bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Rejection Accelerates Graft Coronary Disease in Transplanted Rabbit Hearts
Authors: Nakagawa Tetsuro , Sukhova Galina K. , Rabkin Elena , Winters Gayle L. , Schoen Frederick J. , Libby Peter
Published: June 2012

Background
The relation between episodes of acute rejection and the development of graft coronary arteriosclerosis remains controversial. We examined the hypothesis that acute rejection episodes accelerate graft coronary arteriosclerosis lesion formation in rabbit allografts.

Methods and Results
A control group (n=5) received cyclosporine 5 mg · kg
−1
· d
−1
for 6 weeks after heterotopic heart transplantation. In a rejection group (n=5), cyclosporine was omitted for 4 days at 1 and 4 weeks after transplantation. We studied cross sections of grafted hearts at 6 weeks and evaluated myocardial rejection grade, incidence, and severity and cell composition of intimal lesions in multiple coronary artery profiles. Episodic withdrawal of cyclosporine augmented myocardial rejection (International Society for Heart and Lung Transplantation grades 0, 0, 0, 0, and 1A in the control group to grades 1A, 1B, 2, 3A, and 3B in the rejection group). Episodes of acute rejection significantly increased the incidence (7.8±2.7% to 49.7±1.9%) and severity (from grade 0.10±0.04 to 0.79±0.24) of intimal thickening in graft coronary arteries. Most intimal lesions consisted of smooth muscle cells and contained various degrees of T-lymphocyte infiltration but sparse macrophages.

Conclusions
In this experimental model, episodes of acute rejection precipitated by cyclosporine withdrawal accelerated the development of graft vascular lesion formation. Activation of vascular cells and leukocyte recruitment during acute rejection may thus contribute to the pathogenesis of graft arteriosclerosis.
Regional Heterogeneity of Human Myocardial Infarcts Demonstrated by Contrast-Enhanced MRI
Authors: Lima João A. C. , Judd Robert M. , Bazille Ann , Schulman Steven P. , Atalar Ergin , Zerhouni Elias A.
Published: June 2012

Background
Myocardial reperfusion is pivotal to the prognosis of patients with acute myocardial infarction. In these patients, coronary flow is generally assessed by angiography and tissue perfusion by tracer scintigraphy. This study was designed to examine whether magnetic resonance imaging (MRI) provides information on myocardial perfusion and damage beyond that supplied by angiography and thallium scintigraphy after acute myocardial infarction.

Methods and Results
Twenty-two patients with recent myocardial infarction had ECG, echocardiography, coronary angiography, and fast contrast-enhanced MRI. Twelve patients also had exercise thallium scintigraphy. Time-intensity curves obtained from infarcted and noninfarcted regions were correlated with coronary anatomy and left ventricular function. Two perfusion patterns were observed in infarcted regions by comparison with the normal myocardial pattern. All patients but 1 had persistent myocardial hyperenhancement within the infarcted region up to 10 minutes after contrast. In 10 patients, this hyperenhanced region surrounded a subendocardial area of decreased signal at the center of the infarcted region associated with coronary occlusion at angiography, Q waves on ECG, and greater regional dysfunction by echocardiography. Moreover, the extent and location of the MRI abnormalities correlated well with the extent and location of the fixed single-photon emission computed tomography thallium defects.

Conclusions
Large human infarcts, associated with prolonged obstruction of the infarct-related artery, are characterized by central dark zones surrounded by hyperenhanced regions on MRI. Conversely, reperfused infarcts with less regional dysfunction have uniform signal hyperenhancement. The MRI hyperenhanced segment correlates well with the fixed scintigraphic defect in patients with acute myocardial infarction.
Influence of Sex on the Short-term Outcome of Elderly Patients With a First Acute Myocardial Infarction
Authors: Bueno Héctor , Vidán M. Teresa , Almazán Aureliano , López-Sendón José L. , Delcán Juan L.
Published: June 2012

Background
Sex seems to affect the course of acute myocardial infarction (AMI) in the general population. Although the epidemiological importance of female sex among patients with AMI is more important from the sixth decade of life, little is known about the impact of sex on the outcome of AMI in the elderly.

Methods and Results
To determine the differences between sexes in the outcome of AMI in the elderly, we compared the clinical history and evolution of 204 consecutive patients (99 men, 105 women) ≥75 years of age admitted with a first AMI. Women had a higher prevalence (
P
<.01) of hypertension (60% versus 32%) and diabetes (41% versus 18%), whereas men were more frequently smokers (41% versus 4%,
P
<.0001); these factors were associated with higher rates of congestive heart failure. Women showed lower ejection fractions and higher rates of congestive heart failure (odds ratio [OR], 2.32; 95% CI, 1.32 to 4.12) and shock (OR, 2.78; 95% CI, 1.29 to 6.40). Mortality rate was higher in women (40% versus 23%,
P
=.01; OR, 2.29; 95% CI, 1.26 to 4.26); however, sex was excluded as an independent predictor of in-hospital mortality in every regression model tested (OR, 0.75; 95% CI, 0.25 to 2.21).

Conclusions
After a first AMI, elderly women experience a more complicated hospital course than men. The increase in mortality risk seems to be related to the impact of cardiovascular risk factors on left ventricular function more than to sex itself.
Correlation of Temperature and Pathophysiological Effect During Radiofrequency Catheter Ablation of the AV Junction
Authors: Nath Sunil , DiMarco John P. , Mounsey J. Paul , Lobban John H. , Haines David E.
Published: June 2012

Background
Accelerated junctional rhythms have been observed before the development of AV nodal block during radiofrequency (RF) catheter ablation of the AV junction. However, the time course and temperatures required to induce an accelerated junctional rhythm and AV nodal block during this procedure have not yet been characterized.

Methods and Results
Nineteen patients underwent RF ablation of the AV junction with a thermistor ablation catheter. RF energy was initially delivered at 10 W for 9 seconds and then increased by 5-W increments for 9 seconds at each power level up to a maximum power of 50 W. If a junctional rhythm was observed during the power titration, a 30- to 60-second RF application was then delivered at the same power level. The power was then further increased to a maximum of 50 W if AV nodal block was not observed after 20 seconds of RF delivery. The procedure was successful in all 19 patients. A median of one RF application (range, one to eight applications) was required to produce permanent AV nodal block. An accelerated junctional rhythm was observed during 89% of successful attempts versus 70% of unsuccessful deliveries (
P
=NS). The median time to onset of the junctional rhythm was significantly shorter during successful compared with unsuccessful applications (1.8 versus 7.7 seconds, respectively;
P
<.001). Similarly, the mean time to appearance of AV nodal block was significantly shorter during successful compared with unsuccessful attempts (19.6±9.4 versus 36.8±19.0 seconds, respectively;
P
<.01). The catheter tip temperatures associated with the development of an accelerated junctional rhythm were significantly lower than those associated with the appearance of AV nodal block (51±4°C versus 58±6°C, respectively;
P
<.001). Mean temperatures in the range of 60±7°C were required to produce permanent AV nodal block.

Conclusions
The development of an accelerated junctional rhythm within 5 seconds and the appearance of AV nodal block within 30 seconds of RF onset were both highly characteristic of successful target sites during RF ablation of the AV junction. The accelerated junctional rhythm and AV nodal block were both highly temperature dependent. The temperatures associated with the onset of AV nodal block were significantly higher than the temperatures resulting in an accelerated junctional rhythm.
A Definition of Advanced Types of Atherosclerotic Lesions and a Histological Classification of Atherosclerosis
Authors: Stary Herbert C. , Chandler A. Bleakley , Dinsmore Robert E. , Fuster Valentin , Glagov Seymour , Insull William , Rosenfeld Michael E. , Schwartz Colin J. , Wagner William D. , Wissler Robert W.
Published: June 2012

Abstract
This report is the continuation of two earlier reports that defined human arterial intima and precursors of advanced atherosclerotic lesions in humans. This report describes the characteristic components and pathogenic mechanisms of the various advanced atherosclerotic lesions. These, with the earlier definitions of precursor lesions, led to the histological classification of human atherosclerotic lesions found in the second part of this report. The Committee on Vascular Lesions also attempted to correlate the appearance of lesions noted in clinical imaging studies with histological lesion types and corresponding clinical syndromes. In the histological classification, lesions are designated by Roman numerals, which indicate the usual sequence of lesion progression. The initial (type I) lesion contains enough atherogenic lipoprotein to elicit an increase in macrophages and formation of scattered macrophage foam cells. As in subsequent lesion types, the changes are more marked in locations of arteries with adaptive intimal thickening. (Adaptive thickenings, which are present at constant locations in everyone from birth, do not obstruct the lumen and represent adaptations to local mechanical forces). Type II lesions consist primarily of layers of macrophage foam cells and lipid-laden smooth muscle cells and include lesions grossly designated as fatty streaks. Type III is the intermediate stage between type II and type IV (
atheroma
, a lesion that is potentially symptom-producing). In addition to the lipid-laden cells of type II, type III lesions contain scattered collections of extracellular lipid droplets and particles that disrupt the coherence of some intimal smooth muscle cells. This extracellular lipid is the immediate precursor of the larger, confluent, and more disruptive core of extracellular lipid that characterizes type IV lesions. Beginning around the fourth decade of life, lesions that usually have a lipid core may also contain thick layers of fibrous connective tissue (type V lesion) and/or fissure, hematoma, and thrombus (type VI lesion). Some type V lesions are largely calcified (type Vb), and some consist mainly of fibrous connective tissue and little or no accumulated lipid or calcium (type Vc).
Short-term Pulmonary Vasodilation With
l
-Arginine in Pulmonary Hypertension
Authors: Mehta Sanjay , Stewart Duncan J. , Langleben David , Levy Robert D.
Published: June 2012

Background
Endothelial dysfunction may contribute to the pathogenesis of pulmonary hypertension through impaired production of the endothelium-derived vasodilator nitric oxide (NO).
l
-Arginine, the substrate for NO synthase (NOS), has a vasodilatory effect in systemic vascular beds and can correct abnormal endothelium-dependent vasodilation. It has been suggested that these two effects of
l
-arginine are mediated through NOS metabolism and enhanced NO production. Therefore, we assessed the short-term pulmonary hemodynamic effects of exogenous
l
-arginine in patients with pulmonary hypertension of various origins.

Methods and Results
During continuous hemodynamic monitoring, 10 subjects with pulmonary hypertension (mean pulmonary artery pressure [PAP], 54±5 mm Hg [mean±SEM]) received a 30-minute control infusion of hypertonic saline followed by a 30-minute infusion of 500 mg/kg of
l
-arginine. The hemodynamic effects of
l
-arginine were compared with those of prostacyclin titrated to maximally tolerated doses. The hemodynamic response to
l
-arginine was also studied in 5 subjects with heart failure but without pulmonary hypertension (mean PAP, 20±2 mm Hg) and 5 healthy control subjects. In subjects with pulmonary hypertension, infusion of
l
-arginine reduced mean PAP by 15.8±3.6% (
P
<.005) and pulmonary vascular resistance (PVR) by 27.6±5.8% (
P
<.005) compared with decreases of 13.0±5.5% (
P
<.005) and 46.6±6.2% (
P
<.005), respectively, with prostacyclin.
l
-Arginine infusion also increased the mean plasma level of
l
-arginine from 59±6 μmol/L to 10 726±868 μmol/L (
P
<.005), which was associated with a significant increase in the plasma level of
l
-citrulline, the immediate product of NOS metabolism of
l
-arginine. Moreover, the peak plasma level of
l
-citrulline correlated significantly with the reductions in mean PAP (
r
=.71,
P
<.05) and PVR (
r
=.70,
P
<.05), consistent with vasodilation mediated by NOS metabolism of exogenous
l
-arginine and increased NO production.
l
-Arginine also had a modest hypotensive effect in healthy control subjects and reduced systemic vascular resistance in subjects with heart failure in the absence of pulmonary hypertension. However, only small reductions in absolute pulmonary vascular resistance were observed in this latter group in response to
l
-arginine that did not reach significance.

Conclusions
An exaggerated short-term pulmonary vasodilatory response to
l
-arginine in patients with pulmonary hypertension suggests a relative impairment in pulmonary vascular endothelial NO production that may contribute to increased pulmonary vascular tone and thus be important in the pathophysiology of pulmonary hypertension.
Fractionated Electrograms From a Computer Model of Heterogeneously Uncoupled Anisotropic Ventricular Myocardium
Authors: Ellis Willard S. , Auslander David M. , Lesh Michael D.
Published: June 2012

Background
The relation between heterogeneously coupled myocardium and fractionated electrograms is incompletely understood. The purpose of this study was to use a detailed computer model of nonuniformly anisotropic myocardium to test the hypothesis that spatial variation of morphology of electrograms recorded simultaneously from multiple sites increases with increasing heterogeneity of intercellular coupling.

Methods and Results
A sheet of elements with Beeler-Reuter ionic kinetics was coupled with cytoplasmic resistivity to model cells. Gap junctional resistance values were assigned by recursive randomization to produce a fractal pattern of heterogeneous coupling, simulating damage resulting from infarction. The correlation dimension of the pattern, D, measured heterogeneity of intercellular coupling. The peak-to-peak amplitude, duration, minimum derivative (steepest downslope), number of inflections, frequency of peak power, and bandwidth of unfiltered unipolar electrograms were calculated. Linear regressions indicate (
P
<.001) that the coefficient of variation of five electrogram metrics increases with increasing substrate heterogeneity and that the distance over which electrogram morphology decorrelates decreases with increasing heterogeneity of intercellular coupling.

Conclusions
These findings confirm our hypothesis that the spatial variation of morphology of electrograms recorded simultaneously from multiple sites increases with increasing heterogeneity of intercellular coupling.
Previous Aspirin Use May Attenuate the Severity of the Manifestation of Acute Ischemic Syndromes
Authors: Garcia-Dorado David , Théroux Pierre , Tornos Pilar , Sambola Antonia , Oliveras Juan , Santos Maite , Soler J. Soler
Published: June 2012

Background
The present study was designed to investigate whether the prior use of aspirin could influence the severity of the manifestation of acute coronary artery syndromes, given the well-documented observations that aspirin can prevent myocardial infarction, stroke, and death in cardiovascular disease.

Methods and Results
A series of 539 consecutive patients admitted to the Coronary Care Unit of a General Hospital was carefully characterized in a study with an ambidirectional design, with regard to previous medical history, aspirin use, and subsequent hospital diagnosis. Among the 214 patients previously taking aspirin, the hospital diagnosis was myocardial infarction in 24% and unstable angina in 76% compared with 54% and 46%, respectively, among the 325 not taking aspirin (
P
<.0001), for a reduction in the odds ratio of myocardial infarction with aspirin of 72% (95% CI, 59% to 90%). The decrease in odds was homogeneous in all subsets studied and independent of age, sex, previous angina, or previous myocardial infarction. The myocardial infarction was of a Q-wave type in 62% of aspirin users compared with 76% of nonusers (
P
<.05). By multivariate analysis, previous aspirin use was a strong predictor of unstable angina versus myocardial infarction and the only independent predictor of non–Q-wave versus Q-wave myocardial infarction.

Conclusions
This study, thus, suggests a shift to less severe manifestation of acute coronary syndromes with aspirin use, implying that the failure of the drug in many patients with an acute coronary syndrome is only partial and that aspirin has the potential of attenuating the severity of the underlying acute thrombotic disease process.
Determination of Left Ventricular Chamber Stiffness From the Time for Deceleration of Early Left Ventricular Filling
Authors: Little William C. , Ohno Michiya , Kitzman Dalane W. , Thomas James D. , Cheng Che-Ping
Published: June 2012

Background
A noninvasive measure of left ventricular (LV) chamber stiffness (K
LV
) would be clinically useful. Our theoretical analysis predicts that K
LV
can be calculated from the time for deceleration of LV early filling (t
dec
) by

\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \[K_{LV}{=}\frac{{\rho}\ {\cdot}\ L}{A}\ {\cdot}\ (\frac{{\pi}}{2}\ {\cdot}\ \frac{1}{t_{dec}})^{2}\] \end{document}

where ρ=density of blood, L=effective mitral length, and A=mitral area.

Methods and Results
We tested this hypothesis in eight conscious dogs instrumented for measurement of LV pressure (P) with use of a micromanometer and volume (V) with use of sonomicrometers. K
LV
was determined as the slope of the late diastolic portion of the LV P-V loop. K
LV
was varied from 0.99±0.35 to 2.58±0.92 mm Hg/mL with use of three graded doses of phenylephrine. We assumed that ρ=1.0 and that L/A=3.4. Thus, we predicted that K
LV
=(0.08/t
dec
)

2

. The LV filling pattern was determined from the derivative of LV volume (dV/dt). t
dec
was measured from peak early filling to the end of early filling. Predicted K
LV
and actual K
LV
were closely correlated (
r
=.94, SEE=0.06 mm Hg/mL,
P
<.05). The regression line was close to the line of identity (slope=0.95, intercept=0.13 mm Hg/mL). Dobutamine did not alter the relation between t
dec
and K
LV
. t
dec
determined from the mitral valve flow velocity measured with Doppler echocardiography correlated well with that measured by dV/dt (
r
=.89,
P
<.01) but was 0.02 seconds longer. K
LV
-calculated t
dec
from the corrected Doppler t
dec
provided a good estimate of measured K
LV
(
r
=.75, SEE=0.5 mm Hg/mL,
P
<.01).

Conclusions
LV chamber stiffness can be determined from the time for deceleration of LV early filling, which can be measured noninvasively.
Relation Between Ischemic Threshold Measured During Dobutamine Stress Echocardiography and Known Indices of Poor Prognosis in Patients With Coronary Artery Disease
Authors: Panza Julio A. , Curiel Rodolfo V. , Laurienzo Joy M. , Quyyumi Arshed A. , Dilsizian Vasken
Published: June 2012

Background
Stress echocardiography has become an accepted methodology for the evaluation of coronary artery disease. One potential advantage of dobutamine over other stressors used with echocardiography is the possibility of assessing the ischemic threshold. However, whether this measurement correlates with indices associated with adverse outcome has not been established.

Methods and Results
One hundred four patients (91 men and 13 women; age, 61±9 years) with coronary artery disease were studied with transesophageal echocardiography during infusion of dobutamine 2.5 to 40 μg/kg per minute. When regional dyssynergy developed, the dobutamine ischemic threshold (the dose of dobutamine at which induced regional wall motion abnormalities were first detected) was identified. The dobutamine stress echocardiogram was abnormal in 90 patients (sensitivity, 87%). The dobutamine ischemic threshold was 25.4±11.2 μg/kg per minute in patients with single-vessel disease, 14.4±7.9 in patients with two-vessel disease, and 9.1±7.9 in patients with three-vessel disease (
P
<.0001). The dobutamine ischemic threshold correlated with the ejection fraction response to exercise measured by radionuclide angiography: Patients with low ischemic threshold had a mean fall in ejection fraction, and patients with high ischemic threshold or normal tests had a mean increase in ejection fraction.

Conclusions
In patients with coronary artery disease, the ischemic threshold measured during dobutamine stress echocardiography correlates with both the number of stenosed vessels and the left ventricular ejection fraction response to exercise. Because these variables are associated with poor prognosis, these findings provide further support regarding the utility of dobutamine stress echocardiography in the clinical evaluation of patients with chronic coronary artery disease.
Hyperinsulinemia Inhibits Myocardial Protein Degradation in Patients With Cardiovascular Disease and Insulin Resistance
Authors: McNulty Patrick H. , Louard Rita J. , Deckelbaum Lawrence I. , Zaret Barry L. , Young Lawrence H.
Published: June 2012

Background
Insulin resistance, hyperinsulinemia, and myocardial hypertrophy frequently coexist in patients. Whether hyperinsulinemia directly affects myocardial protein metabolism in humans has not been examined, however. To test the hypothesis that hyperinsulinemia is anabolic for human heart protein, we examined the effects of insulin infusion on myocardial protein synthesis, degradation, and net balance in patients with ischemic heart disease.

Methods and Results
Eleven men (aged 57±3 years) with coronary artery disease who had fasted for 12 to 16 hours received a constant infusion of insulin (50 mU · m
−2
· min
−1
) while plasma concentrations of glucose and amino acids were kept constant. Rates of myocardial protein synthesis, degradation, and net balance were estimated from steady state extraction and isotopic dilution of L-[
ring
-2,6-
3
H]phenylalanine across the heart basally and 90 minutes into infusion. Subjects had elevated fasting plasma insulin concentrations (173±21 pmol/L) and used little exogenous glucose during insulin infusion, suggesting resistance to the effects of insulin on whole-body carbohydrate metabolism. Basally, myocardial protein degradation, as estimated by phenylalanine release (133±28 nmol/min), exceeded protein synthesis, estimated by phenylalanine uptake (31±15 nmol/min), resulting in net negative phenylalanine balance (−102±17 nmol/min). Insulin infusion reduced myocardial protein degradation by 80% but did not affect protein synthesis, returning net phenylalanine balance to neutral.

Conclusions
Acute hyperinsulinemia markedly suppresses myocardial protein degradation in patients with cardiovascular disease who are resistant to its effects on whole-body glucose metabolism. This antiproteolytic action represents a potential mechanism by which hyperinsulinemia could contribute to the development of myocardial hypertrophy in patients with cardiovascular disease.
Immunoglobulins and Left Ventricular Structure and Function in Pediatric HIV Infection
Authors: Lipshultz Steven E. , Orav E. John , Sanders Stephen P. , Colan Steven D.
Published: June 2012

Background
Progressive left ventricular (LV) dilation is common in children infected with HIV-1 and may be a harbinger of congestive heart failure (CHF). In many HIV-infected children, dilation is associated with inadequate LV hypertrophy, elevated afterload, and reduced LV function. Because CHF has been observed empirically to improve after treatment with intravenous immunoglobulin (IVIG) in other conditions and because LV dysfunction in pediatric HIV may be immunologically mediated, we examined retrospectively the relation between immunoglobulins and LV structure and function in 49 HIV-infected infants and children without CHF.

Methods and Results
A total of 106 echocardiograms were performed in these children within 30 days of serum immunoglobulin (IgG, IgA, and IgM) measurements; this includes 12 children treated with IVIG therapy. All echocardiographic parameters, blood pressures, and immunoglobulins were adjusted for age or body surface area and subjected to repeated-measures regression. Regression models were adjusted simultaneously for endogenous IgA, IgG, IgM, IVIG therapy, zidovudine therapy, age, HIV disease stage, and weight. Higher endogenous serum IgG levels and IVIG treatment were associated with significantly greater wall thickness and lower peak wall stress. Higher endogenous serum IgA levels were associated with more normal LV wall thickness and LV thickness-to-dimension ratios. LV contractility, fractional shortening, end-systolic wall stress, and thickness-to-dimension ratio all showed a trend toward more normal values with higher endogenous immunoglobulin values or during IVIG treatment.

Conclusions
LV structure and function appear to be more normal in HIV-infected children who receive IVIG treatment and in those with higher endogenous IgG levels. These results suggest that both the impaired myocardial growth and the LV dysfunction observed may be immunologically mediated and responsive to immunomodulatory therapy.
Mediastinitis After Coronary Artery Bypass Graft Surgery
Authors: Milano Carmelo A. , Kesler Karen , Archibald Nancy , Sexton Daniel J. , Jones Robert H.
Published: June 2012

Background
Mediastinitis is a severe complication of coronary artery bypass graft surgery (CABG). The purpose of the present study was to determine preoperative and intraoperative variables that predict mediastinitis and to determine the impact of this complication on long-term survival.

Methods and Results
Data on 20 preoperative and intraoperative variables were collected prospectively on 6459 consecutive patients who underwent CABG between January 1987 and January 1994. Eighty-three patients (1.3%) developed mediastinitis postoperatively, and a total of 24 patients (29%) died. Multivariate analysis identified 4 of the 20 variables as highly significant independent predictors for the development of mediastinitis: obesity (
P
=.0002), New York Heart Association congestive heart failure class (
P
=.002), previous heart surgery (
P
=.008), and duration of cardiopulmonary bypass (
P
=.05). A comprehensive review of the literature identified 13 other studies that evaluated 48 factors as predictors of mediastinitis; these data were critically analyzed and compared with the results from this series. In this series, postoperative interval mortality during the first 90 days after surgery for the patients with mediastinitis was 11.8% compared with 5.5% for the patients without mediastinitis. Interval mortality between 1 and 2 years after surgery remained high for the mediastinitis group (8.1%) relative to the nonmediastinitis group (2.3%). These differences were not eliminated by adjusting for important variables that influenced late survival in this population.

Conclusions
The present study and a review of the literature suggest that obesity and duration of surgery are the most important predictors of mediastinitis. Furthermore, although the early increase in mortality has been well described, the present study documents for the first time that mediastinitis has a significant negative influence on long-term survival independent of the patient’s preoperative condition.
Determining Surgical Indications for Acute Type B Dissection Based on Enlargement of Aortic Diameter During the Chronic Phase
Authors: Kato Masaaki , Bai Hong-zhi , Sato Kenji , Kawamoto Seiichi , Kaneko Mitsunori , Ueda Takashi , Kishi Daisuke , Ohnishi Kenji
Published: June 2012

Background
In patients with Stanford type B dissection who have been treated successfully with medical hypotensive therapy during the acute phase, a large number have incurred the risk of surgery during their chronic phases because of enlargement of the dissected aorta. The purpose of this study was to determine the indications for surgical treatment of acute type B dissection by studying chronic-phase enlargements of aortic dissections in patients treated successfully with medical hypotensive therapy during the acute phase.

Methods and Results
In 41 patients with type B dissection who had been treated medically during the acute phase, univariate and multivariate factor analyses were made to determine the predominant predictors for chronic-phase enlargement (≥60 mm) of the dissected aorta. Computed tomography was performed every 4 to 14 months to observe whether there was enlargement of the maximum aortic diameter. The predominant predictors for aortic enlargement in the chronic phase were the existence of a maximum aortic diameter of ≥40 mm during the acute phase (
P
<.001) and a patent primary entry site in the thoracic aorta (
P
=.001). The values of actuarial freedom from aortic enlargement for the patients with a large aortic diameter (≥40 mm) during the acute phase and a patent primary entry site in the thorax at 1, 3, and 5 years were 70%, 29%, and 22%, respectively. No aortic enlargement was observed in the other patients throughout the entire follow-up period.

Conclusions
These data suggest that patients with acute type B dissection who have a large aortic diameter (≥40 mm) and a patent primary entry site in the thorax should be treated surgically during the acute phase on the condition that the surgical risk in this phase is limited.
Pressure- and Volume-Induced Left Ventricular Hypertrophies Are Associated With Distinct Myocyte Phenotypes and Differential Induction of Peptide Growth Factor mRNAs
Authors: Calderone Angelino , Takahashi Nobuyuki , Izzo Jr Nicholas J. , Thaik Cynthia M. , Colucci Wilson S.
Published: June 2012

Background
Chronic pressure and volume overload (PO and VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. We tested the hypothesis that PO- and VO-induced left ventricular (LV) hypertrophies are associated with distinct molecular phenotypes and patterns of peptide growth factor induction.

Methods and Results
mRNA levels were quantified in LV myocardium from rats with LV hypertrophy due to PO or VO caused by suprarenal aortic constriction or an abdominal aortocaval fistula, respectively, for 1 week. Although PO and VO caused comparable increases in LV weight and prepro–atrial natriuretic factor mRNA, PO but not VO increased mRNA levels for the fetal genes β-myosin heavy chain and skeletal α-actin and reduced the mRNA level of sarcoplasmic reticulum Ca
2+
ATPase. In a myocyte-enriched myocardial fraction, transforming growth factor-β
3
and insulin-like growth factor-1 mRNA levels were increased with PO but not VO; acidic fibroblast growth factor mRNA was unchanged with PO but decreased with VO. In a nonmyocyte-enriched myocardial fraction, transforming growth factor-β
3
and insulin-like growth factor-1 mRNA levels were decreased with VO but unchanged with PO.

Conclusions
PO- and VO-induced LV hypertrophies are associated with distinct molecular phenotypes and patterns of peptide growth factor induction. Stimulus-specific heterogeneity in the signaling events and peptide growth factors coupled to gene expression could play a role in determining the type of hypertrophy that is caused by various forms of hemodynamic overload.
Does an Additional Source of Pulmonary Blood Flow Alter Outcome After a Bidirectional Cavopulmonary Shunt?
Authors: Frommelt Michele A. , Frommelt Peter C. , Berger Stuart , Pelech Andrew N. , Lewis David A. , Tweddell James S. , Litwin S. Bert
Published: June 2012

Background
The bidirectional cavopulmonary shunt has become an important intermediate step in the treatment of pediatric patients with single ventricle physiology who are ultimately destined for palliative surgery. We wanted to know whether there would be risks or benefits if an additional source of pulmonary blood flow was left after a bidirectional cavopulmonary shunt.

Methods and Results
We retrospectively reviewed the medical and surgical records of all patients who underwent a bidirectional cavopulmonary shunt at the Children’s Hospital of Wisconsin between January 1991 and December 1993. A total of 43 patients were identified. Anatomic diagnoses included double inlet left ventricle (14 patients), tricuspid atresia (8 patients), pulmonary atresia with intact septum (6 patients), single right ventricle (5 patients), hypoplastic left heart (3 patients), unbalanced atrioventricular septal defect (3 patients), and other complex lesions (4 patients). We then divided the patients into two groups for purposes of analysis. Group 1 had only the cavopulmonary shunt as a source of pulmonary flow (22 patients); group 2 had an additional source of pulmonary flow (21 patients). Patient age at the time of cavopulmonary shunt ranged from 6 months to 12 years, with group 1 patients being younger (31 versus 45 months,
P
=.05). Group 2 patients had higher postoperative central venous pressures (17.8 versus 14.1 mm Hg,
P
<.001) and oxygen saturations (86% versus 81%,
P
<.001) than did group 1 patients. There was no statistical difference between groups in the number of chest tube days or hospital days. There was 1 early death in group 1 related to severe ventricular dysfunction and 1 late death in group 2 related to sepsis. Five patients in group 2 were readmitted to the hospital for drainage of a large chylothorax compared with none in group 1 (
P
<.02).

Conclusions
We conclude that patients with an additional source of pulmonary blood flow after bidirectional cavopulmonary shunt have higher postoperative central venous pressures, have higher oxygen saturations, and are at risk for the late development of a chylothorax.
Radical Outcome Method
Authors: Turley Kevin , Tyndall Michael , Turley Kerry , Woo Dewey , Mohr Thomas
Published: June 2012

Background
Treatment of congenital heart disease has entered a new era of healthcare delivery and cost containment. Critical pathway method (CPM) has been previously demonstrated by us to produce a significant reduction in average length of stay (ALOS) in hospital of −44%. A new approach, radical outcome method (ROM), has produced comparable results that appear to improve over time. The dynamic nature is examined.

Methods and Results
Two hundred consecutive patients with congenital heart disease were treated by a single surgeon at a single health maintenance organization (HMO) facility. ROM was used in all patients. This method uses seven critical moments at which shortening rather than confirmation of the ALOS is possible. This process is completed by the second post-operative day. Overall mortality was 1%. The 200 patients were divided into two consecutive groups of 100 patients to determine the effectiveness of ROM over time. Fifty sets were matched. ALOS hospital decreased by 29 days (mean, 0.6 d/set),
P
<.003. Thirty sets who underwent cardiopulmonary bypass had a 16% decrease (
P
<.03), and 20 sets in whom nonbypass procedures were performed had a decrease of 16% (
P
<.02). ALOS in hospital for the 50 sets decreased from 3.7 to 3.1 days (−16%,
P
<.003). Outcome data demonstrated no significant difference.

Conclusions
ROM, a proactive approach to hospital stay, is a dynamic process that reduces ALOS in hospital. This is achieved by both reducing negative variation in the standard CPM and allowing for positive variation. Outcome data confirm that this approach can reduce ALOS in hospital while providing optimal patient care and family satisfaction, a standard for the new era of healthcare delivery.
Left Ventricular Dysfunction on Exercise Long Term After Total Repair of Tetralogy of Fallot
Authors: Kondo Chisato , Nakazawa Makoto , Kusakabe Kiyoko , Momma Kazuo
Published: June 2012

Background
Excellent results regarding mortality are well recognized in the long-term period after intracardiac repair of tetralogy of Fallot. However, it is still unclear how postoperative sequelae affect cardiac performance during exercise.

Methods and Results
Twenty-nine patients with tetralogy of Fallot were studied 16±2 years after intracardiac repair by use of radionuclide first-pass ventriculography with an ultra-high-sensitive gamma camera at rest and at peak exercise on a semi-upright bicycle ergometer. The results were compared with those from 10 age- and sex-matched control subjects. Left and right ventricular ejection fraction and absolute ventricular volume were measured at rest and peak exercise. Regional right ventricular wall motion and diastolic function of the left ventricle were also assessed. Cardiac output of tetralogy was normally preserved both at rest and during exercise. Nevertheless, the incremental response of left ventricular ejection fraction during exercise was depressed in the patients. Left ventricular ejection fraction during exercise was inversely correlated with the right ventricular end-diastolic volume and the severity of pulmonary regurgitation. Regional wall motion at the right ventricular outflow tract was not decreased in the patients. Left ventricular diastolic function was not impaired in the patients compared with control subjects.

Conclusions
Latent left ventricular dysfunction during exercise is related to an enlarged right ventricle due to pulmonary regurgitation after intracardiac repair of tetralogy. Careful follow-up is required in patients having significant pulmonary regurgitation.
Magnesium Sulfate Reduces Myocardial Infarct Size When Administered Before but Not After Coronary Reperfusion in a Canine Model
Authors: Christensen Carl W. , Rieder Michelle A. , Silverstein Eve L. , Gencheff Nelson E.
Published: June 2012

Background
The role of magnesium in treating acute myocardial infarction (AMI) has been controversial. Several small clinical trials indicate that magnesium may have a role in treating AMI early, whereas the other results suggest that magnesium is of questionable benefit.

Methods and Results
We looked at the effect of magnesium on infarct size (IS) when given during a coronary occlusion and after reperfusion. Magnesium sulfate (6-mEq bolus plus 2 mEq/h for 5 hours) was given at 15 or 45 minutes of coronary occlusion or 15 minutes of reperfusion. The left anterior descending coronary artery was occluded for 90 minutes, followed by 300 minutes of reperfusion. IS to area at risk (IS/AR) was measured by planimetry after triphenyltetrazolium chloride staining. Collateral myocardial blood flow was measured with radioactive microspheres. The IS/AR ratio in the control group was 52.3±19.6% compared with 20.5±11.7% and 21.3±6.5% at 15 and 45 minutes of occlusion, respectively (
P
<.05). There were no significant differences in the reduction in IS at 15 and 45 minutes of occlusion. Although there was a reduction in the IS when magnesium was administered during reperfusion (38.2±13.4%), it was not statistically significant. There was no significant difference in the AR relative to the total left ventricular weight between the four groups.

Conclusions
The data suggest that magnesium infusion during a coronary occlusion has a significant benefit in reducing the IS in this model. Magnesium may have a beneficial clinical role in AMI, especially if administered before reperfusion as a bolus followed by a constant infusion.
Endothelial Modulation of β-Adrenergic Dilation of Large Coronary Arteries in Conscious Dogs
Authors: Ghaleh Bijan , Béa Marie-Luce , Dubois-Randé Jean-Luc , Giudicelli Jean-François , Hittinger Luc , Berdeaux Alain
Published: June 2012

Background
Endothelium-derived relaxing factors have been described as important intermediates in β-adrenergic vasodilation of resistance coronary vessels, but their involvement at the level of large epicardial coronary arteries remains controversial. Therefore, we examined the role of vascular endothelium in the β-adrenergic–mediated vasodilation of large epicardial coronary arteries in conscious dogs.

Methods and Results
Nine dogs were instrumented for measurement of left circumflex coronary artery diameter (CD) by sonomicrometry and coronary blood flow velocity (CBFv) with a Doppler technique in response to graded doses of isoproterenol (0.001 to 0.1 μg/kg IV bolus). Under control conditions, isoproterenol induced dose-dependent increases in CD and CBFv. When CBFv was kept constant at its baseline value by inflation of a cuff occluder, isoproterenol still induced dose-dependent increases in CD, but the latter were of lesser magnitude than those observed under normal CBFv conditions (110±20 versus 170±30 μm, respectively, ie, a reduction of 33% of the dilatory response at 0.1 μg/kg,
P
<.01). In the same dogs, the coronary endothelium was then mechanically removed at the site of CD measurement by a balloon angioplasty technique. After this procedure, the dose-dependent increases in CD induced by isoproterenol under either normal or controlled CBFv conditions were overimposable, and their magnitude was similar to that of the increases observed in the presence of an intact endothelium when CBFv was kept constant. After β
1
-adrenergic receptor blockade by atenolol (1 mg/kg), isoproterenol-induced increases in CD were abolished either when CBFv was kept constant or after endothelium removal.

Conclusions
In conscious dogs, the direct stimulating effect of isoproterenol on β
1
-adrenergic receptors is endothelium-independent at the level of large coronary arteries. The endothelium reinforces the dilatory response to isoproterenol through an indirect, flow-dependent mechanism.
Cardiac Renin-Angiotensin System in the Hypertrophied Heart
Authors: Iwai Naoharu , Shimoike Hitoshi , Kinoshita Masahiko
Published: June 2012

Background
The cardiac renin-angiotensin system (RAS) has been suggested to play an important role in heart failure and cardiac hypertrophy. In the present study, we evaluated the expression of each component of the RAS in hypertrophied heart induced by aortocaval shunt.

Methods and Results
The expression levels of renin, angiotensinogen, angiotensin-converting enzyme (ACE), and angiotensin II type Ia and Ib receptor (AT1aR and AT1bR) mRNA were determined by the reverse transcription–polymerase chain reaction method owing to the relatively low expression levels of these mRNAs in the ventricle. The expression level of renin or angiotensinogen mRNA in the ventricle was very low, more than 1000-fold lower than that in the kidney or liver, respectively. The expression of ACE mRNA in the ventricle was relatively abundant and was increased in the hypertrophied ventricle in this model, whereas no significant increases in the expression levels of AT1aR and AT1bR mRNA were observed. Administration of lisinopril attenuated the development of left and right ventricular hypertrophy in this model and was accompanied by an attenuation of the upregulation of the ACE, collagen type I-α, and vimentin mRNAs. Because the activity of the circulating RAS in the aortocaval shunt rats was not higher than that in the sham-operated rats, the effects of lisinopril in attenuating the ventricular hypertrophy may be due to inhibition of the increased ACE in the ventricle.

Conclusions
The present study supports the importance of ACE expressed in the ventricle in the development of hypertrophy induced by aortocaval shunt.
Atrioventricular Nodal Conduction Gap and Dual Pathway Electrophysiology
Authors: Mazgalev Todor , Tchou Patrick
Published: June 2012

Background
The gap phenomenon in atrioventricular (AV) conduction is described as a block that occurs within a range of atrial coupling intervals. This block is assumed to occur between two adjacent parts of the conduction system having different refractory properties; thus, a gap would develop if the functional refractory period of the proximal unit was shorter than the effective refractory period of the distal unit. We describe a new electrophysiological mechanism based on dual pathways electrophysiology of the AV node.

Methods and Results
In vitro experiments were performed on isolated superfused rabbit hearts. Standard electrophysiological pacing and recording techniques were used to generate conduction curves. The gap phenomenon was documented in 9 of 14 nodal preparations. With shortening of the atrial coupling interval, antegrade conduction block of the “fast” pathway wave front occurred while this impulse was still retrogradely interfering with slow pathway conduction. That is, the fast pathway wave front prevented propagation of the anterograde “slow” pathway wave front by collision or by creating a refractory barrier. This mechanism produced a gap and the block persisted until, at even shorter coupling intervals, the fast wave front penetration became insufficient and conduction was restored through the released slow pathway wave front. This mechanism was verified in AV nodal preparations with separated inputs, in which independent fast and slow wave fronts could be induced and programmed to collide.

Conclusions
Our results established the functional interaction of fast and slow pathway wave fronts as an important electrophysiological mechanism underlying the AV conduction gap. This mechanism may be responsible for a variety of clinically observed conduction discontinuities.
Influence of Competitive Pulmonary Blood Flow on the Bidirectional Superior Cavopulmonary Shunt
Authors: Webber Steven A. , Horvath Pavel , LeBlanc Jacques G. , Slavik Zdenek , Lamb Robert K. , Monro James L. , Reich Oleg , Hruda Jaroslav , Sandor George G.S. , Keeton Barry R. , Salmon Anthony P.
Published: June 2012

Background
It is common practice to interrupt all alternative sources of pulmonary blood flow (“competitive flow”) at the time of a bidirectional superior cavopulmonary anastomosis (BCPA), although the merits of this have not been systematically studied.

Methods and Results
We reviewed the early and medium-term clinical and hemodynamic findings in 108 consecutive patients 3 weeks to 25 years old (median, 1.9 years) undergoing BCPA at one of three institutions. Preoperatively, pulmonary blood flow was dependent on antegrade ventricular flow (n=50), systemic-to-pulmonary shunts (n=33), or mixed sources (n=25). Postoperatively, competitive sources of pulmonary blood flow were left patent in 43 of 108 patients (40%). There were four early (3.7%) and four late deaths, none related to persistence of competitive flow. After BCPA, patients with competitive flow had significantly higher systemic oxygen saturations at 1 hour (85% versus 79%), 24 hours (84% versus 78%), and at hospital discharge (84% versus 78%) and required a shorter period of artificial ventilation (median, 9 versus 24 hours) and intensive care (median, 2 versus 4 days). Oxygen saturations at late follow-up (median, 2.8 years; range, 1 to 7) did not differ (83% versus 82%). No patient developed pulmonary arteriovenous malformations.

Conclusions
Competitive flow is well tolerated in the short and medium term after BCPA, and early postoperative systemic oxygen saturations are improved. The long-term influence of competitive flow on pulmonary arterial growth, arteriovenous malformation development, and ventricular function warrants investigation.