bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling Pathways Responsible for Fetal Gene Induction in the Failing Human Heart
Authors: Kinugawa Koichiro , Minobe Wayne A. , Wood William M. , Ridgway E. Chester , Baxter John D. , Ribeiro Ralff C. J. , Tawadrous Magdy F. , Lowes Brian A. , Long Carlin S. , Bristow Michael R.
Published: June 2012

Background
—We have previously demonstrated that changes in myosin heavy chain (MHC) isoforms that occur in failing human hearts resemble the pattern produced in rodent myocardium in response to hypothyroidism. Because thyroid hormone status is usually within normal limits in these patients, we hypothesized that failing/hypertrophied human myocardium might have a defect in thyroid hormone signaling due to alterations in expression of thyroid hormone receptors (TRs).

Methods and Results
—To examine this hypothesis, we used RNase protection assay to measure mRNA levels of TRs in failing left ventricles that exhibited a fetal pattern of gene expression, ie, decreased expression of α-MHC with increased β-MHC expression compared with left ventricles from age-matched controls. We detected expression of TR-α
1
, -α
2
, and -β
1
isoforms in human left ventricles. In failing left ventricles, TR-α
1
was downregulated, whereas TR-α
2
, a splice variant that does not bind thyroid hormone but inhibits responses to liganded TRs, was increased. Expression levels of TR-β
1
did not differ significantly between the 2 groups. According to linear regression analysis, expression levels of TR-α
1
and -α
2
were positively and negatively correlated with those of α-MHC, respectively.

Conclusions
—We conclude that decreases in TR-α
1
and increases in TR-α
2
may lead to local attenuation of thyroid hormone signaling in the failing human heart and that the resulting tissue-specific hypothyroidism is a candidate for the molecular mechanism that induces fetal gene expression in the failing human ventricle.
Mechanisms of Resetting Reentrant Circuits in Canine Ventricular Tachycardia
Authors: Hanna Michael S. , Coromilas James , Josephson Mark E. , Wit Andrew L. , Peters Nicholas S.
Published: June 2012

Background
—Resetting has been used to characterize reentrant circuits causing clinical tachycardias.

Methods and Results
—To determine the mechanisms of resetting, sustained ventricular tachycardia was induced in dogs with 4-day-old myocardial infarctions by programmed stimulation. Premature stimulation was accomplished from multiple regions within reentrant circuits; resetting curves were constructed and compared with activation maps. Monotonically increasing responses, or a “mixed” response (increasing portion preceded by a flat portion), occurred. All reentrant circuits had a fully excitable gap. Interval-dependent conduction delay and concealed retrograde penetration led to increased resetting response curves.

Conclusions
—Multiple mechanisms revealed by mapping cause resetting of reentrant circuits.
C-Reactive Protein–Mediated Low Density Lipoprotein Uptake by Macrophages
Authors: Zwaka Thomas P. , Hombach Vinzenz , Torzewski Jan
Published: June 2012

Background
—LDL and C-reactive protein (CRP) are important cardiovascular risk factors. Both LDL and CRP deposit in the arterial wall during atherogenesis. Stranded LDL is taken up by macrophages, causing foam cell formation. Because native LDL does not induce foam cell formation, we hypothesized that CRP may opsonize native LDL for macrophages.

Methods and Results
—Monocytes were isolated from human blood and transformed into macrophages. CRP/LDL uptake was assessed by immunofluorescent labeling and the use of confocal laser scanning microscopy. Native LDL coincubated with CRP was taken up by macrophages by macropinocytosis. Uptake of the CRP/LDL coincubate was mediated by the CRP receptor CD32.

Conclusions
—We conclude that foam cell formation in human atherogenesis may be caused in part by uptake of CRP-opsonized native LDL.
Genetic Demonstration of p47phox-Dependent Superoxide Anion Production in Murine Vascular Smooth Muscle Cells
Authors: Lavigne Mark C. , Malech Harry L. , Holland Steven M. , Leto Thomas L.
Published: June 2012

Background
—Previous investigations provide evidence that an enzyme related to the phagocyte NADPH oxidase produces superoxide in the blood vessel wall. These data, however, are confounded by observations that both NADPH and NADH serve as substrates for superoxide production in vascular cells. To clarify this issue, we compared the superoxide-generating capabilities of vascular smooth muscle cells (VSMCs) derived from wild-type (p47phox
+/+
;
ph
agocyte
ox
idase) mice with those from mice that lack p47phox (p47phox
−/−
; “knockout”), an essential component of the phagocyte NADPH oxidase.

Methods and Results
—VSMCs were derived from aortic explants harvested from p47phox
+/+
or p47phox
−/−
mice. VSMCs from p47phox
+/+
but not those from p47phox
−/−
mice produced superoxide after stimulation by phorbol myristate acetate. Consistent with this, p47phox was detected only in p47phox
+/+
VSMCs. p47phox-transduced p47phox
−/−
but not enhanced green fluorescent protein–transduced p47phox
−/−
VSMCs generated significant levels of superoxide after stimulation by angiotensin II or platelet-derived growth factor-BB (PDGF-BB). Enhanced expression of recombinant p47phox in p47phox-transduced p47phox
−/−
cells correlated with superoxide production in these cells.

Conclusions
—These data provide direct functional proof that an oxidase requiring the p47phox component mediates superoxide release from VSMCs in the blood vessel wall in response to angiotensin II or PDGF-BB.
Shear-Stress and Wall-Stress Regulation of Vascular Remodeling After Balloon Angioplasty
Authors: Wentzel Jolanda J. , Kloet Jeroen , Andhyiswara Ivan , Oomen Jan A. F. , Schuurbiers Johan C. H. , de Smet Bart J. G. L. , Post Mark J. , de Kleijn Dominique , Pasterkamp Gerard , Borst Cornelius , Slager Cornelis J. , Krams Rob
Published: June 2012

Background
—Constrictive vascular remodeling (VR) is the most significant component of restenosis after balloon angioplasty (PTA). Whereas in physiological conditions VR is associated with normalization of shear stress (SS) and wall stress (WS), after PTA the role of SS and WS in VR is unknown. Furthermore, whereas matrix metalloproteinase inhibition (MMPI) has been shown to modulate VR after PTA, its effect on the SS and WS control mechanisms after PTA is unknown.

Methods and Results
—PTA was performed in external iliac arteries of 12 atherosclerotic Yucatan pigs, of which 6 pigs (7 vessels) received the MMPI batimastat and 6 pigs (10 vessels) served as controls. Before and after the intervention and at 6-week follow-up, intravascular ultrasound pullback was performed, allowing 3D reconstruction of the treated segment and computational fluid dynamics to calculate the media-bounded area and SS. WS was derived from the Laplace formula. Immediately after PTA, media-bounded area, WS, and SS changed by 20%, 16%, and −49%, respectively, in both groups. VR was predicted by SS and WS. In the control group, SS and WS had been normalized at follow-up with respect to the reference segment. In contrast, for the batimastat group, the SS had been normalized, but not the WS. The latter is attributed to an increase in wall area at follow-up.

Conclusions
—Vascular remodeling after PTA is controlled by both SS and WS. MMPI inhibited the WS control system.
Tissue Doppler Imaging Consistently Detects Myocardial Abnormalities in Patients With Hypertrophic Cardiomyopathy and Provides a Novel Means for an Early Diagnosis Before and Independently of Hypertrophy
Authors: Nagueh Sherif F. , Bachinski Linda L. , Meyer Denise , Hill Rita , Zoghbi William A. , Tam James W. , Quiñones Miguel A. , Roberts Robert , Marian A.J.
Published: June 2012

Background

—

Left ventricular hypertrophy (LVH), the clinical hallmark of familial hypertrophic cardiomyopathy (FHCM), is absent in a significant number of subjects with causal mutations. In transgenic rabbits that fully recapitulate the FHCM phenotype, reduced myocardial tissue Doppler (TD) velocities accurately identified the mutant rabbits, even in the absence of LVH. We tested whether humans with FHCM also consistently showed reduced myocardial TD velocities, irrespective of LVH.

Methods and Results

—

We performed 2D and Doppler echocardiography and TD imaging in 30 subjects with FHCM, 13 subjects who were positive for various mutations but did not have LVH, and 30 age- and sex-matched controls (all adults; 77% women). LV wall thickness and mass were significantly greater in FHCM subjects (
P
<0.01 versus those without LVH and controls). There were no significant differences in 2D echocardiographic, mitral, and pulmonary venous flow indices between mutation-positives without LVH and controls. In contrast, systolic and early diastolic TD velocities were significantly lower in both mutation-positives without LVH and in FHCM patients than in controls (
P
<0.001). Reduced TD velocities had a sensitivity of 100% and a specificity of 93% for identifying mutation-positives without LVH.

Conclusions

—

Myocardial contraction and relaxation velocities, detected by TD imaging, are reduced in FHCM, including in those without LVH. Before and independently of LVH, TD imaging is an accurate and sensitive method for identifying subjects who are positive for FHCM mutations.
Fractional Flow Reserve in Patients With Prior Myocardial Infarction
Authors: De Bruyne Bernard , Pijls Nico H.J. , Bartunek Jozef , Kulecki Kemal , Bech Jan-Willem , De Winter Hugo , Van Crombrugge Paul , Heyndrickx Guy R. , Wijns William
Published: June 2012

Background

—

Fractional flow reserve (FFR), an index of coronary stenosis severity, can be calculated from the ratio of hyperemic distal to proximal coronary pressure. An FFR value of 0.75 can distinguish patients with normal and abnormal noninvasive stress testing in case of normal left ventricular function. The present study aimed at investigating the value of FFR in patients with a prior myocardial infarction.

Methods and Results

—

In 57 patients who had sustained a myocardial infarction ≥6 days earlier, myocardial perfusion single photon emission scintigraphy (SPECT) imaging and FFR were obtained before and after angioplasty. The sensitivity and specificity of the 0.75 value of FFR to detect flow maldistribution at SPECT imaging were 82% and 87%. The concordance between the FFR and SPECT imaging was 85% (
P
<0.001). When only truly positive and truly negative SPECT imaging were considered, the corresponding values were 87%, 100%, and 94% (
P
<0.001). Patients with positive SPECT imaging before angioplasty had a significantly lower FFR than patients with negative SPECT imaging (0.52±0.18 versus 0.67±0.16,
P
=0.0079) but a significantly higher left ventricular ejection fraction (63±10% versus 52±10%,
P
=0.0009) despite a similar degree of diameter stenosis (67±13% versus 68±16%,
P
=NS). A significant inverse correlation was found between LVEF and FFR (
R
=0.29,
P
=0.049).

Conclusions

—

The present data indicate (1) that the 0.75 cutoff value of FFR to distinguish patients with positive from patients with negative SPECT imaging is valid after a myocardial infarction and (2) that for a similar degree of stenosis, the value of FFR depends on the mass of viable myocardium.
Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients
Authors: Perticone Francesco , Ceravolo Roberto , Pujia Arturo , Ventura Giorgio , Iacopino Saverio , Scozzafava Angela , Ferraro Alessandro , Chello Massimo , Mastroroberto Pasquale , Verdecchia Paolo , Schillaci Giuseppe
Published: June 2012

Background

—

Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown.

Methods and Results

—

Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48;
P
=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure.

Conclusions

—

Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.
In Vivo Downregulation of T Helper Cell 1 Immune Responses Reduces Atherogenesis in Apolipoprotein E-Knockout Mice
Authors: Laurat E. , Poirier B. , Tupin E. , Caligiuri G. , Hansson G.K. , Bariéty J. , Nicoletti A.
Published: June 2012

Background

—

A chronic immune response involving proinflammatory T helper cell 1 (Th1) lymphocyte activation occurs in the atherosclerotic lesion, but whether this activation is protective or deleterious remains unclear.

Methods and Results

—

We modulated the immune response of the atherosclerosis-prone apolipoprotein E-deficient (apoE
−/−
) mouse. Eight-week-old apoE
−/−
mice were treated daily with pentoxifylline (PTX), a known inhibitor of the Th1 differentiation pathway, or PBS (control) for 4 weeks or 12 weeks. Twelve-week PTX treatment reduced atherosclerotic lesion size by 60% (
P
<0.01). PTX-treated mice developed lesions that were limited to the degree of fatty streaks. In contrast, control mice developed mature fibrofatty atherosclerotic lesions. In parallel, the proportion of interferon (IFN)-γ-producing Th1 splenic lymphocytes was significantly reduced by PTX, and lesion size was correlated to the proportion of IFN-γ
+
T cells. In vitro addition of PTX to cultured spleen cells did not modify the production of IFN-γ but increased the production of IL-10 by T cells, indicating that PTX does not suppress IFN-γ production but rather blocks Th1 polarization while promoting Th2 polarization.

Conclusions

—

Thus, PTX protected mice from atherosclerosis by reducing the Th1 polarization of T helper lymphocytes. This study demonstrates that the Th1 immune response associated with atherosclerosis is deleterious and that a modulation of the Th1 differentiation pathway may provide a new pharmacological tool to treat this disease.
Detection of Monocyte Chemoattractant Protein-1 Receptor Expression in Experimental Atherosclerotic Lesions
Authors: Ohtsuki Katsuichi , Hayase Motoya , Akashi Koichi , Kopiwoda Susan , Strauss H.William
Published: June 2012

Background

—

Monocytes, a common component of atheroma, are attracted to the lesion site in response to chemotactic signals, particularly expression of monocyte chemoattractant peptide 1 (MCP-1). This study assessed the feasibility of using radiolabeled MCP-1 to identify monocytes and macrophages that have localized at sites of experimental arterial lesions.

Methods and Results

—

The biodistribution of radiolabeled MCP-1 was determined in normal mice, and localization in experimental atheroma was determined in cholesterol-fed rabbits 4 weeks after arterial injury of the iliac artery (9 rabbits) and the abdominal aorta (1 rabbit). Vessels were harvested and autoradiographed after intravenous administration of
125
I-labeled MCP-1 and Evans blue dye. The arteries were evaluated histologically by hematoxylin and eosin staining and immune staining with a monoclonal antibody specific for rabbit macrophages (RAM-11).
125
I-MCP-1 has a blood clearance half-time of ≈10 minutes and circulates in association with cells. The liver, lungs, and kidneys had the highest concentration of
125
I-MCP-1 at 5 and 30 minutes after tracer administration. Autoradiograms revealed accumulation of
125
I-MCP-1 in the damaged artery wall, with an average ratio of lesion to normal vessel of 6:1 (maximum 45:1). The accumulation of
125
I-MCP-1 in the reendothelialized (plaque formation) areas was greater than in the deendothelialized (Evans blue-positive) areas (6.55±2.26 versus 4.34±1.43 counts/pixel,
P
<0.05). The uptake of
125
I-MCP-1 correlated with the number of macrophages per unit area (
r
=0.85,
P
<0.0001).

Conclusions

—

Radiolabeled MCP-1 may be a useful tracer for imaging monocyte/macrophage-rich experimental atherosclerotic lesions.
Apoptosis of Endothelial Cells Precedes Myocyte Cell Apoptosis in Ischemia/Reperfusion Injury
Authors: Scarabelli Tiziano , Stephanou Anastasis , Rayment Neil , Pasini Evasio , Comini Laura , Curello Salvatore , Ferrari Roberto , Knight Richard , Latchman David
Published: June 2012

Background

Apoptosis contributes to cell loss after ischemia/reperfusion injury in the heart. This study describes the time course and level of apoptosis in different cell types in the intact heart during ischemia/reperfusion injury.

Methods and Results

Isolated Langendorff-perfused rat hearts were subjected to perfusion alone (control) or to 35 minutes of regional ischemia, either alone or followed by 5, 60, or 120 minutes of reperfusion. Sections were stained by terminal deoxynucleotidyl transferase–mediated dUTP nick-end labeling (TUNEL) and propidium iodide and with anti-von Willebrand factor, anti-desmin, or anti-active caspase 3 antibodies; they were then visualized by confocal microscopy. Sections were also examined by electron microscopy. No TUNEL-positive cells were seen in control hearts or hearts exposed to ischemia alone. Early in reperfusion, TUNEL staining was colocalized with endothelial cells from small coronary vessels. Endothelial apoptosis peaked at 1 hour of reperfusion and, at this time, there was clear perivascular localization of apoptotic cardiac myocytes, whose number was inversely proportional to their distance from a positive vessel. After 2 hours of reperfusion, apoptotic cardiac myocytes assumed a more homogeneous distribution. Active caspase 3 labeling was seen independent of DNA fragmentation during ischemia alone, but it colocalized with TUNEL staining over the 3 time points of reperfusion. Immunocytochemical findings were confirmed by electron microscopy and Western blotting.

Conclusions

In the very early stages of reperfusion, apoptosis is first seen in the endothelial cells from small coronary vessels. The radial spread of apoptosis to surrounding cardiac myocytes suggests that reperfusion induces the release of soluble pro-apoptotic mediators from endothelial cells that promote myocyte apoptosis.
Doppler echocardiographic assessment of the St. Jude Medical prosthetic valve in the aortic position using the continuity equation.
Authors: Chafizadeh E R , Zoghbi W A
Published: June 2012

To test whether the continuity equation can be applied to the noninvasive assessment of prosthetic aortic valve function, Doppler echocardiography was performed in 67 patients (mean age, 58 +/- 14 years) within 10 +/- 6 days after valve replacement with St. Jude Medical valves. All patients were clinically stable and without evidence of valve dysfunction. Valve size ranged from 19 to 31 mm, and ejection fraction ranged from 30% to 75%. With the parasternal long-axis view, the left ventricular outflow diameter measured just proximal to the prosthetic valve correlated well with valve size (r = 0.92). Doppler-derived maximal gradients ranged from 9 to 71 mm Hg. Effective prosthetic aortic valve area by the continuity equation ranged between 0.73 cm2 for a 19-mm valve and 4.23 cm2 for a 31-mm valve. With analysis of variance, effective orifice area differentiated various valve sizes (p less than 10(-14)) better than did gradients alone (p = 0.003) and correlated better with actual valve orifice area (r = 0.83 versus - 0.40). A Doppler velocity index, the ratio of peak velocity in the left ventricular outflow to that of the aortic jet, averaged 0.41 +/- 0.09 and was less dependent on valve size (r = 0.43). Thus, the continuity equation can be applied to the assessment of prosthetic St. Jude valves in the aortic position. By accounting for flow through the valve, it provides an improved assessment over the sole use of gradients in the evaluation of prosthetic valve function.
In vitro and in vivo effects within the coronary sinus of nonarcing and arcing shocks using a new system of low-energy DC ablation.
Authors: Lemery R , Leung T K , Lavallée E , Girard A , Talajic M , Roy D , Montpetit M
Published: June 2012

DC shocks within the coronary sinus have been abandoned because of the risk of cardiac rupture and tamponade. Catheter ablation using DC energy to electrodes straddling the ostium of the coronary sinus, when used clinically, has been reported to result in cardiac tamponade in as many as 16% of patients. A new system of energy delivery maximizes voltage while decreasing the undesirable effects caused by barotrauma. This system includes 1) a low-energy ablation power supply with a brief time-constant capacitive discharge that delivers up to 40 J and 3,000 V and 2) a low-energy ablation catheter with a contoured distal electrode. We performed in vitro and in vivo studies of this new system and compared arcing shocks with nonarcing shocks. Ablations were performed using unipolar distal shocks (D) and unipolar shocks to both electrodes made electrically common (P-D). In vitro studies were done in a large tank filled with physiological saline while recording voltage, current, and pressure. High-speed cinematography (32,000 frames/sec) of shocks of 10-40 J permitted detailed analysis of the vapor globe. Anodal shocks of less than 20 J showed no arcing or only minimal vapor globe formation. For D and P-D anodal shocks of 40 J, the diameters of the vapor globe were 31 and 22 mm, respectively, corresponding to pressure recordings of 11 and 4.9 atm. The pressure rise lasted less than 50 mu sec. In vivo studies involved 18 dogs that received nonarcing shocks (one to six shocks of 15 J) and 18 dogs that received arcing shocks (one to three shocks of 40 J). Each group was divided between D and P-D shocks; catheter ablation was performed at a mean +/- SEM distance of 2.94 +/- 0.92 cm within the coronary sinus. All dogs tolerated the procedure without cardiac rupture or tamponade. When killed 2-4 days later, the dogs had edema and hyperemia or hemorrhage in the area of the coronary sinus. We compared the effects of multiple (three to six) nonarcing shocks with the effects of one to three arcing shocks. Disruption or rupture of the coronary sinus within the epicardial fat space occurred in two of 12 dogs (17%) with multiple nonarcing shocks but in 13 of 18 dogs (72%) with arcing shocks (p less than 0.003). Occlusion of the coronary sinus occurred in two of 12 dogs (17%) with multiple nonarcing shocks and in nine of 18 dogs (50%) with arcing shocks (p less than 0.06).(ABSTRACT TRUNCATED AT 400 WORDS)
Coronary vasodilator reserve. Comparison of the effects of papaverine and adenosine on coronary flow, ventricular function, and myocardial metabolism.
Authors: Christensen C W , Rosen L B , Gal R A , Haseeb M , Lassar T A , Port S C
Published: June 2012

To evaluate coronary flow reserve during cardiac catheterization, intracoronary adenosine and papaverine have been used in the clinical setting. Although papaverine maximizes coronary blood flow, it induces several toxic side effects that reduce its desirability as a coronary dilator. This investigation was designed to compare the subselective intracoronary administration of papaverine with that of adenosine in an animal model. In dogs (n = 34), we studied the effects of each agent on hemodynamics, regional myocardial blood flow, contractility (sonomicrometric and echocardiographic), metabolism (coronary arterial and venous lactate and tissue high-energy phosphates), and electrocardiographic (ST and QT intervals) parameters. Barbiturate and morphine anesthesia/analgesia was induced, and a left thoracotomy was performed. An arterial shunt was created from the left carotid artery to the left anterior descending coronary artery. Two separate groups were studied: group 1 (n = 16) for regional myocardial blood flow and mechanical function and group 2 (n = 18) for biochemical measurements. Adenosine (67 +/- 2 micrograms/min) or papaverine (6 +/- 1 mg/min) was infused into the coronary shunt at a rate of 0.5 + 0.1 ml/min for a maximum duration of 3.5 minutes. Regional myocardial blood flows were determined at control (predrug) and maximal coronary flow using radiolabeled microspheres. All hemodynamic, wall motion, biochemical, and electrocardiographic parameters were also measured at these times. Both drugs produced comparable increases in total and regional coronary blood flows (adenosine, 1.21 +/- 0.15 to 4.83 +/- 0.36 ml/min/g; papaverine, 1.21 +/- 0.05 to 4.89 +/- 0.28 ml/min/g) upon infusion into the left anterior descending coronary artery. Papaverine produced significant (p less than 0.05) changes in subendocardial ST segment electrocardiogram (-2.5 mm), QT prolongation (8 +/- 2%), myocardial creatine phosphate (47% decrease), and coronary sinus serum lactate (277% increase) compared with control. In addition, intracoronary papaverine induced an abnormal contractile pattern. No significant changes in any of these parameters (i.e., ST segment, QT prolongation, myocardial creatine phosphate level, or lactate level) were observed with intracoronary adenosine infusions. We conclude that intracoronary adenosine is comparable to papaverine for maximizing coronary blood flow without the deleterious properties observed with intracoronary papaverine.
Diagnosis of noninfective cardiac mass lesions by two-dimensional echocardiography. Comparison of the transthoracic and transesophageal approaches.
Authors: Mügge A , Daniel W G , Haverich A , Lichtlen P R
Published: June 2012

This study was conducted in 46 patients with cardiac thrombi, 15 patients with atrial myxomas, and 32 patients with other cardiac or paracardiac tumors. Diagnoses were subsequently proven by surgery, autopsy, computed tomography, magnetic resonance imaging, or angiography in all patients. All patients underwent precordial and transesophageal two-dimensional echocardiography to assess the various mass detection rates. Atrial myxomas and predominantly left-sided cardiac tumors were identified by both echocardiographic techniques with comparable detection rates. Left ventricular apical thrombi were detected more frequently by precordial echocardiography. In contrast, transesophageal echocardiography was superior in visualizing left atrial appendage thrombi, small and flat thrombi in the left atrial cavity, thrombi and tumors in the superior vena cava, and masses attached to the right heart and the descending thoracic aorta. These data indicate that transesophageal echocardiography leads to a clinically relevant improvement of the diagnostic potential in patients in whom cardiac masses are suspected or have to be excluded in order to ensure the safety of clinical procedures.
Endothelium-dependent responses in long-term human coronary artery bypass grafts.
Authors: Ku D D , Caulfield J B , Kirklin J K
Published: June 2012

In the present study, responses of long-term human coronary artery bypass grafts (CABGs) to known endothelium-dependent vasodilators, acetylcholine, calcium ionophore A23187, thrombin, and histamine, as well as authentic nitric oxide, the putative endothelium-derived relaxing factor, were studied. Sixteen CAGBs were isolated within 1-2 hours from hearts of 14 patients receiving a cardiac transplant. A total of 109 ring segments were prepared from these CABGs and studied in vitro. The duration of the CABGs ranged from 7 months to 12 years. Addition of acetylcholine (0.01-10 microM), calcium ionophore A23187 (0.01-1.0 microM), thrombin (0.01-1.0 unit/ml), and histamine (0.01-1.0 microM) consistently produced a dose- and endothelium-dependent relaxation, reaching a maximum of -35.3 +/- 3.3%, -45.3 +/- 5.5%, -26.9 +/- 4.8%, and -17.8 +/- 2.5% (mean +/- SEM), respectively. No significant difference was observed among the CABGs with different duration of transplantation, whereas the relaxant responses of different segments along the entire length of a CABG were markedly different. These latter differences in the endothelium-dependent responses appear to correlate inversely with the development of intimal proliferative lesions in these CABGs. Addition of nitric oxide (0.01-10 microM) produced a potent dose- and endothelium-independent relaxation, which was also slightly depressed in CABGs with severe intimal proliferation. These results demonstrate that long-term transplanted human saphenous vein grafts retain their endothelium-dependent responses and that development of severe intimal proliferative lesions, rather than the duration of the grafts, result in marked alterations in the reactivity of these transplanted CABGs.
Accuracy of exercise electrocardiography in detecting physiologically significant coronary arterial lesions.
Authors: Wilson R F , Marcus M L , Christensen B V , Talman C , White C W
Published: June 2012

The accuracy of exercise electrocardiography in detecting a physiologically significant coronary artery stenosis has been assessed previously by comparing the exercise test with a coronary arteriogram. The inherent inaccuracy of visually determined percent diameter stenosis measurements might have lead to the conclusion that the exercise electrocardiogram was less accurate than it truly was. To determine the accuracy of the exercise electrocardiography in detecting a physiologically significant coronary stenosis, we studied 40 patients with one-vessel, one-lesion coronary artery disease, a normal resting electrocardiogram, and no hypertrophy or prior infarction. Each patient underwent exercise electrocardiography (Bruce protocol) that was interpreted as abnormal if the ST segment developed 0.1-mV or greater depression 80 msec after the J point. The physiological significance of each coronary stenosis was assessed by measuring of coronary flow reserve (peak divided by resting blood flow velocity) in the stenotic artery using a Doppler catheter and intracoronary papaverine (normal, 3.5 or greater peak/resting velocity). The percent diameter and percent area stenosis produced by each lesion were determined using quantitative angiography (Brown/Dodge method). Of the 17 patients with reduced coronary flow reserve (3.5 or greater peak/resting blood flow velocity) in the stenotic artery, 14 had an abnormal exercise electrocardiogram (sensitivity, 0.82; 95% confidence interval, 0.70-0.94). Conversely, 20 of 23 patients with normal coronary flow reserves had normal exercise tests (specificity, 0.87; 95% confidence interval, 0.77-0.97). The exercise electrocardiogram was abnormal in each of 11 patients with markedly reduced coronary flow reserve (less than 2.5 peak/resting velocity) and in three of six patients with moderately reduced reserve (2.5-3.4 peak/resting velocity). The products of systolic blood pressure and heart rate at peak exercise were significantly correlated with coronary reserve in patients with truly abnormal exercise tests. In comparison, the sensitivity (0.61; 95% confidence interval, 0.46-0.76) and specificity (0.73; 95% confidence interval, 0.60-0.86) of exercise electrocardiography in detecting a 60% or greater diameter stenosis may be significantly lower (p less than 0.05). Exercise electrocardiography, therefore, was a good predictor of the physiological significance (assessed by coronary flow reserve) of a coronary stenosis in patients with a normal resting electrocardiogram and no hypertrophy or prior infarction. Its value in a broader and larger patient population will require further study. These results, however, underscore the importance of a physiological gold standard in assessing the accuracy of noninvasive studies for detecting coronary artery disease.
What is the best method for assessing the long-term outcome of surgery for accessory pathways and atrioventricular junctional reentrant tachycardias?
Authors: Davis L M , Johnson D C , Uther J B , Nunn G , Richards D A , Meldrum-Hanna W , Ross D L
Published: June 2012

The success of surgery for supraventricular tachycardia (SVT) is evaluated by a variety of methods in different hospitals. Unfortunately, the predictive values of these methods are not known. We therefore compared the various methods in 261 patients undergoing surgery for SVT at Westmead Hospital since 1981. Surgical outcome was assessed by early tests during the first week after surgery (serial 12-lead electrocardiograms, telemetric monitoring of the electrocardiogram, and electrophysiological study performed using epicardial wires); later tests at 6 months after surgery (12-lead electrocardiograms and electrophysiological study); and symptomatic review done by telephone interview at a median of 34 months after surgery. Early tests were obtained in 97%, later tests were obtained in 76%, and symptomatic review was obtained in 98% of patients. All of the examined tests were inaccurate methods of surgical assessment compared with the late electrophysiological study. A large proportion of the patients proven to be surgical failures at the late electrophysiological study were not detected by early tests (83%), by later electrocardiograms (66%), or by symptomatic assessment (41%). Accurate assessment of surgical outcome requires a late electrophysiological study to permit comparison of surgical techniques. Late electrophysiological study also provides accurate information on the current risks and benefits of proposed surgery for communication to patients to enable them to make an informed decision on future treatment. Most patients are willing to have a late electrophysiological study and usually benefit from clarification of their true surgical outcome.
Mechanism of the effect of exogenous fructose 1,6-bisphosphate on myocardial energy metabolism.
Authors: Hassinen I E , Nuutinen E M , Ito K , Nioka S , Lazzarino G , Giardina B , Chance B
Published: June 2012

The effects of fructose 1,6-bisphosphate (F-1,6-P2) on the isolated Langendorff-perfused heart were studied by monitoring flavoprotein fluorescence, oxygen consumption (MVO2), coronary flow (Fc), systolic intraventricular pressure (Psys), diastolic intraventricular pressure, and contraction frequency. The cellular energy state and cytosolic pH were determined by means of 31P nuclear magnetic resonance. Infusion of 5 mM F-1,6-P2 caused a rapid shift toward reduction in the flavoprotein redox state and initial 50% and 44% decreases in Psys and MVO2, respectively. After a partial recovery, these measures remained 11% and 25% below the basal value. Concomitantly, after an initial transient increase of 13%, Fc remained 17% lower than in the basal state. When the F-1,6-P2 concentration was subsequently increased to 10 mM, psys and MVO2 dropped temporarily to 31% and 29% of the basal value and then remained at 50% and 53%, respectively. Simultaneously, a brief increase was observed in Fc, which then fell 34% below the basal value. Rapid reoxidation of the flavoproteins and increases in MVO2, Psys, and Fc occurred on discontinuation of the F-1,6-P2 infusion. 31P nuclear magnetic resonance during infusions of both 5 and 10 mM F-1,6-P2 revealed a decrease in cytosolic inorganic phosphate and a tendency to increase creatine phosphate, suggesting elevation in the cellular energy state. No changes in intracellular pH occurred as estimated from the chemical shift of the nuclear magnetic resonance of inorganic phosphate. F-1,6-P2 (5 mM and 10 mM) lowered the free Ca2+ concentration in the Krebs-Henseleit bicarbonate buffer (by 32% and 47%, respectively). This probably explains the effects of F-1,6-P2 on mechanical work performance and cellular respiration. A direct metabolic effect also exists, however, because flavoprotein reduction by F-1,6-P2 could be observed in the K(+)-arrested heart, where its effects on MVO2 were minimal. This redox effect may not be caused by changes in free Ca2+ concentration because it could not be reproduced by infusion of EGTA.
Diagnostic efficiency of troponin T measurements in acute myocardial infarction.
Authors: Katus H A , Remppis A , Neumann F J , Scheffold T , Diederich K W , Vinar G , Noe A , Matern G , Kuebler W
Published: June 2012

BACKGROUND

The present study was designed to evaluate the efficiency of a newly developed troponin T enzyme immunoassay for the detection of acute myocardial infarction.

METHODS AND RESULTS

The study comprised 388 patients admitted with chest pain and suspected myocardial infarction and 101 patients with skeletal muscle damage and additional suspected myocardial cell damage. Troponin T was elevated to more than twice the analytical sensitivity of the assay (0.5 microgram/l) in all patients with non-Q wave (range, 1.2-5 micrograms/l) and Q wave infarction (range, 3-220 micrograms/l). Troponin T appeared in serum as early as 3 hours after onset of pain in 50% of the patients and remained elevated in all patients for more than 130 hours, revealing release kinetics of both free cytosolic and structurally bound molecules. The diagnostic efficiency of troponin T was superior to that of creatine kinase-MB (98% versus 97%) and remained at 98% until 5.5 days after admission, if patients with unstable angina were excluded from analysis. In the 79 patients with unstable angina, troponin T was elevated (range, 0.55-3.1 micrograms/l) in at least one blood sample from each of 37 patients (56%). Circulating troponin T was correlated to the presence of reversible ST segment or T wave changes on the electrocardiogram (p less than 0.005) and to the frequency of in-hospital complications. In the 101 patients with skeletal muscle damage and suspected additional cardiac muscle damage, troponin T was the most useful test; its efficiency was 89% or 94% (depending on the discriminator value used) as compared with 63% for creatine kinase-MB.

CONCLUSIONS

Thus, the data of the study indicate that the newly developed troponin T test improves the efficiency of serodiagnostic tools for the detection of myocardial cell necrosis as compared with conventionally used cardiac enzymes.
Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens.
Authors: Tobis J M , Mallery J , Mahon D , Lehmann K , Zalesky P , Griffith J , Gessert J , Moriuchi M , McRae M , Dwyer M L
Published: June 2012

BACKGROUND

Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas.

METHODS AND RESULTS

A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media.

CONCLUSIONS

Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.
Evidence for structural sympathetic reinnervation after orthotopic cardiac transplantation in humans.
Authors: Wilson R F , Christensen B V , Olivari M T , Simon A , White C W , Laxson D D
Published: June 2012

BACKGROUND

Cardiac transplantation (CT) causes total cardiac denervation.

METHODS AND RESULTS

To test directly for sympathetic reinnervation in humans, we measured the cardiac release of norepinephrine (NE) in response to tyramine (an agent that causes NE release from intact sympathetic nerve terminals) and sustained handgrip exercise (a reflex sympathetic stimulus) in 12 patients less than 5 months after CT, in 50 patients 1 year or more after CT, and in eight patients without CT. Plasma [NE] was measured in the aorta [( NE]Ao) and coronary sinus [( NE]CS) at rest, after tyramine administration (55 micrograms/kg, i.v.), and during sustained handgrip exercise. Cardiac NE release was determined by subtracting [NE]Ao from [NE]CS [( NE]CS-Ao). NE release was defined as [NE]CS-Ao during the intervention-[NE]CS-Ao at rest (delta [NE]CS-Ao). In patients studied within 5 months of CT, no significant NE release occurred after tyramine administration (delta [NE]CS-Ao, 33 +/- 18 pg/ml; range, -98 to 117 pg/ml) or handgrip exercise (delta [NE]CS-Ao, -34 +/- 10 pg/ml; range, -46 to 8 pg/ml; n = 10). Conversely, in 39 of 50 patients studied 1 year or more after CT, tyramine administration caused a significant cardiac NE release (delta [NE]CS-Ao, 500 +/- 59 pg/ml; range, -11 to 1,918 pg/ml), and handgrip exercise caused a significant NE release in 17 of 41 patients (delta [NE]CS-Ao, 189 +/- 34 pg/ml; range, -211 to 949 pg/ml). In normally innervated patients, tyramine caused an even larger NE release (delta [NE]Ao-CS, 1,943 +/- 210 pg/ml; range, 1,152 to 2,977 pg/ml), and handgrip exercise caused a significant NE release in two of seven patients (delta [NE]CS-Ao, 143 +/- 51 pg/ml; range, -15 to 338 pg/ml).

CONCLUSIONS

Early after CT, neither tyramine nor handgrip exercise caused a significant cardiac release of NE, suggesting sympathetic denervation. Late after CT, most patients had a significant, but subnormal, NE release in response to pharmacological or reflex stimuli, suggesting that limited sympathetic reinnervation occurs in most patients after orthotopic CT.
Patients with two types of atrioventricular junctional (AV nodal) reentrant tachycardia. Evidence that a common pathway of nodal tissue is not present above the reentrant circuit.
Authors: McGuire M A , Lau K C , Johnson D C , Richards D A , Uther J B , Ross D L
Published: June 2012

BACKGROUND

The site of the reentrant circuit in atrioventricular (AV) junctional reentrant tachycardia has not been defined; in particular, the existence of a common pathway of AV nodal tissue above the reentrant circuit is controversial.

METHODS AND RESULTS

Two types of AV junctional reentrant tachycardia were induced in each of three patients at electrophysiological study. In one type of tachycardia (anterior), the onset of atrial activity occurred from 0 to 12 msec before the onset of ventricular activation, and earliest atrial activity was recorded near the His bundle. In the second type of tachycardia (posterior), the ventriculoatrial intervals were longer (76-168 msec), and earliest atrial activity was recorded near the mouth of the coronary sinus. In individual patients, the two types of tachycardia had different cycle lengths. Posterior AV junctional reentrant tachycardia was not a fast-slow form of AV junctional reentry in at least two of the three patients. Surgical cure was attempted in two patients. In one patient, anterior AV junctional reentrant tachycardia was abolished by dissection of the anterior perinodal atrium, but posterior AV junctional reentrant tachycardia could still be induced. At reoperation 4 months later, dissection of the posterior perinodal atrium abolished posterior AV junctional reentrant tachycardia while preserving AV conduction.

CONCLUSION

Differences in ventriculoatrial intervals and cycle lengths and the results of selective surgery suggest that the two types of AV junctional reentrant tachycardia used different reentrant circuits. These observations imply that a common pathway of AV nodal tissue is not present above the reentrant circuit and suggest that perinodal atrium is part of these circuits.
Screening for total cholesterol. Do the National Cholesterol Education Program's recommendations detect individuals at high risk of coronary heart disease?
Authors: Bush T L , Riedel D
Published: June 2012

BACKGROUND

The National Cholesterol Education Program (NCEP) has provided guidelines for identification of persons at high risk of coronary heart disease (CHD) because of lipid abnormalities. These recommendations are based on total cholesterol as the initial screening tool and have become the stimulus for clinic- and community-based screening programs nationwide. However, the use of the guidelines may be problematic because individuals may have total cholesterol levels in the desirable range but low density lipoprotein (LDL) or high density lipoprotein (HDL) levels considered at high risk. This study evaluates the ability of the NCEP screening recommendations to identify correctly persons at high risk of CHD because of lipid abnormalities.

METHODS AND RESULTS

Using the NCEP guidelines, we simulated a population-based screening program with data from visits 1 and 2 of the Lipid Research Clinics Program Prevalence Study. Individuals were considered to be at high risk of CHD if they had LDL levels greater than 160 mg/dl or HDL levels less than 35 mg/dl. Following the NCEP process, 21% of those with high LDL concentrations and 66% of those with low HDL concentrations would not be routinely referred for immediate treatment. Overall, 41% of those at high risk of CHD would not be promptly evaluated. The sensitivity of the guidelines for promptly identifying individuals with lipoprotein abnormalities is 59%.

CONCLUSIONS

This relatively low sensitivity of total cholesterol as a screening tool should be the impetus for rethinking the screening guidelines. Specifically, the cost-benefit ratio of routine screening for lipoproteins, particularly HDL cholesterol, needs to be carefully considered.