bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Heart Rate Variability With Occupational and Environmental Exposure to Particulate Air Pollution
Authors: Magari Shannon R. , Hauser Russ , Schwartz Joel , Williams Paige L. , Smith Thomas J. , Christiani David C.
Published: September 2007

Background

Airborne particulate matter has been linked to excess morbidity and mortality. Recent attention has focused on the effects of particulate exposure on cardiac autonomic control. Inhaled particulates may affect the autonomic nervous system either directly, by eliciting a sympathetic stress response, or indirectly, through inflammatory cytokines produced in the lungs and released into the circulation.

Methods and Results

This longitudinal study examined the association of particulates ≤2.5 μm in diameter (PM
2.5
) with heart rate variability (HRV) in an occupational cohort (N=40). Continuous monitoring of exposure and HR was performed during and away from work. PM
2.5
levels were higher than ambient levels typically reported in Boston, 0.167±3.205 mg/m
3
(geometric mean±geometric SD). We found a 2.66% decrease (95% CI, −3.75% to −1.58%) in the 5-minute SD of normal RR intervals (SDNN) for every 1 mg/m
3
increase in the 4-hour moving PM
2.5
average and a 1.02% increase (95% CI, 0.59% to 1.46%) in HR after adjusting for potential confounding factors. The decrease in SDNN became larger as the averaging interval increased.

Conclusions

Workers experienced altered cardiac autonomic control after exposure to occupational and environmental PM
2.5
. There appears to be either a long-acting (several hours) and a short-acting (several minutes) component to the mechanism of action that may be related to the production of cytokines and the sympathetic stress response, respectively, or a cumulative effect that begins shortly after exposure begins. The clinical significance of these effects in a healthy working population is unclear.
Subvalvular Gradients in Patients With Valvular Aortic Stenosis
Authors: Laskey Warren K. , Kussmaul William G.
Published: September 2007

Background

Although subvalvular gradients in patients with aortic stenosis have been described, their behavior and response to exercise have not been well characterized.

Methods and Results

Left ventricular and aortic pressures and linear flow velocity were measured with a catheter-tip manometer at rest and during supine exercise in 27 patients with valvular aortic stenosis. A subvalvular gradient was measured in each patient that represented, on average, 48% of the total resting transvalvular gradient. With exercise, both total (rest: 80±26 mm Hg; exercise: 90±25 mm Hg) and subvalvular gradients (rest: 37±13 mm Hg; exercise: 60±22 mm Hg) increased significantly. There was a significant inverse relationship between change in exercise cardiac output and total and subvalvular gradients. However, only the exercise subvalvular gradient predicted cardiac output response.

Conclusions

Subvalvular pressure gradients are universally present in patients with severe aortic stenosis and comprise approximately half of the total transvalvular gradient. The extent of exercise cardiac output increase is inversely related to the subvalvular gradient magnitude.
Staphylococcus aureus
Bacteremia in Patients With Permanent Pacemakers or Implantable Cardioverter-Defibrillators
Authors: Chamis Anna Lisa , Peterson Gail E. , Cabell Christopher H. , Corey G. Ralph , Sorrentino Robert A. , Greenfield Ruth Ann , Ryan Thomas , Reller L. Barth , Fowler Vance G.
Published: September 2007

Background

Although cardiac device infections (CDIs) are a devastating complication of permanent pacemakers or implantable cardioverter-defibrillators, the incidence of CDI in patients with bacteremia is not well defined. The objective of this study was to determine the incidence of CDI among patients with permanent pacemakers or implantable cardioverter-defibrillators who develop
Staphylococcus aureus
bacteremia (SAB).

Methods and Results

A cohort of all adult patients with SAB and permanent pacemakers or implantable cardioverter-defibrillators over a 6-year period was evaluated prospectively. The overall incidence of confirmed CDI was 15 of 33 (45.4%). Confirmed CDI occurred in 9 of the 12 patients (75%) with early SAB (<1 year after device placement). Fifteen of 21 patients (71.5%) with late SAB (≥1 year after device placement) had either confirmed (6 of 21, 28.5%) or possible (9 of 21, 43%) CDI. In 60% of the patients (9 of 15) with confirmed CDI, no local signs or symptoms suggesting generator pocket infection were noted.

Conclusions

The incidence of CDI among patients with SAB and cardiac devices is high. Neither physical examination nor echocardiography can exclude the possibility of CDI. In patients with early SAB, the device is usually involved, and ≈40% of these patients have obvious clinical signs of cardiac device involvement. Conversely, in patients with late SAB, the cardiac device is rarely the initial source of bacteremia, and there is a paucity of local signs of device involvement. The cardiac device is involved, however, in ≥28% of these patients.
Microvascular Dysfunction in Chronic Total Coronary Occlusions
Authors: Werner Gerald S. , Ferrari Markus , Richartz Barbara M. , Gastmann Oliver , Figulla Hans R.
Published: September 2007

Background

—

Microvascular dysfunction is defined as reduced coronary flow reserve in the absence of an epicardial stenosis. This study determined its prevalence and relation to regional myocardial function in chronic total coronary occlusions (TCO).

Methods and Results

—

After recanalization and stenting of a TCO (duration, >4 weeks) in 42 patients, coronary flow velocity reserve (CFVR) was measured by intracoronary Doppler. In a subset of 27 patients, intracoronary pressure was recorded to obtain the fractional flow reserve (FFR). In 21 patients, the CFVR was reassessed after 24 hours. CFVR was <2.0 in 55% of all patients. In the subgroup with simultaneous pressure recordings, 52% of patients showed a CFVR<2.0 and a FFR≥0.75, indicating microvascular dysfunction. Both reduced CFVR and reduced FFR occurred in only 2 patients (7.7%). CFVR and FFR were not correlated (
r
=0.03). A low CFVR was associated with a higher baseline average peak velocity (35.6±16.6 versus 22.4±11.5 cm/s;
P
=0.006). Doppler parameters did not change within 24 hours. Regional dysfunction had no influence on CFVR. Patients with diabetes and/or hypertension had a lower CFVR than those without this comorbidity (1.86±0.69 versus 2.36±0.45;
P
<0.05).

Conclusions

—

Microvascular dysfunction was observed in 55% of TCOs, independent of the impairment of regional myocardial function. Dysfunction was observed more often in patients with diabetes and hypertension. Neither CFVR or FFR alone is appropriate for assessing angioplasty results in patients with a TCO; CFVR should be combined with FFR to differentiate microvascular dysfunction from residual coronary stenosis or diffuse disease.
Online Myocardial Viability Assessment in the Catheterization Laboratory via NOGA Electroanatomic Mapping
Authors: Gyöngyösi Mariann , Sochor Heinz , Khorsand Aliashgar , Gepstein Lior , Glogar Dietmar
Published: September 2007

Background

The aim of this prospective study was to investigate the concordance between quantitative resting
201
Tl uptake as an established myocardial viability index and the electrical activity of the heart, determined by NOGA nonfluoroscopic electroanatomic mapping.

Methods and Results

The myocardial resting and late resting thallium uptakes of 384 myocardial segments from 32 patients (27 males aged 65±8 years) with previous myocardial infarction and chronic stable angina were compared with unipolar voltage potentials and local shortening of the left ventricle as assessed by electroanatomic mapping. The quantitative thallium uptake data were analyzed by polar map analysis by division into 12 comparable myocardial segments, as represented in electroanatomic mapping images. Unipolar voltage potentials exhibited a significant logarithmic correlation with both resting and late resting thallium uptake (attenuation corrected:
r
=0.660 and
r
=0.744; non-attenuation corrected:
r
=0.623 and
r
=0.721). Receiver operator characteristic analyses revealed unipolar voltage cutoff points of 12.0 mV (predictive accuracy 0.853,
P
< 0.001; sensitivity/specificity 81%) for normal myocardium and 6.4 mV (predictive accuracy 0.901,
P
< 0.001; sensitivity/specificity 82%) for nonviable myocardium assessed by attenuation-corrected
201
Tl late resting images and of 12.7 mV (predictive accuracy 0.822,
P
<0.001; sensitivity/specificity 75%) and 6.5 mV (predictive accuracy 0.808,
P
<0.001; sensitivity/specificity 73%) for non–attenuation-corrected late resting
201
Tl images.

Conclusions

These results indicate that the unipolar voltage potentials obtained by electroanatomic mapping correlate well with standard quantitative late resting
201
Tl imaging for the evaluation of myocardial viability; thus, NOGA endocardial mapping provides useful “online” data at the time of catheterization, especially when information from other methods for viability assessment is unavailable.
Relation Between Gd-DTPA Contrast Enhancement and Regional Inotropic Response in the Periphery and Center of Myocardial Infarction
Authors: Gerber Bernhard L. , Rochitte Carlos E. , Bluemke David A. , Melin Jacques A. , Crosille Pierre , Becker Lewis C. , Lima João A.C.
Published: September 2007

Background

Gd-DTPA contrast-enhanced (CE) MRI identifies patterns of early hypoenhancement and delayed hyperenhancement in acute myocardial infarction, but their clinical significance for the prediction of myocardial viability remains controversial. Therefore, we closely examined the relationship between these CE patterns and regional inotropic response to low-dose dobutamine infusion at a regional level.

Methods and Results

Thirteen dogs underwent CE and tagged MRI at rest and during 5 μg · kg
−1
· min
−1
dobutamine 48 hours after MI. CE patterns and 3D regional strains were measured in 96 segments per animal. Segments were categorized as being normofunctional (n=828) if resting circumferential shortening was within the range of remote myocardium, or dysfunctional (n=420) if not. Inotropic response in resting dysfunctional segments was assessed according to CE patterns. Significant improvement of radial thickening (from +12±1% [mean±SEM] to +22±2%,
P
<0.05) and circumferential shortening (from +1±1% to −5±1%,
P
<0.05) strains occurred in dysfunctional myocardium with normal CE pattern but not in myocardium with early hypoenhancement. Delayed hyperenhanced myocardium displayed a more complex behavior. Circumferential stretching improved in the peripheral regions (from +4±1% to −2±2%,
P
<0.05), where the infarct was nontransmural (38±3% transmurality), but not in centrally hyperenhanced regions (from +4±1% to +1±1%
P
=NS), where the infarct was 66±3% transmural.

Conclusions

Inotropic reserve was confined to dysfunctional myocardium with normal contrast enhancement but not to myocardium with early hypoenhancement. Inotropic response in delayed hyperenhanced myocardium is influenced by transmurality of necrosis. These observations support the use of CE MRI for the clinical detection of myocardial viability.
Annulus Paradoxus
Authors: Ha Jong-Won , Oh Jae K. , Ling Lieng H. , Nishimura Rick A. , Seward James B. , Tajik A. Jamil
Published: September 2007

Background

The early diastolic velocity of the mitral annulus (E′) is reduced in patients with diastolic dysfunction and increased filling pressures. Because transmitral inflow early velocity (E) increases progressively with higher filling pressures, E/E′ has been shown to have a strong positive relationship with pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure. However, previous studies have primarily involved patients without a pericardial abnormality. In constrictive pericarditis (CP), E′ is not reduced, despite increased filling pressures. This study evaluated the relationship between E/E′ and PCWP in patients with CP.

Methods and Results

We studied 10 patients (8 men; mean age, 64±7 years) with surgically confirmed CP. Doppler echocardiography was performed to measure early and late diastolic transmitral flow velocities. Tissue Doppler echocardiography was performed to measure E′. PCWP was measured with right heart catheterization. All patients were in sinus rhythm. Mean E and E′ were 91±15 cm/s and 11±4 cm/s, respectively. Mean PCWP was 25±6 mm Hg. E′ was positively correlated with PCWP (
r
=0.69,
P
=0.027). There was a significant inverse correlation between E/E′ and PCWP (
r
=−0.74,
P
=0.014). Despite high left ventricular filling pressures, E/E′ (mean, 9±4) was <15 in all but 1 patient.

Conclusions

Paradoxical to the positive correlation between E/E′ and PCWP in patients with myocardial disease, an inverse relationship was found in patients with CP.
Previous Cytomegalovirus Infection and Restenosis After Coronary Stent Placement
Authors: Neumann Franz-Josef , Kastrati Adnan , Miethke Thomas , Mehilli Julinda , Pogatsa-Murray Gisela , Koch Werner , Seyfarth Melchior , Schömig Albert
Published: September 2007

Background

—

Reactivated cytomegalovirus may promote neointima formation after percutaneous coronary interventions by facilitating cell cycle progression through inhibition of the eukariotic tumor suppressor protein p53. This prospective study sought to investigate the effect of previous cytomegalovirus infection on restenosis after coronary stenting.

Methods and Results

—

In 551 consecutive patients with successful stent placement, we determined cytomegalovirus IgG titers. Primary and secondary end points were the rate of angiographic restenosis at 6 months and the rate of target vessel reintervention at 1 year, respectively. Three hundred forty patients (62%) had a positive cytomegalovirus IgG titer. We obtained angiographic follow-up in 82% of all patients. Angiographic restenosis rate was 28.7% in patients with positive cytomegalovirus titers and 34.6% in patients with negative titers (
P
=0.18). Between the groups with and without positive cytomegalovirus titers, there were no significant differences in late lumen loss (1.16±0.90 mm and 1.23±0.86 mm, respectively,
P
=0.44). Target vessel reintervention was performed in 16.8% of the patients with positive cytomegalovirus titers and in 17.5% of those without (
P
=0.82). Even after correction for potential confounding variables by multivariate analysis, positive cytomegalovirus titers did not manifest as a predictor of angiographic restenosis (adjusted odds ratio [95% confidence interval], 0.78 [0.52 to 1.19]).

Conclusions

—

Previous cytomegalovirus infection does not carry an increased risk of restenosis after stenting.
Effects of Calcium, Inorganic Phosphate, and pH on Isometric Force in Single Skinned Cardiomyocytes From Donor and Failing Human Hearts
Authors: van der Velden J. , Klein L.J. , Zaremba R. , Boontje N.M. , Huybregts M.A.J.M. , Stooker W. , Eijsman L. , de Jong J.W. , Visser C.A. , Visser F.C. , Stienen G.J.M.
Published: September 2007

Background
—

During ischemia, the intracellular calcium and inorganic phosphate (P
i
) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the myocardial response to Ca
2+
, P
i
, and pH.

Methods and Results
—

Isometric force was studied in mechanically isolated Triton-skinned single myocytes from left ventricular myocardium. Force declined with added P
i
to 0.33±0.02 of the control force (pH 7.1, 0 mmol/L P
i
) at 30 mmol/L P
i
and increased with pH from 0.64±0.03 at pH 6.2 to 1.27±0.02 at pH 7.4. Force dependency on P
i
and pH did not differ between donor and failing hearts. Incubation of myocytes in a P
i
-containing activating solution caused a potentiation of force, which was larger at submaximal than at maximal [Ca
2+
]. Ca
2+
sensitivity of force was similar in donor hearts and hearts with moderate cardiac disease, but in end-stage failing myocardium it was significantly increased. The degree of myosin light chain 2 phosphorylation was significantly decreased in end-stage failing compared with donor myocardium, resulting in an inverse correlation between Ca
2+
responsiveness of force and myosin light chain 2 phosphorylation.

Conclusions
—

Our results indicate that contractile protein alterations in human end-stage heart failure alter Ca
2+
responsiveness of force but do not affect the force-generating capacity of the cross-bridges or its P
i
and pH dependence. In end-stage failing myocardium, the reduction in force by changes in pH and [P
i
] at submaximal [Ca
2+
] may even be less than in donor hearts because of the increased Ca
2+
responsiveness.
Protection Against Autoimmune Myocarditis by Gene Transfer of Interleukin-10 by Electroporation
Authors: Watanabe Kenichi , Nakazawa Mikio , Fuse Koichi , Hanawa Haruo , Kodama Makoto , Aizawa Yoshifusa , Ohnuki Toshio , Gejyo Fumitake , Maruyama Hiroki , Miyazaki Jun-ichi
Published: September 2007

Background

—

Although immunosuppressive therapy for myocarditis has attracted a great deal of attention, its effectiveness is controversial. Interleukin (IL)-10 has a variety of immunomodulatory properties. Among the nonviral techniques for gene transfer in vivo, the direct injection of plasmid DNA into muscle is simple, inexpensive, and safe.

Methods and Results

—

We examined the applicability of murine IL-10 (mIL-10) gene transfer to the treatment of rats with experimental autoimmune myocarditis. Nine-week-old Lewis rats were inoculated with pig myosin (day 0). A plasmid vector expressing mIL-10 cDNA (800 μg per rat) was transferred into the tibialis anterior muscles by electroporation 3 times (5 days before immunization and at days 4 and 13); control rats received empty plasmid. Electroporation increased the serum mIL-10 levels to >250 pg/mL. The 21-day survival rate in rats treated with mIL-10 cDNA was higher (15 of 15; 100%) than that of the control group (9 of 15; 60%). Furthermore, mIL-10 treatment significantly attenuated myocardial lesions and improved hemodynamic parameters.

Conclusions

—

These findings showed that gene transfer into muscle by electroporation in vivo is an effective means of delivery of IL-10 for the treatment of autoimmune myocarditis.
Endothelium-Mediated Relaxation of Porcine Collateral-Dependent Arterioles Is Improved by Exercise Training
Authors: Griffin Kawanza L. , Woodman Christopher R. , Price Elmer M. , Laughlin M. Harold , Parker Janet L.
Published: September 2007

Background
—

Endothelium-dependent modulation of coronary tone is impaired in the collateral-dependent coronary microcirculation. We used a porcine model of chronic coronary occlusion and collateral development to evaluate the hypothesis that exercise training enhances endothelium-mediated relaxation and increases endothelial nitric oxide synthase (ecNOS) mRNA levels of collateral-dependent microvasculature.

Methods and Results
—

Adult female miniature swine were subjected to chronic, progressive ameroid occlusion of the proximal left circumflex coronary artery (LCx); after 2 months, animals were randomly exposed to 16-week exercise-training (EX group; treadmill running) or sedentary (SED group; cage confinement) protocols. After completion of EX or SED programs, coronary arterioles (≈100 μm in diameter) were isolated from collateral-dependent LCx (distal to occlusion) and nonoccluded left anterior descending coronary artery (LAD) regions of each heart. Arterioles were studied by in vitro videomicroscopy or frozen for ecNOS mRNA analysis (RT-PCR techniques). Relaxation to the endothelium-dependent vasodilator bradykinin was decreased (
P
<0.05) in arterioles isolated from collateral-dependent LCx versus nonoccluded LAD regions of SED animals. Bradykinin-mediated relaxation, however, was not different in LCx versus LAD arterioles isolated from EX animals. Nitroprusside-induced relaxation was unaffected by either chronic occlusion or exercise. Importantly, ecNOS mRNA expression was significantly decreased in arterioles isolated from LCx versus LAD regions of SED animals. After training, ecNOS mRNA expression was not different between LAD and LCx arterioles.

Conclusions
—

These data indicate that exercise training enhances bradykinin-mediated relaxation of collateral-dependent LCx arterioles isolated after chronic coronary occlusion, most likely because of effects on ecNOS mRNA expression and increased production of NO.
17β-Estradiol Attenuates the Development of Pressure-Overload Hypertrophy
Authors: van Eickels Martin , Grohé Christian , Cleutjens Jack P.M. , Janssen Ben J. , Wellens Hein J.J. , Doevendans Pieter A.
Published: September 2007

Background
—

Cardiac hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in men and in women. Epidemiological studies indicate that estrogen replacement therapy is cardioprotective; the mechanisms involved in this process, however, are poorly understood. We therefore studied the effect of 17β-estradiol (E
2
) on the development of pressure-overload hypertrophy.

Methods and Results
—

Ovariectomized mice receiving E
2
or placebo underwent transverse aortic constriction (TAC) or sham operation. TAC led to a significant increase in ventricular mass compared with sham operation. E
2
treatment reduced cardiac hypertrophy by 31% and 26% compared with placebo 4 and 8 weeks after TAC, whereas it had no effect on the degree of pressure overload, as determined by hemodynamic measurements. Furthermore, E
2
blocked the increased phosphorylation of p38-mitogen-activated protein kinase (MAPK) observed in the placebo-treated animals with TAC. No differences were observed in the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK) 1/2 between the groups. E
2
had no effect on the expression of angiotensin-converting enzyme (ACE) or the angiotensin II type 1 receptor. Ventricular atrial natriuretic peptide (ANP) expression was detected only in the animals with TAC. Compared with placebo, E
2
treatment led to an increased expression of ANP in animals with pressure overload.

Conclusions
—

Here, we show that E
2
attenuates the hypertrophic response to pressure overload in mice. This observation demonstrates that hormone replacement therapy with E
2
has direct effects on the heart and may be beneficial in the treatment of postmenopausal women to reduce cardiac hypertrophy.
Mechanism of Syncope in Patients With Isolated Syncope and in Patients With Tilt-Positive Syncope
Authors: Moya Angel , Brignole Michele , Menozzi Carlo , Garcia-Civera Roberto , Tognarini Stefano , Mont Luis , Botto Gianluca , Giada Franco , Cornacchia Daniele ,   on behalf of the International Study on Syncope of Uncertain Etiology (ISSUE) Investigators
Published: September 2007

Background

Because of its episodic behavior, the correlation of spontaneous syncope with an abnormal finding can be considered a reference standard.

Methods and Results

We inserted an implantable loop recorder in 111 patients with syncope, absence of significant structural heart disease, and a normal ECG; tilt-testing was negative in 82 (isolated syncope) and positive in 29 (tilt-positive). The patients had had ≥3 episodes of syncope in the previous 2 years and were followed up for 3 to 15 months. Results were similar in the isolated syncope group and the tilt-positive group: syncope recurred in 28 (34%) and 10 patients (34%), respectively, and electrocardiographic correlation was found in 24 (23%) and 8 (28%) patients, respectively. The most frequent finding, which was recorded in 46% and 62% of patients, respectively, was one or more prolonged asystolic pauses, mainly due to sinus arrest, preceded for a few minutes by progressive bradycardia or progressive tachycardia-bradycardia. Bradycardia without pauses was observed in 8% and 12% of cases, respectively. The remaining patients had normal sinus rhythm or sinus tachycardia, except for one, who had ectopic atrial tachycardia. In the tilt-positive group, an asystolic syncope was also recorded when the type of response to tilt-testing was vasodepressor or mixed. Presyncopal episodes were never characterized by asystolic pauses; normal sinus rhythm was the most frequent finding.

Conclusions

Homogeneous findings were observed during syncope. In most patients, the likely cause was neurally-mediated, and the most frequent mechanism was a bradycardic reflex. In the other cases, a normal sinus rhythm was frequently recorded. Presyncope was not an accurate surrogate for syncope in establishing a diagnosis.
Electrophysiological Alterations After Mechanical Circulatory Support in Patients With Advanced Cardiac Failure
Authors: Harding John D. , Piacentino Valentino , Gaughan John P. , Houser Steven R. , Margulies Kenneth B.
Published: September 2007

Background

Recognizing that mechanical circulatory support with a left ventricular assist device (LVAD) induces changes in myocardial structure and contractile function, we examined whether there are changes in ventricular conduction and/or repolarization among failing human hearts after LVAD implantation.

Methods and Results

We examined 12-lead electrocardiograms before surgery, immediately after LVAD placement, and at a delayed (>1 week) postoperative time point in 23 patients who were receiving LVAD support for refractory heart failure. The immediate effects of hemodynamic unloading via LVAD placement included a decrease in QRS duration from 117±6 to 103±6 ms (
P
<0.01), an increase in absolute QT duration from 359±6 to 378±8 ms (
P
<0.05), and an increase in the heart rate-corrected QT interval (QTc) from 379±10 to 504±11 ms (
P
<0.01). None of these immediate changes were observed among 22 patients undergoing routine coronary artery bypass grafting. With sustained cardiac unloading via LVAD support, there was a marked decrease in the QTc from 504±11 to 445±9 ms (
P
<0.001). Studies in isolated cardiac myocytes, obtained at the time of transplantation, confirmed that delayed decreases in heart rate-adjusted QTc were the result of decreases in action potential duration after LVAD support.

Conclusions

Acute electrocardiogram responses to LVAD placement demonstrate the dependence of QRS and QT duration on load in the failing human heart. Delayed decreases in QTc and action potential duration reflect reversal of electrophysiologic remodeling in the failing heart. Shortening of the action potential duration likely contributes to the improved cellular contractile performance observed after sustained LVAD support.
Demonstration of the Exact Anatomic Tachycardia Circuit in the Fast-Slow Form of Atrioventricular Nodal Reentrant Tachycardia
Authors: Yamabe Hiroshige , Shimasaki Yukio , Honda Osamu , Kimura Yoshihiro , Hokamura Youichi
Published: September 2007

Background

The tachycardia circuit in the fast-slow form of atrioventricular nodal reentrant tachycardia (FS-AVNRT) has not been convincingly defined.

Methods and Results

To define the tachycardia circuit, single extrastimuli were delivered during FS-AVNRT to 9 intra-atrial sites in 12 patients: the His bundle (HB) site; the superior portion of the HB site (S-HB); 3 arbitrarily divided sites on the AV junction extending from the HB site to the coronary sinus ostium (CSOS) (sites S, M, and I); the superior, posterior, and posteroinferior portions of the CSOS (S-CSOS, P-CSOS, and PI-CSOS, respectively); and the CSOS. The inferior portion of coronary sinus ostium (I-CSOS), at which the earliest retrograde activation was observed, was excluded. At each site, the longest coupling interval of the single extrastimulus that reset the tachycardia and the subsequent return cycle was measured. The mean tachycardia cycle length was 370±55 ms. The longest coupling intervals at sites S-HB, HB, S, M, I, CSOS, S-CSOS, P-CSOS, and PI-CSOS were 328±53, 360±55, 358±55, 358±54, 360±55, 338±56, 323±54, 331±56, and 321±58 ms, respectively, and the subsequent return cycles were 408±58, 371±55, 370±55, 372±56, 370±55, 396±56, 411±60, 405±58, and 412±59 ms, respectively. The longest coupling intervals at sites HB, S, M, and I were longer than those at S-HB, CSOS, S-CSOS, P-CSOS, and PI-CSOS (
P
<0.0001). The return cycles at sites HB, S, M, and I did not differ from the tachycardia cycle length, whereas those at CSOS, S-CSOS, P-CSOS, and PI-CSOS were longer than the tachycardia cycle length (
P
<0.0001).

Conclusions

The perinodal atrium extending from the HB site to the I-CSOS is an integral limb of the reentry circuit in FS-AVNRT.
p160 Bcr Mediates Platelet-Derived Growth Factor Activation of Extracellular Signal-Regulated Kinase in Vascular Smooth Muscle Cells
Authors: Che Wenyi , Abe Jun-ichi , Yoshizumi Masanori , Huang Qunhua , Glassman Michael , Ohta Shinsuke , Melaragno Matthew G. , Poppa Veronica , Yan Chen , Lerner-Marmarosh Nicole , Zhang Changxi , Wu Yun , Arlinghaus Ralph , Berk Bradford C.
Published: September 2007

Background
—

The human Bcr gene was originally identified by its presence in the chimeric Bcr/Abl oncogene, which is causative for chronic myeloblastic leukemia. Because Bcr encodes a serine/threonine protein kinase, we studied its kinase activity and determined the role of Bcr in the PDGF signaling pathway to ERK1/2 activation and DNA synthesis in rat aortic smooth muscle cells (RASMCs).

Methods and Results
—

In RASMCs, platelet-derived growth factor-BB (PDGF) stimulated Bcr kinase activity, with a maximum at 1 minute. Because phosphatidylinositol 3′-kinase (PI3-K) is essential for Bcr/Abl leukemogenesis, we evaluated the role of mouse PDGF-β-receptor binding sites for PI3-K (Y708, Y719) and for phospholipase C-γ (Y977, Y989) in PDGF-mediated Bcr kinase activation. The mutant PDGF receptor Y708F/Y719F but not Y977F/Y989F showed significantly reduced Bcr kinase activity. To determine the role of Bcr in PDGF-mediated signal transduction events leading to ERK1/2 and its downstream Elk1 transcription activation, wild-type (WT) and kinase-negative (KN) Bcr were transiently expressed in RASMCs. Bcr WT enhanced, whereas Bcr KN inhibited, PDGF-stimulated ERK1/2 and Elk1 transcriptional activity. Overexpression of Bcr also enhanced PDGF-induced Ras/Raf-1 activity and DNA synthesis, but this regulation is independent of the kinase activity of Bcr. Finally, we found that Bcr expression was increased in the neointimal layer after balloon injury of rat carotid artery.

Conclusions
—

These results demonstrated the importance of Bcr in PDGF-mediated events, such as activation of Ras, Raf-1, ERK1/2, and Elk1, and stimulation of DNA synthesis.
Dissociation of Glycoprotein IIb/IIIa Antagonists From Platelets Does Not Result in Fibrinogen Binding or Platelet Aggregation
Authors: Frelinger Andrew L. , Furman Mark I. , Krueger Lori A. , Barnard Marc R. , Michelson Alan D.
Published: September 2007

Background
—

The primary mechanism of action of glycoprotein (GP) IIb/IIIa antagonists is inhibition of the final common pathway of platelet aggregation: fibrinogen binding to the GP IIb/IIIa complex. However, it has been reported that induction of fibrinogen binding and platelet aggregation is an intrinsic prothrombotic property of low-dose GP IIb/IIIa antagonists. These apparently paradoxical results have been extensively referenced in the cardiology literature.

Methods and Results
—

By platelet aggregation and flow cytometry, we demonstrate that (1) dissociation of GP IIb/IIIa antagonists (abciximab, tirofiban, eptifibatide, or xemilofiban) from platelets does not result in platelet aggregation; (2) tirofiban and eptifibatide can induce a fibrinogen-binding–competent conformation of the GP IIb/IIIa receptor, but stable fibrinogen binding does not occur without fixation; (3) the slow off-rate of abciximab exposes only a small proportion of unblocked GP IIb/IIIa receptors at any time, and these also fail to stably bind fibrinogen; and (4) the GP IIb/IIIa antagonist–induced fibrinogen binding in some previously reported experiments was probably the result of artifactual thrombin generation.

Conclusions
—

Under physiological conditions, GP IIb/IIIa antagonists currently in clinical use do not have an intrinsic activating property that results in platelet aggregation or stable fibrinogen binding to GP IIb/IIIa.
Alterations of Cardiac Structure in Patients With Isolated Office, Ambulatory, or Home Hypertension
Authors: Sega Roberto , Trocino Giuseppe , Lanzarotti Arturo , Carugo Stefano , Cesana Giancarlo , Schiavina Riccardo , Valagussa Franco , Bombelli Michele , Giannattasio Cristina , Zanchetti Alberto , Mancia Giuseppe
Published: September 2007

Background
—

The prevalence and clinical significance of isolated office (or white coat) hypertension is controversial, and population data are limited. We studied the prevalence of this condition and its association with echocardiographic left ventricular mass in the general population of the PAMELA (Pressione Arteriose Monitorate E Loro Associazioni) Study.

Methods and Results
—

The study involved a large, randomized sample (n=3200) representative of the Monza (Milan) population, 25 to 74 years of age. Participants in the study (64% of the sample) underwent measurements of office, home, 24-hour ambulatory blood pressure, and echocardiography. Isolated office hypertension was defined as systolic or diastolic values ≥140 mm Hg or ≥90 mm Hg, respectively. Home and ambulatory normotension were defined according to criteria previously established from the PAMELA Study, for example, <132/83 mm Hg (systolic/diastolic) for home and 125/79 mm Hg for 24-hour average blood pressure. Treated hypertensive subjects were excluded from analysis that was made on a total of 1637 subjects. Depending on normotension being established on systolic or diastolic blood pressure measured at home or over 24 hours, the prevalence of isolated office hypertension ranged from 9% to 12%. In these subjects, left ventricular mass index was greater (
P
<0.01) than in subjects with normotension both in and outside the office. This was the case also for prevalence of left ventricular hypertrophy. Left ventricular mass index and hypertrophy were similarly greater in subjects found to have normal office but elevated home or ambulatory blood pressure (≈10% of the population).

Conclusions
—

Isolated office hypertension has a noticeable prevalence in the population and is accompanied by structural cardiac alterations, suggesting that it is not an entirely harmless phenomenon. This is the case also for the opposite condition, that is, normal office but elevated home or ambulatory blood pressure, which implies that limiting blood pressure measurements to office values may not suffice in identification of subjects at risk.
Short-Term Local Delivery of an Inhibitor of Ras Farnesyltransferase Prevents Neointima Formation In Vivo After Porcine Coronary Balloon Angioplasty
Authors: Work Lorraine M. , McPhaden Allan R. , Pyne Nigel J. , Pyne Susan , Wadsworth Roger M. , Wainwright Cherry L.
Published: September 2007

Background

Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to the progression and development of a restenotic lesion, many signaling through a common pathway involving the small G protein p21
ras
. Our aim was to demonstrate in biochemical studies that farnesyl protein transferase inhibitor III (FPTIII) is an inhibitor of p21
ras
processing and that when it is given locally in vivo at the site of coronary balloon injury in a porcine model, it can inhibit neointima formation.

Methods and Results

FPTIII (1 to 25 μmol/L) concentration-dependently reduced p21
ras
levels in porcine coronary artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK activation and DNA synthesis in response to platelet-derived growth factor in these cells at a concentration of 25 μmol/L. Application of 25 μmol/L FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII-treated pigs had no deterioration in contraction or in endothelium-dependent relaxation.

Conclusions

The study demonstrates in the pig that short-term local delivery of inhibitors of p21
ras
-dependent mitogenic signal transduction prevents restenosis after balloon angioplasty.
c-Jun Decreases Voltage-Gated K
+
Channel Activity in Pulmonary Artery Smooth Muscle Cells
Authors: Yu Ying , Platoshyn Oleksandr , Zhang Jifeng , Krick Stefanie , Zhao Ying , Rubin Lewis J. , Rothman Abraham , Yuan Jason X.-J.
Published: September 2007

Background

Activity of voltage-gated K
+
(K
v
) channels controls membrane potential (E
m
) that regulates cytosolic free Ca
2+
concentration ([Ca
2+
]
cyt
) by regulating voltage-dependent Ca
2+
channel function. A rise in [Ca
2+
]
cyt
in pulmonary artery smooth muscle cells (PASMCs) triggers vasoconstriction and stimulates PASMC proliferation. Whether c-Jun, a transcription factor that stimulates cell proliferation, affects K
v
channel activity in PASMCs was investigated.

Methods and Results

Infection of primary cultured PASMCs with an adenoviral vector expressing
c-jun
increased the protein level of c-Jun and reduced K
v
currents (
I
K(V)
) compared with control cells (infected with an empty adenovirus). Using single-cell reverse transcription–polymerase chain reaction, we observed that the mRNA level of Kv1.5 and the current density of
I
K(V)
were both attenuated in
c-jun
–infected PASMCs compared with control cells and cells infected with antisense
c-jun
. Overexpression of c-Jun also upregulated protein expression of Kvβ
2
and accelerated
I
K(V)
inactivation. Furthermore, E
m
was more depolarized and [
3
H]thymidine incorporation was greater in PASMCs infected with
c-jun
than in control cells and cells infected with antisense
c-jun
.

Conclusions

These results suggest that c-Jun–mediated PASMC proliferation is associated with a decrease in
I
K(V)
. The resultant membrane depolarization increases [Ca
2+
]
cyt
and enhances PASMC growth.
Unstable Angina and Elevated C-Reactive Protein Levels Predict Enhanced Vasoreactivity of the Culprit Lesion
Authors: Tomai Fabrizio , Crea Filippo , Gaspardone Achille , Versaci Francesco , Ghini Anna S. , Chiariello Luigi , Gioffrè Pier A.
Published: September 2007

Background

Because plaque inflammation may modulate coronary vasomotion, the association between systemic levels of C-reactive protein (CRP) and coronary vasoreactivity was assessed in patients with stable or unstable angina.

Methods and Results

In 31 patients with stable angina and 23 patients with unstable angina undergoing coronary angiography, minimal luminal diameter (MLD) of the culprit lesion was measured by quantitative coronary angiography at baseline, during the cold pressor test (CPT), and after intracoronary administration of nitroglycerin (NTG) and expressed as percent change from baseline. MLD of patients with unstable angina exhibited a greater reduction during CPT and a greater increase after NTG than did patients with stable angina (−17±14% versus −5±12%,
P
=0.0013, and 34±25% versus 8±20%,
P
<0.001, respectively). According to preprocedural serum levels of CRP, 36 patients had normal (≤0.5 mg/dL) and 18 patients had elevated CRP levels. MLD of patients with elevated CRP levels exhibited a greater reduction during CPT and a greater increase after NTG than of patients with normal CRP levels (−15±12% versus −7±14%,
P
=0.037, and 31±23% versus 13±25%,
P
=0.011, respectively). Both unstable angina and elevated CRP levels resulted in independent predictors of enhanced vasoreactivity at the multivariate analysis.

Conclusions

This study confirms enhanced vasoreactivity of the culprit lesion in patients with unstable angina compared with those with stable angina. More importantly, it demonstrates that inflammatory mechanisms play a key role in modulating the reactivity of coronary atherosclerotic plaques and may partially account for the enhanced vasoreactivity of the unstable plaques.
Regulation of Endothelial Nitric Oxide Synthase Expression in the Vascular Wall and in Mononuclear Cells From Hypercholesterolemic Rabbits
Authors: Jiménez Ana , Arriero María M. , López-Blaya Almudena , González-Fernandez Fernando , García Rosa , Fortes José , Millás Inmaculada , Velasco Sandra , Sánchez de Miguel Lourdes , Rico Luis , Farré Jerónimo , Casado Santos , López-Farré Antonio
Published: September 2007

Background

We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3′-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction.

Methods and Results

Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg · kg body wt
−1
· d
−1
) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3′-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment.

Conclusions

These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.
Single Oral Dose of Geranylgeranylacetone Induces Heat-Shock Protein 72 and Renders Protection Against Ischemia/Reperfusion Injury in Rat Heart
Authors: Ooie Tatsuhiko , Takahashi Naohiko , Saikawa Tetsunori , Nawata Tomoko , Arikawa Masaya , Yamanaka Kunitoshi , Hara Masahide , Shimada Tatsuo , Sakata Toshiie
Published: September 2007

Background

Induction of heat-shock proteins (HSPs) results in cardioprotection against ischemic insult. Geranylgeranylacetone (GGA), known as an antiulcer agent, reportedly induces HSP72 in the gastric mucosa and small intestine of rats. The present study tested the hypothesis that oral GGA would induce HSP72 in the heart and thus render cardioprotection against ischemia/reperfusion injury in rats.

Methods and Results

Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. Ten minutes of whole-body hyperthermia induced HSP72 expression in the rat hearts. A single oral dose of GGA (200 mg/kg) also induced expression of HSP72, which peaked at 24 hours after administration. Therefore, isolated perfused heart experiments using a Langendorff apparatus were performed 24 hours after administration of 200 mg/kg GGA (GGA group) or vehicle (control group). After a 5-minute stabilization period, no-flow global ischemia was given for 20, 40, or 60 minutes, followed by 30 minutes of reperfusion. During reperfusion, the functional recovery was greater and the released creatine kinase was less in the GGA group than in the control group. Electron microscopy findings revealed that the ischemia/reperfusion-induced damage of myocardial cells was prevented in GGA-treated myocytes.

Conclusions

The results suggest that oral GGA is cardioprotective against ischemic insult through its induction of HSP72.
Prevention and Treatment of Coronary Heart Disease
Authors: LaRosa John C.
Published: September 2007

Coronary heart disease (CHD) remains a leading cause of morbidity and mortality in the United States, despite our better understanding of the pathobiology of atherosclerosis, our knowledge of risk factors, the widespread availability of inexpensive cholesterol screening, and the availability of effective and well-tolerated cholesterol-lowering agents. Advances in these areas have created controversies regarding who should be screened and treated for primary or secondary prevention of coronary events. The advent of the statin class of lipid-lowering agents represented a major advance, because they are much more effective and better tolerated than previous agents. There is general agreement that patients with hypercholesterolemia and established CHD require treatment for secondary prevention of recurrent coronary events. Primary prevention is controversial in all patient groups except those with diabetes, because their risk of developing CHD is dramatically increased. Postmenopausal women and the elderly are undertreated, whereas young adults may be underdiagnosed and undertreated. Several ongoing trials may resolve the controversies about which patient groups will benefit from different prevention and treatment strategies.
Long-Term Clinical Outcomes After Unprotected Left Main Trunk Percutaneous Revascularization in 279 Patients
Authors: Tan Walter A. , Tamai Hideo , Park Seung-Jung , Plokker H.W. Thijs , Nobuyoshi Masakiyo , Suzuki Takahiko , Colombo Antonio , Macaya Carlos , Holmes David R. , Cohen David J. , Whitlow Patrick L. , Ellis Stephen G. ,   for the ULTIMA Investigators
Published: September 2007

Background

Percutaneous coronary revascularization (PCI) has been increasingly applied to unprotected left main trunk (LMT) lesions, with varied long-term success. This study attempts to define the predictors of outcome in this population.

Methods and Results

Two hundred seventy-nine consecutive patients who had LMT PCI at 1 of 25 sites between 1993 and 1998 were studied. Forty-six percent of these patients were deemed inoperable or at high surgical risk. Thirty-eight patients (13.7%) died in hospital, and the rest were followed up for a mean of 19 months. The 1-year incidence was 24.2% for all-cause mortality, 20.2% for cardiac mortality, 9.8% for myocardial infarction, and 9.4% for CABG. Independent correlates of all-cause mortality were left ventricular ejection fraction ≤30%, mitral regurgitation grade 3 or 4, presentation with myocardial infarction and shock, creatinine ≥2.0 mg/dL, and severe lesion calcification. For the 32% of patients <65 years old with left ventricular ejection fraction >30% and without shock, the prevalence of these adverse risk factors was low. No periprocedural deaths were observed in this low-risk subset, and the 1-year mortality was only 3.4%.

Conclusions

Patients undergoing unprotected LMT PCI have frequent serious comorbidities and consequently have high event rates. PCI may be an alternative to CABG for a select proportion of elective patients and may also be appropriate for highly symptomatic inoperable patients. Meticulous follow-up of hospital survivors is required because of the rather high mortality during the first few months after treatment.