bluuebunny/crossref_metadata_2025 huggingface dataset:
TGF-β1 downregulates CFTR expression and function in nasal polyps of non-CF patients
Authors: Prulière-Escabasse Virginie , Fanen Pascale , Dazy Anne Catherine , Lechapt-Zalcman Emmanuèle , Rideau Dominique , Edelman Aleksander , Escudier Estelle , Coste André
Published: September 2004

Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-β1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-β1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-β1 on ion transports could be reversed after 48-h removal of TGF-β1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.
CXCR2 is essential for maximal neutrophil recruitment and methacholine responsiveness after ozone exposure
Authors: Johnston Richard A. , Mizgerd Joseph P. , Shore Stephanie A.
Published: September 2004

Ozone (O3), a common air pollutant, induces airway inflammation and airway hyperresponsiveness. In mice, the neutrophil chemokines KC and macrophage inflammatory protein-2 (MIP-2) are expressed in the lungs following O3exposure. The purpose of this study was to determine whether CXCR2, the receptor for these chemokines, is essential to O3-induced neutrophil recruitment, injury to lungs, and increases in respiratory system responsiveness to methacholine (MCh). O3exposure (1 ppm for 3 h) increased the number of neutrophils in the bronchoalveolar lavage fluid (BALF) of wild-type (BALB/c) and CXCR2-deficient mice. However, CXCR2-deficient mice had significantly fewer emigrated neutrophils than did wild-type mice. The numbers of neutrophils in the blood and concentrations of BALF KC and MIP-2 did not differ between genotypes. Together, these data suggest CXCR2 is essential for maximal chemokine-directed migration of neutrophils to the air spaces. In wild-type mice, O3exposure increased BALF epithelial cell numbers and total protein levels, two indirect measures of lung injury. In contrast, in CXCR2-deficient mice, the number of BALF epithelial cells was not increased by O3exposure. Responses to inhaled MCh were measured by whole body plethysmography using enhanced pause as the outcome indicator. O3exposure increased responses to inhaled MCh in both wild-type and CXCR2-deficient mice 3 h after O3exposure. However, at 24 h after exposure, responses to inhaled MCh were elevated in wild-type but not CXCR2-deficient mice. These results indicate CXCR2 is essential for maximal neutrophil recruitment, epithelial cell sloughing, and persistent increases in MCh responsiveness after an acute O3exposure.
Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells
Authors: Lu Wenju , Lillehoj Erik P. , Kim K. Chul
Published: September 2004

Mucus hypersecretion associated with airway inflammation is reduced by glucocorticoids. Two mechanisms of glucocorticoid-mediated inhibition of mucus production have been proposed, direct inhibition of mucus production by airway epithelial cells and indirectly through inhibition of proinflammatory mediators that stimulate mucus production. In this study, we examined the effect of dexamethasone (DEX) on mRNA expression and synthesis of MUC5AC by A549 human lung adenocarcinoma cells as well as Muc5ac and total high-molecular-weight (HMW) mucins by primary rat tracheal surface epithelial (RTSE) cells. Our results showed that in primary RTSE cells, DEX 1) dose dependently suppressed Muc5ac mRNA levels, but the levels of cellular Muc5ac protein and HMW mucins were unaffected; 2) did not affect constitutive or UTP-stimulated mucin secretion; 3) enhanced the translation of Muc5ac; and 4) increased the stability of intracellular Muc5ac protein by a mechanism other than the inhibition of the proteasomal degradation. In A549 cells, however, DEX suppressed both MUC5AC mRNA levels and MUC5AC protein secretion in a dose-dependent manner. We conclude that whereas DEX inhibits the levels of Muc5ac mRNA in primary RTSE cells, the levels of Muc5ac protein remain unchanged as a consequence of increases in both translation and protein stability. Interestingly, some of the effects of DEX were opposite in a cell line.
Hypoxia-induced dysfunction of rat diaphragm: role of peroxynitrite
Authors: Zhu Xiaoping , Heunks Leo M. A. , Versteeg Elly M. M. , van der Heijden Henricus F. M. , Ennen Leo , van Kuppevelt Toin H. , Vina Jose , Dekhuijzen P. N. Richard
Published: September 2004

Oxidants may play a role in hypoxia-induced respiratory muscle dysfunction. In the present study we hypothesized that hypoxia-induced impairment in diaphragm contractility is associated with elevated peroxynitrite generation. In addition, we hypothesized that strenuous contractility of the diaphragm increases peroxynitrite formation. In vitro force-frequency relationship, isotonic fatigability, and nitrotyrosine levels were assessed under hypoxic (Po2∼6.5 kPa) and hyperoxic (Po2∼88.2 kPa) control conditions and also in the presence of authentic peroxynitrite (60 min), ebselen (60 min), and the nitric oxide synthase inhibitor NG-monomethyl-l-arginine acetate (l-NMMA) (90 min). A hypoxia-induced downward shift of the force-frequency relationship was associated with elevated nitrotyrosine level in the diaphragm. During hypoxia, both ebselen and l-NMMA decreased nitrotyrosine levels but did not affect force generation. Strenuous contractions impaired force generation but did not affect nitrotyrosine levels in the diaphragm during hypoxia. But under hyperoxic conditions, fatiguing contractions were associated with elevated diaphragm nitrotyrosine levels. Under hyperoxic conditions exogenous peroxynitrite impaired force generation and increased nitrotyrosine level. These studies show that hypoxia-induced impairment in diaphragm contractility is associated with increased diaphragm protein nitration, but no causal relationship was found between diaphragm nitrotyrosine formation and in vitro force generation.
Skeletal muscle adaptation: training twice every second day vs. training once daily
Authors: Hansen Anne K. , Fischer Christian P. , Plomgaard Peter , Andersen Jesper Løvind , Saltin Bengt , Pedersen Bente Klarlund
Published: September 2004

Low muscle glycogen content has been demonstrated to enhance transcription of a number of genes involved in training adaptation. These results made us speculate that training at a low muscle glycogen content would enhance training adaptation. We therefore performed a study in which seven healthy untrained men performed knee extensor exercise with one leg trained in a low-glycogen (Low) protocol and the other leg trained at a high-glycogen (High) protocol. Both legs were trained equally regarding workload and training amount. On day 1, both legs (Low and High) were trained for 1 h followed by 2 h of rest at a fasting state, after which one leg (Low) was trained for an additional 1 h. On day 2, only one leg (High) trained for 1 h. Days 1 and 2 were repeated for 10 wk. As an effect of training, the increase in maximal workload was identical for the two legs. However, time until exhaustion at 90% was markedly more increased in the Low leg compared with the High leg. Resting muscle glycogen and the activity of the mitochondrial enzyme 3-hydroxyacyl-CoA dehydrogenase increased with training, but only significantly so in Low, whereas citrate synthase activity increased in both Low and High. There was a more pronounced increase in citrate synthase activity when Low was compared with High. In conclusion, the present study suggests that training twice every second day may be superior to daily training.
Aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle
Authors: Hornberger Troy A. , Mateja R. D. , Chin E. R. , Andrews J. L. , Esser K. A.
Published: September 2004

The capacity for skeletal muscle to recover its mass following periods of unloading (regrowth) has been reported to decline with age. Although the mechanisms responsible for the impaired regrowth are not known, it has been suggested that aged muscles have a diminished capacity to sense and subsequently respond to a given amount of mechanical stimuli (mechanosensitivity). To test this hypothesis, extensor digitorum longus muscles from young (2–3 mo) and old (26–27 mo) mice were subjected to intermittent 15% passive stretch (ex vivo) as a source of mechanical stimulation and analyzed for alterations in the phosphorylation of stress-activated protein kinase (p38), ribosomal S6 kinase (p70S6k), and the p54 jun N-terminal kinase (JNK2). The results indicated that the average magnitude of specific tension (mechanical stimuli) induced by 15% stretch was similar in muscles from young and old mice. Young and old muscles also revealed similar increases in the magnitude of mechanically induced p38, p70S6k (threonine/serine 421/424 and threonine 389), and JNK2 phosphorylation. In addition, coincubation experiments demonstrated that the release of locally acting growth factors was not sufficient for the induction of JNK2 phosphorylation, suggesting that JNK2 was activated by a mechanical rather than a mechanical/growth factor-dependent mechanism. Taken together, the results of this study demonstrate that aging does not alter the mechanosensitivity of the p38, p70S6k, and JNK2 signaling pathways in skeletal muscle.
Diaphragm electromyogram root mean square response to hypercapnia and its intersubject and day-to-day variation
Authors: Singh Bhajan , Panizza Janine A. , Finucane Kevin E.
Published: September 2004

Diaphragm activation can be quantified by measuring the root mean square of crural EMG (RMSdi) (Beck J, Sinderby C, Lindstrom L, and Grassino A, J Appl Physiol 85: 1123–1134, 1998). To examine intersubject and day-to-day variation in the RMSdi-Pco2 relationship, end-tidal Pco2, minute ventilation (V̇e), respiratory frequency (fB), and RMSdi were measured in seven healthy subjects on two occasions during steady-state ventilation at seven levels of inspired O2 fraction (FiCO2) from 0 to 0.08 in random order. RMSdi was measured with a multielectrode esophageal catheter and controlled for signal contamination and diaphragm position. RMSdi was normalized for values obtained during quiet breathing at functional residual capacity, at FiCO2 of 0.04, and during an inspiratory capacity maneuver (RMSdi%max) as well as ECG R-wave amplitude at functional residual capacity (RMSdi/ECGR), fB, and thickness of the costal diaphragm measured by ultrasound. RMSdi increased linearly with Pco2 (mean r2 = 0.83 ± 0.10); at the highest FiCO2, RMSdi%max was 40.2 ± 11.6%. Relative to the intersubject variation in the V̇e-Pco2 relationship, intersubject variations in the slopes and intercepts of the RMSdi-Pco2 relationships were 1.7 and 1.8 times, respectively, and RMSdi%max-Pco2 relationships 0.9 and 1.3 times, respectively, and were unrelated to fB and diaphragm thickness. Relative to the day-to-day variation in the V̇e-Pco2 relationship, day-to-day variation in the slopes and intercepts of the RMSdi-Pco2 relationships were 2.8 and 4.4 times, respectively, and RMSdi/ECGR-Pco2 relationships 1.3 and 2.2 times, respectively. It was concluded that the RMSdi-Pco2 relationship measures chemosensitivity and is best compared between subjects via RMSdi%max and on separate occasions in the same subject via RMSdi/ECGR.
Age-Dependent Biphasic Changes in Ischemic Sensitivity in the Striatum of Huntington's Disease R6/2 Transgenic Mice
Authors: Klapstein Gloria J. , Levine Michael S.
Published: September 2004

We used the oxygen/glucose deprivation (OGD) model of ischemia in corticostriatal brain slices to test the hypothesis that metabolic deficiencies in R6/2 transgenic Huntington's disease (HD) mice will impair their recovery from an ischemic challenge. Corticostriatal extracellular field excitatory postsynaptic potentials (fEPSPs) were evoked in transgenic and wild-type (WT) mice in three age groups: 3–4 wk, before the overt behavioral phenotype develops; 5–9 wk, as overt behavioral symptoms begin; and 10–15 wk when symptoms were most severe. OGD for 8 min completely and reversibly inhibited fEPSPs. Although responses of 3–4 wk WTs showed a tolerance to ischemia and recovered rapidly, ischemic sensitivity developed progressively; at 5–9 and 10–15 wk, responses recovered more slowly from OGD. In contrast, although 3–4 wk R6/2 transgenic fEPSPs showed significantly more ischemic sensitivity than their WT counterparts, the R6/2 fEPSPs maintained a relative tolerance to ischemia at 5–9 and 10–15 wk. As a result, a “crossover” point occurred, roughly coinciding with the development of the overt behavioral phenotype (5–9 wk), after which time R6/2 fEPSPs were significantly more resistant to ischemia than WT responses. The increased ischemic sensitivity in 3–4 wk R6/2 responses was not due to excessive glutamate release during OGD as it persisted in the presence of the glutamate receptor antagonist kynurenic acid (1 mM). Although the mechanism for development of ischemic resistance in R6/2 transgenics remains unknown, it correlates with metabolic and biochemical changes described in this model and in HD patients.
Quasi β‐power increasing sequences
Authors: Bor H. , Debnath L.
Published: September 2004

We prove a theorem of Mazhar (1999) on summability factors under weaker conditions by using a quasi β‐power increasing sequence instead of an almost increasing sequence.
Jordan superderivations. II
Authors: Fošner Maja
Published: September 2004

In a recent paper we have extended the classical Herstein′s theorem on Jordan derivations on prime rings to Jordan superderivations on prime associative superalgebras. In the present paper we extend this result to semiprime associative superalgebras.
Discrete differential operators in multidimensional Haar wavelet spaces
Authors: Cattani Carlo , Ruiz Luis M. Sánchez
Published: September 2004

We consider a class of discrete differential operators acting on multidimensional Haar wavelet basis with the aim of finding wavelet approximate solutions of partial differential problems. Although these operators depend on the interpolating method used for the Haar wavelets regularization and the scale dimension space, they can be easily used to define the space of approximate wavelet solutions.
Real quartic surfaces containing 16 skew lines
Authors: Nieto Isidro
Published: September 2004

It is well known that there is an open three‐dimensional subvariety Ms of the Grassmannian of lines in ℙ3 which parametrizes smooth irreducible complex surfaces of degree 4 which are Heisenberg invariant, and each quartic contains 32 lines but only 16 skew lines, being determined by its configuration of lines, are called a double 16. We consider here the problem of visualizing in a computer the real Heisenberg invariant quartic surface and the real double 16. We construct a family of points l ∈ Ms parametrized by a two‐dimensional semialgebraic variety such that under a change of coordinates of l into its Plüecker, coordinates transform into the real coordinates for a line L in ℙ3, which is then used to construct a program in Maple 7. The program allows us to draw the quartic surface and the set of transversal lines to L. Additionally, we include a table of a group of examples. For each test example we specify a parameter, the viewing angle of the image, compilation time, and other visual properties of the real surface and its real double 16. We include at the end of the paper an example showing the surface containing the double 16.
Complete convergence for arrays of minimal order statistics
Authors: Adler André
Published: September 2004

For arrays of independent Pareto random variables, this paper establishes complete convergence for weighted partial sums for the smaller order statistics within each row. This result improves on past strong laws. Moreover, it shows that we can obtain a finite nonzero limit for our normalized partial sums under complete convergence even though the first moment of our order statistics is infinite.
Targeted Cell Delivery Into Infarcted Rat Hearts by Retrograde Intracoronary Infusion: Distribution, Dynamics, and Influence on Cardiac Function
Authors: Suzuki Ken , Murtuza Bari , Fukushima Satsuki , Smolenski Ryszard T. , Varela-Carver Anabel , Coppen Steven R. , Yacoub Magdi H.
Published: September 2004

Background—

Intracoronary infusion for cell transplantation has potential advantages in disseminating cells globally into the myocardium with less injury over direct intramuscular injection. Arterial route, however, has a risk of coronary embolism and a limitation in cell delivery into ischemic or infarcted areas. We assessed the efficiency of retrograde intracoronary cell implantation into infarcted hearts using a novel rat model.

Methods and Results—

After left coronary artery ligation in rat, a catheter was inserted into the left cardiac vein, which drains the left ventricular free wall. Through this, 1×10
6
skeletal muscle precursor cells expressing nuclear β-galactosidase were infused retrogradely into the vein. In situ staining demonstrated that β-galactosidase–expressing donor cells had disseminated throughout the left ventricular free wall, including both infarcted and surrounding border areas, at 10 minutes after infusion. At 28 days, in contrast, positively stained multinuclear myotubes were found in border zones, whereas no positive cells were seen in infarcted areas. Measurement of β-galactosidase enzyme activity estimated that 29.8±6.9% of total infused cells were retained within the myocardium at 10 minutes and that this number decreased to 23.7±8.1% at 3 days but rapidly increased thereafter, reaching a plateau at 90.2±17.1% by 14 days. Echocardiography and Langendorff perfusion demonstrated that cell implantation improved cardiac function and dimensions by 28 days, compared with both sham-treated and phosphate-buffered saline-infused infarcted hearts, and this was associated with decreased collagen deposition.

Conclusion—

Retrograde intracoronary cell transplantation could provide an effective cell delivery into infarcted hearts and could be a useful strategy for treating myocardial infarction.
Mechanism of Recurrent Ischemic Mitral Regurgitation After Annuloplasty
Authors: Hung Judy , Papakostas Lampros , Tahta Stephen A. , Hardy Bruce G. , Bollen Bruce A. , Duran Carlos M. , Levine Robert A.
Published: September 2004

Background—

Patients who undergo ring annuloplasty for ischemic mitral regurgitation (MR) often have persistent or recurrent MR. This may relate to persistent leaflet tethering from left ventricle (LV) dilatation that is not relieved by ring annuloplasty. Therefore, the purpose of this study was to test the hypothesis that recurrent MR in patients after ring annuloplasty relates to continued LV remodeling.

Methods and Results—

Serial echoes were reviewed in 30 patients (aged 72±11 years) who showed recurrent MR late (47±27 months) versus early (3.8±5.8 months) after ring annuloplasty for ischemic MR during coronary artery bypass grafting without interval infarction. Patients with intrinsic mitral valve disease were excluded. Echocardiographic measures of MR (vena contracta and jet area/left atrial area) and LV remodeling (LV dimensions, volumes, and sphericity) were assessed at each stage. The degree of MR increased from mild to moderate, on average, from early to late postoperative stages, without significant change in LV ejection fraction. Changes in MR paralleled increases in LV volumes and sphericity index at end-systole and end-diastole. The only independent predictor of late postoperative MR was LV sphericity index at end-systole.

Conclusions—

Recurrent MR late after ring annuloplasty is associated with continued LV remodeling, emphasizing its dynamic relation to the LV.
Single Versus Multiple Internal Mammary Artery Grafting for Coronary Artery Bypass
Authors: Burfeind William R. , Glower Donald D. , Wechsler Andrew S. , Tuttle Robert H. , Shaw Linda K. , Harrell Frank E. , Rankin J. Scott
Published: September 2004

Background—

The long-term clinical advantages of using routine multiple internal mammary artery (IMA) grafts for coronary artery bypass (CAB) are not clear. This study was designed to test the hypothesis that multiple IMA grafts would provide better 15-year outcomes when compared with single IMA and vein grafts.

Methods and Results—

Between 1984 and 1987, 1067 consecutive patients undergoing isolated CAB were referred to 1 surgeon practicing primarily single and another surgeon maximizing multiple IMA grafts (clinical practice trial). A 207-patient subset with multiple IMAs underwent postoperative graft angiography at 1 to 32 weeks to define initial IMA patency. Patients were followed-up yearly, and the groups were analyzed as (I) surgical strategy (surgeon operating) (single=413 versus multiple=654), (II) ultimate operation performed (single=418 versus multiple=449), or (III) single versus multiple coronary systems revascularized with IMAs (single=490 versus multiple=377). Advantages of this study design were that an entire referral population was examined, multiple IMAs were applied to the entire spectrum of baseline patient risk, 15-year follow-up provided a complete prognostic picture, and the subgroups were potentially comparable at baseline. In all 3 analyses, single and multiple groups were statistically similar with respect to baseline, operative, and immediate postoperative variables. Early IMA patency was 98.5% (333/338 grafts patent), validating the quality of IMA procedures. Unadjusted and adjusted 15-year outcome analyses for I, II, and III for death, myocardial infarction, percutaneous coronary intervention, redo coronary bypass, and the composite of all events identified multiple versus single as a significant predictor of outcome for the composite end point in adjusted analysis III (hazard ratio=0.808; 95% CI, 0.689 to 0.948;
P
=0.009), because of a 5% to 10% absolute reduction in each of the outcome variables at 15 years. Moreover, >50% reduction in reoperation rate was observed at 15 years in every analysis.

Conclusions—

At 15-year follow-up, multiple IMA grafting was associated with a 19.2% adjusted risk reduction in death and cardiac events, caused by decreases in all adverse end points and fewer reoperations. These data indicate that the clinical advantages of maximizing IMA conduits are significant. Based on this information, it is suggested that multiple IMA grafting to 2 coronary systems should be applied liberally to patients with noncardiac risk profiles predictive of long-term survival.
National Survey of Coronary Artery Bypass Grafting for Coronary Stenosis Caused by Kawasaki Disease in Japan
Authors: Tsuda Etsuko , Kitamura Soichiro ,   The Cooperative Study Group of Japan
Published: September 2004

Background—

We surveyed the national experience of coronary artery bypass grafting (CABG) for coronary sequelae of Kawasaki disease (kDa) in 2002.

Methods and Results—

A questionnaire was returned from 323/552 (59%) institutions. Two hundred forty-four patients (188 male 56 female) since 1975 were identified. The mean number of grafts was 1.8 and the age at operation ranged from 1 to 44 years (median 11 years). The interval from the onset of kDa to operation ranged from 1 month to 42 years (median 8 years), whereas the follow-up period was from 7 days to 25 years (median 5 years). Previous myocardial infarction was found in 70 patients (28%). When the age at operation was older than 12 years, patency rates for internal thoracic artery grafts (ITA) at 1, 5, and 15 years were 95%, 91%, and 91%, respectively (n=156). When the age at operation was younger than 12 years, the corresponding values were significantly lower, with 1, 5, and 15 years being 93%, 73%, and 65%, respectively (n=146) (
P
<0.05). Reoperation was performed in 14 patients (6%). Death occurred in 15 patients (6%). Nine of the 14 late deaths were sudden. Six of 8 patients with a left ventricular ejection fraction (LVEF) <40% died.

Conclusion—

The results of ITA in those aged 12 years or older were favorable. LVEF influenced prognosis.
Extensive Left Ventricular Remodeling Does Not Allow Viable Myocardium to Improve in Left Ventricular Ejection Fraction After Revascularization and Is Associated With Worse Long-Term Prognosis
Authors: Bax Jeroen J. , Schinkel Arend F.L. , Boersma Eric , Elhendy Abdou , Rizzello Vittoria , Maat Alexander , Roelandt Jos R.T.C. , van der Wall Ernst E. , Poldermans Don
Published: September 2004

Background—

Extensive left ventricular (LV) remodeling may not allow functional recovery after revascularization, despite the presence of viable myocardium.

Methods and Results—

Seventy-nine consecutive patients with ischemic cardiomyopathy (left ventricle ejection fraction [LVEF] 29±7%) underwent surgical revascularization. Before revascularization, viability was assessed by metabolic imaging with F18-fluorodeoxyglucose and SPECT. LV volumes and LVEF were assessed by resting echocardiography. LVEF was re-assessed by echocardiography 8 to 12 months after revascularization. Three-year clinical follow-up (events: cardiac death, infarction, and hospitalization for heart failure) was also obtained. Forty-nine patients had substantial viability; 5 died before re-assessment of LVEF. Of the remaining 44 patients, 24 improved ≥5% in LVEF after revascularization, whereas 20 did not improve in LVEF. LV end-systolic volume was the only parameter that was significantly different between the groups (109±46 mL for the improvers versus 141±31 mL for the nonimprovers;
P
<0.05). The change in LVEF after revascularization was linearly related to the baseline LV end-systolic volume, with a higher LV end-systolic volume associated with a low likelihood of improvement in LVEF after revascularization. During the 3-year follow-up, the highest event-rate (67%) was observed in patients without viable myocardium with a large LV size, whereas the lowest event rate (5%) was observed in patients with viable myocardium and a small LV size. Intermediate event rates were observed in patients with viable myocardium and a large LV size (38%), and in patients without viable myocardium and a small LV size (24%).

Conclusion—

Extensive LV remodeling prohibits improvement in LVEF after revascularization and affects long-term prognosis negatively, despite the presence of viability.
Restrictive Annuloplasty and Coronary Revascularization in Ischemic Mitral Regurgitation Results in Reverse Left Ventricular Remodeling
Authors: Bax Jeroen J. , Braun Jerry , Somer Soeresh T. , Klautz Robert , Holman Eduard R. , Versteegh Michel I.M. , Boersma Eric , Schalij Martin J. , van der Wall Ernst E. , Dion Robert A.
Published: September 2004

Background—

Data on combined coronary artery bypass grafting (CABG) and restrictive annuloplasty in patients with ischemic cardiomyopathy are scarce, and the effect on reverse left ventricular (LV) remodeling is unknown.

Methods and Results—

51 patients with ischemic LV dysfunction (LV ejection fraction 31±8%) and severe mitral regurgitation (grade 3 to 4+) underwent CABG and restrictive annuloplasty with stringent downsizing of the mitral annulus (by 2 sizes, Physio-ring, mean size 28±2). Serial transthoracic echocardiographic studies were performed (before surgery and within 3 months and 1.5 years after surgery) to assess mitral regurgitation, transmitral gradient, leaflet coaptation, and left atrial and LV reverse remodeling. Clinical follow-up (New York Heart Association [NYHA] class, survival, events) was assessed at 2-year follow-up. Early operative mortality was 5.6%; at 2-year follow-up, all patients were free of endocarditis and thromboembolism, and 1 needed re-operation for recurrent mitral regurgitation; 2-year survival was 84%. NYHA class improved from 3.4±0.8 to 1.3±0.4 (
P
<0.01), with all patients in class I/II. Intraoperative transesophageal echo showed minimal (grade 1+) mitral regurgitation in 8 patients and none in 43, without stenosis. Leaflet coaptation was 0.8±0.2 cm. These values remained unchanged; all patients had no or minimal (grade 1+) mitral regurgitation at 2-year follow-up. LV end-systolic and end-diastolic dimensions decreased from 51±10 to 43±12 mm (
P
<0.001) and from 64±8 to 58±11 mm (
P
<0.001). Left atrial dimension decreased from 53±8 to 47±7 mm (
P
<0.001).

Conclusion—

Excellent results of combined restrictive annuloplasty and CABG were obtained. Residual mitral regurgitation was absent/minimal at 2-year follow-up, associated with a significant reduction in left atrial dimension and LV reverse remodeling.
Effect of Diabetes and Associated Conditions on Long-Term Survival After Coronary Artery Bypass Graft Surgery
Authors: Leavitt Bruce J. , Sheppard Lynne , Maloney Christopher , Clough Robert A. , Braxton John H. , Charlesworth David C. , Weintraub Ronald M. , Hernandez Felix , Olmstead Elaine M. , Nugent William C. , O’Connor Gerald T. , Ross Cathy S.
Published: September 2004

Background—

The effects of diabetes on short-term results of coronary artery bypass graft (CABG) surgery are known, but less is known about the long-term effects of diabetes and diabetic-related sequelae for patients undergoing this surgery. We studied the 10-year survival of nondiabetic and diabetic patients undergoing CABG surgery.

Methods and Results—

A prospective regional cohort study was conducted of 36 641 consecutive isolated CABG patients in northern New England from 1992 through 2001. Patient records were linked to the National Death Index to assess mortality. There were 154 140 person-years of follow-up and 5779 deaths. Kaplan–Meier techniques were used. Survival was stratified into three categories: no diabetes, diabetes without peripheral vascular disease and renal failure, and diabetes with peripheral vascular disease and/or renal failure. The overall annual incidence rate of death was 3.7 deaths per 100 person-years. Annual incidence rates for nondiabetic subjects and diabetic subjects were similar: 3.1 deaths per 100 person-years and 4.4 deaths per 100 person-years, respectively. The annual incidence rate for diabetic subjects with renal failure, peripheral vascular disease, or both was 9.4 deaths per 100 person-years. The log-rank test showed that the survival curves were significantly different (
P
<0.001).

Conclusion—

Patients that have diabetes without the sequelae of renal failure and/or peripheral vascular disease have long-term survival similar to but slightly less than patients without diabetes who undergo CABG surgery. Survival of CABG surgery patients with diabetes is greatly affected by associated comorbidities of peripheral vascular disease and renal failure. This knowledge may help guide the patient as well as the cardiologist and cardiac surgeon in making appropriate decisions in these critically ill patients.
On-Pump Versus Off-Pump Coronary Artery Bypass Surgery in a Matched Sample of Women
Authors: Mack Michael J. , Brown Phillip , Houser Frank , Katz Mark , Kugelmass Aaron , Simon April , Battaglia Salvatore , Tarkington Lynn , Culler Steven , Becker Edmund
Published: September 2004

Background—

Women have consistently higher mortality and morbidity than men after coronary artery bypass grafting (CABG). Whether elimination of cardiopulmonary bypass and performance of coronary artery bypass grafting off-pump (OPCAB) have a beneficial effect specifically in women has not been defined.

Methods and Results—

From January 1998 through March 2002, 21 902 consecutive female patients at 82 hospitals underwent isolated CABG, as reported in an administrative database. Propensity score computer matching was performed based on 13 variables representing patient characteristics and preoperative risk factors to correct for and minimize selection bias. A total of 7376 (3688 pairs) women undergoing CABG surgery were able to be successfully matched. In a propensity score computer-matched cohort, multivariate logistic regression (odds ratio) revealed that women undergoing on-pump surgery had a 73.3% higher mortality (
P
=0.002) and a 47.2% higher risk of bleeding complications (
P
=0.019).

Conclusions—

In a retrospective analysis of women undergoing CABG, computer-matched to minimize selection bias, off-pump surgery led to decreased mortality and morbidity including bleeding complications.
Differences in Clinical Presentation, Management, and Outcomes of Acute Type A Aortic Dissection in Patients With and Without Previous Cardiac Surgery
Authors: Collins J. Stewart , Evangelista Arturo , Nienaber Christoph A. , Bossone Eduardo , Fang Jianming , Cooper Jeanna V. , Smith Dean E. , O’Gara Patrick T. , Myrmel Truls , Gilon Dan , Isselbacher Eric M. , Penn Marc , Pape Linda A. , Eagle Kim A. , Mehta Rajendra H.
Published: September 2004

Background—

There are less data on the clinical and diagnostic imaging characteristics, management, and outcomes of patients with previous cardiac surgery (PCS) presenting with acute type A aortic dissection (AAD).

Methods and Results—

In 617 patients with AAD, we evaluated the differences in the clinical characteristics, management, and in-hospital outcomes of the cohorts with and without PCS. A history of PCS was present in 100 of 617 patients. Patients with PCS were more likely to be males (
P
=0.02), older (
P
=0.014), and to have a history of previous aortic dissection (
P
<0.001) or aneurysms (
P
<0.001). In contrast, PCS patients were less likely to have presenting chest pain (
P
<0.001). Cardiac tamponade was less common in PCS patients (
P
=0.007). Fewer AAD patients with PCS underwent surgical repair (
P
=0.001). Hospital mortality was not adversely influenced by PCS (odds ratio [OR], 1.46; 95% confidence interval [CI], 0.81 to 2.63), but a trend for increased death was seen in patients with previous aortic valve replacement (AVR) (OR, 2.31; 95% CI, 0.98 to 5.43). Age70 years or older, previous AVR, shock, and renal failure identified PCS patients at risk for death.

Conclusions—

Our study highlights differences in clinical characteristics, management, and outcomes of AAD patients with PCS. Importantly, PCS, with the exception of previous AVR, does not adversely influence early outcomes of AAD patients, including those undergoing surgical repair. However, because of otherwise dismal outcomes with medical management of AAD, our data indicate that a history of PCS (even that of previous AVR) should not preclude physicians from recommending surgical correction of type A aortic dissection in appropriate patients.
Safety and Efficacy of Surgical Ventricular Restoration in Unstable Patients With Recent Anterior Myocardial Infarction
Authors: Di Donato Marisa , Frigiola Alessandro , Benhamouda Melika , Menicanti Lorenzo
Published: September 2004

Background—

The effects and efficacy of surgical ventricular restoration (SVR) in ischemic cardiomiopathy caused by chronic anterior myocardial infarction (MI) are well established. Normally, SVR is delayed at least 3 months after MI to allow the healing of infarcted tissue. Some patients have instability <30days after anterior MI, with increased risk for morbidity and mortality.

Objectives—

This study tests the safety and efficacy of SVR in the setting of subacute complicated anterior MI, in terms of early and late outcome.

Methods and Results—

74 patients (62±10 years) were submitted to SVR at ≤30 days after anterior MI for clinical instability and were retrospectively selected from a series of 430 patients undergoing SVR at our center, between 1998 and 2001. The surgical indications included: angina (60%); New York Heart Association class 4 (62%); clinical signs of heart failure (18%); life-threatening arrhythmias (12%); and cardiogenic shock in 4% (or 3) patients. Follow-up is available for 93% of patients. All patients had coronary artery bypass grafting (CABG) (3.1±1.2) with internal mammary artery (IMA) utilization. An endoventricular patch was used in 17 patients (23%); direct ventriculotomy closure was used in the remaining patients. Operative mortality was 5.4% (4/74). Hemodynamic parameters improved significantly in patients with dilated hearts and reduced ejection fraction. Mitral regurgitation that resulted was significantly reduced. Survival at 3 years was 87% in the overall population and 85% in patients 70 years or older.

Conclusions—

This study reports the largest series of patients with complicated, recent anterior MI treated with SVR. The results show that SVR is feasible, has acceptable in-hospital mortality, and has good early and late outcome. Further experience is needed to establish whether SVR, which excludes the infarcted region, can prevent the long-term adverse remodeling of LV dilated hearts after anterior infarction.
Extending the Boundaries of the Primary Arterial Switch Operation in Patients With Transposition of the Great Arteries and Intact Ventricular Septum
Authors: Kang Nicholas , de Leval Marc R. , Elliott Martin , Tsang Victor , Kocyildirim Ergin , Sehic Igor , Foran John , Sullivan Ian
Published: September 2004

Background—

We have previously suggested that the primary arterial switch operation is a feasible strategy for patients with transposition of the great arteries and intact ventricular septum (TGA-IVS) up to age 2 months. This study reports our current results with this approach and examines whether this policy could be extended beyond age 2 months.

Methods and Results—

380 patients who underwent arterial switch for TGA-IVS were reviewed. 275 patients were younger than 3 weeks at the time of surgery (early switch group); 105 patients were 3 weeks or older (range, 21 to 185 days) (late switch group). There was no difference in outcome in terms of in-hospital mortality (5.5% versus 3.8%) or need for mechanical circulatory support (3.6% versus 5.7%) between early and late switch groups. However, duration of postoperative ventilation (4.9 versus 7.1 days,
P
=0.012) and length of postoperative stay (12.5 versus 18.9 days,
P
<0.001) were significantly prolonged in the late switch group. Primary left ventricular failure resulting in death occurred in 2 patients in the late switch group, with no deaths in 9 patients aged 2 to 6 months.

Conclusions—

This experience confirms that in TGA-IVS, the left ventricle maintains the potential for systemic work well beyond the first month of life. Consequently, neonates at high risk or late referrals can benefit from delayed arterial switch, even beyond age 2 months. However, the need for mechanical support in some of the older patients may limit the widespread adoption of such a strategy.
Early Clinical Results of the Telemetric Adjustable Pulmonary Artery Banding FloWatch-PAB
Authors: Bonnet Damien , Corno Antonio F. , Sidi Daniel , Sekarski Nicole , Beghetti Maurice , Schulze-Neick Ingram , Fasnacht Margrit , Le Bret Emmanuel , Kalangos Afksendyios , Vouhé Pascal R. , von Segesser Ludwig K.
Published: September 2004

Background—

Adjustment of pulmonary artery banding (PAB) may be a challenging procedure in complex congenital heart defects. Whatever the technique used, subsequent re-operations are frequently needed to control the pulmonary blood flow or pressures.

Objective—

To report the efficacy of a new telemetric adjustable PAB (FloWatch-PAB) operated with the help of an external control unit that transmits to the implant energy and commands to further narrow or release the pulmonary artery using radiofrequency waves.

Methods and Results—

In a multicenter, prospective, nonrandomized, single-arm clinical investigation, 13 children (median age, 4.5 months; range, 6 days to 11 years; median weight, 4.2 kg; range, 3.1 to 27kg) underwent implantation of the FloWatch-PAB through median sternotomy in 8 and left thoracotomy in 5. The diagnosis was multiple ventricular septal (VSD) defects with complex anatomy in 3, single ventricle without pulmonary stenosis in 2, VSD with elevated pulmonary vascular resistance (PVR) in 2, atrio-ventricular canal (AVC) with elevated pulmonary vascular resistance in 1, AVC with diminutive right ventricle in 1, complex transposition of the great arteries in 3, and pulmonary atresia with complex pulmonary arteries anatomy in 1. All patients had normosystemic systolic pulmonary artery pressure. Additional procedures were performed in 7: atrial septectomy in 2, double aortic arch division in 1, patent ductus arteriosus ligation in 2, and coarctation repair in 2. There were no early or late deaths or device-related complications in a mean follow-up of 24 weeks (range, 18 to 42 weeks). A mean of 5.8 telemetric regulations per patient using the FloWatch-PAB were required to adjust the tightening of the PAB to the clinical needs (narrowing 74%, releasing 26%). At last follow-up, systolic pulmonary artery pressure was within normal range in all patients but 1. Systemic oxygen saturation demonstrated optimal regulation of the pulmonary blood flow in all according to each specific defect. Four patients were successfully corrected (VSD closure, AVSD repair, and 2 arterial switches with VSD closure). The device was easily removed and the pulmonary artery re-expanded spontaneously.

Conclusion—

This new device is safe and allows optimal adjustment of PAB in complex heart defects. In children requiring PAB, the use of this technology can obviate the need for early re-operations and appears to be a valuable option in the panel of surgical alternatives for selected infants.
Hypoplasia of the Small Pulmonary Arteries in Hypoplastic Left Heart Syndrome With Restrictive Atrial Septal Defect
Authors: Maeda Katsuhide , Yamaki Shigeo , Kado Hideaki , Asou Toshihide , Murakami Arata , Takamoto Shinichi
Published: September 2004

Background—

Restrictive atrial septal defect (ASD) (including intact atrial septum [IAS]) has been reported to be a risk factor that negatively impacts survival in hypoplastic left heart syndrome (HLHS). Although lymphangiectasia and “arterialization” of the veins of the lung in HLHS with restrictive ASD have been reported, they cannot fully explain the high mortality. We have introduced a new method of evaluating the development of the pulmonary vasculature in histological sections and used it to assess patients’ lungs. We tested the hypothesis that the small pulmonary arteries (SPA), which are pulmonary arteries in a histological section whose radii are ≈25 μm to 250 μm, in HLHS with restrictive ASD are hypoplastic, but that the alveoli are not, to elucidate the mechanism underlying the poor outcome of these patients.

Methods and Results—

Fourteen HLHS patients between 1 day and 40 days of age were studied. In 8 cases, the ASD was restrictive [R(+) group], and in the other 6 cases it was not [R(−) group]. Specimens from 12 autopsies of cases with no congenital heart or pulmonary disease were examined as a control group (C group). As a novel histological parameter, we assessed the size of SPA in relation to the size of accompanying bronchioles to identify SPA underdevelopment. To evaluate the development of alveoli and interstitial tissue, radial alveolar counts (RAC), which reflect alveolar maturity and complexity, were also performed. Statistical comparisons between groups were made by analysis of covariance with age as a covariant factor. When the radius of the accompanying bronchiole was 100 μm, the radius of the SPA was 34.0±10.8 μm in the R(+) group, and significantly lower than the 46.6±8.5 μm in R(−) group (
P
=0.0022) and 70.5±8.4 μm in the C group (
P
<0.0001). The RAC was in 3.5±0.9 in the R(+) group, 3.4±0.6 in the R(−) group, and 3.7±0.9 in the C group (no significant differences between groups).

Conclusion—

The SPA in HLHS with restrictive ASD were underdeveloped compared with the SPA in HLHS with nonrestrictive ASD and the controls, but their alveoli were not hypoplastic. Based on these results, it is speculated that SPA hypoplasia may be responsible for the poor outcome of HLHS with restrictive ASD.
Soluble Human Complement Receptor 1 Limits Ischemic Damage in Cardiac Surgery Patients at High Risk Requiring Cardiopulmonary Bypass
Authors: Lazar Harold L. , Bokesch Paula M. , van Lenta Frederick , Fitzgerald Carmel , Emmett Constance , Marsh Henry C. , Ryan Una ,   OBE and the TP10 Cardiac Surgery Study Group
Published: September 2004

Background—

This study was undertaken to determine whether soluble human complement receptor type 1 (TP10), a potent inhibitor of complement activation, would reduce morbidity and mortality in high-risk patients undergoing cardiac surgery on cardiopulmonary bypass (CPB).

Methods—

This was a randomized multicenter, prospective, placebo-controlled, double-blind study in which 564 high-risk patients undergoing cardiac surgery on CPB received an intravenous bolus of TP10 (1, 3, 5, 10 mg/kg) or placebo immediately before CPB. The primary endpoint was the composite events of death, myocardial infarction (MI), prolonged (≥24 hours) intra-aortic balloon pump support (IABP), and prolonged intubation.

Results—

TP10 significantly inhibited complement activity after 10 to 15 minutes of CPB and this inhibition persisted for 3 days postoperatively. However, there was no difference in the primary endpoint between the 2 groups (33.7% placebo versus 31.4% TP10;
P
=0.31). The primary composite endpoint was, however, reduced in all male TP10 patients by 30% (
P
=0.025). TP10 reduced the incidence of death or MI in males by 36% (
P
=0.026), the incidence of death or MI in CABG males by 43% (
P
=0.043) and the need for prolonged IABP support in male CABG and valve patients by 100% (
P
=0.019). There was, however, no improvement seen in female TP10 patients. There were no significant differences in adverse events between the groups.

Conclusion—

TP10 effectively inhibits complement activation during CPB; however, this was not associated with an improvement in the primary endpoint of the study. Nevertheless, TP10 did significantly decrease the incidence of mortality and MI in male patients.