tbuckley/cabot-search huggingface dataset:
Abstract 599: RV Protection Conferred by Chronic Effects of Percutaneous Transluminal Septal Myocardial Ablation During High Level LV Unloading in Sheep
Authors: James Mau, Stuart Menzie, Michael Ward, Stephen N Hunyor
Journal: Circulation (2006)

Background: Severe RV failure is common (~25%) following acute LVAD unloading. The role of IVS dysfunction in this response remains uncertain, so we studied chronic ventricular interactions with incremental LV unloading following IVS damage. Methods: Percutaneous transluminal septal myocardial ablation (PTSMA) with ethanol caused irreversible IVS damage in 6 sheep. Main septal artery catheterization was performed in 6 other sham animals, and both groups underwent hemodynamic assessment 4w later. RV volume was derived from a 3-axis ellipsoidal subtraction model using sonomicrometer dimensions. RV- ejection fraction (EF), pressure recruitable stroke work (PRSW), end-systolic elastance (Ees), 1 st derivative of maximum RV pressure (dP/dt), and Tau were derived from P/V loops during IVC occlusion and LV unloading (25/50/75/100%) using a Bio-Medicus pump. Flow-probes measured % steady-state pulmonary, aortic, and mechanical bypass flow. Results: Response to varying LV assist levels is shown in the Figure ( * =P&lt;0.05). RV- EF, PRSW and Ees decreased in shams, but remained stable in PTSMA during high level LV unloading. DP/dt decreased in shams at 75% LV unloading and trended down at 100%. In contrast, high baseline Tau after PTSMA normalized with moderate ≥50% LV assist. Conclusions: Institution of LV unloading in a chronic IVS damaged but otherwise healthy heart protects against compromised RV function, whereas sham animals respond adversely. Chronic IVS fibrosis may confer protection by limiting changes in RV chamber geometry.
Impact of Primary Coronary Angioplasty Delay on Myocardial Salvage, Infarct Size and Microvascular Damage in Patients With ST-Elevation Myocardial Infarction: Insight From Cardiovascular Magnetic Resonance
Authors: Chiara Bucciarelli-Ducci
Journal: Circulation (2009)

Abstract #249 Chiara Bucciarelli-Ducci, CMR Unit, Royal Brompton Hosp and Cardiovascular and Respiratory Sciences, Univ “La Sapienza” Rome, London, United Kingdom; Marco Francone, Iacopo Carbone, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Emanuele Canali, Raffaele Scardala, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy; Francesca Calabrese, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Gennaro Sardella, Massimo Mancone, Cardiovascular Sciences, Univ Rome La Sapienza, Rome, Italy; Carlo Catalano, Radiological Sciences, Univ Rome La Sapienza, Rome, Italy; Francesco Fedele, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy; Roberto Passariello, Radiological Sciences, Univ Rome La SapienzaSciences, Univ, Rome, Italy; Jan Bogaert, Dept of Medical Imaging, Gasthuisberg Univ Hosp, Leuven, Belgium; Luciano Agati, Cardiovascular and Respiratory Sciences, Univ Rome La Sapienza, Rome, Italy Chiara Bucciarelli-Ducci, 2009 Finalist and Presenting Author
Abstract 4901: Morning Hypertension is the Strong Predictor of Left Ventricular Remodeling in Never-Medicated Hypertensives
Authors: Yoshio Matsui, Kazuo Eguchi, Seiichi Shibasaki, Kazuyuki Shimada, Kazuomi Kario
Journal: Circulation (2009)

We aimed this study to investigate the association between morning hypertension and left ventricular (LV) remodeling. This cross-sectional study enrolled consecutive 356 never-medicated hypertensives, and measured the LV mass and relative wall thickness using echocardiography. Home blood pressure (BP) was measured in the morning and evening for 14 consecutive days with a memory-equipped device. We divided all subjects into 4 groups according to the morning-evening difference in self-measured systolic BP (MEdif) and the average of morning and evening systolic BP (MEave): home normotension (MEave &lt;135 mmHg and MEdif &lt;15 mmHg), morning riser (MEave &lt;135 mmHg and MEdif ≥15 mmHg), sustained hypertension (MEave ≥ 135 mmHg and MEdif &lt;15 mmHg) and morning hypertension (MEave ≥ 135 mmHg and MEdif &lt;15 mmHg). Morning hypertensives was significantly older than normotensives (70 years vs. 64 years, P&lt;0.001). We compared distributions of LV remodeling patterns among the 4 groups ( Figure ). Concentric hypertrophy was more prevalent in morning hypertensives (48.6%) than in normotensives (7.8%, P&lt;0.001), morning risers (20.0%, P = 0.007), and sustained hypertensives (30.0%, P = 0.003). Morning risers had higher percentage of concentric hypertrophy and concentric remodeling than normotensives (20% vs. 7.8%, P = 0.039; 32.5% vs. 14.7%, P = 0.017) despite similar MEave between the 2 groups. The association observed here between morning hypertension and concentric hypertrophy may be related to the mechanism of increased cardiovascular risk of morning hypertension.
Abstract 4956: Intravital Microscopic Analysis Revealed Indoxyl Sulfate-induced Leukocyte Recruitment via E-selectin in Mice After Subtotal Renal Ablation
Authors: Shunsuke Ito, Mizuko Osaka, Yusuke Higuchi, Fuyuhiko Nishijima, Hideto Ishii, Masayuki Yoshida
Journal: Circulation (2009)

[Background] Despite positive correlation between chronic kidney disease (CKD) and atherosclerosis, a causative role of uremic toxins in vascular inflammation has not been well characterized. Indoxyl sulfate (IS) is one of the uremic toxins increased in CKD patients. However, the effect of IS on inflammation had not been tested. We thus examined an effect of IS on leukocyte-endothelial interaction in vivo and in vitro . [Methods and Results] Pretreatment of HUVEC with IS (0.2 mM to 2.0 mM for 20 h) significantly enhanced THP-1 cell adhesion to TNF- α -activated HUVEC under flow condition (p&lt;0.01). IS enhanced expression level of E-selectin, but not ICAM-1 or VCAM-1 in TNF- α -activated HUVEC. IS treatment induced phosphorylation of JNK and p65 component of NF- κ B in TNF- α -activated HUVEC. IS-induced activation of NF- κ B was further confirmed by luciferase assay using HUVEC transfected with an NF- κ B firefly -luciferase cDNA construct. SP600125, a JNK inhibitor, and BAY11–7082, an NF- κ B inhibitor, attenuated IS-induced E-selectin expression and subsequent THP-1 cells adhesion under flow. IS increased dihydroethidium-associated oxidative stress in HUVEC, which is stabilized by apocynin, an NAD(P)H oxidase inhibitor. Next, a pathophysiolocgical role of IS in CKD was examined in nephrectomized mice with (Nx+IS) or without IS (Nx). An intravital microscopic analysis revealed a significant induction of leukocyte adhesion to the femoral artery in the Nx+IS group when compared to Nx group (p&lt;0.05). Expression levels of E-selectin and the NAD(P)H oxidase subunits (p47phox and p22phox) were increased in Nx+IS mice. When we monitored inflammatory markers of monocytes, expression of CD11b and production of ROS was significantly increased in Nx mice, which was blunted by an oral absorbent of IS. [Conclusion] These results suggest that IS enhances leukocyte-endothelial cell interaction through up-regulation of E-selectin. The underlying mechanisms seem to involve oxidative stress-mediated JNK and NF- κ B dependent pathways. These observations provide a novel role for IS in CKD-related vascular inflammation.
Abstract 576: Defective Domain-Domain Interaction Between C-Terminal and Central Regions of Ryanodine Receptor as a Critical Cause of Diastolic Ca <sup>2+</sup> Spark and Delayed Afterdepolarization
Authors: Hiroki Tateishi, Masafumi Yano, Takeshi Yamamoto, Xu Xiaojuan, Makoto Ono, Hitoshi Uchinoumi, Mamoru Mochizuki, Toshiyuki Noma, Shigeki Kobayashi, Tomoko Ohkusa, Masunori Matsuzaki
Journal: Circulation (2006)

Ryanodine receptor-2 (RyR2) central domain peptide, DPc10 (Gly 2460 -Pro 2495 ), was found to mimic channel dysfunction associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) by acting competitively to reduce stabilizing interactions between N-terminal 1– 600 and central domains 2000 –2500 . Using the domain peptide approach, here, we investigated how single point mutation at C-terminal region in CPVT influences on intracellular Ca 2+ handling. Methods and Results: Sarcoplasmic reticulum (SR) vesicles were isolated from dog LV muscles (n= 5), then fluorescently labeled with methylcoumarin acetate (MCA) using DP 4090 – 4123 , a synthetic domain peptide corresponding to Pro-Glu (mutable domain in CPVT), as a site-directing carrier; the carrier was removed after MCA labeling. The DP 4090 – 4123 mediated a specific MCA fluorescence labeling of RyR2. After tryptic digestion, the major MCA-fluorescently labeled fragment of RyR2 (150 kD) was detected by an antibody (Ab) against central region (Ab 2163 ), but not by Ab 2808, N-terminal (Ab 10 ) and C-terminal region (Ab 5030 ). Addition of DP 4090 – 4123 to the MCA-labeled SR induced domain unzipping between C-terminal and its putative counter domains (EC50=30μM), as confirmed by a marked quenching of the MCA fluorescence by a large-size fluorescence quencher. The DP 4090 – 4123 induced a prominent SR Ca 2+ leak (EC50=30μM). In DP 4090 – 4123 -incoporated cardiomyocytes (by protein delivery kit), diastolic Ca 2+ spark frequency was markedly increased (4.0±1.0 s -1 100ìm -1 , p&lt;0.01), compared to normal cardiomyocytes (1.4±0.4 s -1 100ìm -1 ), and after addition of 100nM forskolin both Ca2+ wave and delayed afterdepolarization-mediated Ca 2+ transient (DAD-CaT) were also frequently observed (but not in normal cardiomyocytes). All of these effects of DP 4090 – 4123 were abolished either by addition of 10 μM tetracaine or by Asn-to-Lys mutation made in DP 4090 – 4123 , mimicking human CPVT mutation. Conclusions: Domain-domain interaction between C-terminal and central domains (within 1200 –2850) seems to play an important role in channel gating of RyR2, and its defectiveness by point mutation may induce diastolic Ca 2+ spark and delayed afterdepolarization that triggers lethal arrhythmia.
Abstract 4168: Two Independent Apolipoprotein A5 Haplotypes Modulate Postprandial Lipoprotein Metabolism in a Caucasian Healthy Population.
Authors: Pablo Perez-Martinez, Jose Lopez-Miranda, Rafael Moreno, Yolanda Jimenez-Gomez, Carmen Marin, Maria J Gomez, Mercedes Garcia-Salas, Purificacion Gomez, Enrique Galan, Aquiles Lozano, Francisco Perez-Jimenez
Journal: Circulation (2006)

Background: APOA5 plays an important role in plasma plasma triglyceride (TG) homeostasis. Five polymorphisms (1131T&gt;C, c.-3A&gt;G, c.56C&gt;G, IVS3+476G&gt;A, c.1259T&gt;C) in the APOA5 gene were found to define three common haplotypes (denoted APOA5 *1, APOA5 *2 and APOA5* 3) in Caucasian individuals. Our aim was to determine whether these haplotypes could modulate the postprandial response in young healthy males, in order to explain the higher risk of coronary artery disease (CHD) associated with less common alleles Design and methods: 84 apo E3E3 volunteers [63 with (-1131T and 56C) haplotype 1, 12 with (-1131C and 56C) haplotype 2 and 9 with (-1131T and 56G) haplotype 3] underwent a fat-load test consisting of 1 g of fat/kg body weight and 60,000 IU of vitamin A. Blood samples were taken at time 0 and every hour until the 6 th and every 2.5 hr until the 11 th . Cholesterol (Chol) and TG were determined in plasma and Chol, TG, Apo B-100, Apo B-48, and retinyl palmitate (RP) were determined in lipoprotein fractions. Results: Data of postprandial lipemia revealed that subjects with the haplotypes 2 and 3 had a higher area under the curve than subjects with the haplotype 1 of total plasma TG (0.28±0.1 and 0.31±0.1 vs 0.21±0.1 mmol/L s, p0.04), large triacylglycerol-rich lipoproteins (TRL)-TG (0.19±0.07 and 0.22±0.09 vs 0.10±0.04 mmol/L s, p=0.01), small TRL-TG (0.15±0.06 and 0.14±0.07 vs 0.9±0.05 mmol/L s, p=0.03), large TRL-Cho (0.05±0.01 and 0.06±0.01 vs 0.03±0.061 mmol/L s, p=0.04), and small apoB100 (639±315 and 219±158 vs 140±86, p=0.03). Conclusions : Our findings show that the presence of the haplotype 2 and 3 in the APO5 gene are associated with a higher postprandial response and could be involved in a higher risk of CHD.
Abstract 579: Calcium Handling and Mechanisms of Automaticity in Human Embryonic Stem Cell Derived Cardiomyocytes
Authors: Ilanit Itzhaki, Jonathan Satin, Leighton Izu, Elizabeth A Schroder, Jackie Schiller, C. William Balke, Raphael Beyar, Lior Gepstein
Journal: Circulation (2006)

Human embryonic stem cell derived cardiac myocyte (hES-CM) function is poorly understood. Under normal conditions mature cardiac muscle is quiescent but immature CMs, including hES-CMs display automaticity. In mature nodal cells store Ca contributes to automaticity. Therefore, we tested the hypothesis that cytosolic intracellular store Ca transients in hES-CMs contributes to their spontaneous excitability. Relatively immature hES-CMs were chosen for the study (&lt;40 days differentiation). We used a combination of approaches including RT-PCR, immunocytochemistry, whole-cell voltage-clamp, and simultaneous patch-clamp and laser scanning confocal Ca-imaging of cells co-labeled with di-8-Anepps to delineate surface membrane. hES-CMs reveal two distinct types of Ca transients AP driven global Ca transients (AP-Ca transients) and local Ca transients (LCTs). The LCTs originate at the cell periphery, associated with plasma membrane (PM), do not propagate across the width of the cell and are not interactive with electrical activity. The AP-Ca transients are rhythmic high amplitude events that originate at the PM and spread as a propagated wave to the cell center. Caffeine-releasable store Ca was demonstrated by focal, temporally-limited puffs of caffeine and by long-lasting caffeine depletion of internal store Ca. Spontaneous activity was inhibited by 20 mM caffeine (&gt;20s continual application). Ryanodine caused a progressive decrease in the amplitude of Ca-release and AP rate. Interestingly, 10μM TTX abolishes all Ca transients (AP-Ca transients and LCTs) suggesting that elevated cytosolic Na contributes to the LCTs. High-speed 2D confocal laser scanning imaging showed that LCTs occur out of phase with AP-Ca transients, and separate LCTs within a given cell are often out of phase with one another. This argues against LCTs as a primary rhythm generator in early stage hES-CMs. However ryanodine and caffeine effects argue for internal store Ca requirement for automaticity. We conclude that the molecular mechanism of automaticity in early stage hES-CMs relies on the interplay between AP-Ca and membrane potential. This study provides the first evidence that developing hES-CMs have functional internal store Ca.
Abstract 4889: Coupling Factor 6 Enhances the Action of Angiotensin II and Causes Insulin Resistance in Mice
Authors: Tomohiro Osanai, Makoto Tanaka, Takashi Echizen, Toshiro Ashitate, Kei Izumiyama, Shigeki Sagara, Hirofumi Tomita, Ken Okumura
Journal: Circulation (2009)

The lower values of intracellular pH are commonly observed in the hypertensive states including a high renin state. It is also reported that intracellular acidosis is related to the pathogenesis of diabetes by inducing insulin resistance in the skeletal muscle. We recently showed that the molecular rotary motor F 1 F o complex, ATP synthase, is present at the plasma membrane, and that coupling factor 6 (CF6) forces the backward rotation of F o after binding to F 1 , resulting in cellular acidosis (Hypertension, 2005). Using CF6-overexpressing transgenic (TG) mice and vascular smooth muscle cells (VSMC), we tested the hypothesis that CF6 enhances the action of angiotensin II (AngII) and causes insulin resistance. In TG mice, the introduced gene of human CF6 was expressed in overall tissues, and upregulated by 2 times. In the mesenteric arterioles isolated from TG mice, Ang II-induced vasoconstriction was enhanced compared with WT mice (p&lt;0.05). Blockade of CF6 with its specific antibody remarkably attenuated the Ang II-induced vasoconstriction by 85±5% in TG mice and by 79±5% in WT mice, thereby eliminating the difference in contraction. In CF6-overexpressing (spontaneously hypertensive rats, SHR) VSMC, Ang II (10 −7 M)-induced increase in the spike phase of [Ca 2+ ] i was higher compared with control (Wistar Kyoto rats) VSMC. In VSMC with a high affinity CF6 receptor (SHR), Ang II (10 −7 M)-induced increase in the spike phase of [Ca 2+ ] i was enhanced by the presence of CF6 at 10 −7 M. All were blocked by PP1 at 50 μ M, a c-Src inhibitor. When the mice were fed with high sucrose diet (20%) for 8 weeks, the TG mice exhibited insulin resistance: In glucose-tolerance test, the plasma glucose level was higher until 1.5 hours (p &lt; 0.05, two-way ANOVA), and insulin level at 1 hour was higher in TG mice (1111 ± 118 vs 400 ± 54 pg/ml, p &lt; 0.05). The TG mice exhibited no change in tyrosine phosphorylation of β subunit of insulin receptor but the decreases in the protein expression of insulin receptor substrate-1 by 64 ± 9%, phosphatidylinositol-3 kinase activity, Akt phosporylation, and the plasma membrane GLUT-4 protein by 69 ± 11% in the skeletal muscle (n = 5, all p &lt; 0.05). These indicate that CF6 enhances the action of AngII by c-Src signaling and thereby causes diet-induced insulin resistance in mice.
Abstract 4195: High-Dose Atorvastatin Therapy Can Completely Reverse Monocyte Dysfunction in Hypercholesterolemic Patients with Coronary Artery Disease
Authors: Frauke S Czepluch, Johannes Waltenberger
Journal: Circulation (2006)

Statins, a key component in the primary and secondary CAD prevention, reduce cardiovascular events even in normo- and hypocholesterolemic individuals. Intact monocyte function is crucial for collateral artery development. In the presence of hypercholesterolemia (HC), collateral formation is severely impaired. We could previously show that MCP-1-induced monocyte chemotaxis is significantly decreased in hypercholesterolemic CAD patients. Therefore, we investigated whether a therapy with atorvastatin 40 mg once a day could improve monocyte function in CAD patients with HC, and whether this influences MCP-1 plasma levels. Fifty CAD patients with HC as a single cardiovascular risk factor were randomized to receive either atorvastatin 40 mg or a placebo once daily for 4 weeks. Monocytes were isolated from peripheral blood. Their migratory responsiveness towards MCP-1 (10 ng/ml) was assessed in a micro-chemotaxis chamber before and at the end of the study. MCP-1 plasma levels were analyzed using ELISA. Before starting study medication, monocyte chemotaxis towards MCP-1 did not differ between the atorvastatin group and the placebo group (122% vs. 114%; p=NS). After 4 weeks, the migratory response of monocytes from atorvastatin-treated patients significantly improved, whereas the monocytes from placebo-treated patients showed a further decline in function (149% vs. 109%; p&lt;0.001). A significant negative correlation existed between LDL-C levels and MCP-1-induced monocyte chemotaxis (p&lt;0.001). With regard to MCP-1 plasma levels, there was no significant difference in CAD patients treated with or without atorvastatin (476 vs. 671 pg/ml; p=NS) for 4 weeks.Based on our data, a high-dose atorvastatin therapy can completely reverse the negative influence of HC on monocyte function, whereas monocyte chemotaxis further decreases in the absence of any lipid-lowering therapy. The migratory responsiveness of monocytes is closely associated with LDL-levels indicating that statin effects on monocytes are rather cholesterol-dependent than pleiotropic. High-dose statin therapy might be regarded as an important contribution to primary and secondary prevention in CAD by improving the patients’ ability to form functional coronary collaterals.
2006 William W. L. Glenn Lecture–Rebuilding the Heart: New Horizons for Cardiac Surgeons
Authors: Richard Weisel
Journal: Circulation (2006)

Cardiac surgery is changing today, as it was during the time of Dr William Glenn. In those days, cardiac surgeons were trained to do thoracic and vascular surgery.Today, cardiac surgeons are retraining to do intravascular and minimally invasive cardiac and vascular procedures. However, today’s cardiac surgeons should also retrain to employ gene-enhanced cell therapy to modify both the heart and the vasculature to improve the outcomes of their interventions. Cell transplantation has come of age and is undergoing extensive clinical trials. The implantation of precursor cells induces angiogenesis, improves regional and global function, and enhances the recruitment of reparative cells to the heart. In addition to correcting anatomic cardiac lesions, surgeons may be able to restore function to the heart by a combination of cardiac regeneration and rejuvenation of the response to injury. Tissue engineering may restore heart function without synthetic materials, provided the surgeon employs the right combination of cells and biodegradable scaffolds. These grafts may be ideal for the surgical repair of congenital cardiac defects, and clinical trials are underway. The implanted grafts grow and remodel as the child becomes an adult. Cardiac surgeons are retraining to acquire new skills to correct cardiovascular defects. In addition, surgeons should acquire the knowledge required to regenerate and rebuild the heart and vasculature.
Abstract 4177: High Serum Dehydroepiandrosterone Sulfate Levels are Strikingly Associated with Less Mortality in Men: 27-Year Follow-Up Study
Authors: Mika Enomoto, Hisashi Adachi, Yoshiyuki Shigetoh, Maki Otsuka, Shun-ichi Kumagai, Kumiko Furuki, Akira Satoh, Tsutomu Imaizumi
Journal: Circulation (2006)

Background: Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are secreted adrenal steroids. DHEAS concentrations decline with aging. Supplementary use of DHEAS is common nowadays with a hope of longevity. But, there has been no data available. We investigated whether DHEAS levels could predict survival in humans. Methods: A total of 940 subjects (396 men, 544 women), aged 21 to 88, underwent a health examination in a community-based cohort in 1978–1979. In all subjects, baseline DHEAS measured by radioimmunoassay, and they were followed until 2005. Results: DHEAS levels were higher in men than in women and decreased with aging in both sexes. In a Cox proportional hazards model, age, DHEAS (inversely), systolic and diastolic blood pressure, and fasting plasma glucose were significantly associated with mortality in men. Of these variables, elevated DHEAS levels were the strongest predictor of survival after adjustments for age, systolic blood pressure, and fasting plasma glucose. Although elevated DHEAS levels were significantly related to survival in women, the significance disappeared after adjustment for age. DHEAS levels in men were classified into tertiles: group1 &lt;130, group2 130≤-&lt;200, group3 ≥200 ng/ml. Only 74.4% of subjects in the lowest DHEAS tertiles survived compared with more than 93.4% in the highest DHEAS tertiles, after adjustments for age and possible confounding factors (Hazard ratio:0.206; 95%C.I. 0.067– 0.630, p&lt;0.01). Conclusions: This study is the first demonstration of the favorable effect survival on a DHEAS in men in a 27-year prospective study.