bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrodeposition Under Forced Convection Conditions
Authors: Montes de Oca Yemha María G. , Mostany Jorge L. , Ramírez-Silva María Teresa , Romero-Romo Mario , Scharifker Benjamin R. , Palomar-Pardavé Manuel
Published: September 2007

The copper electrodeposition process was studied under the influence of forced convection conditions, varying the electrode angular speed (ω) with the aid of a rotating disc electrode, using the potential step technique. From the analyses of the experimental current transients it was found that both: the nucleation rate constant (A) and the number density of active sites (N0) for ω > 200 rpm depending on the hydrodynamic conditions imposed. However, the current transient recorded in the 0 < ω < 200 rpm could not be analyzed with any of the theoretical formalisms proposed so far.
Reduction of Nitrate Ion on the Growing Surfaces of Cr Nuclei Formed During Black Chromium Electrodeposition
Authors: Aguilar-Sánchez Miriam , Palomar-Pardavé Manuel , Romero-Romo Mario , Ramírez-Silva María Teresa , Barrera Enrique , Huerta Lázaro , Scharifker Benjamin R.
Published: September 2007

In chromium electrodeposition, as with other metals, it is possible to obtain differences in coloration, whether it is black or white chromium. Both films have been obtained using two very similar baths, except that black chromium has KNO3 in solution. We found that the electrochemical deposits of both kinds of Cr follow a diffusion-controlled nucleation and growth mechanism of 3D centres. In fact, while white chromium exhibited a simple 3D nucleation mechanism, the black chromium was found to be complicated by the concurrent nitrate ions- reduction processes on the surface of recently formed Cr nuclei
Coronene-Iodine Coadsorbed Adlayers on Au(111) Surfaces Promoted by Electrochemical Potential Control
Authors: Kunitake Masashi , Ishikawa Yudai , Matsuda Shuhei , Abe Satoshi , Miyasato Youya , Higuchi Rintarou , Sakata Masayo
Published: September 2007

A coronene and iodine co-adsorbed adlayer on an Au(111) surface in which iodine atoms surrounded each coronene molecule was found by an in situ scanning tunneling microscopy (STM) study with electrochemical potential control.
Small Volume Detection of Plasmodium Falciparum Using a 50 Micrometer Diameter Cavity with Self-contained Electrochemistry
Authors: Aguilar Zoraida P.
Published: September 2007

An electrochemical enzyme-linked solid phase DNA-hybridization assay for the detection of Plasmodium falciparum is reported. The DNA-hybridization assay involves attachment of biotinylated primary DNA probe (10P) via its 5'-amine-terminus to the streptavidin- coated microwells in a 96-well plate. The 10P was used to capture the target by hybridization to a complementary sequence. A 36-mer secondary DNA probe labeled with alkaline phosphatase (20P~AP) on the 3'end was hybridized to a complementary base sequence on the 5' end of the target. The electrochemical detection involved the wall electrode (TNB, 8 μm2) as the detecting electrode and top layer gold (0.7 mm2 when 200 nL is placed on top of microcavity) as pseudoreference/auxiliary electrodes. The peak current from cyclic voltammograms of PAPP incubated inside modified microwells gave a linear relationship with the concentration of the target at 2- 50 ng/mL, where 10P and 20P~AP were 50 ng/mL. A detection limit of 1.4 ng/mL (or 70 pg) of the DNA target was obtained. The electrochemical signals were not affected in the presence of human hepatocytes, pig liver, or chicken serum indicating the viability of this assay in real clinical samples.
Role of 20-HETE in the hypoxia-induced activation of Ca2+-activated K+ channel currents in rat cerebral arterial muscle cells
Authors: Gebremedhin Debebe , Yamaura Ken , Harder David R.
Published: September 2007

The mechanism of sensing hypoxia and hypoxia-induced activation of cerebral arterial Ca2+-activated K+ (KCa) channel currents and vasodilation is not known. We investigated the roles of the cytochrome P-450 4A (CYP 4A) ω-hydroxylase metabolite of arachidonic acid, 20-hydroxyeicosatetraenoic acid (20-HETE), and generation of superoxide in the hypoxia-evoked activation of the KCa channel current in rat cerebral arterial muscle cells (CAMCs) and cerebral vasodilation. Patch-clamp analysis of K+ channel current identified a voltage- and Ca2+-dependent 238 ± 21-pS unitary K+ currents that are inhibitable by tetraethylammonium (TEA, 1 mM) or iberiotoxin (100 nM). Hypoxia (<2% O2) reversibly enhanced the open-state probability ( NPo) of the 238-pS unitary KCa current in cell-attached patches. This effect of hypoxia was not observed on unitary KCa currents recorded from either excised inside-out or outside-out membrane patches. Inhibition of CYP 4A ω-hydroxylase activity increased the NPo of KCa single-channel current. Hypoxia reduced the basal endogenous level of 20-HETE by 47 ± 3% as well as catalytic formation of 20-HETE in cerebral arterial muscle homogenates as determined by liquid chromatography-mass spectrometry analysis. The concentration of authentic 20-HETE was reduced when incubated with the superoxide donor KO2. Exogenous 20-HETE (100 nM) attenuated the hypoxia-induced activation of the KCa current in CAMCs. Hypoxia did not augment the increase in NPo of KCa channel current induced by suicide inhibition of endogenous CYP 4A ω-hydroxylase activity with 17-octadecynoic acid. In pressure (80 mmHg)-constricted cerebral arterial segments, hypoxia induced dilation that was partly attenuated by 20-HETE or by the KCa channel blocker TEA. Exposure to hypoxia caused the generation of intracellular superoxide as evidenced by intense staining of arterial muscle with the fluorescent probe hydroethidine, by quantitation using fluorescent HPLC analysis, and by attenuation of the hypoxia-induced activation of the KCa channel current by superoxide dismutation. These results suggest that the exposure of CAMCs to hypoxia results in the generation of superoxide and reduction in endogenous level of 20-HETE that may account for the hypoxia-induced activation of arterial KCa channel currents and cerebral vasodilation.
C-Reactive Protein Is an Independent Predictor of the Rate of Increase in Early Carotid Atherosclerosis
Authors: Hashimoto Hiroyuki , Kitagawa Kazuo , Hougaku Hidetaka , Shimizu Yoshiomi , Sakaguchi Manabu , Nagai Yoji , Iyama Shigeru , Yamanishi Hachiro , Matsumoto Masayasu , Hori Masatsugu
Published: September 2007

Background
—An elevated plasma concentration of high-sensitivity C-reactive protein (hs-CRP) is a strong predictor of cardiovascular events. However, there have been no longitudinal studies of the relations between development of atherosclerotic lesions and hs-CRP concentrations. Furthermore, it remains unknown whether increased hs-CRP concentrations result in the development of atherosclerosis.

Methods and Results
—The study included 179 outpatients 40 to 79 years of age who were treated at our institute for traditional risk factors for cardiovascular disease. The patients had no evidence of advanced carotid atherosclerosis at the time of baseline examination. Patients underwent repeated ultrasonographic evaluation of the carotid arteries for 35±10 months. Blood samples were collected for hs-CRP measurements. Based on focal intima-media thickening ≥1.1 mm representing plaque, plaque number (PN) and plaque score (PS; the sum of all plaque thicknesses) were calculated. The development of atherosclerosis was estimated by the formula Δvalue/year=(last value−baseline value)/number of follow-up years. Multivariate linear regression analysis revealed that the log-transformed value for hs-CRP concentration was not related to baseline PN or PS but was related to ΔPN/year and ΔPS/year (β=0.29 and 0.30;
P
<0.001 for both) independently of the effect of traditional risk factors.

Conclusions
—During the early stages of carotid atherosclerosis, the hs-CRP concentration is a marker of carotid atherosclerotic activity rather than extent of atherosclerosis.
Pathological Analysis of Local Delivery of Paclitaxel Via a Polymer-Coated Stent
Authors: Farb Andrew , Heller Phillip F. , Shroff Sweta , Cheng Linda , Kolodgie Frank D. , Carter Andrew J. , Scott Douglas S. , Froehlich Jeffrey , Virmani Renu
Published: September 2007

Background—

Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored.

Methods and Results—

Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 μg of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (
P
<0.0003) and 36% (
P
<0.007) with stents containing 42.0 and 20.2 μg of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 μg) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 μg of paclitaxel

Conclusions—

CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer–coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.
Reversing the Direction of Paced Ventricular and Atrial Wavefronts Reveals an Oblique Course in Accessory AV Pathways and Improves Localization for Catheter Ablation
Authors: Otomo Kenichiro , Gonzalez Mario D. , Beckman Karen J. , Nakagawa Hiroshi , Becker Anton E. , Shah Nayyar , Matsudaira Kagari , Wang Zulu , Lazzara Ralph , Jackman Warren M.
Published: September 2007

Background

The purpose of this study was to determine how often accessory atrioventricular (AV) pathways (AP) cross the AV groove obliquely. With an oblique course, the local ventriculoatrial (VA) interval at the site of earliest atrial activation (local-VA) and the local-AV interval at the site of earliest ventricular activation (local-AV) should vary by reversing the direction of the paced ventricular and atrial wavefronts, respectively.

Methods and Results

One hundred fourteen patients with a single AP were studied. Two ventricular and two atrial pacing sites on opposite sides of the AP were selected to reverse the direction of the ventricular and atrial wavefronts along the annulus. Reversing the ventricular wavefront increased local-VA by ≥15 ms in 91 of 106 (91%) patients. With the shorter local-VA, the ventricular potential overlapped the atrial potential along a 17.2±8.5-mm length of the annulus. No overlap occurred with the opposite wavefront. Reversing the atrial wavefront increased local-AV by ≥15 ms in 32 of 44 (73%) patients. With the shorter local-AV, the atrial potential overlapped the ventricular potential along an 11.9±8.9-mm length of the annulus. No overlap occurred with the opposite wavefront. Mapping during longer local-VA or local-AV identified an AP potential in 102 of 114 (89%) patients. Catheter ablation eliminated AP conduction in all 111 patients attempted (median, 1 radiofrequency application in 99 patients with an AP potential versus 4.5 applications without an AP potential).

Conclusions

Reversing the direction of the paced ventricular or atrial wavefront reveals an oblique course in most APs and facilitates localization of the AP potential for catheter ablation.
Differential Impact on Survival of Electrocardiographic Q-Wave Versus Enzymatic Myocardial Infarction After Percutaneous Intervention
Authors: Stone Gregg W. , Mehran Roxana , Dangas George , Lansky Alexandra J. , Kornowski Ran , Leon Martin B.
Published: September 2007

Background

—

The relative prognostic importance of ECG myocardial infarction (MI) after intervention compared with varying degrees of enzymatic elevation has not been characterized, and the device-specific implications of periprocedural MI are also unknown.

Methods and Results

—

Serial creatine phosphokinase (CPK)-MB levels were determined after elective percutaneous intervention of 12 098 lesions in 7147 consecutive patients at a tertiary referral center. Procedural, in-hospital, and follow-up data were collected by independent research nurses, and clinical and ECG events were adjudicated by a separate committee. Stents were implanted in 50.6% of lesions, atheroablation was performed in 54.8%, and PTCA alone was performed in 9.8%. The peak periprocedural CPK-MB level was >3× the upper limit of normal (ULN) in 17.9% of patients, and Q-wave MI developed in 0.6%. By multivariate analysis, the periprocedural development of new Q waves was the most powerful independent determinant of death (2-year mortality rate, 38.3%; hazard ratio, 9.9;
P
<0.0001). Non–Q-wave MI with CPK-MB >8× ULN was also a strong predictor of death (2-year mortality rate, 16.3%; hazard ratio, 2.2;
P
<0.0001); survival was unaffected by lesser degrees of CPK-MB elevation. Though CPK-MB elevation was more common after atheroablation and stenting than PTCA, the rates of Q-wave MI and survival were device-independent.

Conclusions

—

Myonecrosis after percutaneous intervention is common in a high-risk referral population dominated by atheroablation and stent use. Large periprocedural infarctions (signified by new Q waves and CPK-MB >8×ULN) are powerful determinants of death, whereas lesser degrees of CPK-MB release and specific device use do not adversely affect survival.
Increased Inducible Nitric Oxide Synthase Expression Contributes to Myocardial Dysfunction and Higher Mortality After Myocardial Infarction in Mice
Authors: Feng Qingping , Lu Xiangru , Jones Douglas L. , Shen Ji , Arnold J. Malcolm O.
Published: September 2007

Background

—

Inducible nitric oxide synthase (iNOS) is expressed in the myocardium after myocardial infarction (MI) and in heart failure. Its pathophysiological role in these conditions, however, is not clear. We hypothesized that increased NO production from iNOS expression causes myocardial dysfunction and results in higher mortality after MI.

Methods and Results

—

MI was induced by left coronary artery ligation in iNOS
−/−
mutant and wild-type mice. Mortality was followed up for 30 days. MI resulted in a significant increase in mortality in both iNOS
−/−
and wild-type mice compared with sham operation (
P
<0.01). Mortality was significantly decreased and LV myocardial contractility was increased, however, in iNOS
−/−
mice compared with the wild-type mice (
P
<0.05). Five days after MI, myocardial iNOS mRNA expression, plasma nitrate and nitrite concentrations, and myocardial and plasma nitrotyrosine levels were significantly increased in wild-type compared with iNOS
−/−
mutant mice (
P
<0.05). Both basal LV +dP/dt and its response to dobutamine were significantly increased in iNOS
−/−
compared with the wild-type mice (
P
<0.05).

Conclusions

—

Increased NO production from iNOS expression contributes to myocardial dysfunction and mortality after MI in mice.
Activation of Signal Transducer and Activator of Transcription 3 Protects Cardiomyocytes from Hypoxia/Reoxygenation-Induced Oxidative Stress Through the Upregulation of Manganese Superoxide Dismutase
Authors: Negoro Shinji , Kunisada Keita , Fujio Yasushi , Funamoto Masanobu , Darville Martine I. , Eizirik Décio L. , Osugi Tomoaki , Izumi Masahiro , Oshima Yuichi , Nakaoka Yoshikazu , Hirota Hisao , Kishimoto Tadamitsu , Yamauchi-Takihara Keiko
Published: September 2007

Background

Mice with cardiac-specific overexpression of signal transducer and activator of transcription 3 (STAT3) are resistant to doxorubicin-induced damage. The STAT3 signal may be involved in the detoxification of reactive oxygen species (ROS).

Methods and Results

The effects of leukemia inhibitory factor (LIF) or adenovirus-mediated transfection of constitutively activated STAT3 (caSTAT3) on the intracellular ROS formation induced by hypoxia/reoxygenation (H/R) were examined using rat neonatal cardiomyocytes. Either LIF treatment or caSTAT3 significantly suppressed the increase of H/R-induced ROS evaluated by 2′,7′-dichlorofluorescin diacetate fluorescence. To assess whether ROS are really involved in H/R-induced cardiomyocyte injury, the amount of creatine phosphokinase in cultured medium was examined. Both LIF treatment and caSTAT3 significantly decreased H/R-induced creatine phosphokinase release. These results indicate that the gp130/STAT3 signal protects H/R-induced cardiomyocyte injury by scavenging ROS generation. To investigate the mechanism of scavenging ROS, the effects of LIF on the induction of antioxidant enzymes were examined. LIF treatment significantly increased the expression of manganese superoxide dismutase (MnSOD) mRNA, whereas the expression of the catalase and glutathione peroxidase genes were unaffected. This induction of MnSOD mRNA expression was completely blocked by adenovirus-mediated transfection of dominant-negative STAT3. Moreover, caSTAT3 augmented MnSOD mRNA and its enzyme activity. In addition, the antisense oligodeoxyribonucleotide to MnSOD significantly inhibited both LIF and caSTAT3-mediated protective effects.

Conclusions

The activation of STAT3 induces a protective effect on H/R-induced cardiomyocyte damage, mainly by inducting MnSOD. The STAT3-mediated signal is proposed as a therapeutical target of ROS-induced cardiomyocyte injury.
Mechanism of Ventricular Defibrillation for Near-Defibrillation Threshold Shocks
Authors: Chattipakorn Nipon , Banville Isabelle , Gray Richard A. , Ideker Raymond E.
Published: September 2007

Background

To study the mechanism by which shocks succeed (SDF) or fail (FDF) to defibrillate, global cardiac activation and recovery and their relationship to defibrillation outcome were investigated for shock strengths with approximately equal SDF and FDF outcomes (DFT
50
).

Methods and Results

In 6 isolated pig hearts, dual-camera video imaging was used to record optically from ≈8000 sites on the anterior and posterior ventricular surfaces before and after 10 DFT
50
biphasic shocks. The interval between the shock and the last ventricular fibrillation activation preceding the shock (coupling interval, CI) and the time from shock onset to 90% repolarization of the immediate postshock action potential (RT
90
) were determined at all sites. Of 60 shocks, 31 were SDF. The CI (59±7 versus 52±6 ms) and RT
90
(108±19 versus 88±8 ms) were significantly longer for SDF than FDF episodes. Spatial dispersions of CI (36±5 versus 34±3 ms) and RT
90
(40±16 versus 40±8 ms) were not significantly different for SDF versus FDF episodes. The first global activation cycle appeared focally on the left ventricular apical epicardium 78±32 ms after the shock.

Conclusions

For near-threshold shocks, defibrillation outcome correlates with the electrical state of the heart at the time of the shock and on RT. Global dispersion of RT was similar in both SDF and FDF episodes, suggesting that it is not crucial in determining defibrillation outcome after DFT
50
shocks.
Inhibition of Mannose-Binding Lectin Reduces Postischemic Myocardial Reperfusion Injury
Authors: Jordan James E. , Montalto Michael C. , Stahl Gregory L.
Published: September 2007

Background
—

Complement consists of a complex cascade of proteins involved in innate and adaptive immunity. The cascade can be activated through 3 distinct mechanisms, designated the classical, alternative, and lectin pathways. Although complement is widely accepted as participating in the pathophysiology of ischemia-reperfusion injury, the specific role of the lectin pathway has not been addressed.

Methods and Results
—

Monoclonal antibodies (mAbs; P7E4 and 14C3.74, IgG1κ isotypes) were raised against rat mannose-binding lectin (rMBL). Both mAbs recognized rMBL-A by Western analysis or surface plasmon resonance. P7E4, but not 14C3.74, exhibited a concentration-dependent inhibition of the lectin pathway, with maximal effect at 10 μg/mL. In vivo, rats were subjected to 30 minutes of left coronary artery occlusion and 4 hours of reperfusion. Complement C3 deposition was greatly attenuated in hearts pretreated with P7E4 compared with 14C3.74-treated hearts. Pretreatment with P7E4 (1 mg/kg) significantly reduced myocardial creatine kinase loss (48%), infarct size (39%), and neutrophil infiltration (47%) compared with 14C3.74-treated animals. In addition, P7E4 pretreatment significantly attenuated the expression of proinflammatory genes (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and interleukin-6) after ischemia-reperfusion.

Conclusions
—

The lectin complement pathway is activated after myocardial ischemia-reperfusion and leads to tissue injury. Blockade of the lectin pathway with inhibitory mAbs protects the heart from ischemia-reperfusion by reducing neutrophil infiltration and attenuating proinflammatory gene expression.
Point Mutation in the Stalk of Angiotensin-Converting Enzyme Causes a Dramatic Increase in Serum Angiotensin-Converting Enzyme But No Cardiovascular Disease
Authors: Kramers Cornelis , Danilov Sergei M. , Deinum Jaap , Balyasnikova Irina V. , Scharenborg Nicole , Looman Maaike , Boomsma Frans , de Keijzer Marinus H. , van Duijn Cornelia , Martin Sabrina , Soubrier Florent , Adema Gosse J.
Published: September 2007

Background

Angiotensin-converting enzyme (ACE) metabolizes many small peptides and plays a key role in blood pressure regulation. Elevated serum ACE is claimed to be associated with an increased risk for cardiovascular disease. Previously, two families with dramatically increased serum ACE were described, but no systematic survey of affected individuals was performed, and the molecular background of this trait is unknown.

Methods and Results

Eight families were identified with autosomal dominant inheritance of a dramatic (5-fold) increase of serum ACE activity. Strikingly, no clinical abnormalities were apparent in the affected subjects. Isolated blood cells were used for genetic and biochemical analysis. The level of ACE expression on the blood leukocytes and dendritic cells and total cell-associated ACE of the affected individuals was similar to that in nonaffected relatives; however membrane-bound mutant ACE was much more efficiently clipped from the cell surface compared with its wild-type counterpart. A point mutation causing Pro1199Leu in the stalk region of the ACE molecule cosegregates with the increase in serum ACE (LOD score, 6.63).

Conclusions

A point mutation in the stalk region of the ACE protein causes increased shedding, leading to increased serum ACE, whereas cell-bound ACE is unaltered, and affected individuals exhibit no clinical abnormalities. These findings qualify the importance of serum ACE and establish a new determinant of ACE solubilization.
Coincident Linkage of Fasting Plasma Insulin and Blood Pressure to Chromosome 7q in Hypertensive Hispanic Families
Authors: Cheng L.S.-C. , Davis R.C. , Raffel L.J. , Xiang A.H. , Wang N. , Quiñones M. , Wen P.-Z. , Toscano E. , Diaz J. , Pressman S. , Henderson P.C. , Azen S.P. , Hsueh W.A. , Buchanan T.A. , Rotter J.I.
Published: September 2007

Background

Insulin resistance (IR) and hyperinsulinemia are phenotypically associated with hypertension. We have previously provided evidence that blood pressure (BP) and IR cosegregate in Hispanic families, suggesting that this association has a genetic component. In the present study, we provide further support for the hypothesis of a genetic basis for the BP-IR relationship from a genetic linkage study.

Methods and Results

A 10-cM genome scan was conducted in 390 Hispanic family members of 77 hypertensive probands. Detailed measurements of BP, glucose, insulin levels, and insulin sensitivity (euglycemic clamp) were performed in adult offspring of probands. Multipoint variance component linkage analysis was used. A region on chromosome 7q seemed to influence both IR and BP. The greatest evidence for linkage was found for fasting insulin (lod score=3.36 at 128 cM), followed by systolic BP (lod score=2.06 at 120 cM). Fine mapping with greater marker density in this region increased the maximum lod score for fasting insulin to 3.94 at 125 cM (
P
=0.00002); lod score for systolic BP was 2.51 at 112 cM. Coincident mapping at this locus also included insulin sensitivity measured by the homeostasis assessment model (HOMA) and serum leptin concentrations. Insulin sensitivity by euglycemic clamp did not map to the same locus.

Conclusions

Our results demonstrate that a major gene determining fasting insulin is located on chromosome 7q. Linkage of BP, HOMA, and leptin levels to the same region suggests this locus may broadly influence traits associated with IR and supports a genetic basis for phenotypic associations in IR syndrome.
A 30-Year Follow-Up of the Dallas Bed Rest and Training Study
Authors: McGuire Darren K. , Levine Benjamin D. , Williamson Jon W. , Snell Peter G. , Blomqvist C. Gunnar , Saltin Bengt , Mitchell Jere H.
Published: September 2007

Background
—

Aerobic power declines with age. The degree to which this decline is reversible remains unclear. In a 30-year longitudinal follow-up study, the cardiovascular adaptations to exercise training in 5 middle-aged men previously trained in 1966 were evaluated to assess the degree to which the age-associated decline in aerobic power is attributable to deconditioning and to gain insight into the specific mechanisms involved.

Methods and Results
—

The cardiovascular response to acute submaximal and maximal exercise were assessed before and after a 6-month endurance training program. On average, V̇
o
2max
increased 14% (2.9 versus 3.3 L/min), achieving the level observed at the baseline evaluations 30 years before. Likewise, V̇
o
2max
increased 16% when indexed to total body mass (31 versus 36 mL/kg per minute) or fat-free mass (44 versus 51 mL/kg fat-free mass per minute). Maximal heart rate declined (181 versus 171 beats/min) and maximal stroke volume increased (121 versus 129 mL) after training, with no change in maximal cardiac output (21.4 versus 21.7 L/min); submaximal heart rates also declined to a similar degree. Maximal AVD
o
2
increased by 10% (13.8 versus 15.2 vol%) and accounted for the entire improvement of aerobic power associated with training.

Conclusions
—

One hundred percent of the age-related decline in aerobic power among these 5 middle-aged men occurring over 30 years was reversed by a 6-month endurance training program. However, no subject achieved the same maximal V̇
o
2
attained after training 30 years earlier, despite a similar relative training load. The improved aerobic power after training was primarily the result of peripheral adaptation, with no effective improvement in maximal oxygen delivery.
Ninety-Minute Exclusion of Acute Myocardial Infarction By Use of Quantitative Point-of-Care Testing of Myoglobin and Troponin I
Authors: McCord James , Nowak Richard M. , McCullough Peter A. , Foreback Craig , Borzak Steven , Tokarski Glenn , Tomlanovich Michael C. , Jacobsen Gordon , Weaver W. Douglas
Published: September 2007

Background

Diagnostic strategies with ECG and serum cardiac markers have been used to rule out acute myocardial infarction in 6 to 12 hours. The present study evaluated whether a multimarker strategy that used point-of-care measurement of myoglobin, creatine kinase (CK)-MB, and troponin I could exclude acute myocardial infarction in ≤3 hours.

Methods and Results

We prospectively enrolled consecutive patients (n=817) in the emergency department who were evaluated for possible acute myocardial infarction. In patients with nondiagnostic ECGs, we measured CK-MB, troponin I, and myoglobin with a point-of-care device at presentation and at 90 minutes, 3 hours, and 9 hours. Standard central laboratory testing of CK-MB was done at the same time intervals, and triage decisions were made by emergency physicians who were unaware of point-of-care results. Sensitivity and negative predictive value were compared for both the multimarker, point-of-care approach and the central laboratory strategy. Sensitivity and negative predictive value for point-of-care combination of myoglobin and troponin I by 90 minutes was 96.9% and 99.6%, respectively. CK-MB measurements and blood sampling at 3 hours did not improve sensitivity or negative predictive value. Median time from sampling to reporting of results was 71.0 minutes for the central laboratory versus 24.0 minutes for the point-of-care device (
P
<0.001).

Conclusions

Acute myocardial infarction can be excluded rapidly in the emergency department by use of point-of-care measurements of myoglobin and troponin I during the first 90 minutes after presentation.
Real-Time Quantification and Display of Skin Radiation During Coronary Angiography and Intervention
Authors: den Boer Ad , de Feijter Pim J. , Serruys Patrick W. , Roelandt Jos R.T.C.
Published: September 2007

Background

Radiographically guided investigations may be associated with excessive radiation exposure, which may cause skin injuries. The purpose of this study was to develop and test a system that measures in real time the dose applied to each 1-cm
2
area of skin, taking into account the movement of the x-ray source and changes in the beam characteristics. The goal of such a system is to help prevent high doses that might cause skin injury.

Methods and Results

The entrance point, beam size, and dose at the skin of the patient were calculated by use of the geometrical settings of gantry, investigation table, and x-ray beam and an ionization chamber. The data are displayed graphically. Three hundred twenty-two sequential cardiac investigations in adult patients were analyzed. The mean peak entrance dose per investigation was 0.475 Gy to a mean skin area of 8.2 cm
2
. The cumulative KERMA-area product per investigation was 52.2 Gy/cm
2
(25.4 to 99.2 Gy/cm
2
), and the mean entrance beam size at the skin was 49.2 cm
2
. Twenty-eight percent of the patients (90/322) received a maximum dose of <1 Gy to a small skin area (≈6 cm
2
), and 13.5% of the patients (42/322) received a maximum dose of >2 Gy.

Conclusions

Monitoring of the dose distribution at the skin will alert the operator to the development of high-dose areas; by use of other gantry settings with nonoverlapping entrance fields, different generator settings, and extra collimation, skin lesion can be avoided.
Risk Factors for Cardiovascular Disease in Systemic Lupus Erythematosus
Authors: Svenungsson Elisabet , Jensen-Urstad Kerstin , Heimbürger Mikael , Silveira Angela , Hamsten Anders , de Faire Ulf , Witztum Joseph L. , Frostegård Johan
Published: September 2007

Background

Cardiovascular disease (CVD) is overrepresented in patients with systemic lupus erythematosus (SLE). We determined the prevalence of traditional and nontraditional risk factors for CVD in SLE patients with and without CVD compared with controls.

Methods and Results

Twenty-six women (aged 52±8.2 years) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE but without manifest CVD (SLE controls) and 26 age-matched population-based control women (population controls). Common carotid intima-media thickness (IMT) was measured by B-mode ultrasound as a surrogate measure of atherosclerosis. SLE cases had increased IMT compared with SLE controls (
P
=0.03) and population controls (
P
=0.001), whereas IMT of SLE controls did not differ from population controls. SLE cases had raised plasma concentrations of circulating oxidized LDL (OxLDL;
P
=0.03), as measured by the monoclonal antibody EO6, and autoantibodies to epitopes of OxLDL (
P
<0.001); dyslipidemia with raised triglycerides (
P
<0.001) and lipoprotein(a) (
P
=0.002) and decreased HDL-cholesterol concentrations (
P
=0.03); raised α-1-antitrypsin (
P
=0.002), lupus anticoagulant (
P
=0.007), and homocysteine levels (
P
=0.03); more frequent osteoporosis (
P
=0.03); and a higher cumulative prednisolone dose (
P
=0.05) compared with SLE controls. Disease duration, smoking, blood pressure, body mass index, and diabetes mellitus did not differ significantly between the groups.

Conclusions

α set of distinct CVD risk factors separate SLE cases from SLE controls and population controls. If confirmed in a prospective study, they could be used to identify SLE patients at high risk for CVD in order to optimize treatment.
Central Hypotensive Action of Clonidine Requires Nitric Oxide
Authors: Dobrucki Lawrence W. , Cabrera Camilo L. , Bohr David F. , Malinski Tadeusz
Published: September 2007

Background

Clonidine has an antihypertensive effect by its action in the brain and, because we observed that the tonic production of nitric oxide (NO) in the brain is required to maintain blood pressure at its low, normotensive level, the current study was designed to determine whether the hypotensive action of clonidine resulted from its stimulation of excess NO in the brain.

Methods and Results

Porphyritic microsensors were used to quantify NO concentration in the nucleus tractus solitarius (NTS) in vitro in brain slices and in vivo in the anesthetized rat. In both preparations, the basal production of NO in the NTS was 15±3 nmol/L. In vitro stimulation of the NTS with clonidine (50 nmol/L) resulted in an increase in the NO concentration to 84±7 nmol/L. In vivo, the intracerebroventricular (ICV) infusion of clonidine (0.03 μg) caused an increase in NO concentration in the NTS to 128±17 nmol/L. This ICV injection of clonidine caused a fall in mean arterial pressure of −22±1 mm Hg and a decrease of heart rate of −18±2%. The blockade of NO production with N
G
-nitro-
l
-arginine-methyl ester (2 μmol; delivered ICV, 30 minutes before the clonidine) reduced responses to clonidine for both mean arterial pressure and heart rate (−3±1 mm Hg and −2±1% change, respectively).

Conclusion

The stimulation of the release of NO in the brain by clonidine contributes to its central antihypertensive action.
Ultrasound Assessment of Inflammation and Renal Tissue Injury With Microbubbles Targeted to P-Selectin
Authors: Lindner Jonathan R. , Song Ji , Christiansen Jonathan , Klibanov Alexander L. , Xu Fang , Ley Klaus
Published: September 2007

Background

Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging.

Methods and Results

Phospholipid microbubbles targeted to P-selectin (MB
p
) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB
p
and control microbubbles without antibody (MB) or with isotype control antibody (MB
iso
) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-α–stimulated wild-type mice. Retention of all microbubbles increased (
P
<0.05) with TNF-α treatment because of increased attachment to activated leukocytes. Extensive attachment of MB
p
directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-α–stimulated mice, resulting in 4-fold greater (
P
<0.01) retention of MB
p
than either MB
iso
or MB. Enhanced retention of MB
p
was completely abolished in TNF-α–stimulated P-selectin–deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (
P
<0.05) for MB
p
(12±2 U) than either MB
iso
(6±3 U) or MB (5±3 U). In P-selectin–deficient mice, the signal for MB
p
was equivalent to that from control microbubbles.

Conclusions

Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.
Effects of Nitric Oxide Synthase Inhibition on Basal Function and the Force-Frequency Relationship in the Normal and Failing Human Heart In Vivo
Authors: Cotton James M. , Kearney Mark T. , MacCarthy Philip A. , Grocott-Mason Richard M. , McClean Dougal R. , Heymes Christophe , Richardson Peter J. , Shah Ajay M.
Published: September 2007

Background

Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved.

Methods and Results

We compared the effects of intracoronary NO synthase inhibition with N
G
-monomethyl-
l
-arginine (L-NMMA; 25 μmol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt
max
(from 1826 to 1578 mm Hg/s;
P
<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt
max
were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt
max
(from 1313 to 1337 mm Hg/s;
P
=NS). The blunted pacing-induced rise in LV dP/dt
max
in these patients was unaltered by L-NMMA.

Conclusion

Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.
Pl
A2
Polymorphism of β
3
Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury
Authors: Undas Anetta , Brummel Kathleen , Musial Jacek , Mann Kenneth G. , Szczeklik Andrew
Published: September 2007

Background

Mechanisms by which the Pl
A2
(Leu33Pro) polymorphism of β
3
integrins could lead to an increased risk for coronary events are unclear. This study was designed to examine the effect of this polymorphism on blood coagulation.

Methods and Results

In normal subjects (12 with Pl
A1A1
, 9 with Pl
A1A2
, and 3 with Pl
A2A2
), we evaluated the activation of prothrombin, factor V, and factor XIII and fibrinogen removal by quantitative immunoblotting; thrombin-antithrombin III complex generation using ELISA; and levels of fibrinopeptide A and B by high-performance liquid chromatography in blood collected every 30 seconds at sites of standardized microvascular injury before and after 7 days of aspirin ingestion (75 mg/d). Compared with the Pl
A1A1
subjects, the Pl
A2
carriers exhibited higher maximum rates of thrombin B-chain generation (by 31.6%;
P
=0.005), thrombin-antithrombin III complex generation (by 30.7%;
P
=0.003), fibrinogen consumption (by 31.3%;
P
=0.002), prothrombin consumption (by 26.1%;
P
=0.011), and activation of factor V (by 14.1%;
P
=0.033) and factor XIII (by 27.0%;
P
=0.012). In the Pl
A1A1
homozygotes, aspirin ingestion resulted in reductions in the velocity of thrombin B-chain formation (by 32.1%;
P
=0.007), prothrombin consumption (by 30.4%;
P
=0.018), factor Va generation (by 28.9%;
P
=0.014), fibrinogen removal (by 41.2%;
P
=0.001), and factor XIII activation (by 22.6%;
P
=0.026). In the Pl
A2
carriers, aspirin did not alter the velocity of all these processes. After aspirin ingestion, fibrinopeptide A and B concentrations in the last 30-second interval were significantly reduced, but only in the Pl
A1A1
subjects.

Conclusions

The presence of the Pl
A2
allele is associated with enhanced thrombin formation and an impaired antithrombotic action of aspirin, which might favor coronary thrombosis in the Pl
A2
carriers.
New Approaches to Antiarrhythmic Therapy, Part II
Authors:   Members of the Sicilian Gambit
Published: September 2007

Cardiac arrhythmias complicate many diseases affecting the heart and circulation, and they incorporate a multiplicity of underlying mechanisms. The evolution of scientific knowledge has made the complex changes produced by cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design in mechanism-specific and disease-specific fashions facilitates the targeting of therapy using the methods of molecular, structural, and translational biology. Additional approaches, using similar drug design strategies but based on gene therapy and transcriptional and translational modification, are on the horizon. Hence, there is reason to be optimistic regarding the design, testing, and clinical availability of novel antiarrhythmic therapies.
Sequential Modulation of Cardiac Autonomic Control Induced by Cardiopulmonary and Arterial Baroreflex Mechanisms
Authors: Furlan Raffaello , Jacob Giris , Palazzolo Laura , Rimoldi Alexandra , Diedrich Andre , Harris Paul A. , Porta Alberto , Malliani Alberto , Mosqueda-Garcia Rogelio , Robertson David
Published: September 2007

Background
—

Nonhypotensive lower body negative pressure (LBNP) induces a reflex increase in forearm vascular resistance and muscle sympathetic neural discharge without affecting mean heart rate. We tested the hypothesis that a reflex change of the autonomic modulation of heartbeat might arise during low intensity LBNP without changes of mean heart rate.

Methods and Results
—

Ten healthy volunteers underwent plasma catecholamine evaluation and a continuous recording of ECG, finger blood pressure, respiratory activity, and central venous pressure (CVP) during increasing levels of LBNP up to −40 mm Hg. Spectrum and cross-spectrum analyses assessed the changes in the spontaneous variability of R-R interval, respiration, systolic arterial pressure (SAP), and CVP and in the gain (α
LF
) of arterial baroreflex control of heart rate. Baroreceptor sensitivity was also evaluated by the SAP/R-R spontaneous sequences technique. LBNP began decreasing significantly: CVP at −10, R-R interval at −20, SAP at −40, and the indexes α
LF
and baroreceptor sensitivity at −30 and −20 mm Hg, compared with baseline conditions. Plasma norepinephrine increased significantly at −20 mm Hg. The normalized low-frequency component of R-R variability (LF
R-R
) progressively increased and was significantly higher than in the control condition at −15 mm Hg.

Conclusions
—

Nonhypotensive LBNP elicits a reflex increase of cardiac sympathetic modulation, as evaluated by LF
R-R
, which precedes the changes in the hemodynamics and in the indexes of arterial baroreflex control.
Comparison of Use of Medications After Acute Myocardial Infarction in the Veterans Health Administration and Medicare
Authors: Petersen Laura A. , Normand Sharon-Lise T. , Leape Lucian L. , McNeil Barbara J.
Published: September 2007

Background
—

There is concern that care provided in the Veterans Health Administration (VA) may be of poorer quality than non-VA health care. We compared use of medications after acute myocardial infarction in the VA with that in non-VA healthcare settings under fee-for-service (FFS) Medicare financing.

Methods and Results
—

We used clinical data from 2486 VA and 29 249 FFS men >65 years old discharged with a confirmed diagnosis of acute myocardial infarction from 81 VA hospitals and 1530 non-VA hospitals. We reported odds ratios (ORs) for use of thrombolytics, β-blockers, ACE inhibitors, or aspirin among ideal candidates adjusted for age, sample design (hospital academic affiliation, availability of cardiac procedures, and volume), and within-hospital clustering. Ideal VA candidates were more likely to undergo thrombolytic therapy at arrival (OR [VA relative to Medicare] 1.40 [1.05, 1.74]) or to receive ACE inhibitors (OR 1.67 [1.12, 2.45]) or aspirin (OR 2.32 [1.81, 3.01]) at discharge and equally likely to receive β-blockers (OR 1.09 [1.03, 1.40]) at discharge.

Conclusions
—

Ideal candidates in VA were at least as likely as those in FFS to receive medical therapies of known benefit for acute myocardial infarction.
Mitochondrial Coupling Factor 6 Is Present on the Surface of Human Vascular Endothelial Cells and Is Released by Shear Stress
Authors: Osanai Tomohiro , Okada Satoko , Sirato Kenichi , Nakano Takao , Saitoh Masayuki , Magota Koji , Okumura Ken
Published: September 2007

Background
—

We showed that mitochondrial coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, is present in the systemic circulation as a pressor substance in rats. We investigated the possibility of vascular endothelial cells as a source of circulating CF6.

Methods and Results
—

We used 2 cultured endothelial cell lines, human umbilical vein endothelial cells (HUVECs) and ECV 304 cells (transformed HUVECs), for this study. Immunofluorescence microscopy of both ECV 304 and HUVECs confirmed the surface-associated immunoreactivity of anti-CF6 antibody on the plasma membrane. The concentration of CF6 in the medium increased gradually with time in both ECV 304 and HUVECs in static conditions. Exposure of ECV 304 and HUVECs to a fluid shear stress enhanced the release of CF6: In ECV 304, the concentration of CF6 in the medium (ng · well
−1
· 6 hours
−1
) was 2.1±0.8 at baseline, 4.3±0.8 after shear at 15 dynes/cm
2
, and 57.7±8.4 after shear at 25 dynes/cm
2
. CF6 contents in the cell homogenate and mitochondria were both significantly increased after exposure of ECV 304 to 6-hour shear at 15 dynes/cm
2
, whereas they were unchanged after shear stress at 25 dynes/cm
2
. The ratio of CF6 to GAPDH mRNA was enhanced significantly, by 1.8±0.2-fold, after 6-hour shear stress at 25 dynes/cm
2
. Flow cytometry analysis revealed that the surface-associated CF6 was significantly increased in a 3-hour static condition after the previous exposure of the cells to shear stress for 3 hours.

Conclusions
—

Vascular endothelial cells are a source of CF6, and shear stress regulates the release of the surface-associated CF6.