 than in group 2 (all p < .04). CONCLUSION Combined treatment with bone marrow-derived endothelial progenitor cells and extracorporeal shock wave is superior to either bone marrow-derived endothelial progenitor cells or extracorporeal shock wave alone in improving ischemia in rodent critical limb ischemia.

Aim: This study investigated the impact of the circulating galectin-3 level on the 30-day prognostic outcome in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).Methods: From May 2009 to March 2011, blood samples for assessment of the circulating galectin-3 level were collected from 196 consecutive STEMI patients treated by primary PCI and from 30 healthy volunteers.Results: The galectin-3 level was determined using ELISA. Our results demonstrated that the circulating level of galectin-3 was significantly higher in STEMI patients than in healthy control subjects (p

We investigated the potential benefits and the underlying mechanisms of autologous bone marrow-derived mononuclear cell (BMDMNC) implantation in a porcine model of acute anterior wall myocardial infarction (AAWMI) by studying 6-month left ventricular (LV) function and LV remodeling.After being aspirated from the iliac crest and cultured for 1 week, BMDMNCs were implanted immediately after AAWMI induction through the left anterior descending artery ligation. Thirty male mini-pigs (16-18 kg) were equally divided into group 1 [AAWMI plus saline injection into infarct-ischemia area (IA)], group 2 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into non-IA), group 3 (AAWMI plus 3.0 × 10⁷ BMDMNC transplantation into IA), group 4 (sham control plus 3.0 × 10⁷ BMDMNC transplantation into LV myocardium), and group 5 (normal control).By day 90, echocardiography demonstrated an increased LV end-diastolic and end-systolic dimensions but reduced LV ejection fraction (LVEF) in groups 1 and 2 than in other groups (all p0.01). Six-month angiographic study showed a lower LVEF and wall motion score but a higher mitral regurgitation in groups 1 and 2 than in other groups (all p0.01). In IA and peri-infarct area, the number of small vessels and mRNA expressions of endothelial nitric oxide synthase, Bcl-2, interleukin (IL)-10, and peroxisome proliferator-activated receptor-γ coactivator-1α were lower, whereas the number of apoptotic nuclei, caspase-3, Bax, endothelin-1, IL-8, and matrix metalloproteinase was higher in groups 1 and 2 than in other groups (all p0.01).Autologous BMDMNC transplantation into IA rather non-IA improves LV function and reduces LV remodeling via eliciting a broad-spectrum of molecular-cellular defensive mechanisms.

Erythropoietin (EPO) has been shown to have anti-inflammatory, antiapoptotic, and proangiogenic effects. This study investigated whether early EPO treatment effectively preserves left ventricular (LV) function in porcine acute myocardial infarction (AMI). Eighteen male mini-pigs divided into groups 1 (sham), 2 (AMI), and 3 (AMI with 2 consecutive EPO doses [7500 IU per animal each time] at 30 minutes and 24 hours after AMI induction) underwent echocardiography before and 14 days after AMI induction through left anterior descending artery (LAD) ligation with myocardium harvested for analysis. Larger infarcted areas (IA) were noted in group 2 than in group 3. In both IA and peri-IA, percentage of apoptotic nuclei and CD40-positive cells, messenger RNA expressions of IL-8, matrix metalloproteinase-9, caspase-3, and Bcl-2 associated x protein were highest, whereas proliferator-activated receptor-γ coactivator-1α, endothelial nitric oxide synthase and Bcl-2 were lowest in group 2. Oxidative stress and cytosolic cytochrome c in IA were increased ( P < 0.001), whereas protein expression of connexin43, cytochrome c, and protein kinase C-ε in mitochondria were reduced in group 2 than in other groups ( P < 0.045). The fibrosis in IA was notably decreased in group 3 compared with that in group 2. The number of small arterioles and capillary density in IA was highest in group 3, whereas LV performance was lowest in group 2 ( P < 0.045). In conclusion, the results demonstrated that early EPO administration in a porcine AMI model effectively limits infarct size, attenuates LV remodeling, and preserves LV function.

Background: Long-term follow-up studies revealed a significant decline in the benefits of intracoronary radiation for in-stent restenosis. Methods and Results: A total of 25 study and 25 contemporaneous control patients with diffuse in-stent restenosis who underwent cutting balloon angioplasty (CBA) transradially, followed by subsequent intracoronary irradiation with a liquid β-emitter Rhenium-188 (188Re)-filled balloon were enrolled in the study. The mean clinical follow-up durations were 64.9±13.0 and 66.3±13.8 months for the irradiated and control patients, respectively. Six-month angiographic restenosis was observed in 16% (4 of 25) of the patients in the irradiated group and 48% (12 of 25) of the patients in the control groups (P=0.03). The 6-month major adverse cardiac events (MACE) rate was 12% and 44%, respectively (P=0.025). The 3-year follow-up angiography was performed in 16 of 21 (76%) irradiated patients and in 4 of 13 (31%) control patients who had no significant restenosis at the 6-month angiographic follow-up. Restenosis occurred in 1 of 16 (7%) irradiated patients and 2 of 4 (50%) control patients. Late target lesion revascularization was performed in 1 irradiated and 2 control patients. The MACE rate within 6 years was significantly reduced in the irradiated group (20% vs. 56%, P=0.019). Conclusions: Brachytherapy using 188Re-filled balloon following CBA for diffuse in-stent restenotic native coronary arteries is effective in reducing target lesion restenosis and improving long-term outcomes. (Circ J 2011; 75: 113-120)

Background The impact of epoetin beta (recombinant human erythropoietin) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) induced by distal left internal carotid artery occlusion was investigated. Methods Adult male Sprague-Dawley rats (n = 30) were categorized into group 2 (IS only) and group 3 (IS plus intraperitoneal erythropoietin 5000 IU/kg at 0, 12, and 24 hours after IS). Healthy Sprague-Dawley rats (n = 10) served as group 1. Results Analysis of brain tissues showed larger BIA in group 2 than in group 3 ( P < 0.001). Corner test identified highest frequency of left turn in group 2 ( P < 0.05). The mRNA expressions of Bax, caspase 3, interleukin 18, toll-like receptor 4, and plasminogen activator inhibitor 1 were highest, whereas Bcl-2 was lowest in group 2 ( P < 0.05). Lower CXCR4 and stromal cell-derived factor 1 expressions were noted in group 2 than in group 3 ( P < 0.01). Immunohistofluorescence staining showed lower expressions of CXCR4, stromal cell-derived factor 1, von Willebrand factor, and doublecortin with higher number of apoptotic nuclei in group 2 than in group 3 ( P < 0.001). Immunohistochemical staining demonstrated lower cellular proliferation and number of small vessels with higher glial fibrillary acid protein expression in group 2 than in group 3 ( P < 0.01). Conclusions Erythropoietin significantly limited BIA and improved sensorimotor dysfunction after acute IS.

Myocardial ischemia-reperfusion (IR) injury contributes to adverse cardiac outcomes after myocardial ischemia, cardiac surgery, or circulatory arrest. In this study, we evaluated the ability of combined SS31-mitochondria (Mito) therapy to protect heart cells from myocardial IR injury. Adult male SD rats (n = 8/each group) were randomized: group 1 (sham-operated control), group 2 (IR, 30-min ischemia/72 h reperfusion), group 3 (IR-SS31 (2 mg intra-peritoneal injection at 30 min/24 h/48 h after IR)), group 4 (IR-mitochondria (2 mg/derived from donor liver/intra-venous administration/30 min after IR procedure)), and group 5 (IR-SS31-mitochondria). In H9C2 cells, SS31 suppressed menadione-induced oxidative-stress markers (NOX-1, NOX-2, oxidized protein) while it increased SIRT1/SIRT3 expression and ATP levels. In adult male rats 72 h after IR, left ventricular ejection fraction (LVEF) was highest in sham-operated control animals and lowest in the IR group. LVEF was also higher in IR rats treated with SS31-Mito than untreated IR rats or those treated with Mito or SS31 alone. Areas of fibrosis/collagen-deposition showed the opposite pattern. Likewise, levels of oxidative-stress markers (NOX-1, NOX-2, oxidized protein), inflammatory markers (MMP-9, CD11, IL-1&beta, TNF-&alpha, ), apoptotic markers (mitochondrial-Bax, cleaved-caspase-3, PARP), fibrosis markers (p-Smad3, TGF-&beta, ), DNA-damage (&gamma, H2AX), sarcomere-length, and pressure/volume overload markers (BNP, &beta, MHC) all showed a pattern opposite that of LVEF. Conversely, anti-apoptotic (BMP-2, Smad1/5) and energy integrity (PGC-1&alpha, /mitochondrial cytochrome-C) markers exhibited a pattern identical to that of LVEF. This study demonstrates that the combined SS31-Mito therapy is superior to either therapy alone for protecting myocardium from IR injury and indicates that the responsible mechanisms involved increased SIRT1/SIRT3 expression, which suppresses inflammation and oxidative stress and protects mitochondrial integrity.

Objectifs Nous avons examine si une onde de choc (OC) offre un benefice additionnel pour ameliorer la fonction ventriculaire gauche (VG) apres un infarctus du myocarde aigu (AMI) chez des lapins recevant une transplantation de cellules mononucleees de moelle osseuse autologue traitees par OC (BMDMNCs). Methodes et resultats Du serum physiologique (750 μL ; groupe 2), des BMDMNCs (1,0 × 107 ; groupe 3), ou des BMDMNCs traitees par OC avant implant (groupe 4) ont ete implantes dans la zone d’infarctus de lapins males 15 min apres ligature de l’artere coronaire gauche, tandis que huit lapins sans IMA servaient de controles (groupe 1 ; n = 8 par groupe). Les resultats ont montre que dans la region infarcie du VG, l’expression de la proteine Cx43 et du cytochrome C dans les mitochondries et l’expression endotheliale de l’ARNm de la synthetase de l’oxyde nitrique etaient moindres dans le groupe 2 que dans les autres groupes, et diminuees dans le groupe 3 par rapport aux groupes 1 et 4 (toutes valeurs de p Conclusions L’application de BMDMNCs autologues traitees par OC est superieure aux BMDMNCs seules pour preserver la fonction VG apres IMA.

We tested whether shock wave (SW) offers additional benefits in improving left ventricular (LV) function after acute myocardial infarction (AMI) in rabbits receiving SW-treated autologous bone marrow-derived mononuclear cells (BMDMNCs) transplantation.Saline (750 microL; group 2), BMDMNCs (1.0 x 10(7); group 3), or preimplant SW-treated BMDMNCs (group 4) were implanted into the infarct area of male rabbits 15 minutes after left coronary artery ligation, whereas eight rabbits without AMI served as controls (group 1; n = 8 per group). The results showed that in infarct area of LV, protein expressions of Cx43 and cytochrome C in mitochondria and endothelial nitric oxide synthase mRNA expression were lower in group 2 than in other groups, and decreased in group 3 as compared with groups 1 and 4 (all p values0.01). Conversely, mRNA expressions of endothelin-1 and matrix metalloproteinase-9, mitochondrial oxidative stress, and total fibrotic area were higher in group 2 than in other groups (all p values0.05). Furthermore, 6-month LV function by 2-D echo/angiogram showed significant impairment in group 2 than in other groups and in group 3 than in groups 1 and 4 (all p values0.005).Application of SW-treated autologous BMDMNCs is superior to BMDMNCs alone for preserving LV function after AMI.

We hypothesize that sildenafil attenuates pulmonary hypertension through suppressing pulmonary vascular remodeling. Thirty male adult Sprague-Dawley rats were randomized to receive saline injection (Group 1), subcutaneous monocrotaline (MCT) (60 mg/kg) (Group 2), and MCT plus oral sildenafil (30 g/kg per day) (Group 3) 5 days after MCT administration. By Day 35, Western blot showed lower connexin43 and membranous protein kinase C epsilon expressions but higher oxidative stress in right ventricle in Group 2 compared with the other groups. Additionally, pulmonary Smad1/5 was lowest, whereas connexin43 and Smad3 were highest in Group 2. Pulmonary mRNA expressions of tumor necrosis factor-alpha, caspase-3, plasminogen activator inhibitor-1, and transforming growth factor-beta were higher, whereas bone morphogenetic protein Type II receptor, Bcl-2, and endothelial nitric oxide synthase were lower in Group 2 than in the other groups. Similarly, mRNA expressions of tumor necrosis factor-alpha, caspase-3, and beta-myosin heavy chain were increased, whereas Bcl-2, endothelial nitric oxide synthase, and alpha-myosin heavy chain expressions in right ventricle were reduced in Group 2 compared with the other groups. Number of lung arterioles was lowest, whereas number of arterioles with muscularization of the medial layer was highest in Group 2. Right ventricle systolic pressure and weight were elevated in Group 2 compared with the other groups. In conclusion, sildenafil effectively alleviates MCT-induced pulmonary hypertension through suppressing pulmonary vascular remodeling.

The optimal right ventricular pacing site remains controversial. The aim of this study was to assess how acute right ventricular outflow tract (RVOT) pacing affects global left ventricular function and intraventricular dyssynchrony of the left ventricle.Thirty-six patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were enrolled. All patients underwent dual-chamber permanent pacemaker implantation, with the atrial lead placed in the right atrial appendage and the right ventricle lead positioned at the septal site of the RVOT. Chamber size, dyssynchrony index, myocardial performance index, and global left ventricular ejection fraction were determined using transthoracic two-dimensional echocardiography, tissue Doppler echocardiography, and real-time three-dimensional echocardiography.RVOT pacing increased the myocardial performance index (0.42 +/- 0.21 with RVOT pacing vs 0.35 +/- 0.21 without RVOT pacing, P = .002) and decreased the global left ventricular ejection fraction on real-time 3-dimensional echocardiography (51.4 +/- 6.2% with RVOT pacing vs 55.9 +/- 7.1% without RVOT pacing, P = .001). Intraventricular dyssynchrony of the left ventricle induced by RVOT pacing was determined by increased septal-to-posterior wall motion delay (69.7 +/- 54.0 ms with RVOT pacing vs 22.8 +/- 22.3 ms without RVOT pacing, P.0001), increased systolic and diastolic dyssynchrony by tissue Doppler echocardiography, and increased systolic dyssynchrony index when assessed using real-time three-dimensional echocardiography (5.56 +/- 1.74% with RVOT pacing vs 4.05 +/- 1.61% without RVOT pacing, P.0001).Acute RVOT pacing adversely affects left ventricular function and increases intraventricular dyssynchrony in patients with sick sinus syndrome.

Background: Propylthiouracil (PTU) enhances nitric oxide production and inhibits smooth muscle cell proliferation, suggesting a possible role in the prevention of pulmonary arterial hypertension (PAH). Methods and Results: The 30 male Sprague-Dawley rats were randomized to receive saline injection only (group 1), monocrotaline (MCT) (70 mg/kg) only (group 2) or MCT + 0.1% PTU in drinking water (group 3) given on day 5 after MCT administration. By day 35, western blot showed lower connexin43 (Cx43) and membranous protein kinase C-e expressions in the right ventricle (RV) of group 2 animals than in the other groups (all P

This experimental study investigated the impact of hyperglycemic control on left ventricular (LV) function using a model of diabetes mellitus (DM) (induced by streptozocin 60 mg/kg). Sixteen adult-Sprague Dawley rats were divided into group 1 (poor hyperglycemic control, n = 8) and group 2 (good hyperglycemic control, n = 8). Diabetic rats and 8 healthy rats serving as controls (group 3) were sacrificed on day 28 after DM induction. The results demonstrated that HbA1C on day 28 was higher in group 1 than in groups 2 and 3 (P < 0.0001). The mRNA expressions of MMP-9 and endothelin-1 were elevated in group 1 compared with that in groups 2 and 3 (P < 0.05), whereas PGC-1α and eNOS were lower in group 1 than in groups 2 and 3 (P < 0.05). The number of apoptotic nuclei was higher in group 1 than in groups 2 and 3 (P < 0.01). The integrated area (μm2) of connexin43 (Cx43), Cx43 protein expression, and LV function were lower in group 1 than in groups 2 and 3 (P < 0.05). Moreover, PKC-e expression in the mitochondrial compartment was decreased in group 1 compared to that in groups 2 and 3 (P < 0.005).

The relationships among the circulating levels of endothelial progenitor cells (EPC), stromal cell-derived factor (SDF)-1alpha, interleukin (IL)-10 and outcome were examined in patients with ST-segment elevation acute myocardial infarction (ST-se AMI) undergoing primary coronary angioplasty.Circulating levels of IL-10, SDF-1alpha, and EPCs [defined by staining markers: CD31/CD34 (E(1)) and KDR/CD34 (E(2))] were examined by ELISA and flow cytometry, respectively. The IL-10 level was higher, whereas the circulating level of EPCs (E(1-2)) was lower (all P0.05) in AMI patients than in normal subjects. Additionally, the SDF-1alpha level was significantly and independently predictive of an increased level of circulating EPCs (E(1-2)) (P0.0001). Furthermore, patients with a high SDF-1alpha level (1,500 pg/ml) had lower left ventricular performance, higher Killip score (defined asor=3), and increased 30-day mortality than those with low SDF-1alpha level (or=1,500 pg/ml) (all P0.007). Moreover, high circulating levels of E(2) and IL-10 were the most significant independent predictors of increased 30-day major adverse clinical outcome (MACO) (defined as advanced Killip scoreor=3 or 30-day mortality) (P0.01).The serum SDF-1alpha level is independently predictive of an increased level of circulating EPCs (E(1-2)). E(2) and IL-10 are major independent predictors of 30-day MACO in ST-se AMI patients undergoing primary coronary angioplasty.

Background Planimetry of mitral valve area (MVA) is difficult in calcific mitral stenosis (CaMS) in which limiting orifice is near the annulus, and unlike rheumatic mitral stenosis (RhMS), does not present an area for planimetry at the leaflet tips. Moreover, pressure half time (PHT)-derived MVA (MVA PHT ) has limitations in patients with CaMS in whom there are coexisting conditions that affect LV chamber compliance. We tested the hypothesis that real-time 3-dimensional echocardiography (RT3D) can guide measurement at the narrowest orifice in CaMS. Methods In 34 patients with CaMS, MVA by RT3D (MVA RT3D ) was obtained using a color-defined planimetry technique performed "en face" at the smallest annular orifice cross-section (diastolic maximum). MVA RT3D and MVA PHT were compared with an independent standard: MVA by continuity equation (MVA CEQ ). In a subgroup of 10 patients with CaMS or RhMS, the 3-dimensional shape of the stenotic mitral valve was examined, guided by color flow mapping. Results MVA PHT overestimated the mitral orifice area compared with MVA CEQ (2.01 ± 0.52 cm 2 vs 1.75 ± 0.46 cm 2 ; P = .037), whereas there was no significant difference in MVA RT3D and MVA CEQ (1.83 ± 0.52 cm 2 vs 1.75 ± 0.46 cm 2 , respectively, P = .61). MVA RT3D had a greater correlation with MVA CEQ than MVA PHT (R = 0.86 vs 0.59 MVA RT3D vs MVA PHT , respectively). There was better agreement between MVA by RT3D and MVA by continuity equation than MVA by PHT and MVA by continuity equation (difference in MVA: 0.23 ± 0.15 cm 2 vs 0.43 ± 0.29 cm 2 ; P RT3D − MVA CEQ vs MVA PHT − MVA CEQ, respectively). In CaMS, there was a tubular geometry to the valve shape. In contrast, RhMS had a doming funnel-shaped geometry. Conclusion RT3D provides an accurate measurement of MVA in CaMS. In contrast with the doming valve shape present in RhMS, the limiting anatomic orifice area occurs at the annulus in CaMS as measured by RT3D and reflects the effective orifice area as present in a tubular valve geometry.

We compared the effects of losartan and carvedilol on preserving left ventricular (LV) function in an experimental model of dilated cardiomyopathy (DCM) and examined the mechanisms of their pharmacological effects. The rats were divided into group 1 (normal control), group 2 (DCM), group 3 (DCM plus carvedilol 8 mg/kg/day bid orally), and group 4 (DCM plus losartan 20 mg/kg/day orally). All rats were sacrificed on day 90 following DCM induction. The results indicated that connexin43 protein expression and mRNA expressions of peroxisome proliferator-activated receptor-gamma coactivator-1alpha, endo-thelial nitric oxide synthase, and interleukin-10 were significantly lower, whereas mRNA expressions of endothelin-1 and matrix metalloproteinase-9 were significantly higher in group 2 than in groups 1, 3, and 4 in LV myocardium (all P < 0.05). Additionally, cytochrome C levels in LV myocardium and LV contractility were significantly lower, whereas fibrosis area, cellular apoptosis, and mitochondrial oxidative response of LV myocardium were significantly higher in group 2 than in groups 1, 3, and 4 (all P < 0.005). In conclusion, losartan is comparable to carvedilol in attenuating inflammation, oxidative response, myocardial fibrosis and apoptosis, as well as in preserving energy transcription factors and LV function in DCM.

Background The prognostic value of interleukin (IL)-10 in patients with ST-segment elevation acute myocardial infarction (ST-se AMI) is currently unclear. The purpose of this study was to test whether the serum IL-10 level can predict 30-day mortality in patients with ST-se AMI undergoing primary percutaneous coronary intervention (PCI). Methods and Results The study design was a prospective cohort study of 250 consecutive patients with ST-se AMI of onset

This study tests the hypothesis that peroxisome proliferator activated receptor-gamma coactivator 1alpha (PGC-1alpha) and the integrity of gap junctions (GJs) were suppressed and the number of apoptotic bodies was increased in remote viable areas of left ventricle following acute myocardial infarction (AMI), which can be reversed by losartan therapy. Open chest surgery was consecutively performed on 32 adult male Sprague-Dawley rats. These rats were classified into 4 groups (n = 8/each group): group I, AMI (by ligation of left coronary artery (LCA) without treatment); group II, AMI with losartan 20 mg/kg/day; group III, sham control (without LAD ligation); and group IV, sham control with losartan 20 mg/kg/day. Echocardiography was performed on day 1 prior to AMI and on day 14 just before the rats were to be sacrificed for cellular and molecular studies. The results showed that mRNA expression of PGC-1alpha, integrated area (microm(2)) of clustered connexin43 (Cx43) spots, and Cx43 GJs were substantially down-regulated and the number of apoptotic bodies was markedly increased in nontreated AMI rats compared with healthy control and losartan-treated AMI rats on day 14 following AMI (all values of P0.001). Additionally, day 14 left ventricular (LV) ejection fraction was significantly lower in nontreated AMI rats than in healthy control and losartan-treated AMI rats (all values of P0.0001). Down-regulation of GJs and PGC-1alpha gene expression and cellular death were frequently observed in remote viable areas of LV following AMI. Losartan therapy reversed the adverse effects of AMI and preserved LV function.

Background This study tested the hypothesis that in the acute phase of myocardial infarction (MI), the circulating level of soluble CD40 ligand (sCD40L), an index of platelet activation, is predictive of angiographic morphologic features that indicate high-burden thrombus formation (HBTF) in the infarct-related artery (IRA). Methods and Results This prospective study included 162 consecutive patients: 64 with HBTF and 98 with low-burden thrombus formation (LBTF). All patients had a Killip's classification ≤3 ST-segment elevation acute myocardial infarction (AMI) of onset