bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of Superior Vena Caval Flow to Total Cardiac Output in Children
Authors: Salim Mubadda A. , DiSessa Thomas G. , Arheart Kristopher L. , Alpert Bruce S.
Published: June 2012

Background
After a cavopulmonary anastomosis, the superior vena caval flow, by virtue of being the effective pulmonary blood flow, is the most important factor influencing the systemic arterial saturation. Determination of the amount of this blood flow will allow a better understanding of the physiology of the circulation after this anastomosis. The purposes of this study were to determine the volumetric flow in the superior vena cava and to evaluate its contribution to the cardiac output as children grow.

Methods and Results
Using two-dimensional and Doppler echocardiography, we measured the diameter of and mean flow velocities in the superior venae cavae and the pulmonary arteries of 145 healthy children. We calculated the volumetric flow in each vessel and determined the ratio of superior vena caval flow to total cardiac output. Cardiac output and superior vena caval flow increased with increasing age and body surface area. The superior vena caval flow accounted for 49% of cardiac output in newborn infants. This contribution increased to a maximum of 55% at the age of 2.5 years. Afterward, there was a slow decline in the ratio of superior vena caval–pulmonary arterial flow; it reached the adult value of 35% by 6.6 years of age.

Conclusions
There is a maturational change in the superior vena caval contribution to total cardiac output in children. This is most likely related to somatic growth and changes in body segment proportions. This flow maturation may explain the higher systemic saturation in infants compared with older children after cavopulmonary anastomosis.
A Study of Biochemical Markers of Reperfusion Early After Thrombolysis for Acute Myocardial Infarction
Authors: Laperche Thierry , Steg P. Gabriel , Dehoux Monique , Benessiano Joëlle , Grollier Gilles , Aliot Etienne , Mossard Jean-Marie , Aubry Pierre , Coisne Damien , Hanssen Michel , Iliou Marie-Christine
Published: June 2012

Background
In acute myocardial infarction (AMI), early noninvasive identification of patients with occluded infarct-related arteries (IRAs) after thrombolysis has important prognostic and therapeutic implications. The aims of this study were to evaluate biochemical methods for the early diagnosis of patency after thrombolysis prospectively and to establish the optimal diagnostic criteria retrospectively.

Methods and Results
In 97 patients with AMI treated with thrombolytic agents ≤6 hours after the onset of symptoms, myoglobin, troponin T, creatine kinase, the MB isoenzyme and MM isoforms of creatine kinase were measured just before thrombolysis began and 90 minutes later. IRA patency was assessed by means of 90-minute coronary angiography. For each marker, compared with the expected sensitivity and specificity based on published thresholds for the diagnosis of patency, the observed values were consistently lower but were markedly improved in a subset of patients treated >3 hours after the onset of symptoms. With receiver-operator characteristic curve analysis of the slopes of increase and relative increases in each marker over 90 minutes, the best diagnostic performance was achieved by use of the relative increase in myoglobin, troponin T, and MM3/MM1 creatine kinase isoforms in patients treated >3 hours after onset (areas under the curve of 0.84, 0.83, and 0.85, respectively).

Conclusions
Effective early noninvasive diagnosis of patency after thrombolysis is possible in patients treated >3 hours after symptom onset by use of criteria derived from the relative increase over 90 minutes in plasma markers, particularly myoglobin, troponin T, and MM3/MM1 creatine kinase isoforms. The diagnostic performance of the relative increase in myoglobin appears to be less susceptible to small changes in the diagnostic threshold value.
Dietary Antioxidants and Carotid Artery Wall Thickness
Authors: Kritchevsky Stephen B. , Shimakawa Tomoko , Tell Grethe S. , Dennis Barbara , Carpenter Myra , Eckfeldt John H. , Peacher-Ryan Holmes , Heiss Gerardo
Published: June 2012

Background
Evidence that dietary antioxidants may prevent atherosclerotic disease is growing. The relationship between the intake of dietary and supplemental vitamin C, α-tocopherol, and provitamin A carotenoids and average carotid artery wall thickness was studied in 6318 female and 4989 male participants 45 to 64 years old in the Atherosclerosis Risk in Communities Study.

Methods and Results
Intake was assessed by use of a 66-item semiquantitative food-frequency questionnaire. Carotid artery intima-media wall thickness was measured as an indicator of atherosclerosis at multiple sites with B-mode ultrasound. Among men and women >55 years old who had not recently begun a special diet, there was a significant inverse relationship between vitamin C intake and average artery wall thickness adjusted for age, body mass index, fasting serum glucose, systolic and diastolic blood pressures, HDL and LDL cholesterol, total caloric intake, cigarette use, race, and education (test for linear trend across quintiles of intake,
P
=.019 for women and
P
=.035 for men). An inverse relationship was also seen between wall thickness and α-tocopherol intake but was significant only in women (test for linear trend,
P
=.033 for women and
P
=.13 for men). There was a significant inverse association between carotene intake and wall thickness in older men (test for linear trend,
P
=.015), but the association weakened after adjustment for potential confounders. No significant relationships were seen in participants <55 years old.

Conclusions
These data provide limited support for the hypothesis that dietary vitamin C and α-tocopherol may protect against atherosclerotic disease, especially in individuals >55 years old.
Nitric Oxide Inhibits the Positive Inotropic Response to β-Adrenergic Stimulation in Humans With Left Ventricular Dysfunction
Authors: Hare Joshua M. , Loh Evan , Creager Mark A. , Colucci Wilson S.
Published: June 2012

Background
Nitric oxide (NO) attenuates the contractile response to β-adrenergic stimulation in cultured cardiac myocytes in vitro and in myocardium in vivo. We tested the hypothesis that NO synthesized in the heart inhibits the positive inotropic response to β-adrenergic stimulation in humans with left ventricular (LV) dysfunction.

Methods and Results
Patients with various degrees of LV dysfunction and free from epicardial coronary artery disease were instrumented with an infusion catheter in the left main coronary artery and a high-fidelity micromanometer-tipped catheter in the LV. Measurements included LV pressure, aortic pressure, heart rate, and LV peak +dP/dt. In eight subjects, dobutamine was infused via the left main coronary artery (25 or 50 μg/min) before and concurrent with intracoronary infusion of the NO synthase inhibitor
N
G
-monomethyl-
l
-arginine (L-NMMA, 20 μmol/min for 10 minutes). In six other subjects, dobutamine was infused (6, 10, or 15 μg · kg
−1
· min
−1
) via a peripheral vein. Intracoronary (n=8) dobutamine infusions increased LV peak +dP/dt by an average of 33±3%. The intracoronary infusion of L-NMMA had no effect on baseline LV peak +dP/dt, LV systolic or end-diastolic pressures, aortic pressure, or heart rate. The intracoronary infusion of L-NMMA, concurrent with a second infusion of dobutamine, potentiated the +dP/dt response to dobutamine by 30±10% (
P
<.04 versus dobutamine alone). The intracoronary infusion of L-NMMA likewise potentiated the +dP/dt response to the peripheral infusion of dobutamine by 37±18%.

Conclusions
Nitric oxide produced in the heart attenuates the positive inotropic response to β-adrenergic stimulation in humans with LV dysfunction. NO may contribute to β-adrenergic hyporesponsiveness in patients with LV dysfunction.
Long-term Outcome of Cardiac Surgery in Patients With Mitral Stenosis and Severe Pulmonary Hypertension
Authors: Vincens James J. , Temizer Dogan , Post James R. , Edmunds L. Henry , Herrmann Howard C.
Published: June 2012

Background
Pulmonary hypertension increases perioperative risk in patients having mitral valve replacement, but most studies have included patients with mixed mitral valve disease and have not examined long-term outcome.

Methods and Results
We retrospectively examined the results and predictors of outcome of cardiac surgery in 43 patients (age, 62±13 years [mean±SD]; 81% women) with a primary diagnosis of mitral stenosis and severe pulmonary hypertension (pulmonary artery systolic pressure ≥60 mm Hg or mean pressure ≥50 mm Hg). Patients with more than mild mitral regurgitation were excluded. Thirty-eight patients (88%) were in NYHA functional class III or IV, and 11 patients (26%) had an acute presentation requiring urgent surgery. Preoperative hemodynamics demonstrated a mean mitral valve area of 0.7±0.3 cm
2
, mean pulmonary artery pressure of 50±9 mm Hg, and pulmonary artery systolic pressure of 81±18 mm Hg. Other characteristics included right ventricular failure (18 patients), coronary artery disease (16 patients), and critical aortic stenosis (11 patients). Forty patients underwent mitral valve replacement with St Jude prostheses; 3 had open commissurotomy. Additional surgical procedures included aortic valve replacement (42%), coronary artery bypass graft surgery (26%), and tricuspid valvuloplasty (16%). There were 5 perioperative deaths (11.6%), and 7 other patients (16%) had major complications, including reoperation for hemorrhage, stroke, respiratory failure, myocardial infarction, or a >30-day hospitalization. Univariate analysis of demographic, hemodynamic, and operative characteristics identified the following predictors of perioperative death (
P
<.05): acute presentation, clinical evidence of right ventricular failure, impaired left ventricular ejection fraction, and increased left ventricular diastolic pressure. Predictors of complications (
P
<.05) were acute presentation, ECG evidence of right ventricular hypertrophy, and elevated right ventricular systolic pressure. Multivariate analysis showed only acute presentation and right ventricular hypertrophy as predictors of perioperative death or major complications, respectively. Five- and 10-year actuarial survivals were 80% and 64%, respectively. The only predictor of long-term mortality was advanced age. Functional NYHA status was improved by one grade or more in 76% of survivors.

Conclusions
Patients referred to a tertiary care hospital in the United States with mitral stenosis and severe pulmonary hypertension often have other associated cardiac diseases and comorbid conditions. Cardiac surgery can be successfully performed with an acceptable mortality, and risk factors for poor perioperative outcome can be identified by preoperative clinical characteristics. Younger patients have the best long-term survival, and most survivors experienced long-term improvement in functional status.
Determinants of Early Mortality and Late Survival in Mitral Valve Endocarditis
Authors: Aranki Sary F. , Adams David H. , Rizzo Robert J. , Couper Gregory S. , Sullivan Timothy E. , Collins John J. , Cohn Lawrence H.
Published: June 2012

Background
Infective mitral valve endocarditis continues to be a significant surgical challenge. The objective of this study was to examine our experience with mitral valve endocarditis surgery and identify determinants of early mortality and late survival.

Methods and Results
Over a 24-year period, mitral valve surgery was performed in 96 patients for infective mitral valve endocarditis. Patient age ranged from 20 to 78 years (median age, 52 years). There were 44 women (46%), and 48 of the 96 patients (50%) were in New York Heart Association functional class IV before surgery. Native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE) were present in 72 patients (75%) and 24 patients (25%), respectively. Surgery during the active phase of endocarditis (AE) was required in 60 patients (62%) and during the healed phase (HE) in 36 (38%). The main indications for surgery in the AE group were congestive heart failure (60%), active sepsis (67%), peripheral emboli (47%), and acute renal failure (20%), and for the HE group the main indication was progressive congestive heart failure (69%). The overall operative mortality was 5.2%. Multivariate logistic regression analysis identified PVE (odds ratio [OR] 22.5; ±95% confidence interval, CI, 1.9 to 268;
P
=.014) and an associated procedure (OR 13.3; ±95% CI, 1.5 to 120;
P
=.021) to be independent predictors for early mortality. Follow-up was 97% complete, with a median of 3.5 years. Overall 5- and 10-year survivals were 83±4% and 63±8%, respectively. Multivariate analysis for late mortality identified PVE to be a significant predictor of late mortality (hazards ratio=3.1, ±95% CI, 1.4 to 6.8,
P
=.006). There were no significant differences in long-term morbidity results among the various subsets of mitral valve endocarditis.

Conclusions
Mitral valve surgery for infective endocarditis is a significant high-risk procedure for PVE and when combined with associated procedures. The activity of endocarditis does not appear to have any influence on early mortality or long-term survival.
Low Serum Cholesterol and Mortality
Authors: Iribarren Carlos , Reed Dwayne M. , Chen Randi , Yano Katsuhiko , Dwyer James H.
Published: June 2012

Background
Many studies have reported an association between a low or lowered blood total cholesterol (TC) level and subsequent nonatherosclerotic disease incidence or death. The question of whether low TC is a true risk factor or alternatively a consequence of occult disease at the time of TC measurement remains unsettled. To shed new light onto this problem, we analyzed TC change over a 6- year period (from exam 1 in 1965 through 1968 to exam 3 in 1971 through 1974) in relation to subsequent 16-year mortality in a cohort of Japanese American men.

Methods and Results
The study was based on 5941 men 45 to 68 years of age without prior history of coronary heart disease, stroke, cancer, or gastrointestinal-liver disease at exam 1 who also participated in exam 3 of the Honolulu Heart Program. The association of TC change with mortality end points was investigated with two different approaches (continuous and categorical TC change) with standard survival analysis techniques. Falling TC level was accompanied by a subsequent increased risk of death caused by some cancers (hemopoietic, esophageal, and prostate), noncardiovascular noncancer causes (particularly liver disease), and all causes. The risk-factor–adjusted rate of all-cause mortality was 30% higher (relative risk, 1.30; 95% CI, 1.06 to 1.59) among persons with a decline from middle (180 to 239 mg/dL) to low (<180 mg/dL) TC than in persons remaining at a stable middle level. By contrast, there was no significant increase in all-cause mortality risk among cohort men with stable low TC levels. Nonillness mortality (deaths caused by trauma and suicide) was not related to either TC change or the average of TC levels in exams 1 and 3.

Conclusions
These results add strength to the reverse-causality proposition that catabolic diseases cause TC to decrease.
Compensatory Vascular Changes of Remote Coronary Segments in Response to Lesion Progression as Observed by Sequential Angiography From a Controlled Clinical Trial
Authors: Shircore Anne M. , Mack Wendy J. , Selzer Robert H. , Lee Paul L. , Azen Stanley P. , Alaupovic Petar , Hodis Howard N.
Published: June 2012

Background
Local coronary artery enlargement to compensate for atherosclerotic plaques preserves the vessel lumen. The extent to which coronary segments remote from progressing lesions enlarge is unknown. This is clinically relevant since compensatory enlargement may be important in determining whether clinical complications result from progression of coronary artery disease (CAD). Additionally, compensatory change has implications for quantitative coronary angiographic (QCA) trials, since the effect of progression on diameter means may be mitigated by compensatory changes in remote coronary segments when QCA change is averaged over all lesions.

Methods and Results
Serial QCA data from 78 subjects in the Monitored Atherosclerosis Regression Study were used to demonstrate compensatory changes in coronary segments remote from progressing or regressing lesions. Coronary segments were first classified as progressing (regressing) if percent diameter stenosis (PS) increased or decreased by >10 with a concurrent decrease or increase in minimum lumen diameter (MLD) of either >0.32 mm or >10% of the normal baseline reference diameter (DNORM). Segments not meeting these criteria were labeled stenosis stable. Stenosis-stable segments opposite progressing lesions showed increases in MLD (
P
=.0006), DNORM (
P
=.001), and average diameter (
P
=.001). On-trial apolipoprotein (apo) B, apo C-III, and blood pressure levels inversely correlated with these compensatory changes.

Conclusions
Lesion progression in one coronary segment is associated with significant increases in segmental diameter of remote parts of the coronary tree. We hypothesize these increases to be vascular compensatory changes in response to progression of CAD. Vascular compensatory change is enhanced by LDL cholesterol and triglyceride-rich lipoprotein reduction and appears to be part of the treatment effect itself.
In-Hospital and One-Year Economic Outcomes After Coronary Stenting or Balloon Angioplasty
Authors: Cohen David J. , Krumholz Harlan M. , Sukin Craig A. , Ho Kalon K.L. , Siegrist Richard B. , Cleman Michael , Heuser Richard R. , Brinker Jeffrey A. , Moses Jeffrey W. , Savage Michael P. , Detre Katherine , Leon Martin B. , Baim Donald S.
Published: June 2012

Background
Coronary stenting has been shown to improve initial success, reduce angiographic restenosis, and reduce the need for repeat revascularization compared with conventional balloon angioplasty (PTCA). Although previous studies have demonstrated that initial hospital costs for stenting are considerably higher than those for conventional PTCA, the impact of coronary stenting on long-term medical care costs remains unknown.

Methods and Results
Between January 1991 and June 1993, 207 consecutive patients with symptomatic coronary disease requiring revascularization of a single coronary lesion were randomized to receive initial treatment by either PTCA (n=105) or Palmaz-Schatz coronary stent implantation (n=102) in the multicenter STRESS trial. Detailed resource utilization and cost data were collected for each patient’s initial hospitalization and for any subsequent hospital visits for 1 year after randomization. Compared with conventional angioplasty, coronary stenting resulted in additional catheterization laboratory costs, increased vascular complications, and longer length of stay. Initial hospital costs were thus ≈$2200 higher for stenting than for PTCA ($9738±3248 versus $7505±5015;
P
<.001). Over the first year of follow-up, however, patients assigned to initial stenting were less likely to require rehospitalization for a cardiac condition and underwent fewer subsequent revascularization procedures. Follow-up medical care costs thus tended to be lower for stenting than for conventional angioplasty ($1918±4841 versus $3359±7100,
P
=.21). Nonetheless, cumulative 1-year medical care costs remained higher for patients undergoing initial stenting ($11 656±5674 versus $10 865±9073,
P
<.001). Even after adjustment for the higher incidence of vascular complications in the stent group, total 1-year costs were $300 higher for stenting than for balloon angioplasty.

Conclusions
Elective coronary stenting, as performed in the randomized STRESS trial, increased total 1-year medical care costs by ≈$800 per patient compared with conventional angioplasty. Future studies will be necessary to determine whether ongoing refinements in stent design, implantation techniques, and anticoagulation regimens can narrow this cost difference further by reducing stent-related vascular complications or length of stay.
Radionuclide Monitoring of Cardiac Adaptations to Volume Loading in Patients With Dilated Cardiomyopathy and Mild Heart Failure
Authors: Volpe Massimo , Rao Maria A.E. , Cuocolo Alberto , Russo Rosaria , Nappi Antonio , Mele Alessandro F. , Enea Iolanda , Trimarco Bruno , Condorelli Mario
Published: June 2012

Background
Cardiac adaptations to volume overload have been poorly investigated in heart failure. The aim of this study was to assess dynamic left ventricular responses to acute volume loading by continuous radionuclide monitoring in patients with asymptomatic to mildly symptomatic left ventricular dysfunction.

Methods and Results
Left ventricular end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction (EF), and peak filling rate (PFR) were monitored by a radionuclide detector (Vest) before and during volume expansion (sodium chloride, 0.9%, 0.25 mL · kg
−1
· min
−1
for 2 hours) in 10 patients with idiopathic dilated cardiomyopathy (DCM) and mild heart failure (New York Heart Association class I or II, ejection fraction <50%). The patients were studied off treatment and after 6 to 8 weeks of oral treatment with enalapril (5 mg/d). A control group of 11 age- and sex-matched healthy volunteers (N group) was also studied. In the N group, volume loading caused prompt and sustained increases of EDV, EF, and PFR (all
P
<.001), whereas ESV was progressively reduced (
P
<.001), and heart rate and blood pressure did not change. In contrast, in DCM, EDV showed a smaller increase than in the N group (two-way ANOVA:
F
=5.98,
P
<.001), ESV increased (
P
<.001), and EF and PFR remained unchanged. After enalapril, the cardiac adaptations to volume loading were restored to normal. In particular, EDV, EF, and PFR increased (
P
<.001), and ESV was reduced (
P
<.001). In 6 additional DCM patients studied before and after 6 to 8 weeks of placebo treatment, left ventricular responses to volume loading remained unchanged.

Conclusions
Left ventricular dynamic adaptations to acute volume loading are compromised in patients with idiopathic DCM and mild heart failure. These impaired responses are ameliorated by treatment with enalapril.
Seeding With Omental Cells Prevents Late Neointimal Hyperplasia in Small-Diameter Dacron Grafts
Authors: Pasic Miralem , Müller-Glauser Werner , Odermatt Bernhard , Lachat Mario , Seifert Burkhardt , Turina Marko
Published: June 2012

Background
The influence of complete endothelialization of a prosthetic graft on development of late neointimal hyperplasia is unknown. This study was designed to investigate the effect of complete coverage with endothelial-like cells on late neointimal hyperplasia in small-diameter Dacron grafts seeded with omental cells in a canine model.

Methods and Results
Four-mm-ID Dacron grafts were seeded with cells from omentum and implanted in the carotid arteries in 24 mongrel dogs. Each dog received one seeded and one nonseeded graft. The graft patencies were assessed by angiography at 1, 5, 12, 26, and 52 weeks after surgery. The prostheses were explanted at 5, 12, 26, and 52 weeks after surgery and underwent microscopic studies. The actuarial patency rates at 1, 5, 12, 26, and 52 weeks were 100%, 95%, 95%, 95%, and 95% for seeded grafts and 100%, 86%, 49%, 40%, and 13% for nonseeded grafts, respectively. The seeded grafts exhibited a uniform endothelial-like luminal monolayer without the development of late neointimal proliferation or anastomotic neointimal hyperplasia. Neointimal tissue thickness increased up to 6 months; no additional progression of the subendothelial tissue thickness was observed, in fact there was an insignificant decrease.

Conclusions
Seeding with omental cells prevents development of late neointimal hyperplasia of small diameter prosthetic vascular grafts in a canine model.
Ten-Year Institutional Experience With Palliative Surgery for Hypoplastic Left Heart Syndrome
Authors: Forbess Joseph M. , Cook Nancy , Roth Stephen J. , Serraf Alain , Mayer John E. , Jonas Richard A.
Published: June 2012

Background
We reviewed 212 consecutive patients who underwent stage I palliative surgery for hypoplastic left heart syndrome (HLHS) at our institution between January 1983 and June 1993.

Methods and Results
Six surgeons participated in the care of these patients. Follow-up is 97% complete. Preoperative anatomic and physiological factors and procedural features of the stage I operation were analyzed for impact on stage I mortality, survival to stage II palliation, and actuarial survival. Hospital mortality was not significantly lower during the second half of the study period (
P
=.242). Operative mortality was 46.2%. Multivariate analysis revealed improved stage I operative survival in patients with mitral stenosis (MS) and aortic stenosis (AS;
P
=.006). Additional risk factors for stage I mortality were a lower immediately pre–stage I pH (
P
=.034) and weight <3 kg (
P
=.015). Overall first-year actuarial survival for MS/AS was 59%, and it was 33% for all others (
P
=.001). Among stage I survivors, patients with MS/AS were more likely to survive to stage II palliation (
P
=.031). Analysis of actuarial survival of stage I survivors showed that a smaller ascending aorta (
P
<.001), aortic atresia (
P
<.001), and mitral atresia (
P
=.002) were all risk factors for intermediate death.

Conclusions
Preoperative anatomic and physiological state are predictors of stage I mortality. HLHS anatomic subtype also influences intermediate outcome, most notably pre–stage II attrition. These data may be useful in choosing initial management for patients with HLHS.
Angiotensin II Augments Cytokine-Stimulated Nitric Oxide Synthesis in Rat Cardiac Myocytes
Authors: Ikeda Uichi , Maeda Yoshikazu , Kawahara Yasuhiro , Yokoyama Mitsuhiro , Shimada Kazuyuki
Published: June 2012

Background
Nitric oxide (NO) has been shown to modulate cardiac function. We investigated the effect of angiotensin II (Ang II) on NO synthase activity in cardiac myocytes.

Methods and Results
Using the Griess reagent, we measured the production of nitrite, a stable metabolite of NO, by cultured neonatal rat cardiac myocytes. The expression of inducible NO synthase (iNOS) mRNA was assayed by Northern blotting. Incubation of cardiac myocytes for 24 hours with interleukin-1β (IL-1β) caused a significant increase in NO production. Ang II significantly augmented NO synthesis in IL-1β–stimulated but not in unstimulated cells in a dose-dependent manner. The angiotensin type I receptor antagonist CV 11974 inhibited the effect of Ang II dose-dependently. Simultaneous incubation of Ang II with
N
G
-monomethyl-
l
-arginine or actinomycin D also completely inhibited the effect of Ang II. The Ang II–induced NO production by IL-1β–stimulated cells was accompanied by increased iNOS mRNA accumulation. Phorbol 12-myristate 13-acetate (PMA) also augmented NO synthesis in IL-1β–stimulated but not in unstimulated cells in a dose-dependent manner. The protein kinase C inhibitor calphostin C dose-dependently blocked the effect of Ang II. After protein kinase C activity was functionally depleted by treatment of cells with PMA for 24 hours, Ang II did not augment IL-1β–induced NO production.

Conclusions
These results indicate that Ang II upregulates IL-1β–induced iNOS expression in cardiac myocytes, which is mediated at least partially via activation of protein kinase C.
Induction of Interleukin-8 Messenger RNA in Heart and Skeletal Muscle During Pediatric Cardiopulmonary Bypass
Authors: Burns Stephanie A. , Newburger Jane W. , Xiao Min , Mayer John E. , Walsh BSN Amy Z. , Neufeld Ellis J.
Published: June 2012

Background
Interleukin-8 (IL-8), the major neutrophil chemoattractant factor, contributes to inflammatory tissue injury by activating neutrophils and promoting their migration into tissue. IL-8 levels increase in serum of patients undergoing cardiopulmonary bypass (CPB). The purpose of this study was to determine if IL-8 gene expression is activated in tissues subjected to CPB with or without hypothermic arrest.

Methods and Results
IL-8 transcript levels were measured by ribonuclease protection in samples of human atrium and skeletal muscle from children before and after CPB for repair of congenital heart defects. Results were quantified by PhosphorImager. Atrial IL-8 mRNA levels increased during CPB in 14 of 16 patients tested (median increase, 2.9-fold;
P
=.0029). In skeletal muscle, IL-8 mRNA increased in 11 of 12 patients (median, 12-fold;
P
=.012). Degree of IL-8 induction in atrium and muscle was not directly associated with total support time or cross-clamp time. Transcript increase in skeletal muscle occurred with or without a period of circulatory arrest, suggesting that the stimulus of CPB alone was sufficient to induce message production. Baseline values for IL-8 mRNA varied widely among patients in atrium and skeletal muscle. In situ hybridization analysis revealed diffuse increase in IL-8 mRNA throughout the tissue after CPB, with striking increase in some small veins.

Conclusions
We conclude that production of IL-8 mRNA occurs in most patients during CPB in both myocardium and skeletal muscle. This may result in high local IL-8 concentrations, contributing to the tissue injury after CPB.
Right Gastroepiploic-to-Coronary Artery Bypass
Authors: Pym John , Brown Peter , Pearson Mary , Parker John
Published: June 2012

Background
The right gastroepiploic artery was first used by us as a coronary artery bypass graft (CABG) in June 1984 and has become an accepted alternative conduit for myocardial revascularization.

Methods and Results
We have now performed this operation in 126 patients (111 of whom were men) aged 32 to 78 years. The right gastroepiploic artery was used as a pedicle graft to the right main coronary artery in 25 patients, to its posterior descending branch in 90, to a left ventricular branch in 2, to branches of the circumflex system in 6, and to the left anterior descending artery in 1. Free (aortocoronary) gastroepiploic grafts were placed to circumflex branches in 2 patients. There were 2 hospital deaths (stroke, arrhythmia), and mean±SD postoperative stay was 7.5±2.0 days. All survivors were symptomatically improved and are functionally in New York Heart Association functional class I or II. There have been 3 late deaths (at 34, 50, and 84 months) in 2 to 120 months of follow-up (mean, 41.4 months). Angiography of bypass grafts and coronary arteries was performed in 44 patients at 7 days to 80 months postoperatively, providing direct evidence of gastroepiploic graft patency in 34 patients and strong indirect evidence in another 6; adequate data could not be obtained in 3 patients for technical reasons, and 1 graft was occluded.

Conclusions
These short-term, intermediate, and long-term results demonstrate the suitability of the right gastroepiploic artery as a CABG. The use of the right gastroepiploic artery as a graft to coronary arteries on the posterior wall of the heart, in conjunction with one or both internal mammary arteries, has the potential to allow complete myocardial revascularization with viable arterial grafts.
Clenbuterol Induces Hypertrophy of the Latissimus Dorsi Muscle and Heart in the Rat With Molecular and Phenotypic Changes
Authors: Petrou Mario , Wynne Dylan G. , Boheler Kenneth R. , Yacoub Magdi H.
Published: June 2012

Background
Skeletal muscle assistance of the circulation for patients in end-stage heart failure requires electrical training of the latissimus dorsi flap to produce fatigue resistance. This process of electrical transformation and the development of postmobilization atrophy results in a profound loss in peak power generated. The β
2
-adrenoceptor agonist clenbuterol was used to investigate its potential to selectively induce skeletal muscle hypertrophy, particularly the latissimus dorsi muscle (LDM), independent of adverse effects on cardiac muscle.

Methods and Results
Forty-one male Sprague-Dawley rats were divided into four groups and used in this study. Clenbuterol 2 μg · g body wt
−1
· d
−1
was administered subcutaneously for a period of either 5 weeks (group A) or 2 weeks (group A1). Groups B and B1 (controls) were injected with 0.5 mL normal saline once daily. At the end of the experimental period, all rats were weighed and terminally anesthetized for removal of the left LDM, left gastrocnemius-plantaris-soleus (GPS) muscles, and heart. The results showed that the increase in body weight did not differ significantly between the clenbuterol-treated and control groups (
P
>.5). The ratio of LDM to tibial length (hypertrophic index) for groups A and A1 was significantly greater than controls (
P
<.01), which represented a 20% to 29% increase. The hypertrophy was more pronounced for hindlimb skeletal muscle (21% to 35% for GPS), and the effects of this relatively high dose of clenbuterol on the heart were less marked (18% to 20% hypertrophy). RNA analyses indicate that ventricles of clenbuterol-treated rats express elevated levels of mRNA to atrial natriuretic factor without a concomitant increase in skeletal α-actin and β-myosin heavy chain, consistent with a “physiological” form of cardiac hypertrophy.

Conclusions
Clenbuterol induces significant hypertrophy of the LDM associated with specific changes in cardiac gene expression.
Basic Fibroblast Growth Factor Restores Endothelium-Dependent Responses After Balloon Injury of Rabbit Arteries
Authors: Meurice Thibaud , Bauters Christophe , Auffray Jean-Luc , Vallet Benoı̂t , Hamon Martial , Valero Franck , Van Belle Eric , Lablanche Jean-Marc , Bertrand Michel E.
Published: June 2012

Background
After experimental angioplasty, partial or complete reendothelialization of the denuded surface occurs; the function of the regenerated endothelium has, however, been shown to be abnormal. Basic fibroblast growth factor (bFGF) is mitogenic for endothelial cells in vitro and in vivo. We investigated whether chronic administration of bFGF in a rabbit model of balloon denudation might not only improve endothelial regrowth but also restore normal physiological responses to endothelium-dependent agonists.

Methods and Results
Thirty-nine New Zealand White rabbits underwent balloon denudation of the right iliac artery. Twenty rabbits received intravenous administration of bFGF (2.5 μg twice a week for 2 weeks). Nineteen rabbits receiving saline injections served as controls. Animals were killed on day 28 for assessment of reendothelialization and neointimal thickening and for analysis of in vitro vasoreactivity. Animals in the bFGF group had a significantly (
P
<.005) greater degree of reendothelialization than controls (115±13 versus 55±6 mm
2
). Neointimal thickening was similar in the two groups. Four weeks after denudation, endothelium-independent responses did not differ significantly between the two groups. In contrast, the maximal endothelium-dependent acetylcholine-induced relaxation of the bFGF-treated animals (E
max
, 40±7%) was significantly greater than that of the control group (E
max
, 11±9%;
P
<.05).

Conclusions
Systemic administration of bFGF restores, in large part, the responses of previously denuded arterial segments to endothelium-dependent vasodilators. Angiogenic growth factors may help to reestablish normal endothelial cell function in patients who have undergone angioplasty.
Outmigration For Coronary Bypass Surgery in an Era of Public Dissemination of Clinical Outcomes
Authors: Omoigui Nowamagbe A. , Miller Dave P. , Brown Kimberly J. , Annan Kingsley , Cosgrove Delos , Lytle Bruce , Loop Floyd , Topol Eric J.
Published: June 2012

Background
Since 1989, New York State has disseminated comparative information on outcomes of coronary bypass surgery to the public. It has been suggested that this program played a significant role in the 41% decrease in the risk-adjusted mortality rate between 1989 and 1992. We hypothesized that some high-risk patients had migrated out of state for surgery.

Methods and Results
We reviewed 9442 isolated coronary bypass operations performed from 1989 through 1993 to assess referral patterns of case-mix and outcome. Expected and risk-adjusted mortality rates were computed using logistic regression models derived from the Cleveland Clinic and New York State databases. A mortality comparison was performed using the 1980 to 1988 time period as a historical control. Patients from New York (n=482) had a higher frequency of prior open heart surgery (44.0%) than patients from Ohio (n=6046) (21.5%,
P
<.001), other states (n=1923) (37.4%,
P
=.008), and other countries (n=991) (17.3%,
P
<.001). They were also more likely to be in NYHA functional class III or IV (47.6% versus Ohio 42.7%,
P
=.037; other states, 41.2%,
P
=.011; other countries, 34.1%,
P
=.001). The expected mortality rate was thus higher than among other referral cohorts. The observed 5.2% mortality rate among these patients was significantly greater than the 2.9%, 3.1%, and 1.4% mortality rates observed for patients from Ohio (
P
=.004), other states (
P
=.028), and other countries (
P
<.001). These differences in outcome were not apparent between 1980 and 1988 among referrals from within the United States.

Conclusions
Public dissemination of outcome data may have been associated with increased referral of high-risk patients from New York to an out-of-state regional medical center.
Energetically Optimal Left Ventricular Pressure for the Failing Human Heart
Authors: Asanoi Hidetsugu , Kameyama Tomoki , Ishizaka Shinji , Nozawa Takashi , Inoue Hiroshi
Published: June 2012

Background
An energy-starved failing heart would benefit from more effective transfer of the mechanical energy of ventricular contraction to blood propulsion. However, the energetically optimal loading conditions for the failing heart are difficult to establish. In the present study, we analyzed the optimal left ventricular pressure to achieve maximal mechanical efficiency of the failing heart in humans.

Methods and Results
We determined the relation between left ventricular pressure-volume area and myocardial oxygen consumption per beat (V
o
2
), stroke work, and mechanical efficiency (stroke work/V
o
2
) in 13 patients with different contractile states. We also calculated the optimal end-systolic pressure that would theoretically maximize mechanical efficiency for a given end-diastolic volume and contractility. Left ventricular pressure-volume loops were constructed by plotting the instantaneous left ventricular pressure against the left ventricular volume at baseline and during pressure loading. The contractile properties of the ventricle were defined by the slope of the end-systolic pressure-volume relation. In patients with less compromised ventricular function, the operating end-systolic pressure was close to the optimal pressure, achieving nearly maximal mechanical efficiency. As the heart deteriorated, however, the optimal end-systolic pressure became significantly lower than normal, whereas the actual pressure remained within the normal range. This discrepancy resulted in worsening of ventriculoarterial coupling and decreased mechanical efficiency compared with theoretically maximal efficiency.

Conclusions
Homeostatic mechanisms to maintain arterial blood pressure within the normal range cause the failing heart to deviate from energetically optimal conditions.
Missense Mutation in the Pore Region of
HERG
Causes Familial Long QT Syndrome
Authors: Benson D. Woodrow , MacRae Calum A. , Vesely Mark R. , Walsh Edward P. , Seidman J.G. , Seidman Christine E. , Satler Carol Ann
Published: June 2012

Background
Long QT syndrome (LQT) is an inherited cardiac disorder that results in syncope, seizures, and sudden death. In a family with LQT, we identified a novel mutation in human
ether-a-go-go
–related gene
(HERG)
, a voltage-gated potassium channel.

Methods and Results
We used DNA sequence analysis, restriction enzyme digestion analysis, and allele-specific oligonucleotide hybridization to identify the
HERG
mutation. A single nucleotide substitution of thymidine to guanine (T1961G) changed the coding sense of
HERG
from isoleucine to arginine (Ile593Arg) in the channel pore region. The mutation was present in all affected family members; the mutation was not present in unaffected family members or in 100 normal, unrelated individuals.

Conclusions
We conclude that the Ile593Arg missense mutation in
HERG
is the cause of LQT in this family because it segregates with disease, its presence was confirmed in three ways, and it is not found in normal individuals. The Ile593Arg mutation may result in a change in potassium selectivity and permeability leading to a loss of
HERG
function, thereby resulting in LQT.
Retinoid Receptor Expression and all-
trans
Retinoic Acid–Mediated Growth Inhibition in Vascular Smooth Muscle Cells
Authors: Miano Joseph M. , Topouzis Stavros , Majesky Mark W. , Olson Eric N.
Published: June 2012

Background
Retinoids have been used in the successful treatment of a variety of human hyperproliferative diseases. Their role in smooth muscle cell (SMC) growth control, however, has not been clearly established. The present study was designed to assess the retinoid receptor mRNA expression profile in SMCs and to determine whether retinoids exert a growth-inhibitory effect in these cells.

Methods and Results
Five of the six retinoid receptors were expressed in both cultured SMCs and aorta as determined by Northern blotting or reverse transcription-polymerase chain reaction. Receptor activity was demonstrated in SMCs with the use of a reporter assay with a retinoid receptor DNA binding sequence linked to a chloramphenicol acetyltransferase reporter gene. DNA synthesis and cell proliferation assays were performed to show that all-
trans
retinoic acid (atRA) antagonized platelet-derived growth factor-BB and serum-stimulated SMC growth. Growth inhibition was distal to early growth-signaling events because induction of c-
fos
, c-
jun
, and
egr
-1 mRNA was unaffected by atRA. However, with an activated protein-1–linked chloramphenicol acetyltransferase reporter, atRA was shown to inhibit the activity of activated protein-1–dependent transcription in a transient transfection assay.

Conclusions
These results establish the presence of functional retinoid receptors in SMCs and document the growth-inhibitory action of atRA on these cells. Retinoid compounds, already in clinical use as antiproliferative agents for nonvascular indications, should be assessed further in in vivo models of intimal disease.
Monoclonal Antibody Against Tissue Factor Shortens Tissue Plasminogen Activator Lysis Time and Prevents Reocclusion in a Rabbit Model of Carotid Artery Thrombosis
Authors: Ragni Massimo , Cirillo Plinio , Pascucci Immacolata , Scognamiglio Annalisa , D’Andrea Davide , Eramo Nicola , Ezekowitz Michael D. , Pawashe Aruna B. , Chiariello Massimo , Golino Paolo
Published: June 2012

Background
Tissue factor (TF)–dependent activation of the coagulation is important in the pathophysiology of intravascular thrombus formation. We tested the effects of a monoclonal antibody against TF (AP-1) on lysis time induced by tissue-type plasminogen activator (TPA) and on reocclusion rate in a rabbit model of carotid artery thrombosis.

Methods and Results
Intravascular thrombosis was obtained by placing an external constrictor around carotid arteries with endothelial injury. Carotid blood flow velocity was measured continuously with a Doppler flow probe. Thirty minutes after thrombus formation, the rabbits received either AP-1 (0.15 mg/kg IV, n=8) or placebo (n=8). All rabbits also received TPA (80 μg/kg bolus plus 8 μg·kg
−1
·min
−1
infusion for up to 90 minutes or until reperfusion was achieved) and heparin (200 U/kg IV as a bolus). At reperfusion, TPA was discontinued, and the rabbits were followed for an additional 90 minutes. AP-1 shortened lysis time from 44±8 minutes (mean±SEM) in control rabbits to 26±7 minutes in AP-1–treated rabbits (
P
<.01). Reocclusion occurred in all control rabbits in 10±3 minutes, whereas it occurred in only two of eight AP-1–treated rabbits in 72 and 55 minutes (
P
<.01). No changes in prothrombin time and ex vivo platelet aggregation in response to various agonists were observed after AP-1 administration, indicating the absence of systemic effects by this antibody.

Conclusions
TF exposure and activation of the extrinsic coagulation pathway play an important role in prolonging lysis time and mediating reocclusion after thrombolysis in this model. AP-1, a monoclonal antibody against TF, might be suitable as adjunctive therapy to TPA.
Predictive Value of Electron Beam Computed Tomography of the Coronary Arteries
Authors: Arad Yadon , Spadaro Louise A. , Goodman Ken , Lledo-Perez Alfonso , Sherman Scott , Lerner Gail , Guerci Alan D.
Published: June 2012

Background
Coronary electron beam computed tomography (EBCT) detects atherosclerotic coronary artery disease by measuring calcium deposition in the walls of coronary arteries. EBCT-derived coronary artery calcium (CAC) scores correlate with the severity of underlying coronary artery disease.

Methods and Results
We followed 1173 asymptomatic patients who underwent EBCT between September 1993 and March 1994. During average follow-up of 19 months, 18 subjects had 26 cardiovascular events: 1 death, 7 myocardial infarctions, 8 coronary artery bypass graft procedures, 9 coronary angioplasties, and 1 nonhemorrhagic stroke. For CAC score thresholds of 100, 160, and 680, EBCT had sensitivities of 89%, 89%, and 50% and specificities of 77%, 82%, and 95%, respectively. Odds ratios ranged from 20.0 to 35.4 (
P
<.00001 for all).

Conclusions
Coronary EBCT predicts future atherosclerotic cardiovascular disease events in asymptomatic subjects.
Evidence for Load-Dependent and Load-Independent Determinants of Cardiac Natriuretic Peptide Production
Authors: Ogawa Tsuneo , Linz Wolfgang , Stevenson Michelle , Bruneau Benoit G. , Kuroski de Bold Mercedes L. , Chen Jia Hua , Eid Hoda , Schölkens Bernward A. , de Bold Adolfo J.
Published: June 2012

Background
In hypertension with cardiac hypertrophy, the specific contributions to increased production of the cardiac natriuretic peptides (NP) atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) by load and the hypertrophic process are not known. In the present work we determine ANF and BNP synthesis and secretion in the aortic-banded rat treated with dosage schedules of the ACE inhibitor ramipril that result in the prevention or regression of both hypertension and hypertrophy (high dosage) or in the prevention or regression of hypertrophy alone with persistent hypertension (low dosage). Myosin heavy chain (MHC) isoform switch was studied as an indicator of ventricular cardiocyte hypertrophy as well as the levels of collagen III mRNA as a measure of changes in extracellular matrix.

Methods and Results
Ramipril was administered for 6 weeks just after suprarenal aortic banding, or rats were banded for 6 weeks, after which ramipril was administered during the following 6 weeks. Banding caused an increase in blood pressure, left ventricular weight–to–body weight ratio, plasma and ventricular NP, ventricular NP mRNA, collagen III, and β-MHC mRNA. Ramipril at 1 mg/kg normalized all these parameters while ramipril at 10 μg/kg normalized left ventricular weight–to–body weight ratio but not blood pressure. Plasma and ventricular NP content and mRNA levels were partially normalized by ramipril (10 μg/kg). Ramipril (10 μg/kg) prevented increased collagen III mRNA levels but did not affect β-MHC mRNA levels.

Conclusions
(1) NP production and secretion in aortic-banded rats are independently related to increased blood pressure and hypertrophy. (2) A load-dependent component is more important than a load-independent component in regulating left ventricular NP production. (3) ANF production is more sensitive than BNP production to the load-independent component. (4) Low-dose ramipril treatment reverses hypertrophy and the increased collagen III expression but does not reverse the increased β-MHC isoform expression, suggesting that these are independently regulated processes. (5) Aortic banding and ACE inhibition do not affect atrial NP production and content.