bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiotensin-Converting Enzyme and Apolipoprotein E Genotypes and Restenosis After Coronary Angioplasty
Authors: van Bockxmeer Frank M. , Mamotte Cyril D. S. , Gibbons Frances A. , Burke Valerie , Taylor Roger R.
Published: June 2012

Background
An insertion/deletion (
I/D
) polymorphism in the gene for angiotensin-converting enzyme (ACE) has been associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin-angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene was postulated to be a candidate gene affecting the important clinical problem of restenosis after percutaneous transluminal balloon coronary angioplasty (PTCA). Because restenosis is influenced by the apolipoprotein E (apoE) genotype, the possibility of a relation between ACE and apoE genotypes and restenosis was also sought.

Methods and Results
Subjects (<70 years of age) were prospectively followed and had coronary angiography 6 months after PTCA to determine the presence or absence of restenosis. Those who had angiography earlier and did not have restenosis (≥50% loss of gain at PTCA plus ≥50% luminal diameter stenosis) also had angiography at 6 months. The whole group (n=207) had a higher
DD
genotype frequency than did 136 population control subjects (38% versus 26%,
P
<.02); in PTCA patients, the frequency was the same in those with and without prior myocardial infarction. The distribution of ACE genotypes was not different in the 88 patients with and 119 patients without restenosis, while the ε4/4 genotype was more frequent in those with restenosis (8 of 88 versus 3 of 118,
P
<.05). There was no effect of the ACE genotype in noncarriers of the ε4 allele, but there was a significant effect in ε4 carriers (
P
<.005). The combined
D
and ε4 carrier state showed a 16-fold increase in the odds ratio for restenosis (
P
<.02). Multiple linear regression examining the loss of lumen as a continuous variable showed significant independent effects of the ACE and apoE genotypes.

Conclusions
Overall, the ACE genotype had no clear influence on restenosis, but there was an interaction between ACE and apoE genotypes. The combined carrier state for the
D
and apoE ε4 alleles substantially increased restenosis. For loss of lumen as a continuous variable, there were significant effects of both ACE and apoE genotypes. While the observations may not affect current management, they no doubt have implications in pathophysiology.
Quantitative Assessment of Coronary Vasoreactivity in Humans In Vivo
Authors: Schächinger Volker , Zeiher Andreas M.
Published: June 2012

Background
Disturbances in vasomotor tone are closely linked to the development of atherosclerosis and play an integral part in the pathophysiology of myocardial ischemia in patients with coronary artery disease. Currently, evaluation of coronary vasomotor tone relies on assessment of luminal changes in response to vasoactive stimuli by quantitative angiography. Assessment of luminal changes, however, may be misleading because of the effects of geometric magnification induced by atherosclerotic wall thickening and differences in basal tone, which may obscure potential effects of vasoactive stimuli.

Methods and Results
Combining angiographic measurements of luminal changes with measurements of coronary wall architecture determined by intracoronary ultrasound, we calculated absolute coronary arterial vasomotor tone in 34 patients with angiographically normal or “minimally diseased” coronary arteries. Epicardial artery vasodilator capacity in response to intracoronary nitroglycerin decreased significantly with increasing atherosclerotic wall thickening. An inverse relation existed between local atherosclerotic plaque load and nitroglycerin-induced changes in vasomotor tone (
r
=−.65,
P
<.0001) regardless of potential systematically operative factors. At the same time, basal vasomotor tone significantly decreased with increasing local atherosclerotic wall thickening (
r
=−.38,
P
=.004). The vasomotor effects of acetylcholine, an endothelium-dependent vasodilator, were inversely related to wall thickening only in segments with very minor degrees of atherosclerosis, whereas no such relation was observed for epicardial artery segments with more advanced atherosclerotic wall thickening. In these segments, however, vasoreactivity to acetylcholine was closely correlated with basal vasomotor tone (
r
=−.62,
P
=.0002).

Conclusions
Atherosclerosis is associated with impairment of the vasodilator response to both nitroglycerin and acetylcholine in epicardial arteries in vivo. Basal vasomotor tone appears to be the primary determinant of the altered coronary vasoreactivity in response to vasoactive stimuli.
Carotid Intima-Media Thickness Is Only Weakly Correlated With the Extent and Severity of Coronary Artery Disease
Authors: Adams Mark R. , Nakagomi Akihiro , Keech Anthony , Robinson Jacqui , McCredie Robyn , Bailey Brian P. , Freedman S. Ben , Celermajer David S.
Published: June 2012

Background
Intima-media thickness (IMT) of the common carotid artery (CCA), measured with external vascular ultrasound, has been widely used in clinical trials as a surrogate marker for coronary atherosclerosis. Despite this, the degree of correlation between carotid IMT and the extent and severity of coronary artery disease (CAD) is not known.

Methods and Results
Common carotid IMT was measured by ultrasound in 350 consecutive subjects of age 60±10 years (range, 30 to 85 years) on the day of coronary angiography. Carotid mean IMT was 0.83±0.20 mm (range, 0.43 to 1.80 mm), and maximum IMT was 1.04±0.27 mm (range, 0.49 to 2.19 mm). Coronary angiograms were analyzed by independent observers for disease severity (number of vessels with ≥70% stenosis), extent score, and a modified Gensini score. Mean carotid IMT was weakly but significantly correlated with CAD severity (
r
=.26), extent (
r
=.23), and modified Gensini score (
r
=.29,
P
<.0001 for all correlations). Carotid IMT was not clinically useful, however, because it was not specific or sensitive enough to identify patients with or without significant CAD. Increasing age, male sex, and presence of diabetes were all associated with a significantly (
P
<.01) higher CAD score than the average for any level of carotid IMT, suggesting differential effects of these traditional risk factors on the coronary and common carotid arteries.

Conclusions
Although carotid IMT is significantly correlated with extent and severity of CAD, the relationship is weak. This relatively poor correlation (
r

2

<.10) should be considered in the interpretation of clinical trials that use carotid IMT as a surrogate end point for coronary atherosclerosis.
Osteopontin Is Expressed in Human Aortic Valvular Lesions
Authors: O’Brien Kevin D. , Kuusisto Johanna , Reichenbach Dennis D. , Ferguson Marina , Giachelli Cecilia , Alpers Charles E. , Otto Catherine M.
Published: June 2012

Background
Nonrheumatic stenosis of trileaflet aortic valves, in which calcification is a prominent feature, has been termed a “degenerative” condition, but it has been demonstrated recently that chronic inflammation is a characteristic feature of the developing lesion of aortic stenosis. This observation raised the possibility that calcification in the aortic valve might be actively regulated. Thus, the present study investigated whether osteopontin, a protein implicated in the regulation of both normal and dystrophic calcification, could be detected in lesions of valvular aortic stenosis.

Methods and Results
Morphological and immunohistochemical studies were performed on 14 human aortic valves, representing a range of pathology from normal to clinically stenotic. The extent of calcification and macrophage accumulation and their relation to the presence of osteopontin protein were characterized. Highly statistically significant associations were found between the degree of osteopontin expression and the degrees of both calcification and macrophage accumulation in early through late lesions of aortic stenosis. Further, in situ hybridization localized osteopontin mRNA to a subset of lesion macrophages.

Conclusions
These results suggest that, rather than representing a degenerative and unmodifiable process, calcification in aortic stenosis may be, in part, an actively regulated process with the potential for control either through modification of inflammation or synthesis of proteins such as osteopontin, which may modulate calcification in this tissue.
Quantification of Mitral Regurgitation by the Proximal Convergence Method Using Transesophageal Echocardiography
Authors: Pu Min , Vandervoort Pieter M. , Griffin Brian P. , Leung Dominic Y. , Stewart William J. , Cosgrove Delos M. , Thomas James D.
Published: June 2012

Background
Proximal flow convergence is a promising method to quantify mitral regurgitation but may overestimate flow when the flow field is constrained. This has not been investigated clinically, nor has a correction factor been validated.

Methods and Results
Eighty-five patients were studied intraoperatively with transesophageal echocardiography and divided into two groups: central convergence (no constraining wall) and eccentric convergence (at least one constraining wall). Regurgitant stroke volume (RSV) and orifice area (ROA) were calculated by ROA=2π r
2
V
a
/V
p
and RSV=ROA×VTI
cw
, where r and v
a
are the radius and velocity of the aliasing contour and v
p
and VTI
cw
are the peak and integral of regurgitant velocity. In eccentric convergence patients, convergence angle (α) was measured from two-dimensional Doppler color flow maps, and ROA and RSV were corrected by multiplying by α/180. For reference, RSV was the difference between thermodilution and pulsed Doppler stroke volumes. In central convergence patients (n=45), RSV (
r
=.95, Δ=2.5±10.8 mL) and ROA (
r
=.96, Δ=0.02±0.08 cm
2
) were accurately calculated, but significant overestimation was noted in the eccentric convergence patients (n=40, ΔRSV=63.9±38.0 mL, ΔROA=0.54±0.31 cm
2
), 68% of whom had leaflet prolapse or flail. ΔRSV was correlated with α (
r
=–.69,
P
<.001). After correction by α/180, overestimation was largely eliminated (ΔRSV=15.5±19.3 mL and ΔROA=0.14±0.14 cm
2
) with excellent correlation for the whole group (RSV,
r
=.91; ROA,
r
=.95).

Conclusions
A simple geometric correction factor largely eliminates overestimation caused by flow constraint with the proximal convergence method and should extend the clinical utility of this technique.
Pressure-Diameter Relation of the Human Aorta
Authors: Stefanadis Christodoulos , Stratos Costas , Vlachopoulos Charalambos , Marakas Stelios , Boudoulas Harisios , Kallikazaros Ioannis , Tsiamis Eleftherios , Toutouzas Konstantinos , Sioros Lambros , Toutouzas Pavlos
Published: June 2012

Background
Pressure-diameter relation of the aorta provides important information about the elastic properties of the vessel. However, owing to methodological limitations, data regarding this relation are limited in conscious humans. In the present study, we assessed a new method for the direct estimation of the elastic properties of the aorta in conscious humans by simultaneous acquisition of instantaneous aortic pressure and diameter.

Methods and Results
With this method, instantaneous diameter of the thoracic aorta was acquired by a newly designed intravascular catheter developed in our institution that incorporates an ultrasonic displacement meter at its distal end. Instantaneous aortic pressure was acquired simultaneously at the same aortic level with a catheter-tip micromanometer. Aortic pressure-diameter loops were derived from computer analysis of data. After in vitro and animal testing, elastic properties of the aorta were investigated in coronary artery disease (CAD) patients (n=15) and compared with those of control subjects (n=10). Aortic distensibility was less in the CAD group than in the control group (1.73±0.33 versus 3.95±1.09×10
−6
×cm
2
×dyne
−1
,
P
<.001). Compared with control subjects, the mean value of the slope of the pressure-diameter loops was significantly greater in the CAD group (38.89±8.75 versus 19.62±5.46 mm Hg · mm
−1
,
P
<.001), whereas the mean value of the intercept was lower in this latter group of patients (−785.60±177.55 versus −313.43±126.41 mm Hg,
P
<.001). An excellent correlation was found between the slope of pressure-diameter loop and age in the group of control subjects (
r
=.827). Ninety-three percent of the patients with CAD had values above the upper 95% confidence limits of the control subjects (
P
<.001). In a third group of patients (n=16) in whom assessment of pulse wave velocity was also included in the study of the elastic properties of the aorta, pulse wave velocity had a strong inverse correlation with aortic distensibility (
r
=−.95) and a strong positive correlation with the slope of the pressure-diameter loop (
r
=.97).

Conclusions
This new method of determination of pressure-diameter of the aorta enables an accurate and reliable evaluation of the elastic properties of the aorta in conscious humans and may be useful for a profound study of human aorta mechanics.
A Multicenter, Double-Blind, Placebo-Controlled Trial of Aprotinin for Reducing Blood Loss and the Requirement for Donor-Blood Transfusion in Patients Undergoing Repeat Coronary Artery Bypass Grafting
Authors: Levy Jerrold H. , Pifarre Roque , Schaff Hartzell V. , Horrow Jan C. , Albus Robert , Spiess Bruce , Rosengart Todd K. , Murray Jeffrey , Clark Richard E. , Smith Peter , Nadel Andrea , Bonney Sharon L. , Kleinfield Robert
Published: June 2012

Background
Aprotinin is a serine protease inhibitor that reduces blood loss and transfusion requirements when administered prophylactically to cardiac surgical patients. To examine the safety and dose-related efficacy of aprotinin, a prospective, multicenter, placebo-controlled trial was conducted in patients undergoing repeat coronary artery bypass graft (CABG) surgery.

Methods and Results
Two hundred eighty-seven patients were randomly assigned to receive either high-dose aprotinin, low-dose aprotinin, pump-prime-only aprotinin, or placebo. Drug efficacy was determined by the reduction in donor-blood transfusion up to postoperative day 12 and in postoperative thoracic-drainage volume. The percentage of patients requiring donor–red-blood-cell (RBC) transfusions in the high- and low-dose aprotinin groups was reduced compared with the pump-prime-only and placebo groups (high-dose aprotinin, 54%; low-dose aprotinin, 46%; pump-prime only, 72%; and placebo, 75%; overall
P
=.001). The number of units of donor RBCs transfused was significantly lower in the aprotinin-treated patients compared with placebo (high-dose aprotinin, 1.6±0.2 U; low-dose aprotinin, 1.6±0.3 U; pump-prime-only, 2.5±0.3 U; and placebo, 3.4±0.5 U;
P
=.0001). There was also a significant difference in total blood-product exposures among treatment groups (high-dose aprotinin, 2.2±0.4 U; low-dose aprotinin, 3.4±0.9 U; pump-prime-only, 5.1±0.9 U; placebo, 10.3±1.4 U). There were no differences among treatment groups for the incidence of perioperative myocardial infarction (MI).

Conclusions
This study demonstrates that high- and low-dose aprotinin significantly reduces the requirement for donor-blood transfusion in repeat CABG patients without increasing the risk for perioperative MI.
Single Lung Transplantation for Pulmonary Hypertension
Authors: Pasque Michael K. , Trulock Elbert P. , Cooper Joel D. , Triantafillou Anastasios N. , Huddleston Charles B. , Rosenbloom Michael , Sundaresan Sudhir , Cox James L. , Patterson G. Alexander
Published: June 2012

Background
The present study considered the uniformity and durability of the cardiopulmonary response to single lung transplantation in patients with severe pulmonary hypertension, as well as its effect on length and quality of survival.

Methods and Results
Thirty-four patients with pulmonary hypertension underwent evaluation, single lung transplantation, and follow-up assessment between November 1, 1989, and June 1, 1994. Operative survival for the entire group of patients was reasonable, with 91% (31 of 34 patients) surviving and being discharged from the hospital following transplantation. The actuarial survival for these 34 patients at 1-, 2-, and 3-year follow-up was 78%, 66%, and 61%, respectively. In the subgroup of 24 patients with primary pulmonary hypertension (PPH), 96% (23 of 24) were successfully discharged from the hospital after transplantation. The actuarial survival for this isolated PPH subgroup at 1-, 2-, and 3-year follow-up was 87%, 76%, and 68%, respectively. The uniform, early posttransplant normalization of pulmonary vascular resistance and right ventricular ejection fraction appears to persist throughout the 4-year follow-up period. Despite a high prevalence of bronchiolitis obliterans, the majority of survivors remain in New York Heart Association functional class I or II and are employed.

Conclusions
Single lung transplantation can be performed in patients with end-stage pulmonary vascular disease with reasonable expectations for a relatively low operative mortality; immediate, complete, and durable amelioration of pulmonary hypertension and right ventricular failure; and optimal use of limited donor organ supply.
Logistic Time Constant of Isovolumic Relaxation Pressure–Time Curve in the Canine Left Ventricle
Authors: Matsubara Hiromi , Takaki Miyako , Yasuhara Shingo , Araki Junichi , Suga Hiroyuki
Published: June 2012

Background
The time constant of left ventricular (LV) relaxation derived from a monoexponential model has been widely used as an index of LV relaxation rate or lusitropism, although this model has several well-recognized problems. In the present study, we proposed a logistic model and derived a “logistic” time constant (
T
L
) as a better alternative to the conventional “exponential” time constant (
T
E
).

Methods and Results
A total of 189 beats (147 isovolumic and 42 ejecting beats) were investigated in seven canine excised cross–circulated heart preparations. We found that the logistic model fitted much more precisely all the observed LV isovolumic relaxation pressure–time [P(t)] curves than the monoexponential model (
P
<.05). The logistic model also fitted well both the time curve of the first derivative of the observed P(t) (dP/dt) and the dP/dt–P(t) phase–plane curve. Like
T
E
,
T
L
indicated that volume loading depressed LV lusitropism and that increasing heart rate and ejection fraction augmented it.
T
L
was independent of the choice of cutoff point defining the end of isovolumic relaxation;
T
E
was dependent on that choice.

Conclusions
We conclude that the logistic model better fits LV isovolumic relaxation P(t) than the monoexponential model in the present heart preparation. We therefore propose
T
L
as a better alternative to
T
E
for evaluating LV lusitropism.
Adrenergic Control of the Force-Frequency Relation
Authors: Ross John , Miura Toshiro , Kambayashi Masashi , Eising Gregory P. , Ryu Kyu-Hyung
Published: June 2012

Abstract
This article briefly reviews recent experimental studies which show that β-adrenergic receptor stimulation produces an important enhancement of the force-frequency relation on myocardial contractility. The basic property of the force-frequency effect to progressively enhance myocardial contractility as heart rate increases is augmented at each level of increasing adrenergic stimulation. This newly described intrinsic mechanism for the control of cardiac inotropic state, graded β-adrenergic amplification of the force-frequency relation, is strongly manifested during normal exercise and infusion of a β-adrenergic agonist at rest, and it influences both systolic and diastolic ventricular function. Significant impairment of adrenergic amplification of the force-frequency relation is observed in experimental heart failure and could contribute to impaired cardiac function during stress or exercise in this setting.
Asymptomatic Cardiac Ischemia Pilot (ACIP) Study
Authors: Bourassa Martial G. , Knatterud Genell L. , Pepine Carl J. , Sopko George , Rogers William J. , Geller Nancy L. , Dyrda Ihor , Forman Sandra A. , Chaitman Bernard R. , Sharaf Barry , Davies Richard F. , Conti C. Richard
Published: June 2012

Background
Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome.

Methods and Results
A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n=184), ischemia-guided medical strategy (n=182), or revascularization (n=192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (
P
=.002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (
P
=.005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (
P
=.001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (
P
<.001).

Conclusions
Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.
Surgical Management of Aortic Dissection During a 30-Year Period
Authors: Fann James I. , Smith Julian A. , Miller D. Craig , Mitchell R. Scott , Moore Kathleen A. , Grunkemeier Gary , Stinson Edward B. , Oyer Philip E. , Reitz Bruce A. , Shumway Norman E.
Published: June 2012

Background
Certain recent studies have demonstrated improved surgical outcome in patients with aortic dissection. We analyzed the surgical survival rates of patients with acute aortic dissections and the late prognosis of those with aortic dissection during a 30-year period.

Methods and Results
Between 1963 and 1992, 360 patients (256 men and 104 women; mean±1 SD age, 57±14 years) underwent surgery for aortic dissection: 174 patients had an acute type A (AcA), 46 an acute type B (AcB), 106 a chronic type A (ChA), and 34 a chronic type B (ChB) aortic dissection. The overall operative mortality rate was 24±8% (26±3% for AcA, 39±8% for AcB, 17±4% for ChA, and 15±6% for ChB, [±70% confidence limit]). The operative mortality rates for patients with acute aortic dissection (AcA or AcB) were assessed for five time “windows”: 1963 to 1972 (42±8%), 1973 to 1977 (37±8%), 1978 to 1982 (15±6%), 1983 to 1987 (27±6%), and 1988 to 1992 (26±6%). Logistic regression analysis suggested that the low operative mortality rate during the 1978-to-1982 interval occurred by chance. Multivariate analysis showed earlier operative year, hypertension, cardiac tamponade, renal dysfunction, and older age were independent determinants of operative death. Actuarial survival rates (including early deaths) after 5, 10, and 15 years for AcA patients were 55%, 37%, and 24%; for AcB, 48%, 29%, and 11%; for ChA, 65%, 45%, and 27%; and for ChB, 59%, 45%, and 27%. Multivariate analysis revealed that older age and previous operation were significant predictors for late death. Freedom from reoperation for all patients was 84%, 67%, and 57% at 5, 10, and 15 years, respectively.

Conclusions
Although the operative mortality rate decreased over time for patients with aortic dissection, the risk for those with acute aortic dissection during the last 10 years (1983 to 1992) is probably more realistic than that observed in the preceding 5-year interval (1978 to 1982). The operative mortality rates for patients with chronic aortic dissection have remained relatively static. Earlier diagnosis of acute aortic dissection before development of cardiac tamponade and renal impairment is critical to improve the operative salvage rate. Long-term outcome still is not optimal, which emphasizes the need for better serial postoperative aortic imaging surveillance and medical follow-up and blood pressure control.
Right Ventricular Performance and Mass by Use of Cine MRI Late After Atrial Repair of Transposition of the Great Arteries
Authors: Lorenz Christine H. , Walker Eloisa S. , Graham Thomas P. , Powers Thomas A.
Published: June 2012

Background
The long-term adaptation of the right ventricle after atrial repair of transposition of the great arteries (TGA) remains a subject of major concern. Cine magnetic resonance imaging (MRI), with its tomographic capabilities, allows unique quantitative evaluation of both right and left ventricular function and mass. Our purpose was to use MRI and an age-matched normal population to examine the typical late adaptation of the right and left ventricles after atrial repair of TGA.

Methods and Results
Cine MRI was used to study ventricular function and mass in 22 patients after atrial repair of TGA. Images were obtained in short-axis sections from base to apex to derive normalized right and left ventricular mass (RVM and LVM, g/m
2
), interventricular septal mass (IVSM, g/m
2
), RV and LV end-diastolic volumes (EDV, mL/m
2
), and ejection fractions (EF). Results 8 to 23 years after repair were compared with analysis of 24 age- and sex-matched normal volunteers and revealed markedly elevated RVM, decreased LVM and IVSM, normal RV size, and only mildly depressed RVEF. Only 1 of 22 patients had clinical RV dysfunction, and this patient had increased RVM.

Conclusions
Cine MRI allows quantitative evaluation of both RV and LV mass and function late after atrial repair of TGA. Longitudinal studies that include these measurements should prove useful in determining the mechanism of late RV failure in these patients. On the basis of these early data, inadequate hypertrophy does not appear to be the cause of late dysfunction in this patient group.
Endothelin in Coronary Endothelial Dysfunction and Early Atherosclerosis in Humans
Authors: Lerman Amir , Holmes David R. , Bell Malcolm R. , Garratt Kirk N. , Nishimura Rick A. , Burnett John C.
Published: June 2012

Background
The endothelium modulates vascular tone through release of vasodilating substances, such as endothelium-derived relaxing factors, and vasoconstricting substances, such as endothelin. Endothelin concentrations are elevated in humans with atherosclerosis and in hypercholesterolemic pigs. Furthermore, the endothelium-dependent vasodilator acetylcholine increases endothelin in hypercholesterolemia in association with coronary vasoconstriction. The present study was designed to test the hypotheses that coronary endothelial dysfunction in humans is characterized by enhanced coronary and circulating endothelin and that the vasoconstriction associated with acetylcholine results in further release of coronary endothelin.

Methods and Results
Coronary and circulating endothelin concentrations were measured at baseline and during intracoronary acetylcholine administration in 20 patients undergoing diagnostic coronary angiography. Patients were divided into two groups on the basis of their response to intracoronary acetylcholine. Group 1 (n=7) demonstrated a normal vasodilatory response, but group 2 (n=13) demonstrated coronary vasoconstriction. Baseline coronary and circulating endothelin concentrations (as determined by coronary sinus and femoral artery measurements, respectively) were higher in patients who responded to acetylcholine with coronary vasoconstriction (group 2) than in group 1 patients (coronary sinus, 15.9±1.0 pg/mL versus 7.1±1.0 pg/mL; femoral, 14.1±0.9 pg/mL versus 6.8±1.0 pg/mL, respectively;
P
<.01). In response to intracoronary acetylcholine, a further increase in coronary endothelin was observed only in group 2; this increase correlated with changes in coronary artery diameter.

Conclusions
This study demonstrates that endothelin immunoreactivity is enhanced in the coronary and systemic circulation in humans with coronary endothelial dysfunction. Moreover, acetylcholine further increased coronary endothelin concentration in patients with coronary endothelial dysfunction and was associated with coronary vasoconstriction. These observations strongly support a role for endothelin as an early participant in and marker for coronary endothelial dysfunction in humans.
Cigarette Smoking Acutely Increases Platelet Thrombus Formation in Patients With Coronary Artery Disease Taking Aspirin
Authors: Hung Joseph , Lam Jules Y.T. , Lacoste Lucie , Letchacovski Glaci
Published: June 2012

Background
Smoking is associated with an increased risk of myocardial infarction and sudden death. Platelet activation and thrombosis at sites of vessel stenosis and injury or plaque disruption play a crucial role in these acute coronary events. Thus, the aim of this study was to determine whether cigarette smoking acutely increases platelet thrombus formation on an injured arterial surface at local shear rates typical of a stenotic artery.

Methods and Results
Twelve habitual smokers with stable coronary disease, on aspirin 325 mg/d, were studied immediately before and 5 minutes after smoking two cigarettes each. Ex vivo platelet thrombus formation on porcine arterial media (simulating deep arterial injury) was measured after exposure to the patient’s circulating venous blood for 3 minutes in cylindrical flow chambers at 37°C. The flow chambers were designed to produce shear rates of 754 or 2546 s
−1
, the latter being typical of the high shear rates produced by vessel stenosis. Plasma catecholamine, thromboxane B
2
, and 6-ketoprostaglandin F
1α
(6-keto-PGF
1α
) levels and whole blood platelet aggregation responses to thrombin were also measured before and after smoking. Compared with before smoking, morphometrically measured platelet thrombus formation on arterial media at shear rates of 754 and 2546 s
−1
increased by an average of 48% (
P
=.19) and 64% (
P
=.014), respectively, after smoking. Plasma epinephrine increased by more than twofold after smoking (
P
=.026). Plasma thromboxane B
2
and 6-keto-PGF
1α
levels did not change. Smoking also increased whole blood platelet aggregation to thrombin (
P
≤.05).

Conclusions
These results suggest that smoking-enhanced platelet thrombosis may be an important contributory mechanism for acute coronary events in smokers that is not prevented by aspirin treatment. Catecholamine release and heightened platelet aggregation response to in vivo agonists may contribute to the prothrombotic effects of smoking.
Echocardiographic Assessment of Spontaneously Occurring Feline Hypertrophic Cardiomyopathy
Authors: Fox Philip R. , Liu Si-Kwang , Maron Barry J.
Published: June 2012

Background
Necropsy studies in domestic cats have suggested the occurrence of a primary cardiac disease resembling hypertrophic cardiomyopathy (HCM) in humans. We used two-dimensional echocardiography to define morphological and functional features of HCM during life in 46 domestic cats evaluated in a subspecialty veterinary clinic. Cats were 8 months to 14 years old (mean, 6 years).

Methods and Results
During the follow-up period of as long as 49 months, 18 cats died (or were euthanatized) due to congestive heart failure, peripheral embolization, or both, and 3 other cats experienced out-of-hospital sudden, unexpected death. Echocardiography showed a small left ventricular cavity, associated with a variety of patterns of hypertrophy. Wall thickening was most often diffuse (involving ventricular septum and free wall) in 31 cats (67%) and segmental in 15 (33%), including 12 with thickening confined to anterior septum; wall thickening was judged to be asymmetrical in 42 and symmetrical (concentric) in 4. In 30 cats (65%), marked mitral valve systolic anterior motion produced dynamic obstruction to left ventricular outflow (Doppler estimated gradients, 25 to 110 mm Hg). Compared with survivors, cats with HCM that died with heart failure had greater left ventricular thickness (8.1±1.5 versus 7.3±0.9 mm;
P
<.05) and larger left atria (20.1±4.6 versus 16.8±3.4 mm;
P
=.01) and more often had the nonobstructive form (89% versus 48%;
P
<.01).

Conclusions
A spontaneously occurring disease of domestic cats was identified by echocardiography and was similar in its phenotypic expression to HCM in humans; it was characterized by unexplained left ventricular hypertrophy in a variety of patterns with or without evidence of outflow obstruction. Unfavorable prognosis was associated with greater magnitude of hypertrophy and absence of outflow obstruction. Feline HCM may prove to be a valuable animal model of the human disease.
The Pathogenic Role of
Staphylococcus epidermidis
Capsular Polysaccharide/Adhesin in a Low-Inoculum Rabbit Model of Prosthetic Valve Endocarditis
Authors: Shiro Hiroyuki , Meluleni Gloria , Groll Andreas , Muller Eugene , Tosteson Tor D. , Goldmann Donald A. , Pier Gerald B.
Published: June 2012

Background
The capsular polysaccharide/adhesin (PS/A) antigen of
Staphylococcus epidermidis
was required to produce endocarditis in a rabbit model in which infection resulted from hematogenous spread of bacteria from a contaminated catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE) infections probably result from direct contamination of the valve with small numbers of bacteria during surgery. The role of PS/A in this situation was evaluated by modifying a rabbit model of endocarditis to partially mimic PVE.

Methods and Results
A Teflon catheter was contaminated with graded inocula of either PS/A-positive
S epidermidis
strain M187sp11 or the PS/A-negative, isogenic strain M187sn3 and inserted into the left ventricle through the aortic valve. The PS/A-positive strain had a 50% infectious dose of 1.1×10
2
cfu (95% CI, 3.3 to 3.7×10
3
) compared with 8.5×10
4
cfu of the PS/A-negative strain (95% CI, 8.6×10
3
to 8.5×10
5
). The odds for developing endocarditis were estimated to be 42 times higher for any given inoculum level of the PS/A-positive strain (
P
=.1). When the PS/A-positive strain was adherent to a catheter surface it survived in rabbit blood, whereas under the same conditions the PS/A-negative strain was killed ≈90% in 1 hour.

Conclusions
Direct contamination of an intraventricular foreign body by low levels of PS/A-positive
S epidermidis
results in endocarditis in rabbits, but at suitably high doses PS/A-negative strains have sufficient virulence to infect cardiac vegetations. PS/A enhances but is not absolutely required for bacterial virulence in a rabbit model of PVE.
Thromboembolic Complications After Fontan Operations
Authors: Rosenthal David N. , Friedman Alan H. , Kleinman Charles S. , Kopf Gary S. , Rosenfeld Lynda E. , Hellenbrand William E.
Published: June 2012

Background
Despite the increasing recognition of thromboembolic complications of the Fontan procedure, data characterizing such events are limited. The total cavopulmonary connection is believed to be less prone to this complication than other modifications of Fontan operations. We examined our experience with thromboembolism after Fontan operations to better characterize these events and their relation to the type of Fontan operation performed.

Methods and Results
We retrospectively identified 70 patients who underwent a Fontan operation between January 1978 and March 1994. Patients were divided into three groups: (1) total cavopulmonary connection, (2) atriopulmonary connection, and (3) conduit interposition. Fourteen patients (20%) developed a thromboembolic complication during a mean (±SD) follow-up of 5.2±4.7 years. The rate of thrombosis was similar in each group. The time from Fontan operation to thrombosis averaged 6.1±5.0 years. The overall rate of thromboembolic events was 3.9 per 100 patient-years. Twelve of the 14 thrombi were located within the venous circulation, 1 was in the left ventricle, and the location of 1 was undetermined. Six of the patients (43%) were asymptomatic, 3 (21%) presented with cerebrovascular events, and 5 (36%) presented with other symptoms. Thromboembolic events occurred from the perioperative period to 15 years after surgery.

Conclusions
Thromboembolic complications occur frequently after the Fontan operation and its modifications and are a cause of significant morbidity. The time of presentation varies greatly. The rate of thrombosis appears to be similar in all modifications of the Fontan operation.
Bidirectional Glenn
Authors: Mainwaring Richard D. , Lamberti John J. , Uzark Karen , Spicer Robert L.
Published: June 2012

Background
The bidirectional Glenn (BDG) is frequently used in the staged surgical management of single ventricle patients. Controversy exists whether accessory pulmonary blood flow (APBF) sources should be left at the time of the BDG to augment systemic saturation or should be eliminated to reduce volume load of the ventricle. The present study was a retrospective review to assess the influence of APBF on outcome after the BDG.

Methods and Results
Ninety-two patients have undergone BDG at our institute during the interval from 1986 through 1994. At the time of BDG, 40 patients had either a systemic-to–pulmonary artery shunt or patent right ventricular outflow tract as an additional source of pulmonary blood flow. Fifty-two patients had elimination of APBF. There were three operative deaths (two with and one without APBF) and four procedures (two in each group) that failed and required subsequent revision. Thus, there were 85 patients who underwent successful operation. Effusions (defined as chest tube drainage exceeding 7 days’ duration) occurred in 8 of 85 patients; this complication was seen in 7 of 36 patients (19%) with APBF and 1 of 49 patients (2%) without APBF (
P
<.05). There were 11 deaths, including 6 patients (17%) with APBF, 2 patients (4%) without APBF, and 3 of the patients (75%) who had a failed BDG.

Conclusions
The data suggest that morbidity and mortality are lower in patients in whom APBF is eliminated at the time of the BDG.
Development of Pulmonary Arteriovenous Fistulae in Children After Cavopulmonary Shunt
Authors: Bernstein Harold S. , Brook Michael M. , Silverman Norman H. , Bristow James
Published: June 2012

Background
The cavopulmonary shunt procedure is now used for palliation of complex congenital heart lesions in infants. While pulmonary arteriovenous fistulae (PAVF) are a well-known complication of this surgery in older patients, no study of the prevalence of this condition in children and young infants has been reported.

Methods and Results
We compared 29 patients with cavopulmonary shunts or total caval exclusion with 53 control subjects evaluated by contrast echocardiography at the University of California, San Francisco. The primary cardiac lesion, age at the time of surgery, type of right heart bypass procedure, provision of auxiliary pulmonary blood flow, and changes in oxygen saturation over time were compared. The prevalence of PAVF in children after cavopulmonary anastomosis is 60%, higher than previously reported. The prevalence is significantly higher in infants <6 months old and in those with a heterotaxy syndrome. The provision of an additional source of pulsatile, pulmonary blood flow appears to have little effect on the development of PAVF. Patients who developed PAVF had arterial oxygen saturations at the time of discharge from surgery similar to those who did not develop them. Those with PAVF had significantly lower arterial and pulmonary venous oxygen saturations at follow-up as a result of their intrapulmonary shunt.

Conclusions
Contrast echocardiography provides a sensitive method for the detection of PAVF. While the origins, natural history, and ultimate clinical significance of PAVF in children after cavopulmonary anastomosis are unclear, surveillance by contrast echocardiography is indicated for all patients who have had this procedure because PAVF may cause significant intrapulmonary right-to-left shunting in some patients.
Improved Preservation of Saphenous Vein Grafts by the Use of Glyceryl Trinitrate–Verapamil Solution During Harvesting
Authors: Roubos Nick , Rosenfeldt Franklin L. , Richards Stephen M. , Conyers Robert A.J. , Davis Bruce B.
Published: June 2012

Background
High-pressure distension during harvesting damages the saphenous vein (SV) and may contribute to subsequent coronary artery bypass graft (CABG) occlusion. Application of vasodilator agents to the SV during harvesting may reduce the need for high-pressure distension and improve graft quality. We tested the effects of a vasodilator solution containing glyceryl trinitrate and verapamil (GV) or the conventional agent papaverine (Pap) on the pressure necessary to overcome SV spasm and on the structure and biochemistry of the SV graft.

Methods and Results
Thirty-six patients undergoing CABG were randomly allocated to receive an application of either topical and intraluminal GV solution, topical Pap, or topical and intraluminal Ringer’s solution (untreated) to the SV during harvesting. The peak and mean pressures required to distend the vein were recorded. Samples of SV were taken for microscopy and biochemical analysis just before we performed the anastomosis. The percentage of endothelial coverage was calculated by area measurements of stained en face preparations of the vein intima. The results for peak pressures (mm Hg) were: untreated, 479.2±27.5; Pap, 384.8±29.0; and GV, 309.5±28.3 (
P
<.001, GV plus Pap versus untreated); and the results for mean pressures (mm Hg) were untreated, 136.2±9.6; Pap, 102.2±10.8; and GV, 98.0±8.3 (
P
<.01, GV plus Pap versus untreated). The results for endothelial cover (%) were: untreated, 43.7±7.0; Pap, 44.1±9.2; and GV, 68.7±7.0 (
P
<.05, GV versus Pap); and the results for ATP (nmol/g wet wt) were: untreated, 67.3±12.7; Pap, 112.0±19.4; and GV, 132.5±22.7 (
P
<.05, GV plus Pap versus untreated).

Conclusions
First, pharmacological treatment of SV during harvesting, especially with GV solution, allows the use of a lower distension pressure and reduces the breakdown of high-energy phosphates in the vein wall. Second, topical and intraluminal use of GV solution during vein harvesting improves endothelial coverage compared with the topical use of Pap or no pharmacological treatment.
Comparison by Computerized Numeric Modeling of Energy Losses in Different Fontan Connections
Authors: Van Haesdonck Jean-Marie , Mertens Luc , Sizaire Renaud , Montas Gilberto , Purnode Bruno , Daenen Wim , Crochet Marcel , Gewillig Marc
Published: June 2012

Background
Different surgical techniques for creating a Fontan circulation can be used. The option of including an atrium in the circuit, or the technique used for connecting the caval veins to the pulmonary artery in a total cavopulmonary connection, frequently is empirical and is based on personal experience and preference. The hemodynamic and energetic differences between the different circuits are small, and short-term results are comparable. However, small, energetic differences may have significant implications for the long-term follow-up. The finite element method allows a computer-based modeling of the flow dynamics and pressure losses. It permits comparison of different Fontan connections in a single patient with identical geometry and functional conditions.

Methods and Results
We compared the atriopulmonary connection with different types of cavopulmonary connections, which differed in the degree of symmetry of implantation of both caval veins into the right pulmonary artery. Based on anatomic models and physiological flow dynamics, three-dimensional geometries and finite element meshes were created with
patran
; flows were calculated with
polyflow (b)
, and results were visualized with
data visualizer
.

Conclusions
The atriopulmonary connection produces higher energy losses than the cavopulmonary connection (±1 mm Hg at rest). The cavopulmonary connection is more efficient when the connection of the caval veins to the pulmonary artery is asymmetrical.
Steroid Inhibition of Cytokine-Mediated Vasodilation After Warm Heart Surgery
Authors: Teoh Kevin H.T. , Bradley Christine A. , Gauldie Jack , Burrows Heather
Published: June 2012

Background
Peripheral vasodilation, a potentially adverse effect of warm heart surgery, may be mediated by the perioperative release of cytokines. Corticosteroids may abolish cytokine production and vasodilation. We investigated cytokine production and its inhibition by steroids in patients undergoing elective coronary bypass surgery.

Methods and Results
Twenty-five patients undergoing coronary bypass surgery with normothermic cardiopulmonary bypass received either preoperative steroid (Solumedrol 250 mg IV, n=16) or no steroid (n=9, control group). Blood samples were obtained serially for 24 hours and assayed for interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-8 (IL-8). In the control patients, the IL-6, TNF, and IL-8 levels were elevated postoperatively and peaked between 3 and 6 hours after surgery (IL-6, 1330±295 [mean±SEM] pg/mL; TNF, 18.4±9.8 pg/mL; and IL-8, 150±51 pg/mL). Cytokine release was abolished in patients receiving preoperative corticosteroid (IL-6, 75±38 pg/mL; TNF, 2.6±0.5 pg/mL; and IL-8, 33±6.7 pg/mL;
P
<.05). Patients receiving steroid premedication had higher arterial pressure, lower cardiac index, and higher systemic vascular resistance, indicating less vasodilation.

Conclusions
Our findings demonstrate that cytokine production occurs after normothermic cardiopulmonary bypass. Preoperative administration of steroids abolishes cytokine release and vasodilation.