bluuebunny/crossref_metadata_2025 huggingface dataset:
Intravenous Administration of Metoprolol Is More Effective Than Oral Administration in the Prevention of Atrial Fibrillation After Cardiac Surgery
Authors: Halonen Jari , Hakala Tapio , Auvinen Tommi , Karjalainen Jari , Turpeinen Anu , Uusaro Ari , Halonen Pirjo , Hartikainen Juha , Hippeläinen Mikko
Published: July 2006

Background—

Atrial fibrillation (AF) is the most common arrhythmia to occur after cardiac surgery, with an incidence of 20% to 40%. AF is associated with postoperative complications, including increased risk of stroke and need of additional treatment, as well as prolonged hospital stay and increased costs. It has been shown that prophylactic oral administration of β-blocker therapy reduces the incidence of postoperative AF after cardiac surgery. However, it is possible that absorption of drugs is impaired after cardiopulmonary perfusion associated with cardiac surgery. The purpose of this prospective, controlled, randomized trial was to study compare intravenous and per oral metoprolol administration in the prevention of AF after cardiac surgery.

Methods and Results—

240 consecutive patients who were scheduled to undergo their first on-pump coronary artery bypass graft (CABG), aortic valve replacement, or combined aortic valve replacement and CABG were randomized to receive 48-hour infusion of metoprolol or oral metoprolol starting on the first postoperative morning. Patients were excluded if they had contraindications for β-blocker or had to stay >1 day in the intensive care unit. Dosage of metoprolol was adjusted according to heart rate. The dosage was 1 to 3 mg/h in the intravenous group and from 25 mg twice per day to 50 mg 3 times per day in the oral group. The incidence of postoperative AF was significantly lower in the intravenous group than in the oral group (16.8% versus 28.1%,
P
=0.036). No serious adverse effects were associated with intravenous metoprolol therapy.

Conclusions—

Our study suggests that intravenous metoprolol is well-tolerated and more effective than oral metoprolol in the prevention of AF after cardiac surgery.
Inhibition of Toll-like Receptor 4 With Eritoran Attenuates Myocardial Ischemia-Reperfusion Injury
Authors: Shimamoto Akira , Chong Albert J. , Yada Masaki , Shomura Shin , Takayama Hiroo , Fleisig Ani J. , Agnew Matthew L. , Hampton Craig R. , Rothnie Christine L. , Spring Denise J. , Pohlman Timothy H. , Shimpo Hideto , Verrier Edward D.
Published: July 2006

Background—

We previously reported that the functional mutation of Toll-like receptor 4 (TLR4) in C3H/HeJ mice subjected to myocardial ischemia-reperfusion (MI/R) injury resulted in an attenuation of myocardial infarction size. To investigate the ligand-activating TLR4 during MI/R injury, we evaluated the effect of eritoran, a specific TLR4 antagonist, on MI/R injury, with the goal of defining better therapeutic options for MI/R injury.

Methods and Results—

C57BL/6 mice received eritoran (5 mg/kg) intravenously 10 minutes before 30 minutes of in situ of transient occlusion of the left anterior descending artery, followed by 120 minutes of reperfusion. Infarct size was measured using triphenyltetrazoliumchloride staining. A c-Jun NH
2
-terminal kinase (JNK) activation was determined by Western blotting, nuclear factor (NF)-κB activity was detected by gel-shift assay, and cytokine expression was measured by ribonuclease protection assay. Mice treated with eritoran developed significantly smaller infarcts when compared with mice treated with vehicle alone (21.0±6.4% versus 30.9±13.9%;
P
=0.041). Eritoran pretreatment resulted in a reduction in JNK phosphorylation (eritoran versus vehicle: 3.98±0.81 versus 7.01±2.21-fold increase;
P
=0.020), less nuclear NF-κB translocation (2.70±0.35 versus 7.75±0.60-fold increase;
P
=0.00007), and a decrease in cytokine expression (
P
<0.05).

Conclusions—

We conclude that inhibition of TLR4 with eritoran in an in situ murine model significantly reduces MI/R injury and markers of an inflammatory response.
Long-Term Survival of Patients With Chronic Obstructive Pulmonary Disease Undergoing Coronary Artery Bypass Surgery
Authors: Leavitt Bruce J. , Ross Cathy S. , Spence Brian , Surgenor Stephen D. , Olmstead Elaine M. , Clough Robert A. , Charlesworth David C. , Kramer Robert S. , O’Connor Gerald T.
Published: July 2006

Background—

Chronic obstructive pulmonary disease (COPD) is associated with increased in-hospital mortality in patients undergoing coronary artery bypass surgery (CABG). Long-term survival is less well understood. The present study examined the effect of COPD on survival after CABG.

Methods and Results—

We conducted a prospective study of 33 137 consecutive isolated CABG patients between 1992 and 2001 in northern New England. Records were linked to the National Death Index for long-term mortality data. Cox proportional hazards regression was used to calculate hazard ratios (HRs). Patients were stratified by: no comorbidities (none), COPD, COPD plus comorbidities, and other comorbidities with no COPD. There were 131 434 person years of follow-up and 5344 deaths. The overall incidence rate (deaths per 100 person years) was 4.1. By group, rates were: 2.1 (none), 4.0 (COPD alone), 5.5 (other), and 9.4 (COPD plus; log rank
P
<0.001). After adjustment, survival with COPD alone was worse compared with none (HR, 1.8; 95% CI, 1.6 to 2.1;
P
<0.001). Patients with other comorbidities compared with none had even worse survival (HR, 2.2; 95% CI, 2.1 to 2.4;
P
<0.001). Patients with COPD plus other comorbidities compared with none had the worst long-term survival (HR, 3.6; 95% CI, 3.3 to 3.9;
P
<0.001).

Conclusions—

Patients with only COPD had significantly reduced long-term survival compared with patient with no comorbidities. Patients with COPD and ≥1 other comorbidity had the worst survival rate when compared with all of the other groups.
Are Stentless Valves Superior to Modern Stented Valves?
Authors: Ali Ayyaz , Halstead James C. , Cafferty Fay , Sharples Linda , Rose Fiona , Coulden Richard , Lee Evelyn , Dunning John , Argano Vincenzo , Tsui Steven
Published: July 2006

Background—

It is presumed that stentless aortic bioprostheses are hemodynamically superior to stented bioprostheses. A prospective randomized controlled trial was undertaken to compare stentless versus modern stented valves.

Methods and Results—

Patients with severe aortic valve stenosis (n=161) undergoing aortic valve replacement (AVR) were randomized intraoperatively to receive either the C-E Perimount stented bioprosthesis (n=81) or the Prima Plus stentless bioprosthesis (n =80). We assessed left ventricular mass (LVM) regression with transthoracic echocardiography (TTE) and magnetic resonance imaging (MRI). Transvalvular gradients were measured postoperatively by Doppler echocardiography to compare hemodynamic performance. There was no difference between groups with regard to age, symptom status, need for concomitant coronary artery bypass surgery, or baseline LVM. LVM regressed in both groups but with no significant difference between groups at 1 year. In a subset of 50 patients, MRI was also used to assess LVM regression, and again there was no significant difference between groups at 1 year. Hemodynamic performance of the 2 valves was similar with no difference in mean and peak systolic transvalvular gradients 1 year after surgery. In patients with reduced ventricular function (left ventricular ejection fraction [LVEF] <60%), there was a significantly greater improvement in LVEF from baseline to 1 year in stentless valve recipients.

Conclusions—

Both stented and stentless bioprostheses are associated with excellent clinical and hemodynamic outcomes 1 year after AVR. Comparable hemodynamics and LVM regression can be achieved using a second-generation stented pericardial bioprosthesis. In patients with ventricular impairment, stentless bioprostheses may allow for greater improvement in left ventricular function postoperatively.
Natural History and Predictors of Outcome in Patients With Concomitant Functional Mitral Regurgitation at the Time of Aortic Valve Replacement
Authors: Ruel Marc , Kapila Varun , Price Joel , Kulik Alexander , Burwash Ian G. , Mesana Thierry G.
Published: July 2006

Background—

Concomitant functional mitral regurgitation (FMR) in patients undergoing aortic valve replacement (AVR) is frequently not corrected because it may improve after AVR; however, data supporting this assumption are sparse. We ascertained the impact of clinical and echocardiographic parameters on the outcome of patients with or without concomitant FMR at the time of AVR.

Methods and Results—

Clinical and echocardiographic follow-up was performed on 848 patients who underwent AVR after 1990. Risk factors for mortality and a composite outcome of heart failure (CHF) symptoms, CHF death, or subsequent mitral repair or replacement, were examined with bootstrapped Cox proportional hazard models. Follow-up was 4591 patient-years (mean 5.4±3.4 years; maximum 14.2 years). FMR ≥2+ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI). However, AS patients with FMR ≥2+ and 1 additional risk factor (left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation) were at increased risk for the composite outcome (hazard ratio [HR]: 2.7;
P
=0.004). AI patients with FMR ≥2+ and a left ventricular end-systolic diameter <45 mm were also at risk (HR: 4.0;
P
=0.02). Clinical risk factors in the AS and AI subgroups were associated with an increased likelihood of mitral regurgitation ≥2+ at 18 months postoperatively.

Conclusions—

AS patients with FMR ≥2+ and a left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation have a significantly higher risk of CHF and persistent mitral regurgitation after AVR than other AS patients. AI patients with FMR ≥2+ and a left ventricular end-systolic diameter <45 mm preoperatively are also at increased risk. Others fare well after AVR.
Clinical Application of Tissue Engineered Human Heart Valves Using Autologous Progenitor Cells
Authors: Cebotari Serghei , Lichtenberg Artur , Tudorache Igor , Hilfiker Andres , Mertsching Heike , Leyh Rainer , Breymann Thomas , Kallenbach Klaus , Maniuc Liviu , Batrinac Aurel , Repin Oleg , Maliga Oxana , Ciubotaru Anatol , Haverich Axel
Published: July 2006

Background—

Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up.

Methods and Results—

Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m
2
and 1.07 to 1.46 m
2
, respectively). No signs of valve degeneration were observed in both patients.

Conclusions—

TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.
A Novel Role of Extracellular Nucleotides in Valve Calcification
Authors: Osman Lana , Chester Adrian H. , Amrani Mohamed , Yacoub FRS Magdi H. , Smolenski MD Ryszard T.
Published: July 2006

Background—

Calcific aortic valve disease is a common condition and is associated with inflammatory changes and expression of osteoblast-like cell phenotypes, but the cellular mechanisms are unclear. Recent studies identified extracellular ATP and P2Y receptor cascade as important regulators of bone remodeling, whereas its breakdown product, adenosine, is known to have anti-inflammatory properties. We hypothesize that extracellular ATP and adenosine have important roles in regulating osteoblast differentiation in human valve interstitial cells, and that this can be a potential target for therapy.

Method and Results—

Primary cultures of human valve interstitial cells (ICs) treated for 21 days with osteogenic media, ATP, and ATP-γ-S (a stable agonist of the P2Y receptor) revealed a significant increase in alkaline phosphatase (ALP) (an osteoblast marker) activity and expression as measured using spectrophotometric assay and immunocytochemistry staining. Valve ICs treated with adenosine alone did not cause an increase in ALP activity; however, adenosine treatment decreased the ALP activity and expression induced by osteogenic media after 21 days of incubation. In addition, atorvastatin inhibited the activity of ALP induced by ATP in human valve ICs, and enzyme studies revealed that atorvastatin upregulated the breakdown of extracellular ATP into adenosine in human valve ICs after 24-hour treatment.

Conclusion—

These findings identify a novel role for extracellular nucleotides in inducing osteoblast differentiation in human valve ICs in vitro and provide a potential therapeutic target for preventing the disease progression.
Failure of Right Ventricular Adaptation in Children With Tetralogy of Fallot
Authors: Reddy Sushma , Osorio Juan Carlos , Duque Ana M. , Kaufman Beth D. , Phillips Alistair B. , Chen Jonathan M. , Quaegebeur Jan , Mosca Ralph S. , Mital Seema
Published: July 2006

Background—

The left ventricle (LV) adapts to chronic hypoxia by expressing protective angiogenic, metabolic, and antioxidant genes to improve O
2
delivery and energy production, and to minimize reoxygenation injury. The ability of the right ventricle (RV) to adapt to hypoxia in children with tetralogy of Fallot (TOF) is unknown.

Methods and Results—

Gene expression using real-time polymerase chain reaction was measured in RV myocardium obtained during surgical repair of TOF from 23 patients: 13 cyanotic and 10 acyanotic. Results were compared between the 2 groups and correlated with age at surgery, severity of cyanosis, and early postoperative course. The cyanotic patients were younger at surgery compared with acyanotic (5±3 versus 9±4 months;
P
=0.01), had higher hematocrit (43±4 versus 38±3 grams/dL;
P
=0.004), and lower O
2
saturations (84±4% versus 98±2%; (
P
<0.001). Cyanotic patients had a significantly lower expression of vascular endothelial growth factor (VEGF), glycolytic enzymes, and glutathione peroxidase (GPX) (
P
<0.05), and a higher expression of collagen (
P
<0.01) compared with acyanotic patients. Gene expression correlated inversely with severity of cyanosis ie, preoperative hematocrit (
P
<0.01) and positively with preoperative saturation (
P
<0.05). The relationship between gene expression and cyanosis was independent of age at surgery. Ca
2+
handling genes did not correlate with the severity of hypoxia. Lower angiogenic, glycolytic, and antioxidant gene expression correlated with increasing postoperative lactate (
P
<0.05).

Conclusions—

The RV fails to up regulate adaptive pathways in response to increasing hypoxia in children with TOF. The implications of an early maladaptive response of the RV on long-term RV function require further investigation.
Intraoperative Red Blood Cell Transfusion During Coronary Artery Bypass Graft Surgery Increases the Risk of Postoperative Low-Output Heart Failure
Authors: Surgenor Stephen D. , DeFoe Gordon R. , Fillinger Mary P. , Likosky Donald S. , Groom Robert C. , Clark Cantwell , Helm Robert E. , Kramer Robert S. , Leavitt Bruce J. , Klemperer John D. , Krumholz Charles F. , Westbrook Benjamin M. , Galatis Dean J. , Frumiento Carmine , Ross Cathy S. , Olmstead Elaine M. , O’Connor Gerald T.
Published: July 2006

Background—

Hemodilutional anemia during cardiopulmonary bypass (CPB) is associated with increased mortality during coronary artery bypass graft (CABG) surgery. The impact of intraoperative red blood cell (RBC) transfusion to treat anemia during surgery is less understood. We examined the relationship between anemia during CPB, RBC transfusion, and risk of low-output heart failure (LOF).

Methods and Results—

Data were collected on 8004 isolated CABG patients in northern New England between 1996 and 2004. Patients were excluded if they experienced postoperative bleeding or received ≥3 units of transfused RBCs. LOF was defined as need for intraoperative or postoperative intra-aortic balloon pump, return to CPB, or ≥2 inotropes at 48 hours. Having a lower nadir HCT was also associated with an increased risk of developing LOF (adjusted odds ratio, 0.90; 95% CI, 0.82 to 0.92;
P
=0.016), and that risk was further increased when patients received RBC transfusion. When adjusted for nadir hematocrit, exposure to RBC transfusion was a significant, independent predictor of LOF (adjusted odds ratio, 1.27; 95% CI, 1.00 to 1.61;
P
=0.047).

Conclusions—

In this study, we observed that exposure to both hemodilutional anemia and RBC transfusion during surgery are associated with increased risk of LOF, defined as placement of an intraoperative or postoperative intra-aortic balloon pump, return to CPB after initial separation, or treatment with ≥2 inotropes at 48 hours postoperatively, after CABG. The risk of LOF is greater among patients exposed to intraoperative RBCs versus anemia alone.
Determinants of Recurrent or Residual Functional Tricuspid Regurgitation After Tricuspid Annuloplasty
Authors: Fukuda Shota , Gillinov A. Marc , McCarthy Patrick M. , Stewart William J. , Song Jong-Min , Kihara Takashi , Daimon Masao , Shin Mi-Seong , Thomas James D. , Shiota Takahiro
Published: July 2006

Background—

The durability of tricuspid valve (TV) repair by annuloplasty is limited. Identification of mechanisms of recurrent or residual tricuspid regurgitation (TR) after annuloplasty is necessary to improve results of TV repair. The purpose of this study was to investigate echocardiographic determinants of mid-term outcome after TV annuloplasty.

Methods and Results—

This study consisted of 39 patients with functional TR who had echocardiography preoperatively, early postoperatively (5±2 days), and >1 year (20±6 months) after TV annuloplasty. Detailed echocardiographic measurements were performed, including TR severity, TV annular dimension, TV leaflet displacement, left ventricular (LV) function, and right ventricular (RV) function and pressures. Preoperative leaflet tethering height and area predicted early and mid-term outcome of annuloplasty. Early postoperative LV ejection fraction and TR severity influenced degree of TR >1 year after surgery. In addition, increased RV pressure was related to worse TR during late follow-up.

Conclusions—

Although TV tethering is an important determinant of recurrent or residual TR, LV and RV function and pressures impact repair durability. These factors identify patients at risk for repair failure; such individuals require development of additional surgical strategies to improve results of tricuspid valve repair and close surveillance after surgery.
Coronary Flow Velocity Pattern and Coronary Flow Reserve by Contrast-Enhanced Transthoracic Echocardiography Predict Long-Term Outcome in Heart Transplantation
Authors: Tona Francesco , Caforio Alida L.P. , Montisci Roberta , Gambino Antonio , Angelini Annalisa , Ruscazio Massimo , Toscano Giuseppe , Feltrin Giuseppe , Ramondo Angelo , Gerosa Gino , Iliceto Sabino
Published: July 2006

Background—

We assessed coronary flow velocity pattern and coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) as markers of major adverse cardiac events (MACE) related to cardiac allograft vasculopathy (CAV) after heart transplantation (HT).

Methods and Results—

Deceleration time of diastolic flow velocity (DDT) and CFR were measured in the left anterior descending coronary artery (LAD) by CE-TTE in 66 consecutive HT patients (follow-up 19±5 months). CFR was calculated as the ratio of hyperemic to basal diastolic flow velocity. Angiographies were analyzed by a qualitative grading system; CAV was defined as changes grade II or higher. MACE were cardiac death, stent implantation, and heart failure. Patients with MACE had higher CAV incidence (
P
=0.004) and grade (
P
=0.008), shorter DDT (
P
=0.006), and lower CFR (
P
=0.008). A receiver-operating characteristic–derived DDT cutpoint ≤840 ms (area under the curve 0.793;
P
=0.01) was 75% specific and 86% sensitive for predicting MACE, with positive predictive value (PPV) and negative predictive value (NPV) of 33% and 97%, respectively (
P
=0.002). A CFR cutpoint of ≤2.6 (area under the curve 0.746;
P
=0.01) was 62% specific and 91% sensitive for predicting MACE (PPV =32%, NPV =97%) (
P
=0.001). Patients with CFR ≤2.6 and patients with DDT ≤840 ms had a lower survival free from MACE (
P
=0.006 and
P
=0.009, respectively). By Cox regression, only a lower CFR predicted the risk of MACE (relative risk 3.1; 95% CI, 1.26 to 7.9;
P
=0.01).

Conclusions—

In HT patients, shorter DDT and lower CFR by CE-TTE are reliable markers for CAV-related MACE. CFR is the main independent predictor of MACE.
Predictors of Early Neurocognitive Deficits in Low-Risk Patients Undergoing On-Pump Coronary Artery Bypass Surgery
Authors: Boodhwani Munir , Rubens Fraser D. , Wozny Denise , Rodriguez Rosendo , Alsefaou Abdualla , Hendry Paul J. , Nathan Howard J.
Published: July 2006

Background—

Postoperative cognitive deficits (POCDs) are a source of morbidity and occur frequently even in low-risk patients undergoing cardiac surgery. Predictors of neurocognitive deficits can identify potentially modifiable risk factors as well as high-risk patients in whom alternate revascularization strategies may be considered.

Methods and Results—

448 patients undergoing coronary surgery (coronary artery bypass graft [CABG]) underwent standardized preoperative and postoperative neurocognitive testing as part of 2 randomized trials evaluating the effects of mild hypothermia during coronary surgery. Prospectively collected data were used to identify univariate predictors of POCDs and multivariable logistic regression models were constructed. Models were bootstrapped 1000 times. POCDs occurred in 59% of patients. Significant univariate predictors included intraoperative normothermia, impaired left ventricular (LV) function, higher educational level, elevated serum creatinine and reduced creatinine clearance, prolonged intubation time, intensive care unit (ICU) stay, and hospital stay. Advanced age, presence of carotid disease, and cardiopulmonary bypass time were not associated with increased POCDs in this cohort. Multivariable modeling identified intraoperative normothermia (odds ratio [95% confidence interval] −1.15 [1.01, 1.31]), poor LV function (1.53 [1.02, 2.30]), and elevated preoperative creatinine (1.01 [1.00 to 1.03] for every 1 mmol/L increase), prolonged (>24 hours) ICU stay (1.88 [1.27 to 2.79]), and higher educational level (1.52 [1.01 to 2.28]) as independent predictors of POCD occurrence.

Conclusions—

Mild hypothermia, in the intraoperative and perioperative period, may be a protective strategy for the prevention of POCDs. Patients with elevated pre-operative creatinine and poor LV function carry a higher risk of POCDs and may benefit from revascularization strategies other than conventional on-pump CABG.
Adenoviral Human BCL-2 Transgene Expression Attenuates Early Donor Cell Death After Cardiomyoblast Transplantation Into Ischemic Rat Hearts
Authors: Kutschka Ingo , Kofidis Theo , Chen Ian Y. , von Degenfeld Georges , Zwierzchoniewska Monika , Hoyt Grant , Arai Takayasu , Lebl Darren R. , Hendry Stephen L. , Sheikh Ahmad Y. , Cooke David T. , Connolly Andrew , Blau Helen M. , Gambhir Sanjiv S. , Robbins Robert C.
Published: July 2006

Background—

Cell transplantation for myocardial repair is limited by early cell death. Gene therapy with human Bcl-2 (hBcl-2) has been shown to attenuate apoptosis in the experimental setting. Therefore, we studied the potential benefit of hBcl-2 transgene expression on the survival of cardiomyoblast grafts in ischemic rat hearts.

Methods and Results—

H9c2 rat cardiomyoblasts were genetically modified to express both firefly luciferase and green fluorescent protein (mH9c2). The cells were then transduced with adenovirus carrying hBcl-2 (AdCMVhBcl-2/mH9c2). Lewis rats underwent ligation of the left anterior descending artery (LAD) to induce a sizable left ventricular (LV) infarct. Hearts were explanted and the infarcted region was restored using collagen matrix (CM) seeded with 1×10
6
mH9c2 cells (n=9) or AdCMVhBcl-2/mH9c2 cells (n=9). Control animals received CM alone (n=6) or no infarct (n=6). Restored hearts were transplanted into the abdomen of syngeneic recipients in a “working heart” model. Cell survival was evaluated using optical bioluminescence imaging on days 1, 5, 8, 14, and 28 after surgery. The left heart function was assessed 4 weeks postoperatively using echocardiography and magnetic resonance imaging. During 4 weeks after surgery, the optical imaging signal for the AdCMVhBCL2/mH9c2 group was significantly (
P
<0.05) higher than that of the mH9c2-control group. Both grafts led to better fractional shortening (AdCMVhBcl-2/mH9c2: 0.21±0.03; mH9c2: 0.21±0.04; control: 0.15±0.03;
P
=0.04) and ejection fraction (AdCMVhBcl-2/mH9c2: 47.0±6.2; mH9c2: 48.7±6.1; control: 34.3±6.0;
P
=0.02) compared with controls. Importantly, no malignant cells were found in postmortem histology.

Conclusion—

Transduction of mH9c2 cardiomyoblasts with AdCMVhBcl-2 increased graft survival in ischemic rat myocardium without causing malignancies. Both AdCMVhBcl-2/mH9c2 and mH9c2 grafts improved LV function.
Protein Kinase C Isoform Activation and Endothelin-1 Mediated Defects in Myocyte Contractility After Cardioplegic Arrest and Reperfusion
Authors: Mukherjee Rupak , Apple Kimberly A. , Squires Christina E. , Kaplan Brooke S. , McLean Julie E. , Saunders Stuart M. , Stroud Robert E. , Spinale Francis G.
Published: July 2006

Background—

Endothelin-1 (ET-1) is released after hyperkalemic cardioplegic arrest (CA) and reperfusion and may contribute to contractile dysfunction. ET-1 receptor transduction causes activation of protein kinase C (PKC) isoforms, which can cause differential intracellular events. The goal of this study was to determine which PKC isoforms contribute to myocyte contractile dysfunction with ET-1 and CA.

Methods and Results—

Percent shortening (PERSHORT) and the time to 50% relaxation (T50) were measured in porcine (n =22) left ventricular myocytes, randomized (minimum: 30 cells/group) to normothermia: (cell media for 2 hours/37°C), and CA: (2 hours/4°C, 24 mEq K
+
solution followed by reperfusion in cell media), ET-1/CA: (100 pM ET-1 during CA). Studies were performed in the presence and absence of PKC inhibitors (500 nM) against the classical (Beta-I, Beta-II, Gamma) and novel (Epsilon, Eta) isoforms (myocytes from a minimum of 3 pigs per inhibitor). CA reduced PERSHORT by &35% from normothermia (
P
<0.05), which was further reduced with ET-1. PKC-Beta-II or PKC-Gamma inhibition increased PERSHORT from ET-1/CA as well as CA only (
P
<0.05). CA prolonged T50 by &19% from normothermia (
P
<0.05) and was further prolonged with ET-1. Inhibition of the classical PKC isoforms reduced T50 from ET-1/CA (
P
<0.05). Inhibition of novel PKC isoforms did not yield similar effects on either PERSHORT or T50 with ET-1/CA.

Conclusions—

Inhibition of the classical PKC isoforms relieved the negative inotropic and lusitropic effects of ET-1 after CA. These findings provide mechanistic support for developing targeted inhibitory strategies with respect to ET-1 signaling and myocyte contractile dysfunction with cardioplegic arrest and reperfusion.
Impact of Early Coronary Artery Bypass Graft in an Unselected Acute Coronary Syndrome Patient Population
Authors: Monteiro Pedro
Published: July 2006

Background—

Performance of coronary artery bypass graft (CABG) during an acute coronary syndrome (ACS) is mainly used in high-risk patients. Although potentially life-saving, patients undergoing early CABG are traditionally associated with a worse outcome than those not requiring CABG. Is this really true in an unselected ACS population? The aim of this study was to evaluate, in an ACS population, if the performance of CABG during the index hospitalization influences in-hospital outcome.

Methods and Results—

Retrospective analysis of a nationwide database of 12 988 ACS patients admitted since 2002. Of those, 267 patients underwent CABG during the index hospitalization (group A) and 12 721 did not (group B). Group B patients were further divided in 2 subgroups: those submitted to percutaneous coronary interventions (PCI) (group B
1
; n=3948) during the index hospitalization and those not submitted to mechanical revascularization (group B
2
; n =8773). Patients from group A more frequently had diabetes, hypercholesterolemia, hypertension, and previous angina; they were also more often on cardiovascular medication before admission. Patients that underwent CABG were more often in Killip class IV at admission (4.8% versus 1.4% versus 2.0%); they also received more nitrates and catecholamines. Left ventricular function was better in group B
1
. Group A patients were more often on mechanical ventilation and intra-aortic pump and they had more in-hospital complications (31.1% versus 18.7% versus 17.3%), namely recurrent angina, re-infarction, and mechanical complications. They had a more severe coronary anatomy and the culprit lesion was more frequently on the left main (7.7% versus 0.5% versus 2.2%). However, their in-hospital mortality was significantly lower (1.1% versus 2.2% versus 6.8%;
P
<0.001). Multivariate analysis showed that performance of early CABG was an independent predictor of lower mortality (odds ratio of 0.12), as were the use of low-molecular-weight heparins, beta-blockers, and angiotensin-converting enzyme inhibitors.

Conclusions—

In unselected patients admitted for ACS, performance of early CABG, despite being performed in higher-risk patients, is associated with very low in-hospital mortality, even when compared with the mortality of lower-risk population not submitted to early CABG. Therefore, early performance of this procedure should be considered more often in eligible patients.
Implantation of Mesenchymal Stem Cells Overexpressing Endothelial Nitric Oxide Synthase Improves Right Ventricular Impairments Caused by Pulmonary Hypertension
Authors: Kanki-Horimoto Sachiko , Horimoto Hitoshi , Mieno Shigetoshi , Kishida Kenji , Watanabe Fusao , Furuya Eisuke , Katsumata Takahiro
Published: July 2006

Background—

Pulmonary hypertension (PH) is a life-threatening disease. Bone marrow cell transplantation is reported to reduce the development of PH by increasing vascular beds in pulmonary circulation. However, adenoviral overexpression of endothelial nitric oxide synthase (eNOS) in the lung is also known to reduce PH. Because mesenchymal stem cells (MSCs) are potential cell sources for neovascularization, the implantation of MSCs overexpressing eNOS (MSCs/eNOS) may further improve the surgical results. We evaluated the efficacy of MSCs/eNOS implantation in monocrotaline (MCT)-induced PH rats.

Methods and Results—

MSCs were isolated from rat bone marrow. PH was induced in rats by subcutaneous injection of MCT. One week after MCT administration, the rats received 3 different treatments: MSCs (MSC group), MSCs/eNOS (MSC/eNOS group), or nontreatment (PH group). As the negative control, rats received saline instead of MCT (control group). Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated 3 weeks after MCT administration. Moreover, the effects of MSCs/eNOS on survival were investigated in PH induced by MCT 3 weeks earlier. RVSP in both the MSC and MSC/eNOS groups was significantly lower than the PH group. RVSP in the MSC/eNOS group was significantly lower than the MSC group. The RV weight to body weight ratio was significantly lower in the MSC and MSC/eNOS groups than the PH group. The survival time of rats receiving MSCs/eNOS was significantly longer than the nontreatment rats.

Conclusion—

Intravenous implantation of MSCs/eNOS may offer ameliorating effects on PH-related RV impairment and survival time.
Elevated Endothelin-1 Levels Impair Nitric Oxide Homeostasis Through a PKC-Dependent Pathway
Authors: Ramzy Danny , Rao Vivek , Tumiati Laura C. , Xu Ning , Sheshgiri Rohit , Miriuka Santiago , Delgado Diego H. , Ross Heather J.
Published: July 2006

Background—

Endothelin-1 (ET-1) plays an important role in the maintenance of vascular tone and pathological states such as ischemia/reperfusion (I/R) injury, coronary vasospasm, and cardiac allograft vasculopathy. We assessed the effects of elevated ET-1 levels as seen after I/R to determine if ET-1 modulates nitric oxide (NO) production via the translocation of specific protein kinase C (PKC) isoforms.

Methods and Results—

Human saphenous vein endothelial cells (HSVECs) (n=8) were incubated with ET-1 or phosphate-buffered saline (PBS) for 24 hours. NO production was determined in the supernatant by measuring nitrate/nitrite levels. Protein expression of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), caveolin-1 and PKC were determined. Lastly, PKC translocation and activity were assessed after exposure to the drug of interest. HSVECs exposed to ET-1 displayed decreased NO production. PKC inhibition reduced NO production, whereas PKC activation increased production. NO production was maintained when HSVECs exposed to ET-1 were treated with the PKC agonist, PMA. eNOS protein expression was reduced after ET-1 treatment. PKC inhibition also downregulated eNOS protein expression, whereas PMA upregulated expression. ET-1 exposure led to a significant increase in PKCδ and PKCα translocation compared with control, whereas translocation of PKCλ was inhibited. ET-1 exposure significantly reduced overall PKC activity compared with control.

Conclusions—

Our study demonstrates that high levels of ET-1 impair endothelial NO production via an isoform-specific PKC-mediated inhibition of eNOS expression. ET-1 antagonism with bosentan stimulates translocation of PKCλ and leads to increased PKC activity and NO production. ET-1 antagonism may provide a novel therapeutic strategy to improve vascular homeostasis.
Emergency Coronary Artery Bypass Graft Surgery for Acute Coronary Syndrome
Authors: Rastan Ardawan Julian , Eckenstein Judith Isabell , Hentschel Bettina , Funkat Anne Kathrin , Gummert Jan Fritz , Doll Nicolas , Walther Thomas , Falk Volkmar , Mohr Friedrich Wilhelm
Published: July 2006

Background—

Aim of this study was to compare the outcome of beating heart versus conventional coronary artery bypass graft (CABG) strategies in acute coronary syndromes for emergency indications.

Methods and Results—

638 consecutive patients with acute coronary syndrome (ACS) receiving emergency CABG surgery via midline sternotomy from January 2000 to September 2005 were evaluated. Propensity score analysis was used to predict the probability of undergoing beating heart (BH) (n=240) versus cardioplegic cardiac arrest (CA) (n=398) strategies. Patients presented with stable hemodynamics (n=531) or in cardiogenic shock (CS) (n=107). Hospital and follow-up outcome was compared by propensity score adjusted multiregression analysis. BH included 116 on-pump and 124 off-pump (OPCAB) procedures. There was a propensity to operate CS patients on the beating heart (multivariate odds ratio [OR], 3.8;
P
=0.001). Under stable hemodynamics significant predictors for BH selection were logEuroSCORE >20% (OR, 2.05), creatinine >1.8 mg/dL (OR, 4.12), complicated percutaneous coronary intervention (OR, 1.88), ejection fraction <30% (OR, 2.64), whereas left main disease (OR, 0.68), circumflex artery (OR, 0.32), and 3-vessel disease (OR, 0.67) indicated preference for cardioplegic arrest. Time from skin incision to culprit lesion revascularization was significantly reduced in BH patients. BH surgery led to a significant benefit in terms of less drainage loss, less transfusion requirement, less inotropic support, shorter ventilation time, lower stroke rate, and shorter intensive care unit stay. In CS, BH was associated with lower incidence of stroke, inotropic support, acute renal failure, new atrial fibrillation and sternal wound healing complications. In CS patients, hospital mortality rate was reduced when using beating heart strategies (
P
=0.048). Overall survival, major adverse cerebral and cardiovascular event rate, and repeated revascularization was comparable during a 5-year follow-up.

Conclusions—

Beating heart strategies are associated with an improved hospital outcome and comparable long-term results for high-risk patients presenting acute coronary syndrome with or without CS.
Optimizing Engineered Heart Tissue for Therapeutic Applications as Surrogate Heart Muscle
Authors: Naito Hiroshi , Melnychenko Ivan , Didié Michael , Schneiderbanger Karin , Schubert Pia , Rosenkranz Stephan , Eschenhagen Thomas , Zimmermann Wolfram-Hubertus
Published: July 2006

Background—

Cardiac tissue engineering aims at providing heart muscle for cardiac regeneration. Here, we hypothesized that engineered heart tissue (EHT) can be improved by using mixed heart cell populations, culture in defined serum-free and Matrigel-free conditions, and fusion of single-unit EHTs to multi-unit heart muscle surrogates.

Methods and Results—

EHTs were constructed from native and cardiac myocyte enriched heart cell populations. The former demonstrated a superior contractile performance and developed vascular structures. Peptide growth factor-supplemented culture medium was developed to maintain contractile EHTs in a serum-free environment. Addition of triiodothyronine and insulin facilitated withdrawal of Matrigel from the EHT reconstitution mixture. Single-unit EHTs could be fused to form large multi-unit EHTs with variable geometries.

Conclusions—

Simulating a native heart cell environment in EHTs leads to improved function and formation of primitive capillaries. The latter may constitute a preformed vascular bed in vitro and facilitate engraftment in vivo. Serum- and Matrigel-free culture conditions are expected to reduce immunogenicity of EHT. Fusion of single-unit EHT allows production of large heart muscle constructs that may eventually serve as optimized tissue grafts in cardiac regeneration in vivo.
Passive Ventricular Constraint Prevents Transmural Shear Strain Progression in Left Ventricle Remodeling
Authors: Cheng Allen , Nguyen Tom C. , Malinowski Marcin , Langer Frank , Liang David , Daughters George T. , Ingels Neil B. , Miller D. Craig
Published: July 2006

Background—

Passive ventricular constraint provides external cardiac support to reduce left ventricular (LV) wall stress and myocardial stretch, which are primary determinants of LV remodeling. Altered wall strain results in cytokine and reactive oxygen species production, which, in turn, stimulates apoptosis and extracellular matrix disruption and could be an important trigger for adverse global LV dilatation and remodeling. The effects of the Acorn cardiac support device (CSD) on regional transmural LV wall strains, however, remain unknown.

Methods and Results—

Thirty-three sheep had transmural radiopaque beadsets surgically inserted into the anterior basal and lateral equatorial LV walls, with additional markers silhouetting the left ventricle. Eight animals had CSD implanted (myocardial infarction [MI]+CSD). One week thereafter, the MI+CSD group and 10 animals without CSD (MI) underwent posterior LV infarction by snaring obtuse marginal coronary arteries. Fifteen animals (Sham) had no infarction or CSD. 4D marker dynamics were measured with biplane videofluoroscopy 1 and 8 weeks postoperatively. LV volumes, sphericity index, and transmural circumferential, longitudinal, and radial systolic strains were analyzed. Compared with Sham, infarction (MI) dilated the heart, reduced sphericity index (LV length/width), and increased longitudinal–radial shear strains in the inner half of both the anterior and lateral LV walls. CSD prevented this shear strain perturbation, minimized LV end diastolic volume increase, and augmented the LV sphericity index.

Conclusions—

Prophylactic CSD prevented infarct-induced shear strain progression not only in myocardium adjacent to, but also remote from, the infarct. CSD also prevented LV dilatation and sphericalization. By attenuating shear strain abnormalities, CSD could prevent the heart from entering into a positive feedback loop of further LV dilatation and exaggeration of LV wall stress and may reduce biochemical triggers portending adverse LV remodeling.
Is Blood Superior to Crystalloid Cardioplegia?
Authors: Guru Veena , Omura John , Alghamdi Abdullah A. , Weisel Richard , Fremes Stephen E.
Published: July 2006

Background—

Many small, randomized, controlled trials have evaluated the effectiveness of blood as compared with crystalloid cardioplegia for myocardial protection during cardiac surgery. Blood cardioplegia provides a closer approximation to normal physiology, which may translate into measurable clinical benefits. This meta-analysis describes the effectiveness of blood cardioplegia in lowering adverse postoperative outcomes.

Methods and Results—

MEDLINE, EMBASE, and the Cochrane registry of controlled trials were searched for clinical trials. The search was restricted to peer-reviewed English language publications of randomized controlled trials that primarily compared blood and crystalloid cardioplegia in adult patients. Each trial was blindly assessed and abstracted by 2 reviewers. The primary outcomes were: low output syndrome (LOS), myocardial infarction (MI), and death. Surrogate outcomes included postoperative creatinine kinase MB (CKMB) increase. Random effects summary odds ratio (OR) for binary outcomes, and weighted mean difference for continuous outcomes were calculated. A total of 34 trials were included. The majority of trials were conducted in patients undergoing elective CABG surgery (n=18). The incidence of LOS was decreased significantly with blood cardioplegia (OR, 0.54; 95% confidence interval [CI], 0.34 to 0.84;
P
=0.006; 879 patients, 10 trials). The incidence of MI and death were similar between treatment groups (MI: OR, 0.78; 95% CI, 0.54 to 1.13; 4316 patients, 23 trials) (death: OR, 0.80; 95% CI, 0.46 to 1.40; 4022 patients, 17 trials). CKMB release after surgery at 24 hours was reduced with blood cardioplegia (5.9 U/L; 95% CI, 1.6 to 10.2;
P
=0.007; 821 patients, 7 trials).

Conclusions—

Blood cardioplegia provides superior myocardial protection as compared with crystalloid cardioplegia, including lower rates of LOS, and early CKMB increase, whereas the incidence of myocardial infarction and death are similar.
Long-Term Results After Systematic Off-Pump Coronary Artery Bypass Graft Surgery in 1000 Consecutive Patients
Authors: El-Hamamsy Ismail , Cartier Raymond , Demers Philippe , Bouchard Denis , Pellerin Michel
Published: July 2006

Background—

Off-pump coronary artery bypass surgery (OPCAB) is currently used as an alternative to conventional “on-pump” surgery, but there are very little data available on long-term follow-up. The aim of this study was to review our long-term experience with the use of systematic OPCAB.

Methods and Results—

1000 consecutive OPCAB surgeries were systematically performed between 1996 and 2004, representing 95% of all coronary revascularization during that same time frame, with a 97% complete follow-up. Average age of the patients was 64±10 years (778 men and 222 women). Seventy-three percent had triple-vessel disease. Operative 30-day mortality was 1.6%. Overall survival at 96 months was 74±3.5% and cardiac survival was 94±1.3%. By Cox regression analysis, age (odds ratio [OR], 1.07), congestive heart failure (CHF) (OR, 1.90), peripheral vascular disease (OR, 1.74), chronic renal insufficiency (OR, 2.04), previous myocardial infarction (MI) (OR, 1.60), and New York Heart Association functional class (OR, 1.60) were risk factors for long- term mortality. Survival free of any cardiac events (cardiac death, MI, unstable angina, heart failure, or reintervention) was 80±3.4%. Survival free of any type of reintervention alone was 90±3%. By Cox regression analysis, mitral regurgitation (OR, 2.3), peripheral vascular disease (OR, 2.1), and diffuse coronary disease (OR, 2.3) were significant predictors of recurrent cardiac events. Conversion to “on-pump” (OR, 14.3) was predictor of long-term need for repeat revascularization.

Conclusion—

In this series, systematic OPCAB surgery was shown to be an acceptable alternative to conventional “on-pump” coronary artery bypass graft for the treatment of coronary artery disease.
Protecting the Myocardial Cell During Coronary Revascularization
Authors: Levitsky Sidney
Published: July 2006

Background—

Using the ischemic myocardial cell as a paradigm, competitive coronary revascularization technologies will be analyzed for their potential in causing additional myocardial cell damage during the course of therapeutic procedures.

Methods and Results—

Percutaneous coronary intervention (PCI) using balloon and/or stent (bare metal or coated) approaches may be associated with myonecrosis related to atherosclerotic debris plugging the downstream coronary microcirculation as well as ischemia/reperfusion injury associated with revascularization of occluded coronary vessels. The placement of distal mechanical devices and filters during the course of PCI has not been successful in ameliorating this problem. Coronary revascularization using coronary artery bypass grafting (CABG) similarly may be associated with myocardial stunning and cell necrosis associated with ischemia/reperfusion injury. Surgically induced myocardial ischemia secondary to aortic cross clamping, results from the attenuation or cessation of coronary blood flow such that oxygen delivery to the myocardium is insufficient to meet basal myocardial requirements to preserve cellular membrane stability and viability. Recovery involves: (1) resumption of normal oxidative metabolism and the restoration of myocardial energy reserves; (2) reversal of ischemia induced cell swelling and loss of membrane ion gradients and the adenine nucleotide pool; (3) repair of damaged cell organelles such as the mitochondria and the sarcoplasmic reticulum. Despite meticulous adherence to presently known principles of surgical myocardial protection using advanced cardioplegic technologies, some patients require inotropic support and/or mechanical assist devices postoperatively, when none was required preoperatively.

Conclusions—

Which method of coronary revascularization causes the least amount of myocardial cell injury and is associated with superior long-term outcomes remains an area of increasing controversy.