bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Menopause on Trends of Serum Cholesterol, Blood Pressure, and Body Mass Index
Authors: Akahoshi Masazumi , Soda Midori , Nakashima Eiji , Shimaoka Katsutaro , Seto Shinji , Yano Katsusuke
Published: June 2012

Background
To elucidate the impact of menopause on coronary risk factors, we determined the trends of serum cholesterol (mg/dL), blood pressure (BP, mm Hg), and body mass index (BMI, kg/m
2
) and investigated whether menopause affects these trends in women in Nagasaki, Japan.

Methods and Results
Trends of cholesterol, systolic BP (SBP), and BMI from 9 years before menopause through 9 years after menopause in 579 women with natural menopause (ranging in age from 40.2±3.1 to 57.9±3.1 years; age at menopause, 49.4±3.0 years) and 134 women with surgical menopause (hysterectomy with or without bilateral oophorectomy; ranging in age from 34.9±4.5 to 51.7±5.1 years; age at menopause, 42.9±5.0 years) and those in 579 and 134 age- and time-matched male subjects (ranging in age from 40.1±3.1 to 57.8±3.2 years and from 35.2±4.5 to 51.6±5.0 years, respectively) in Nagasaki were determined by rearrangement of the data from 1958 to 1989 with time of menopause as the datum line. Although cholesterol tended to increase with age in both sexes, it increased significantly in women from 3 years before natural menopause to 1 year after natural menopause and from 1 year before surgical menopause to 1 year after surgical menopause. SBP and BMI did not exhibit a significant increase in relation to natural or surgical menopause. In male subjects, no significant increase of cholesterol, SBP, or BMI was observed at the age corresponding to natural or surgical menopause.

Conclusions
Natural menopause and surgical menopause exert an effect only on cholesterol, and an increase in cholesterol precedes natural menopause by 3 years and occurs at the time of surgical menopause.
Efficacy of Routine Fetal Ultrasound Screening for Congenital Heart Disease in Normal Pregnancy
Authors: Buskens E. , Grobbee D.E. , Frohn-Mulder I.M.E. , Stewart P.A. , Juttmann R.E. , Wladimiroff J.W. , Hess J.
Published: June 2012

Background
Second trimester routine ultrasound evaluation of the fetal heart by means of the four-chamber view has been proposed for prenatal detection of cardiac anomalies. The aim of this study was to evaluate the efficacy of this procedure.

Methods and Results
A prospective follow-up study on 6922 scanned fetuses was performed. Pregnant women without known risk factors who were scheduled for a routine fetal ultrasound examination between 16 and 24 weeks gestation were invited to participate. Follow-up until 6 months postpartum was available for 5660 subjects (81.8%), of whom 5319 fulfilled all eligibility criteria. By comparing the prenatal diagnosis to the postnatal diagnosis, we obtained sensitivity, specificity, and predictive value (positive and negative). A total of 80 cases of congenital malformations were diagnosed during the study: 44 cases of congenital heart disease, 40 cases of noncardiac malformations, and a combination of the two in 4 cases. The fetal four chamber–view examination was considered abnormal in 7 women who were subsequently referred for extensive fetal ultrasound examination. Two proved to be carrying an affected fetus. Similarly, prenatal referral of 14 women because of suspected noncardiac malformations yielded 12 such cases. The fetal four chamber–view examination had a sensitivity of 4.5% (95% CI, 0.6% to 15%). Sensitivity for noncardiac anomalies was 30% (95% CI, 16.6% to 46.5%). Overall sensitivity of ultrasound examination was 16.3% (95% CI, 2.09% to 48.8%). Specificity and negative predictive value were high (>98%). The positive predictive value was low with wide CIs.

Conclusions
These results suggest that the current mode of routine prenatal ultrasound screening for congenital malformations is inefficient, particularly for cardiac anomalies.
Rate of Collagen Deposition During Healing and Ventricular Remodeling After Myocardial Infarction in Rat and Dog Models
Authors: Jugdutt Bodh I. , Joljart Michael J. , Khan Mohammad I.
Published: June 2012

Background
We hypothesized that the rate and amount of infarct collagen deposition during healing after myocardial infarction might influence ventricular remodeling in rat and dog models. The purpose of this study was to compare rates of infarct collagen deposition and ventricular remodeling in the two models.

Methods and Results
Infarcted rat and dog hearts were removed at fixed time intervals between 1 and 50 days for measuring remodeling parameters and infarct and noninfarct collagen content (mg/g hydroxyproline). Collagen was less in sham rat (n=29) than dog (n=30) ventricles (3.32 versus 4.57 mg/g,
P
<.001) and markedly lower in the rat (n=48) than dog (n=59) infarcts throughout healing and by 50 days (9.98 versus 56.74 mg/g,
P
<.0001). Infarct collagen leveled off earlier and healing (histology) was completed sooner in the rat. Infarct scars were also thinner in the rat, with more (
P
<.0001) thinning and bulging (mm/g), and greater increase in ventricular volume. Although the mass to volume ratio decreased (
P
<.001) in both models, global remodeling was different, with greater transverse axis widening and globularity in the dog. Although infarct size, transmurality, heart rate, filling pressure, and blood pressure were greater in the rat, infarcts 10% to 30% in size in both models showed similar differences in infarct collagen and remodeling.

Conclusions
Compared with dog infarcts, rat infarcts exhibited faster healing and infarct collagen deposition and markedly lower infarct collagen. In addition to larger, more transmural, and thinner infarcts, and greater hemodynamic load, the lower infarct collagen in that model might be an important factor in the greater regional remodeling.
Effects of Endovascular Radiation From a β-Particle–Emitting Stent in a Porcine Coronary Restenosis Model
Authors: Carter Andrew J. , Laird John R. , Bailey Lynn R. , Hoopes Timothy G. , Farb Andrew , Fischell David R. , Fischell Robert E. , Fischell Tim A. , Virmani Renu
Published: June 2012

Background
Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and rabbit iliac arteries. The objective of this study was to evaluate the dose-related effects of a β-particle–emitting radioactive stent in a porcine coronary restenosis model.

Methods and Results
Thirty-seven swine underwent placement of 35 nonradioactive and 39 β-particle–emitting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 μCi of
32
P. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth muscle cell density were inversely related to increasing stent activity. The neointima of the high-activity (3.0- to 23.0-μCi) stents consisted of fibrin, erythrocytes, occasional inflammatory cells, and smooth muscle cells with partial endothelialization of the luminal surface. In the 1.0-μCi stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of the low-activity (0.15- and 0.5-μCi) stents was composed of smooth muscle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in neointimal area (low, 1.63±0.67 mm
2
and high, 1.73±0.97 mm
2
versus control, 2.40±0.87 mm
2
) and percent area stenosis (low, 26±7% and high, 26±12%) compared with control stents (37±12%,
P
≤.01). The 1.0-μCi stents, however, had greater neointimal formation (4.67±1.50 mm
2
) and more luminal narrowing (64±16%) than the control stents (
P
<.0001).

Conclusions
The differential response to the doses of continuous β-particle irradiation used in this experimental model suggests a complex biological interaction of endovascular radiation and vascular repair after stent placement. Further study is required to determine the clinical potential for this therapy to prevent stent restenosis.
Plasma Protein Acute-Phase Response in Unstable Angina Is Not Induced by Ischemic Injury
Authors: Liuzzo Giovanna , Biasucci Luigi M. , Rebuzzi Antonio G. , Gallimore J. Ruth , Caligiuri Giuseppina , Lanza Gaetano A. , Quaranta Gaetano , Monaco Claudia , Pepys Mark B. , Maseri Attilio
Published: June 2012

Background
Elevated levels of C-reactive protein (CRP) are associated with an unfavorable clinical outcome in patients with unstable angina. To determine whether ischemia-reperfusion injury causes this acute-phase response, we studied the temporal relation between plasma levels of CRP and ischemic episodes in 48 patients with unstable angina and 20 control patients with active variant angina, in which severe myocardial ischemia is caused by occlusive coronary artery spasm.

Methods and Results
Blood samples were taken on admission and subsequently at 24, 48, 72, and 96 hours. All patients underwent Holter monitoring for the first 24 hours and remained in the coronary care unit under ECG monitoring until completion of the study. On admission, CRP was significantly higher in unstable angina than in variant angina patients (
P
<.001). In unstable angina, 70 ischemic episodes (1.5±2 per patient) and in variant angina 192 ischemic episodes (9.6±10.7 per patient) were observed during Holter monitoring (
P
<.001), for a total ischemic burden of 14.8±30.2 and 44.4±57.2 minutes per patient, respectively (
P
<.001). The plasma concentration of CRP did not increase in either group during the 96 hours of study, even in patients who had episodes of ischemia lasting >10 minutes.

Conclusions
The normal levels of CRP in variant angina, despite a significantly larger number of ischemic episodes and greater total ischemic burden, and the failure of CRP values to increase in unstable angina indicate that transient myocardial ischemia, within the range of duration observed, does not itself stimulate an appreciable acute-phase response.
Serum Lipids and Incidence of Coronary Heart Disease
Authors: Frost Philip H. , Davis Barry R. , Burlando Alfredo J. , Curb J. David , Guthrie Gordon P. , Isaacsohn Jonathan L. , Wassertheil-Smoller Sylvia , Wilson Alan C. , Stamler Jeremiah
Published: June 2012

Background
The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age ≥60 years.

Methods and Results
The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of <4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of <4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate.

Conclusions
The results of this study support the concept that serum lipids are CHD risk factors in older Americans.
Distinct Effects of Recombinant Desulfatohirudin (Revasc) and Heparin on Plasma Levels of Fibrinopeptide A and Prothrombin Fragment F1.2 in Unstable Angina
Authors: Rao A. Koneti , Sun Ling , Chesebro James H. , Fuster Valentin , Harrington Robert A. , Schwartz Darryl , Gallo Paul , Matos Deborah , Topol Eric J.
Published: June 2012

Background
Thrombin plays an important role in the pathogenesis of acute coronary thrombosis. We studied the effects of a direct thrombin inhibitor, recombinant desulfatohirudin, and heparin on plasma levels (at 0, 4, 12, and 24 hours) of fibrinopeptide A (FPA), which reflects thrombin action, and prothrombin fragment F1.2, which reflects thrombin generation, in patients with unstable angina.

Methods and Results
Patients were randomized to one of two doses of heparin (n=50) (target activated partial thromboplastin time, 65 to 90 seconds or 90 to 110 seconds) or one of four doses of r-hirudin (n=113) (0.05, 0.10, 0.20, or 0.30 mg·kg
−1
·h
−1
by infusion). r-Hirudin induced a dose-dependent decline in plasma FPA. At 24 hours, FPA levels with 0.1- to 0.3-mg·kg
−1
·h
−1
r-hirudin regimens were significantly lower than with 0.05 mg·kg
−1
·h
−1
r-hirudin; levels with 0.1- to 0.2-mg·kg
−1
·h
−1
r-hirudin regimens were lower than with both heparin regimens. Plasma F1.2 did not decline significantly during therapy with heparin or hirudin except at 0.3 mg·kg
−1
·h
−1
hirudin. At 24 hours, they were higher with the 0.05-mg·kg
−1
·h
−1
r-hirudin regimen than with other regimens. For comparable levels of thrombin generation (F1.2 levels), FPA levels were higher in heparin patients than in hirudin patients. For the same FPA values, the corresponding F1.2 values were higher in the hirudin group.

Conclusions
Our findings provide evidence for distinct in vivo effects of the two agents and suggest that r-hirudin is a relatively more potent inhibitor of thrombin action but a less effective inhibitor of thrombin generation than heparin. The lower FPA levels in hirudin patients may reflect its ability to inactivate clot-bound thrombin. The relative clinical efficacies of the two agents need to be defined by clinical trials in progress.
Ischemic, Hemodynamic, and Neurohormonal Responses to Mental and Exercise Stress
Authors: Goldberg A. David , Becker Lewis C. , Bonsall Robert , Cohen Jerome D. , Ketterer Mark W. , Kaufman Peter G. , Krantz David S. , Light Kathleen C. , McMahon Robert P. , Noreuil Todd , Pepine Carl J. , Raczynski James , Stone Peter H. , Strother Dawn , Taylor Herman , Sheps David S.
Published: June 2012

Background
The pathophysiology of mental stress–induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood.

Methods and Results
The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress.

Conclusions
Mental stress–induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanisms involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.
Coronary Artery Bypass Mortality Rates in Ontario
Authors: Tu Jack V. , Naylor C. David
Published: June 2012

Background
This study was conducted to assess the overall mortality rate and the amount of interhospital variation in risk-adjusted mortality rates after coronary artery bypass graft (CABG) surgery in Ontario, Canada. CABG outcomes data are not publicly disseminated in Ontario.

Methods and Results
Clinical risk factors and surgical outcomes were collected on 15 608 patients undergoing isolated CABG surgery between April 1, 1991, and March 31, 1994, at the nine hospitals performing adult cardiac surgery in Ontario. The data were analyzed on the basis of a fiscal year. The overall mortality rate was 3.01%, and the risk-adjusted mortality rate declined from 3.17% in 1991 to 2.93% in 1993. In 1991, one of the nine hospitals had a risk-adjusted mortality rate significantly lower than the provincial average. Otherwise, the hospitals all had risk-adjusted mortality rates within the expected range during the time period of the study. All hospitals performed >300 CABG procedures in 1992 and 1993, and only 2 of 42 cardiac surgeons performed <50 CABG procedures in 1993.

Conclusions
The in-hospital mortality rate after CABG surgery in Ontario is low, and the amount of interhospital variation in risk-adjusted mortality rates is no greater than that expected by chance alone. These outcomes are probably attributable to regionalization of CABG surgery and a very low prevalence of low-volume cardiac surgeons in Ontario.
Evolution of Early TIMI 2 Flow After Thrombolysis for Acute Myocardial Infarction
Authors: Reiner Jonathan S. , Lundergan Conor F. , Fung Anthony , Coyne Karin , Cho Shyuan , Israel Noah , Kazmierski John , Pilcher George , Smith James , Rohrbeck Steven , Thompson Mark , Van de Werf Frans , Ross Allan M.
Published: June 2012

Background
Patients with early Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolysis appear to have outcomes similar to thrombolytic failures. To evaluate the origin and evolution of early TIMI 2 flow, we examined early and late angiographic and ventriculographic data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-1) angiographic study.

Methods and Results
Of the 914 patients with both 90-minute and 5- to 7-day catheterizations, 278 patients had TIMI grade 2 flow at 90 minutes. At follow-up, 188 (67%) had improved to TIMI grade 3 flow. At 90 minutes, patients with TIMI grade 2 flow had greater infarct vessel narrowing and a significantly greater incidence of thrombus than patients with TIMI grade 3 flow. At the 5- to 7-day follow-up, patients whose flow had improved from TIMI grade 2 at 90 minutes to grade 3 flow at follow-up had larger-caliber vessels (minimum luminal diameter, 0.99±0.47 versus 0.84±0.48 mm;
P
=.03) and a lower incidence of visible thrombus (26% versus 38%,
P
=.04) than those with persistent TIMI grade 2 flow. These patients also had a higher mean ejection fraction (57.5±14.1% versus 52.8±12.9%,
P
=.02) and better infarct zone wall motion (−2.1±1.5 versus −2.6±1.3 SD per chord,
P
=.01) at the 5- to 7-day follow-up. Patients in whom flow improved from TIMI grade 2 at 90 minutes to TIMI grade 3 by 5 to 7 days had significantly better left ventricular function than patients with persistent TIMI grade 0, 1, or 2 flow and constituted a group whose left ventricular function was intermediate between those who had no reperfusion (TIMI grades 0 and 1) and those whose reperfusion was complete (TIMI grade 3).

Conclusions
These data suggest that incomplete clot lysis plays a significant role in the pathogenesis of TIMI grade 2 flow. Furthermore, early TIMI grade 2 flow may be sufficient to provide prolonged myocyte viability, which will further recover if flow normalizes.
Surgery for Aortic Regurgitation in Women
Authors: Klodas Elizabeth , Enriquez-Sarano Maurice , Tajik A. Jamil , Mullany Charles J. , Bailey Kent R. , Seward James B.
Published: June 2012

Background
Indications for surgical correction of aortic regurgitation have been established mostly in men and have not been validated in women. The outcome of this surgical correction in women is unknown.

Methods and Results
Baseline characteristics and postoperative outcomes were compared between 51 women and 198 men undergoing surgery for isolated aortic regurgitation between 1980 and 1989. Compared with men, women had surgery rarely for severe left ventricular enlargement (systolic diameter ≥55 mm in 11% versus 27%,
P
=.031; diastolic diameter ≥80 mm in 0% versus 16%,
P
<.0001) and more often for class III to IV symptoms (59% versus 32%,
P
<.0001). Operative mortalities were similar in women and men (3.9% and 4.5%, respectively). Among operative survivors, 10-year survival was worse for women than for men (39±9% versus 72±4%,
P
=.0002) and, in contrast with men, was worse than expected for women (
P
<.0001). Independent predictors of late survival were different for men (age and ejection fraction) and women (age and concomitant coronary bypass grafting). By multivariate analysis, female sex was an independent predictor of worse late survival (adjusted relative risk, 1.80; 95% CI, 1.04 to 3.11).

Conclusions
The generalization to women of the unadjusted left ventricular diameter surgical criteria established in men results in irrelevant criteria almost never reached in women, who often undergo surgery after developing severe symptoms. After surgery, women exhibit an excess late mortality, suggesting that surgical correction of aortic regurgitation should be considered at an earlier stage in women.
Human Ventricular Action Potential Duration During Short and Long Cycles
Authors: Taggart Peter , Sutton Peter M.I. , Boyett Mark R. , Lab Max , Swanton Howard
Published: June 2012

Background
Mechanisms underlying the initiation of ventricular arrhythmias in ischemia by a premature beat or after a pause remain unclear. The kinetics of electrical restitution, which is the modulation of action potential duration (APD) by an abrupt alteration in cycle length, may be important.

Methods and Results
We recorded one or two simultaneous monophasic action potentials (MAPs) from the right ventricular septum during balloon occlusion of the left anterior descending coronary artery (LAD) (14 patients), which is expected to induce ischemia at the recording site, and during occlusion of the right coronary artery (RCA) (7 patients), which is not expected to induce ischemia at the recording area. The latter acted as a control. A test pulse sequence was incorporated whereby during steady-state pacing, test beats of altered cycle length were interposed. During LAD occlusion, APD for basic beats shortened from 260±4 to 236±4 ms (
P
<.0001), whereas the control group (RCA occlusion) showed no significant change (251±7 to 249±9 ms;
P
=NS). LAD occlusion resulted in flattening of the slope relating APD of test beats to diastolic interval (
P
=.001), whereas in the control group (RCA occlusion) the slope remained unchanged. Similar results were obtained during a second occlusion.

Conclusions
LAD occlusion in patients during balloon angioplasty shortened MAP duration of basic beats and minimized, abolished, or reversed the normal APD/diastolic-interval relation of test beats of altered cycle length at sites served by the occluded vessel. The results suggest that ischemia flattens the electrical restitution curve in the human endocardium. These findings may have important implications in arrhythmogenesis.
Prognostic Value of Exercise
201
Tl Tomography in Patients Treated With Thrombolytic Therapy During Acute Myocardial Infarction
Authors: Dakik Habib Abbas , Mahmarian John J. , Kimball Kay T. , Koutelou Maria G. , Medrano Rafael , Verani Mario S.
Published: June 2012

Background
Although myocardial perfusion scintigraphy is of proven value in the risk stratification of patients with a recent myocardial infarction who receive conventional therapy, its value in patients undergoing thrombolytic therapy remains controversial.

Methods and Results
Seventy-one patients who received thrombolytic therapy for acute myocardial infarction had exercise
201
Tl tomography and coronary angiography before hospital discharge. Eleven (15%) of 71 patients had ischemic ST-segment depression during exercise, whereas 27 patients (38%) had scintigraphic ischemia. Twenty-five (37%) of 68 patients had a cardiac event consisting of either death (n=2), recurrent myocardial infarction (n=5), congestive heart failure (n=7), or unstable angina (n=11) during a follow-up of 26±18 months. Univariate predictors of cardiac events were as follows: Killip class (
P
=.04); left ventricular ejection fraction (
P
<.0005); total (
P
=.002) and ischemic (
P
<.0005) perfusion defect size; percent thallium lung uptake (
P
=.001); presence of infarct-zone redistribution (
P
=.02); and multivessel coronary artery disease (
P
=.01). By multivariate analysis, the significant joint predictors of risk were ejection fraction (
P
<.0005) and ischemic perfusion defect size (
P
=.005). The combination of ejection fraction and thallium tomography added significant incremental prognostic information to the clinical data, whereas angiography did not further improve a model that included clinical, ejection fraction, and tomographic variables.

Conclusions
Quantitative exercise
201
Tl tomography provides important incremental, long-term prognostic information in patients receiving thrombolytic therapy for acute myocardial infarction.
Mast Cells in Rupture-Prone Areas of Human Coronary Atheromas Produce and Store TNF-α
Authors: Kaartinen Maija , Penttila¨ Antti , Kovanen Petri T.
Published: June 2012

Background
Mast cells, a cell type involved in inflammatory reactions, are present in coronary atheromas and localize to the erosion or rupture site of atheromas in myocardial infarction. Here we report the presence of TNF-α, a proinflammatory cytokine, in mast cells of human coronary atheromas.

Methods and Results
From samples of 37 coronary arteries from subjects autopsied for medicolegal reasons, sections of the bifurcation area of the left coronary artery were stained immunohistochemically for mast cells and TNF-α. In addition, macrophages, T lymphocytes, smooth muscle cells, and endothelial cells were investigated for their content of TNF-α. In normal intimas and fatty streaks, none of the cell types studied were TNF-α–positive. In 14 of the 24 atheromas found, TNF-α–positive cells were present. Of the total number of mast cells, 23% stained for TNF-α; of the macrophages, 1.3%; and of the smooth muscle cells, 0.4%. The majority (55%) of TNF-α–positive mast cells in the atheromas were located in the shoulder region and the remaining 35% in the cap and 10% in the core regions. Immunoelectron microscopy showed that the TNF-α in mast cells resided within their cytoplasmic secretory granules, demonstrating that these cells contain stores of TNF-α that will be released on degranulation.

Conclusions
This study demonstrates the presence of mast cells with TNF-α–containing secretory granules, particularly in the shoulder region of human coronary atheromas. By releasing their TNF-α, mast cells may play an active role in the inflammatory reactions of these rupture-prone areas of atheromas.
Endogenous Cell Seeding
Authors: Rogers Campbell , Parikh Sahil , Seifert Philip , Edelman Elazer R.
Published: June 2012

Background
Endothelial integrity is essential for maintaining vascular homeostasis, and endothelial denudation results in neointimal thickening. Balloon-expandable endovascular stents provide a luminal scaffolding within atherosclerotic arteries with minimal direct contact between balloon and endothelium. We wondered whether stents cause diminished endothelial ablation, and if so, whether the degree of endothelial damage might determine later proliferative sequelae.

Methods and Results
Stainless steel stents were expanded in normal or previously denuded iliac arteries of New Zealand White rabbits. Stented arteries were harvested 15 minutes, 1 hour, 3 days, or 14 days later. En face staining of the luminal surfaces of stented arteries demonstrated that endothelial cell loss began immediately after stent expansion and was restricted to interstices between stent struts. Remnant endothelium adjacent to struts provided the foundation for complete endothelial regeneration of the stented segment within 3 days. Both early monocyte adhesion and later intimal macrophage accumulation were reduced >80% in nonballooned but stented arteries, in concert with a twofold reduction in intimal thickening after 14 days, compared with arteries completely denuded with a balloon before stent expansion.

Conclusions
It is accepted that deep injury caused by balloon-expanded endovascular stents is a critical contributor to experimental stent-induced neointimal hyperplasia. Our data indicate that the degree of endothelial injury may also be an important component of vascular repair after stenting and an important consideration in stent and balloon design and use. The use of stents for primary endovascular intervention may allow partial retention of endothelium within treated arteries, thereby modulating vascular repair with less need for adjunctive pharmacological therapy.
Turbulent/Viscous Interactions Control Doppler/Catheter Pressure Discrepancies in Aortic Stenosis
Authors: Cape Edward G. , Jones Michael , Yamada Izumi , VanAuker Michael D. , Valdes-Cruz Lilliam M.
Published: June 2012

Background
Despite good correlation between Doppler and catheter pressure drops in numerous reports, it is well known that Doppler tends to apparently overestimate pressure drops obtained by cardiac catheterization. Neither (1) simplification of the Bernoulli equation nor (2) pressure recovery effects can explain this dilemma when taken alone. This study addressed the hypothesis that a Reynolds number–based approach, which characterizes (1) and (2), provides a first step toward better agreement of catheter and Doppler assessments of pressure drops.

Methods and Results
Doppler and catheter pressure drops were studied in an in vitro model designed to isolate the proposed Reynolds number effect and in a sheep model with varying degrees of stenosis. Doppler pressure drops in vitro correlated with the directly measured pressure drop for individual valves (
r
=.935, .960, .985, .984, .989, and .975) but with markedly different slopes and intercepts. A Bland-Altman type plot showed no useful pattern of discrepancy. The Reynolds number was successful in collapsing the data into the profile proposed in the hypothesis. Parallel results were found in the animal model.

Conclusions
Apparent overestimation of net pressure drop by Doppler is due to pressure recovery effects, and these effects are countered by both viscous effects and inertial/turbulent effects. Only by reconciliation of discrepancies by use of a quantity such as Reynolds number that embodies the relative importance of competing factors can the noninvasive and invasive methods be connected. This study shows that a Reynolds number–based approach accomplishes this goal both in the idealized in vitro setting and in a biological system.
Opposite Effects of Angiotensin AT
1
and AT
2
Receptor Antagonists on Recovery of Mechanical Function After Ischemia-Reperfusion in Isolated Working Rat Hearts
Authors: Ford William R. , Clanachan Alexander S. , Jugdutt Bodh I.
Published: June 2012

Background
Angiotensin II type 1 (AT
1
) receptor antagonists, when given over the long term, reduce the deleterious consequences of ischemia-reperfusion injury. Whether short-term administration of AT
1
or angiotensin II type 2 (AT
2
) receptor antagonists is cardioprotective has not been investigated.

Methods and Results
The effects of short-term administration of selective AT
1
and AT
2
receptor antagonists on the recovery of mechanical function during reperfusion after 30 minutes of global, no-flow ischemia were studied in left atrium–perfused isolated working rat hearts. Control hearts (n=8) showed incomplete recovery of left ventricular minute work (LV work) and cardiac efficiency during reperfusion to 51±15% and 61±19% of preischemic levels, respectively. Compared with control hearts, the selective AT
2
receptor antagonist PD123,319 (0.3 μmol/L) given before ischemia (n=7) improved the recovery of LV work and efficiency to 82±4% and 98±7% of preischemic levels, respectively (
P
<.01). In contrast, the selective AT
1
antagonist losartan (1 μmol/L) blocked the recovery of LV work and depressed efficiency to 0±0% and 1±0% (n=7) of preischemic levels, respectively (
P
<.01; n=7). Neither antagonist altered coronary vascular conductance.

Conclusions
This is the first demonstration that short-term treatment with a selective AT
1
versus AT
2
antagonist exerts different effects on recovery of mechanical function after ischemia-reperfusion: the AT
2
antagonist was cardioprotective, whereas the AT
1
antagonist was not. These data suggest that AT
2
antagonists and AT
1
agonists may offer novel approaches for the treatment of mechanical dysfunction after ischemia-reperfusion.
C-Type Natriuretic Peptide in Human Coronary Atherosclerotic Lesions
Authors: Naruko Takahiko , Ueda Makiko , van der Wal Allard C. , van der Loos Chris M. , Itoh Hiroshi , Nakao Kazuwa , Becker Anton E.
Published: June 2012

Background
C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and is considered to have regulatory effects on vascular tone and smooth muscle growth. Since these features play a role in atherogenesis, the presence of CNP at such sites was studied.

Methods and Results
Thirty-three coronary artery segments were harvested at autopsy: 10 normal, with diffuse intimal thickening, and 23 atherosclerotic lesions. Samples were snap-frozen and processed for immunohistochemical staining. For the identification of CNP, a mouse monoclonal antibody (KY-CNP-1) was used. 1A4, EBM-11 (CD68), and von Willebrand factor antibodies were used to stain smooth muscle cells, macrophages, and endothelial cells, respectively. CNP is present in several cell types. Normal arterial segments show CNP-positive endothelial cells. Hypercellular atherosclerotic lesions show distinct CNP positivity of smooth muscle cells and macrophages but a decrease in positivity of endothelial cells. Advanced atherosclerotic lesions contain CNP-positive macrophages, but the smooth muscle cells within the fibrous cap and the surface endothelial cells are almost all CNP-negative.

Conclusions
These observations suggest that CNP has functional significance in atherogenesis.
Reduced Coronary Flow Reserve in Hypercholesterolemic Patients Without Overt Coronary Stenosis
Authors: Yokoyama Ikuo , Ohtake Tohru , Momomura Shin-ichi , Nishikawa Junichi , Sasaki Yasuhito , Omata Masao
Published: June 2012

Background
Reduced coronary flow reserve (CFR) in hypercholesterolemic patients without evidence of ischemia has been reported. However, it remains uncertain whether this abnormality occurs without overt coronary atherosclerosis. This study aimed to clarify whether CFR is impaired even in anatomically normal coronary arteries in hypercholesterolemic patients and to compare CFR between familial hypercholesterolemic (FH) patients and secondary hypercholesterolemic (SH) patients.

Methods and Results
Twenty-two patients with hypercholesterolemia (11 FH, 11 SH) and 11 control subjects were studied. Baseline myocardial blood flow (MBF) and MBF during dipyridamole loading were measured in segments perfused by angiographically normal coronary arteries with the use of positron emission tomography and
13
N-ammonia, and CFR was calculated. Baseline MBF (mL/min per 100 g heart wt) in FH (81.3±31.4) and SH (70.0±20.7) patients was not different from that in control subjects (75.0±34.9). However, MBF during dipyridamole loading was significantly lower in FH patients (129±19.1) than in control subjects (322±174,
P
<.01) and SH patients (210±71.2,
P
<.01). CFR in FH patients (1.59±0.41) was also significantly lower compared with both control subjects (4.22±1.42,
P
<.01) and SH patients (3.00±0.96,
P
<.01). CFR in SH patients was also significantly lower than that in control subjects (
P
<.05). CFR correlated significantly with both plasma total cholesterol (
r
=.67,
P
<.01) and LDL cholesterol concentrations (
r
=.69,
P
<.01).

Conclusions
CFR was decreased even in anatomically normal coronary arteries in hypercholesterolemic patients. This abnormality was more prominent in FH patients.
Contribution of Collagen, Elastin, and Smooth Muscle to In Vivo Human Brachial Artery Wall Stress and Elastic Modulus
Authors: Bank Alan J. , Wang Hongyu , Holte James E. , Mullen Kathleen , Shammas Roger , Kubo Spencer H.
Published: June 2012

Background
The contributions of collagen, elastin, and smooth muscle to arterial mechanical properties in the in vivo human artery are not known.

Methods and Results
We used a recently developed intravascular ultrasound technique to measure total brachial artery wall stress and incremental elastic modulus (E
inc
) in seven normal human subjects at baseline and after intra-arterial norepinephrine (1.2 μg) and nitroglycerin (100 μg). Then we applied a modified Maxwell model to estimate the elastic modulus of elastin (E
E
); the recruitment of collagen fibers supporting wall stress; and the differential contributions of collagen, elastin, and smooth muscle to wall stress and E
inc
over a wide range of pressure and smooth muscle tone. With this model, E
E
was 3×10
6
dynes/cm
2
. Collagen fibers were recruited increasingly as transmural arterial pressure increased and reached a value of ≈5% to 6% at 100 mm Hg under each of the conditions studied. Isobaric smooth muscle contraction resulted in a small decrease in total wall stress and no significant change in total E
inc
while shifting the predominant element contributing to these mechanical parameters from collagen in parallel with the smooth muscle to collagen in series with the smooth muscle. In contrast, isometric smooth muscle contraction produced large increases in total wall stress (from 0.11×10
6
dynes/cm
2
after nitroglycerin administration to 1.35×10
6
dynes/cm
2
after norepinephrine administration) and E
inc
(from 3.84×10
6
dynes/cm
2
after nitroglycerin administration to 57.8×10
6
dynes/cm
2
after norepinephrine administration) entirely as a result of the additional contribution of the smooth muscle and its associated series collagen.

Conclusions
This study describes a technique for determining arterial elastic properties and a model that can be used to estimate a number of mechanical parameters of the human brachial artery in vivo. This technique may be useful in studies of the arterial elastic properties of arteries in patients with vascular pathology.
Antithrombotic Potential of Polymer-Coated Stents Eluting Platelet Glycoprotein IIb/IIIa Receptor Antibody
Authors: Aggarwal Rajesh K. , Ireland Deborah C. , Azrin Michael A. , Ezekowitz Michael D. , de Bono David P. , Gershlick Anthony H.
Published: June 2012

Background
Monoclonal anti-rabbit platelet glycoprotein (GP) IIb/IIIa antibody (AZ1) was adsorbed onto cellulose polymer–coated intracoronary stents to enhance their thromboresistance. We evaluated the antithrombotic efficacy of AZ1 antibody–eluting stents.

Methods and Results
Twenty-three polymer-coated stents with AZ1 antibody bound by passive adsorption (AZ1-eluting) were compared with 23 control polymer-coated stents adsorbed with either no antibody (base-polymer, n=12) or isotype-matched irrelevant antibody (anti-CMV–eluting, n=11) by implantation into balloon-damaged, flow-reduced iliac arteries of New Zealand White rabbits. In 13 animals (acute group), flow measurements were made with transit-time flow probes and platelet adhesion was ascertained by use of
111
In-labeled autologous platelets. In the other 10 animals (chronic group), stent occlusion was assessed macroscopically after they were killed 28 days after stenting. Arteries with AZ1-eluting stents had significantly less platelet deposition (15.8±4.5×10
7
) than either base-polymer (32.1±4.3×10
7
) or anti-CMV–eluting (35.2±8.8×10
7
) controls (ANOVA,
P
<.0001). Compared with base-polymer or anti-CMV–eluting controls, arteries with AZ1-eluting stents showed a marked reduction in cyclic blood flow variation (
P
<.0001) and a significantly greater mean blood flow 2 hours after stent deployment (
P
<.0001). There was a significant improvement in the patency rate of AZ1-eluting stents compared with controls at both 2 hours (92% versus 46%,
P
=.034) and 28 days (100% versus 40%,
P
=.015).

Conclusions
Platelet GP IIb/IIIa antibody eluting from polymer-coated stents reduces platelet deposition, improves blood flow, virtually abolishes cyclic flow variation, and improves patency rates after stent implantation in a rabbit iliac artery model. Its potential for reducing stent-related thrombosis in humans warrants further evaluation.
Influence of Aortic Impedance on the Development of Pressure-Overload Left Ventricular Hypertrophy in Rats
Authors: Kobayashi Shigeki , Yano Masafumi , Kohno Michihiro , Obayashi Masakazu , Hisamatsu Yuji , Ryoke Tsutomu , Ohkusa Tomoko , Yamakawa Katsutoshi , Matsuzaki Masunori
Published: June 2012

Background
Aortic input impedance, which represents LV afterload, is considered to be a major determinant for the development of pressure-overload left ventricular (LV) hypertrophy.

Methods and Results
To test whether the sustained change in aortic input impedance might affect the mode of development of LV hypertrophy, coarctation of either the ascending aorta (G1, n=13) or suprarenal abdominal aorta (G2, n=12) was performed over 4 weeks in 6-week-old Wistar rats. Although peak LV pressure and total systemic resistance were increased similarly in G1 and G2, time to peak LV pressure was decreased by 24% (
P
<.01) in G1 compared with G2. The aortic input impedance spectra revealed that the early systolic loading in G1 was characterized by an increase in characteristic impedance, whereas the late systolic loading in G2 was by an augmented arterial wave reflection. G1 showed a smaller increase (
P
<.01) in either the ratio of LV weight (mg) to body weight (g) or LV wall thickness than G2 after aortic banding. Myocyte diameter was also smaller (
P
<.05) in G1 (14.3±0.7 mm) than in G2 (16.1±1.2 mm). The ex vivo passive pressure-volume relation had a rightward shift in G1 compared with G2, suggesting less concentric LV hypertrophy in G1.

Conclusions
The sustained early systolic loading due to the increase in characteristic impedance was accompanied by less concentric, reduced hypertrophy, whereas the sustained late systolic loading due to the augmented arterial wave reflection was accompanied by concentric, adequate hypertrophy.
Effects of
l
-Arginine Supplementation on Endothelium-Dependent Coronary Vasodilation in Patients With Angina Pectoris and Normal Coronary Arteriograms
Authors: Egashira Kensuke , Hirooka Yoshitaka , Kuga Takeshi , Mohri Masahiro , Takeshita Akira
Published: June 2012

Background
The pathogenesis of impaired endothelium-dependent coronary vasodilation in angina pectoris and normal coronary arteriograms (microvascular angina pectoris) is not known. We examined whether supplementation with
l
-arginine, a precursor of endothelium-derived nitric oxide, improves endothelium-dependent coronary vasodilation in patients with microvascular angina.

Methods and Results
The effect of intracoronary infusion of
l
-arginine (50 mg/min) on acetylcholine-induced coronary vasomotion was studied in eight patients with microvascular angina and eight control subjects. The responses of the large epicardial coronary artery diameter and coronary blood flow were measured with coronary arteriography and an intracoronary Doppler catheter, respectively. Acetylcholine increased coronary blood flow with modest vasoconstriction of the large coronary artery without altering arterial pressure and heart rate. The acetylcholine-induced increases in coronary blood flow were significantly less (
P
<.01) in patients than in control subjects.
l
-Arginine significantly augmented the coronary blood flow responses to acetylcholine in patients, but not in control subjects.
l
-Arginine did not alter responses of the large coronary artery in either group.

Conclusions
Study results suggest that
l
-arginine improved endothelium-dependent vasodilation of coronary microcirculation in patients with microvascular angina pectoris.
Quality of Life, Employment Status, and Anginal Symptoms After Coronary Angioplasty or Bypass Surgery
Authors: Pocock Stuart J. , Henderson Robert A. , Seed Paul , Treasure Tom , Hampton John R.
Published: June 2012

Background
The Randomized Intervention Treatment of Angina (RITA) trial compares initial policies of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass graft surgery (CABG) in 1011 patients with angina. This report assesses the impact of these revascularization procedures on angina, quality of life (according to the Nottingham Health Profile), and employment over 3 years of follow-up.

Methods and Results
Both interventions produced marked improvement in all quality-of-life dimensions (energy, pain, emotional reactions, sleep, social isolation, and mobility) and seven aspects of daily living. Patients with angina at 2 years had more quality-of-life impairment than angina-free patients, whose perceived health was similar to population norms. This reflects the close link at baseline between angina grade and quality of life. The slightly greater impairment of quality of life in PTCA compared with CABG patients is a result of their significantly higher chances of having angina, especially after 6 months. Employment status was investigated mainly for men ≤60 years old. PTCA patients returned to work sooner (40% at 2 months compared with 10% of CABG patients), but the latter caught up by 5 months. After 2 years, 22% and 26% of CABG and PTCA patients, respectively, were not working for cardiac reasons. Patients with angina at 2 years were much more likely to be unemployed than those without.

Conclusions
The impact of angina on quality of life and unemployment is greatly alleviated by PTCA or CABG. Angina is avoided more successfully with CABG, but PTCA offers a speedier return to work. Both intervention strategies then produce similar benefits for quality of life and employment over several years.