bluuebunny/crossref_metadata_2025 huggingface dataset:
Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia
Authors: Robich Michael P. , Osipov Robert M. , Nezafat Reza , Feng Jun , Clements Richard T. , Bianchi Cesario , Boodhwani Munir , Coady Michael A. , Laham Roger J. , Sellke Frank W.
Published: September 2010

Background—

Resveratrol may provide protection against coronary artery disease. We hypothesized that supplemental resveratrol will improve cardiac perfusion in the ischemic territory of swine with hypercholesterolemia and chronic myocardial ischemia.

Methods and Results—

Yorkshire swine were fed either a normal diet (control, n=7), a hypercholesterolemic diet (HCC, n=7), or a hypercholesterolemic diet with supplemental resveratrol (100 mg/kg/d orally, HCRV, n=7). Four weeks later, an ameroid constrictor was placed on the left circumflex artery. Animals underwent cardiac MRI and coronary angiography 7 weeks later before euthanasia and tissue harvest. Total cholesterol was lowered about 30% in HCRV animals (
P
<0.001). Regional wall motion analysis demonstrated a significant decrease in inferolateral function from baseline to 7 weeks in HCC swine (
P
=0.04). There was no significant change in regional function in HCRV swine from baseline to 7 weeks (
P
=0.32). Tissue blood flow during stress was 2.8-fold greater in HCRV swine when compared with HCC swine (
P
=0.04). Endothelium-dependent microvascular relaxation response to Substance P was diminished in HCC swine, which was rescued by resveratrol treatment (
P
=0.004). Capillary density (PECAM-1 staining) demonstrated fewer capillaries in both HCC and HCRV swine versus control swine (
P
=0.02). Immunoblot analysis demonstrated significantly greater expression in HCRV versus HCC swine of the following markers of angiogenesis: VEGF (
P
=0.002), peNOS (ser1177) (
P
=0.04), NFkB (
P
=0.004), and pAkt (thr308) (
P
=0.001).

Conclusions—

Supplemental resveratrol attenuates regional wall motion abnormalities, improves myocardial perfusion in the collateral dependent region, preserves endothelium-dependent coronary vessel function, and upregulates markers of angiogenesis associated with the VEGF signaling pathway.
Alteration of Parasympathetic/Sympathetic Ratio in the Infarcted Myocardium After Schwann Cell Transplantation Modified Electrophysiological Function of Heart
Authors: Zhang Hao , Yuan Xin , Jin Pei-feng , Hou Jian-feng , Wang Wei , Wei Ying-jie , Hu Shengshou
Published: September 2010

Background—

Neural remodeling after myocardial infarction (MI) may cause fatal ventricular arrhythmia. Schwann cells (SCs), which are important for neurogenesis, are dramatically reduced after MI. We investigated the feasibility of modifying nervous system regeneration after MI and the efficacy by which it may prevent ventricular arrhythmia following SC transplantation.

Methods and Results—

Immediately after creation of MI, syngenic Lewis rats were randomized into cell transplantation (n=80) and control groups (n=72). SCs were isolated from sciatic nerves, and 5×10
6
cells were intramyocardially injected into the infarct region. Expression levels of myocardial nerve growth factor, vascular endothelial growth factor, growth-associated protein 43, connexin 43, and laminin in the SC group were significantly higher than control at 7 and 14 days after cell transplantation. Immunohistochemical staining illustrated increases in sympathetic and parasympathetic nerves in both groups. However, SC transplantation significantly increased the parasympathetic/sympathetic ratio at 14 days after cell injection. Dynamic electrocardiography and programmed electric stimulation were also performed. The SCs significantly decreased the low-/high-frequency ratio and arrhythmia score of programmed electric stimulation-induced ventricular arrhythmia at 2 weeks after cell injection. However, SCs did not restore heart function.

Conclusion—

Transplanted SCs in the infarcted myocardium secrete multiple biological molecules, which alter the ratio of parasympathetic/sympathetic nerve density to normalize irritable myocardium. SC transplantation might be a novel cell-based antiarrhythmic therapy following MI.
Chromosome 9p21 Variant Predicts Mortality After Coronary Artery Bypass Graft Surgery
Authors: Muehlschlegel Jochen D. , Liu Kuang-Yu , Perry Tjörvi E. , Fox Amanda A. , Collard Charles D. , Shernan Stanton K. , Body Simon C.
Published: September 2010

Background—

Recent genome-wide association studies have identified several chromosome 9p21 single nucleotide polymorphisms associated with coronary artery disease and myocardial infarction in nonsurgical populations. We have recently demonstrated an independent association between these 9p21 variants and perioperative myocardial injury after isolated primary coronary artery bypass graft (CABG) surgery. This study investigated the association of a 9p21 variant with mortality in patients after CABG surgery and its prognostic value to improve the EuroSCORE.

Methods and Results—

In a 2-center, prospective, observational study of 846 white primary CABG surgery patients, we genotyped rs10116277, the 9p21 variant with the strongest association to perioperative myocardial injury in our cohort. To estimate the utility of rs10116277 for predicting all-cause mortality within 5 years after surgery, a Cox proportional hazard model was constructed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for demographics and clinical covariates.

The homozygote minor allele of rs10116277 was associated with significantly increased risk of all-cause mortality even after adjusting for other clinical predictors of mortality in a Cox proportional hazards model (HR, 1.7; 95% CI, 1.1–2.7;
P
=0.026). Addition of rs10116277 to the logistic EuroSCORE also significantly improved model prediction for mortality (HR, 1.82; 95% CI, 1.15–2.88;
P
=0.01).

Conclusion—

The 9p21 variant rs10116277 is independently associated with all-cause mortality after primary CABG surgery in whites and significantly improves the predictive value of the logistic EuroSCORE.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00281164.
Five-Year Follow-Up of a Randomized Comparison Between Off-Pump and On-Pump Stable Multivessel Coronary Artery Bypass Grafting. The MASS III Trial
Authors: Hueb Whady , Lopes Neuza H. , Pereira Alexandre C. , Hueb Alexandre C. , Soares Paulo Rogério , Favarato Desidério , D'Oliveira Vieira Ricardo , Lima Eduardo Gomes , Garzillo Cibele Larrosa , da Silva Paulitch Felipe , César Luiz A.M. , Gersh Bernard J. , Ramires José A.F.
Published: September 2010

Background—

Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body’s response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes.

Methods and Results—

In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22;
P
=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes;
P
<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours;
P
<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours;
P
<0.001), hospital stay (6±2 versus 9±2 days;
P
<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients;
P
<0.001), and blood requirements (31 versus 61% of patients;
P
<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient;
P
<0.001).

Conclusions—

No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes.

Clinical Trial Registration—

URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.
Late Outcomes of Reintervention on the Descending Aorta After Repair of Aortic Coarctation
Authors: Brown Morgan L. , Burkhart Harold M. , Connolly Heidi M. , Dearani Joseph A. , Hagler Donald J. , Schaff Hartzell V.
Published: September 2010

Background—

After repair of aortic coarctation, patients may develop restenosis, aneurysms, and pseudoaneurysms at the site of prior repair. We assessed the outcomes of late reintervention on the descending aorta after aortic coarctation repair.

Methods and Results—

From March 1954 to July 2008, 130 patients had operations or endovascular procedures on the descending aorta after previous coarctation repair. We excluded patients who had complex left-sided cardiac lesions or interrupted aortic arch. Mean age at reintervention was 32±24 years and 28% were female. The interval between coarctation repair and reintervention was 17±13 years. Seventy-four percent of patients had hypertension. Reasons for reintervention were restenosis (n=122 [94%]), aneurysm (n=4 [3%]), and pseudoaneurysm (n=4 [3%]). Ninety-five patients (73%) underwent operative procedures including an extra-anatomic conduit (n=41), patch repair (n=32), interposition graft (n=14), end–end anastomosis (n=6), and subclavian flap (n=2). Thirty-five patients underwent endovascular treatment (balloon dilatation, n=22 or stenting, n=13). There was no early mortality. In the surgical group, 5 patients required early reoperation for bleeding and 5 patients had early vocal cord paralysis. One patient in the endovascular group had aortic rupture at the time of intervention requiring urgent operation. Survival was 97% at 10 years. At 5 years, freedom from a second repeat procedure on the descending aorta was 96% in the surgical group and 72% in the endovascular group (
P
<0.001). Five years after reintervention, fewer patients required treatment for hypertension (57% versus 74%
, P
<0.001) and a median of 1 antihypertensive medication was prescribed compared with a median of 2 medications preintervention.

Conclusions—

Operative and endovascular management of recoarctation can be performed safely with good late outcomes.
Major Adverse Cardiac and Cerebrovascular Events After the Ross Procedure
Authors: Sievers Hans-H. , Stierle Ulrich , Charitos Efstratios I. , Hanke Thorsten , Misfeld Martin , Matthias Bechtel J.F. , Gorski Armin , Franke Ulrich F.W. , Graf Bernhard , Robinson Derek R. , Bogers Ad J.J.C. , Dodge-Khatami Ali , Boehm Juergen O. , Rein Joachim G. , Botha Cornelius A. , Lange Ruediger , Hoerer Juergen , Moritz Anton , Wahlers Thorsten , Breuer Martin , Ferrari-Kuehne Katharina , Hetzer Roland , Huebler Michael , Ziemer Gerhard , Takkenberg Johanna J.M. , Hemmer Wolfgang
Published: September 2010

Background—

The purpose of the study is to report major cardiac and cerebrovascular events after the Ross procedure in the large adult and pediatric population of the German-Dutch Ross registry. These data could provide an additional basis for discussions among physicians and a source of information for patients.

Methods and Results—

One thousand six hundred twenty patients (1420 adults; 1211 male; mean age, 39.2±16.2 years) underwent a Ross procedure between 1988 and 2008. Follow-up was performed on an annual basis (median, 6.2 years; 10 747 patient-years). Early and late mortality were 1.2% (n=19) and 3.6% (n=58; 0.54%/patient-year), respectively. Ninety-three patients underwent 99 reinterventions on the autograft (0.92%/patient-year); 78 reinterventions in 63 patients on the pulmonary conduit were performed (0.73%/patient-year). Freedom from autograft or pulmonary conduit reoperation was 98.2%, 95.1%, and 89% at 1, 5, and 10 years, respectively. Preoperative aortic regurgitation and the root replacement technique without surgical autograft reinforcement were associated with a greater hazard for autograft reoperation. Major internal or external bleeding occurred in 17 (0.15%/patient-year), and a total of 38 patients had composite end point of thrombosis, embolism, or bleeding (0.35%/patient-year). Late endocarditis with medical (n=16) or surgical treatment (n=29) was observed in 38 patients (0.38%/patient-year). Freedom from any valve-related event was 94.9% at 1 year, 90.7% at 5 years, and 82.5% at 10 years.

Conclusions—

Although longer follow-up of patients who undergo Ross operation is needed, the present series confirms that the autograft procedure is a valid option to treat aortic valve disease in selected patients. The nonreinforced full root technique and preoperative aortic regurgitation are predictors for autograft failure and warrant further consideration.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00708409.
Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC)
Authors: Portman Michael A. , Slee April , Olson Aaron K. , Cohen Gordon , Karl Tom , Tong Elizabeth , Hastings Laura , Patel Hitendra , Reinhartz Olaf , Mott Antonio R. , Mainwaring Richard , Linam Justin , Danzi Sara
Published: September 2010

Background—

Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome.

Methods and Results—

The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (
P
=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (
P
=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7–22) for placebo and 20 hours (CI, 16–45) for Triostat and (hazard ratio, 0.60;
P
=0.0220).

Conclusions—

T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.
Remote Ischemic Preconditioning in Human Coronary Artery Bypass Surgery
Authors: Rahman Ishtiaq A. , Mascaro Jorge G. , Steeds Rick P. , Frenneaux Michael P. , Nightingale Peter , Gosling Peter , Townsend Peter , Townend John N. , Green David , Bonser Robert S.
Published: September 2010

Background—

We assessed whether remote ischemic preconditioning (RIPC) improves myocardial, renal, and lung protection after on-pump coronary surgery.

Methods and Results—

This was a single-center, prospective, randomized (1:1), placebo-controlled trial. Patients, investigators, anesthetists, surgeons, and critical care teams were blinded to group allocation. Subjects received RIPC (or placebo) stimuli (×3 upper limb (or dummy arm), 5-minute cycles of 200 mm Hg cuff inflation/deflation) before aortic clamping. Anesthesia, perfusion, cardioplegia, and surgical techniques were standardized. The primary end point was 48-hour area under the curve (AUC) troponin T (cTnT) release. Secondary end points were 6-hour and peak cTnT, ECG changes, cardiac index, inotrope and vasoconstrictor use, renal dysfunction, and lung injury. Hospital survival was 99.4%. Comparing placebo and RIPC, median (interquartile range) AUC 48-hour cTnT (ng/mL
−1
/48 h
−1
); 28 (19, 39) versus 30 (22, 38), 6-hour cTnT (ng/mL
−1
); 0.93(0.59, 1.35) versus 1.01(0.72, 1.43), peak cTnT (ng/mL
−1
); 1.02 (0.74, 1.44) versus 1.04 (0.78, 1.51), de novo left bundle-branch block (4% versus 0%) and Q waves (5.3% versus 5.5%), serial cardiac indices, intraaortic balloon pump usage (8.5% versus 7.5%), inotrope (39% versus 50%) and vasoconstrictor usage (66% versus 64%) were not different. Dialysis requirement (1.2% versus 3.8%), peak creatinine (median [interquartile range], 1.2 mg/dL
−1
(1.1, 1.4) versus 1.2 (1.0, 1.4)), and AUC urinary albumin-creatinine ratios 69 (40, 112) versus 58 (32, 85) were not different. Intubation times; median (interquartile range), 937 minutes(766, 1402) versus 895(675, 1180), 6-hour; 278 (210, 338) versus 270 (218, 323) and 12-hour pO
2
:FiO
2
ratios 255 (195, 323) versus 263 (210, 308) were similar.

Conclusions—

In contrast to prior smaller studies, RIPC did not reduce troponin release, improve hemodynamics, or enhance renal or lung protection.

Clinical Trial Registration—

URL: http://www.ukcrn.org.uk. Unique identifier: 4659.
Correlates and Causes of Death in Patients With Severe Symptomatic Aortic Stenosis Who Are Not Eligible to Participate in a Clinical Trial of Transcatheter Aortic Valve Implantation
Authors: Ben-Dor Itsik , Pichard Augusto D. , Gonzalez Manuel A. , Weissman Gaby , Li Yanlin , Goldstein Steven A. , Okubagzi Petros , Syed Asmir I. , Maluenda Gabriel , Collins Sara D. , Delhaye Cedric , Wakabayashi Kohei , Gaglia Michael A. , Torguson Rebecca , Xue Zhenyi , Satler Lowell F. , Suddath William O. , Kent Kenneth M. , Lindsay Joseph , Waksman Ron
Published: September 2010

Background—

Transcatheter aortic valve implantation is currently being evaluated in patients with severe aortic stenosis who are considered high-risk surgical candidates. This study aimed to detect incidences, causes, and correlates of mortality in patients ineligible to participate in transcatheter aortic valve implantation studies.

Methods and Results—

From April 2007 to July 2009, a cohort of 362 patients with severe aortic stenosis were screened and did not meet the inclusion/exclusion criteria necessary to participate in a transcatheter aortic valve implantation trial. These patients were classified into 2 groups: group 1 (medical): 274 (75.7%): 97 (35.4%) treated medically and 177 (64.6%) treated with balloon aortic valvuloplasty; and group 2 (surgical): 88 (24.3%). The medical/balloon aortic valvuloplasty group had significantly higher clinical risk compared with the surgical group, with significantly higher Society of Thoracic Surgeons score (12.8±7.0 versus 8.5±5.1;
P
<0.001) and logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (42.4±22.8 versus 24.4±18.1;
P
<0.001). The medical/balloon aortic valvuloplasty group had a higher New York Heart Association functional class, incidence of renal failure, and lower ejection fraction. During median follow-up of 377.5 days, mortality in the medical/balloon aortic valvuloplasty group was 102 (37.2%), and during median follow-up of 386 days, mortality in the surgical group was 19 (21.5%). Multivariable adjustment analysis identified renal failure (hazard ratio [HR]: 5.60), New York Heart Association class IV (HR: 5.88), and aortic systolic pressure (HR: 0.99) as independent correlates for mortality in the medical group, whereas renal failure (HR: 7.45), Society of Thoracic Surgeons score (STS; HR: 1.09) and logistic EuroSCORE (HR: 1.45) were correlates of mortality in the in the surgical group.

Conclusion—

Patients with severe symptomatic aortic stenosis not included in transcatheter aortic valve implantation trials do poorly and have extremely high mortality rates, especially in nonsurgical groups, and loss of quality of life in surgical groups.
Preoperative Atorvastatin Treatment in CABG Patients Rapidly Improves Vein Graft Redox State by Inhibition of Rac1 and NADPH-Oxidase Activity
Authors: Antoniades Charalambos , Bakogiannis Constantinos , Tousoulis Dimitris , Reilly Svetlana , Zhang Mei-Hua , Paschalis Andreas , Antonopoulos Alexios S. , Demosthenous Michael , Miliou Antigoni , Psarros Costas , Marinou Kyriakoula , Sfyras Nikolaos , Economopoulos George , Casadei Barbara , Channon Keith M. , Stefanadis Christodoulos
Published: September 2010

Background—

Statins improve clinical outcome of patients with atherosclerosis, but their perioperative role in patients undergoing coronary artery bypass grafting (CABG) is unclear. We hypothesized that short-term treatment with atorvastatin before CABG would improve the redox state in saphenous vein grafts (SVGs), independently of low-density lipoprotein cholesterol (LDL)-lowering.

Methods and Results—

In a randomized, double-blind controlled trial, 42 statin-naïve patients undergoing elective CABG received atorvastatin 40 mg/d or placebo for 3 days before surgery. Circulating inflammatory markers and malondialdehyde (MDA) were measured before and after treatment. SVG segments were used to determine vascular superoxide (O
2
·−
) and Rac1 activation. For ex vivo studies, SVG segments from 24 patients were incubated for 6 hours with atorvastatin 0, 5, or 50 μmol/L. Oral atorvastatin reduced vascular basal and NADPH-stimulated O
2
·−
in SVGs (
P
<0.05 for all versus placebo) and reduced plasma MDA (
P
<0.05), independently of LDL-lowering and of changes in inflammatory markers. In SVGs exposed to atorvastatin ex vivo, without exposure to LDL, basal and NADPH-stimulated O
2
·−
were significantly reduced (
P
<0.01 for both concentrations versus 0 μmol/L) in association with a striking reduction in Rac1 activation and 1 membrane-bound Rac1 and p67
phox
subunit. The antioxidant effects of atorvastatin were reversed by mevalonate, implying a dependence on vascular HMG-CoA reductase inhibition.

Conclusions—

Short-term treatment with atorvastatin 40 mg/d before CABG improves redox state in SVGs, by inhibiting vascular Rac1-mediated activation of NADPH-oxidase. These novel findings suggest that statin therapy should be maintained or initiated in patients undergoing CABG, independently of LDL levels.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01013103.
Epidermal Growth Factor-Like Domain 7 Suppresses Intercellular Adhesion Molecule 1 Expression in Response to Hypoxia/Reoxygenation Injury in Human Coronary Artery Endothelial Cells
Authors: Badiwala Mitesh V. , Tumiati Laura C. , Joseph Jemy M. , Sheshgiri Rohit , Ross Heather J. , Delgado Diego H. , Rao Vivek
Published: September 2010

Background—

Epidermal growth factor-like domain 7 (Egfl7) is a chemoattractant for endothelial cells, and its expression is restricted to endothelial cells. Hypoxia/reoxygenation (H/R) induced endothelial injury that occurs during transplantation contributes to the subsequent development of allograft vasculopathy. We investigated the effect of Egfl7 on endothelial cell intercellular adhesion molecule 1 expression in response to H/R injury.

Methods and Results—

Human coronary artery endothelial cells were submitted to hypoxia (0.1% O
2
) followed by normoxia (21% O
2
) in the presence or absence of Egfl7 (100 ng/mL). Hypoxia alone increased the expression of Egfl7×140±8% of control at 3 hours (n=6;
P
<0.05) and 385±50% of control at 6 hours (n=6;
P
<0.001). Incubation with Egfl7 during the reoxygenation period prevented intercellular adhesion molecule 1 upregulation (mean fluorescence intensity: 5.37±0.92 versus 3.81±0.21;
P
<0.05; n=4 per group). Nuclear factor-κB nuclear localization on H/R injury was blocked by Egfl7 administration (cytosolic/nuclear ratio of 0.93±0.01 versus 1.44±0.24;
P
<0.05; n=4 per group). Inhibitor of nuclear factor-κB protein level was significantly reduced on H/R injury (26±4.6% of control expression;
P
<0.05; n=4 per group); however, concurrent incubation with Egfl7 attenuated this reduction (46±6.2% of control expression;
P
<0.05 when compared with H/R injury alone; n=4 per group).

Conclusions—

Our study reveals the novel observation that hypoxia upregulates human coronary artery endothelial cells expression of Egfl7 and that Egfl7 inhibits expression of intercellular adhesion molecule 1 subsequent to H/R injury. Mechanistically, Egfl7 prevented nuclear factor-κB nuclear localization and augmented inhibitor of nuclear factor-κB protein levels, suggesting that it inhibits nuclear factor-κB activation, a key step in the inflammatory activation of endothelial cells. Egfl7 may be protective against H/R injury incurred during transplantation and may modulate the events that lead to the development of graft vasculopathy.
Assessment of Changes in Mitral Valve Configuration With Multidetector Computed Tomography
Authors: Shudo Yasuhiro , Matsumiya Goro , Sakaguchi Taichi , Miyagawa Shigeru , Yoshikawa Yasushi , Yamauchi Takashi , Takeda Koji , Saito Shunsuke , Nakatani Satoshi , Taniguchi Kazuhiro , Izutani Hironori , Sawa Yoshiki
Published: September 2010

Background—

The optimal surgical procedures in functional mitral regurgitation remain controversial. We applied papillary muscle imbrication (PMI) combined with undersized mitral annuloplasty (UMAP). Multidetector computed tomography (MDCT) provides images of different phases of the cardiac cycle, allowing an assessment of the geometry. In the present study, we evaluated the mitral valve configuration and subvalvular apparatus before and after UMAP and/or PMI using MDCT imaging.

Methods and Results—

We studied 26 patients with functional mitral regurgitation (3+ to 4+) with an ejection fraction ≥35% who underwent diagnostic MDCT examinations before and early after the operation. Of these, 15 underwent UMAP and PMI (UMAP+PMI group) and 11 underwent UMAP (UMAP group). The annular anteroposterior diameter, tenting height, tenting area, and interpapillary muscle distance at end-systole were quantified. The annular anteroposterior diameter, tenting height, and tenting area were significantly decreased after the operation in both groups. Whereas the average change in annular anteroposterior diameter, tenting area, and interpapillary muscle distance did not differ between the 2 groups, the average change in tenting height was greater in the UMAP+PMI group than in the UMAP group (5.1±1.3 versus 3.8±2.3 mm,
P
=0.036). There was a significant correlation between the change in interpapillary muscle distance and the change in tenting height in the UMAP+PMI group (
r
=0.788,
P
=0.0005).

Conclusions—

Our results examined with MDCT indicated that UMAP combined with PMI improved leaflet tethering compared with UMAP, reflecting differences in the effects of the surgical procedures used, and suggested that concomitant PMI might be beneficial in some cases.
Long-Term Clinical and Hemodynamic Performance of the Hancock II Versus the Perimount Aortic Bioprostheses
Authors: Chan Vincent , Kulik Alexander , Tran Anthony , Hendry Paul , Masters Roy , Mesana Thierry G. , Ruel Marc
Published: September 2010

Background—

The Medtronic Hancock II and the Carpentier-Edwards Perimount are among the world’s most commonly used aortic bioprostheses. However, a direct comparison of their clinical performance is lacking. To minimize biases inherent to between-center comparisons, we examined these prostheses within a large, contemporary, single-center cohort.

Methods and Results—

Between 1990 and 2007, 1659 patients (mean age, 73.1±9.3 years) underwent aortic valve replacement with either the Hancock II (N=1021) or the Perimount (N=638). Patients were prospectively followed-up with serial clinic visits and echocardiograms for up to 16 years (mean, 5.0±3.3 years). There was no significant difference in aortic root size preoperatively (
P
=0.7). Aortic root enlargement was more commonly performed with the Perimount (
P
<0.001), and the manufacturer valve size of the implanted prosthesis was larger with the Hancock II (
P
<0.001). Postoperatively, peak and mean transprosthesis gradients were higher for the Hancock II (32.7±0.7 and 16.0±0.3 mm Hg, respectively) than for the Perimount (24.9±0.7 and 13.4±0.4 mm Hg, respectively;
P
<0.001). However, no difference in left ventricular mass regression was observed at late follow-up (
P
=0.9). Unadjusted 10-year survival was 59.4%±2.4% for the Hancock II and 70.2%±3.8% for the Perimount (
P
=0.07). Multivariable predictors of survival did not include prosthesis type (
P
=0.2).

Conclusions—

For the same manufacturer valve size, the Perimount is larger, which may warrant enlarging the aortic root more often, and it is associated with better hemodynamics than the Hancock II. These differences do not impact survival or left ventricular mass regression, and the long-term clinical performances of the Hancock II and Perimount bioprostheses are equivalent.
MicroRNA-210 as a Novel Therapy for Treatment of Ischemic Heart Disease
Authors: Hu Shijun , Huang Mei , Li Zongjin , Jia Fangjun , Ghosh Zhumur , Lijkwan Maarten A. , Fasanaro Pasquale , Sun Ning , Wang Xi , Martelli Fabio , Robbins Robert C. , Wu Joseph C.
Published: September 2010

Background—

MicroRNAs are involved in various critical functions, including the regulation of cellular differentiation, proliferation, angiogenesis, and apoptosis. We hypothesize that microRNA-210 can rescue cardiac function after myocardial infarction by upregulation of angiogenesis and inhibition of cellular apoptosis in the heart.

Methods and Results—

Using microRNA microarrays, we first showed that microRNA-210 was highly expressed in live mouse HL-1 cardiomyocytes compared with apoptotic cells after 48 hours of hypoxia exposure. We confirmed by polymerase chain reaction that microRNA-210 was robustly induced in these cells. Gain-of-function and loss-of-function approaches were used to investigate microRNA-210 therapeutic potential in vitro. After transduction, microRNA-210 can upregulate several angiogenic factors, inhibit caspase activity, and prevent cell apoptosis compared with control. Afterward, adult FVB mice underwent intramyocardial injections with minicircle vector carrying microRNA-210 precursor, minicircle carrying microRNA-scramble, or sham surgery. At 8 weeks, echocardiography showed a significant improvement of left ventricular fractional shortening in the minicircle vector carrying microRNA-210 precursor group compared with the minicircle carrying microRNA-scramble control. Histological analysis confirmed decreased cellular apoptosis and increased neovascularization. Finally, 2 potential targets of microRNA-210, Efna3 and Ptp1b, involved in angiogenesis and apoptosis were confirmed through additional experimental validation.

Conclusion—

MicroRNA-210 can improve angiogenesis, inhibit apoptosis, and improve cardiac function in a murine model of myocardial infarction. It represents a potential novel therapeutic approach for treatment of ischemic heart disease.
Visceral Arterial Compromise During Intra-Aortic Balloon Counterpulsation Therapy
Authors: Rastan Ardawan Julian , Tillmann Eugen , Subramanian Sreekumar , Lehmkuhl Lukas , Funkat Anne Kathrin , Leontyev Sergej , Doenst Torsten , Walther Thomas , Gutberlet Matthias , Mohr Friedrich Wilhelm
Published: September 2010

Background—

Intraaortic balloon pump (IABP) therapy is a widely used method of circulatory support. Based on frequent findings of balloon malposition with visceral arterial compromise on computerized tomographic (CT) imaging studies, we conducted a systematic review of cardiac surgical IABP patients with available CT scans to determine reasons, incidence, and clinical relevance of malposition.

Methods and Results—

From January 2007 to March 2009, a total of 621 of 7756 cardiac surgical patients (8.0%) received perioperative IABP support, of whom 63 (10.1%) received a thoracoabdominal CT scan during IABP support. Proximal and distal balloon positions were analyzed. The anatomic distance from the left subclavian artery to celiac trunk and aortic transverse diameter were measured in all patients and compared with implanted balloon dimensions. Mean age was 67.1±11.9 years; 33.3% were female, and height was 169±9 cm. Based on radiography, proximal balloon position was correct in 96.8% but only appropriate in 38.1% based on CT. In 61 of 63 patients, compromise of at least 1 visceral artery was found: celiac trunk, 96.8%; superior mesenteric artery, 87.3%; and renal arteries, 66.7%. Left subclavian artery to celiac trunk distance was 241±23 mm, and balloon length was 248±17 mm and corresponded to an anatomic to balloon length mismatch in 68.2%. Spinal deformations were found in 42.9%. Laparotomy for mesenteric ischemia was required in 23.8%. Hospital mortality rate was 60.3%.

Conclusions—

IABP malposition was commonly identified by CT. Reasons included incorrect proximal balloon position as well as an anatomic-to-balloon length mismatch. Thus, shorter than recommended balloon sizes and better positioning strategies had to be considered.
Stromal Cell-Derived Factor-1α Activation of Tissue-Engineered Endothelial Progenitor Cell Matrix Enhances Ventricular Function After Myocardial Infarction by Inducing Neovasculogenesis
Authors: Frederick John R. , Fitzpatrick J. Raymond , McCormick Ryan C. , Harris David A. , Kim Ah-Young , Muenzer Jeffrey R. , Marotta Nicole , Smith Maximilian J. , Cohen Jeffrey E. , Hiesinger William , Atluri Pavan , Woo Y. Joseph
Published: September 2010

Background—

Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPCs) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that implantation of a tissue-engineered extracellular matrix (ECM) scaffold seeded with EPCs primed with SDF could induce borderzone neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after myocardial infarction.

Methods and Results—

Lewis rats (n=82) underwent left anterior descending artery ligation to induce myocardial infarction. EPCs were isolated, characterized, and cultured on a vitronectin/collagen scaffold and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular wall, which included the region of ischemia. Control animals received sutures but no EPCM. Additional groups underwent application of the ECM alone, ECM primed with SDF (ECM+SDF), and ECM seeded with EPCs but not primed with SDF (ECM+SDF). At 4 weeks, borderzone myocardial tissue demonstrated increased levels of vascular endothelial growth factor in the EPCM group. When compared to controls, Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 versus 6.2 vessels/high-powered field;
P
<0.001), and microvascular perfusion measured by lectin microangiography was enhanced 4-fold (0.7% versus 2.7% vessel volume/section volume;
P
=0.04). Comparisons to additional groups also showed a significantly improved vasculogenic response in the EPCM group. Ventricular geometry and scar fraction assessed by digital planimetric analysis of sectioned hearts exhibited significantly preserved left ventricular internal diameter (9.7 mm versus 8.6 mm;
P
=0.005) and decreased infarct scar formation expressed as percent of total section area (16% versus 7%;
P
=0.002) when compared with all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure-volume conductance, and Doppler flow.

Conclusions—

Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after myocardial infarction.
Adropin Is a Novel Regulator of Endothelial Function
Authors: Lovren Fina , Pan Yi , Quan Adrian , Singh Krishna K. , Shukla Praphulla C. , Gupta Milan , Al-Omran Mohammed , Teoh Hwee , Verma Subodh
Published: September 2010

Background—

Adropin is a recently identified protein that has been implicated in the maintenance of energy homeostasis and insulin resistance. Because vascular function and insulin sensitivity are closely related, we hypothesized that adropin may also exert direct effects on the endothelium.

Methods and Results—

In vitro cell culture models were partnered with an in vivo murine injury model to determine the potential vascular effects of adropin. Adropin was expressed in human umbilical vein and coronary artery endothelial cells (ECs). Adropin-treated endothelial cells exhibited greater proliferation, migration and capillary-like tube formation and less permeability and tumor necrosis factor-α–induced apoptosis. In keeping with a vascular protective effect, adropin stimulated Akt Ser
473
and endothelial nitric oxide (NO) synthase Ser
1177
phosphorylation. The former was abrogated in the presence of the phosphatidylinositol 3-kinase inhibitor LY294002, whereas the latter was attenuated by LY294002 and by mitogen-activated protein kinase kinase 1 inhibition with PD98059. Together, these findings suggest that adropin regulates NO bioavailability and events via the phosphatidylinositol 3-kinase-Akt and extracellular signal regulated kinase 1/2 signaling pathways. Adropin markedly upregulated vascular endothelial growth factor receptor-2 (VEGFR2) transcript and protein levels, and in VEGFR2-silenced endothelial cells, adropin failed to induce phosphorylation of endothelial NO synthase, Akt, and extracellular signal regulated kinase 1/2, supporting VEGFR2 as an upstream target of adropin-mediated endothelial NO synthase activation. Last, adropin improved murine limb perfusion and elevated capillary density following induction of hindlimb ischemia.

Conclusions—

We report a potential endothelial protective role of adropin that is likely mediated via upregulation of endothelial NO synthase expression through the VEGFR2-phosphatidylinositol 3-kinase-Akt and VEGFR2-extracellular signal regulated kinase 1/2 pathways. Adropin represents a novel target to limit diseases characterized by endothelial dysfunction in addition to its favorable metabolic profile.
Structure of AGCM-Simulated Convectively Coupled Kelvin Waves and Sensitivity to Convective Parameterization
Authors: Frierson Dargan M. W. , Kim Daehyun , Kang In-Sik , Lee Myong-In , Lin Jialin
Published: September 2010

A study of the convectively coupled Kelvin wave (CCKW) properties from a series of atmospheric general circulation model experiments over observed sea surface temperatures is presented. The simulations are performed with two different convection schemes (a mass flux scheme and a moisture convergence scheme) using a range of convective triggers, which inhibit convection in different ways. Increasing the strength of the convective trigger leads to significantly slower and more intense CCKW activity in both convection schemes. With the most stringent trigger in the mass flux scheme, the waves have realistic speed and variance and also exhibit clear shallow-to-deep-to-stratiform phase tilts in the vertical, as in observations. While adding a moisture trigger results in vertical phase tilts in the mass flux scheme, the moisture convergence scheme CCKWs show no such phase tilts even with a stringent convective trigger.

The changes in phase speed in the simulations are interpreted using the concept of “gross moist stability” (GMS). Inhibition of convection results in a more unstable tropical atmosphere in the time mean, and convection is shallower on average as well. Both of these effects lead to a smaller GMS, which leads to slower propagation of the waves, as expected from theoretical studies. Effects such as changes in radiative heating, atmospheric humidity, and vertical velocity following the wave have a relatively small effect on the GMS as compared with the time mean state determined by the convection scheme.
Convectively Generated Potential Vorticity in Rainbands and Formation of the Secondary Eyewall in Hurricane Rita of 2005
Authors: Judt Falko , Chen Shuyi S.
Published: September 2010

Eyewall replacements in mature tropical cyclones usually cause intensity fluctuations. One reason for eyewall replacements remaining a forecasting challenge is the lack of understanding of how secondary eyewalls form. This study uses high-resolution, full-physics-model forecast fields of Hurricanes Katrina and Rita (2005) to better understand potential vorticity (PV) generation in the rainbands and the role that convectively generated PV played in the formation of a secondary eyewall in Hurricane Rita. Previous studies have focused on dynamic processes in the inner core and/or the effects of certain specified PV distributions. However, the initial development of a concentric PV ring in the rainband region has not been fully addressed. Katrina and Rita were extensively observed by three research aircraft during the Hurricane Rainband and Intensity Change Experiment (RAINEX), which was designed to study the interaction of the rainbands and the inner core. Rita developed a secondary eyewall and went through an eyewall replacement cycle, whereas Katrina maintained a single primary eyewall during the RAINEX observation period before landfall. These distinct features observed in RAINEX provide a unique opportunity to examine the physical and dynamical processes that lead to formation of concentric eyewalls. A triply nested high-resolution model with 1.67-km resolution in the innermost domain, initialized with operational model forecasts in real time during RAINEX, is used in this study. Analyses of wind, vorticity, PV, and vortex Rossby wave (VRW) activity in the inner-core region were conducted using both RAINEX airborne observations and model output. The results show that a higher PV generation rate and accumulation in the rainband region in Rita leads to a secondary PV/vorticity maximum, which eventually became the secondary eyewall. A strong moat area developed between the primary eyewall and the concentric ring of convection in Rita, prohibiting VRW activity. In contrast, VRWs propagated radially outward from the inner core to the rainband region in Katrina. The VRWs were not a contributing factor in the initial formation of the secondary eyewall in Rita since the moat region with near-zero PV gradient did not allow for radial propagation of VRWs. The large accumulation of convectively generated PV in the rainband region was the key factor in the formation of the secondary eyewall in Rita.
The Position of the Midlatitude Storm Track and Eddy-Driven Westerlies in Aquaplanet AGCMs
Authors: Lu Jian , Chen Gang , Frierson Dargan M. W.
Published: September 2010

The sensitivity of the midlatitude storm track and eddy-driven wind to the sea surface temperature (SST) boundary forcing is studied over a wide range of perturbations using both simple and comprehensive general circulation models over aquaplanet lower boundary conditions. Under the single-jet circulation regime similar to the conditions of the present climate in the Northern Hemisphere winter or the Southern Hemisphere summer, the eddy-driven jet shifts monotonically poleward with both the global mean and the equator-to-pole gradient of the SST. The eddy-driven jet can have a reverse relationship to the gradient if it is well separated from the subtropical jet and Hadley cell boundary in a double-jet circulation regime.

A simple scaling is put forward to interpret the simulated sensitivity of the storm-track/eddy-driven westerly wind position within the single-jet regime in both models. The rationale for the scaling is based on the notion that the wave activity flux can propagate horizontally away from the source region, resulting in a broader distribution of eddy potential vorticity (PV) flux in the upper troposphere than that of the flux in the opposite direction in the lower troposphere. As a consequence, the position of the maximum of the eddy-driven westerlies tends to be controlled by the profile of the relatively sharp-peaked low-level PV flux, which is dominated by the eddy heat flux component of the Eliassen–Palm (EP) flux. Thus, the position of the eddy-driven surface westerlies may be inferred from the vertical EP flux coming out of the lower troposphere. The vertical EP flux can be parameterized by a measure of baroclinicity, whose latitudinal variations show a linear relationship with the meridional displacement of the eddy-driven westerlies and the storm track. This relationship still holds well within the single-jet regime, even when only the variation of static stability is taken into consideration in estimating the baroclinicity (the temperature gradient component of which is fixed). To the extent that the static stability is deterministically constrained by and hence can be predicted from the given SST conditions through a moist scaling for the midlatitude stratification, one may, given SST perturbations, predict which way the storm track and eddy-driven wind should shift with respect to a chosen reference climate state. The resultant anomaly-wise scaling turns out to be valid for both the idealized and comprehensive models, regardless of the details in the model physics.

By corollary, it can be argued that the poleward shift of storm track found in the global warming simulations by fully coupled climate models may be attributed, at least partially, to the increase in the subtropical and midlatitude static stability with global warming.
Response of Tropical Precipitation to Global Warming
Authors: Romps David M.
Published: September 2010

Using high-resolution cloud-resolving simulations with different CO2 concentrations, local precipitation fluxes are found to obey Clausius–Clapeyron (CC) scaling. Previous studies of the effect of CO2 concentration on precipitation extremes have used general circulation models, which are poor platforms for studying tropical convection because convection is parameterized. In idealized cloud-resolving simulations, it is possible to identify not only the changes in local precipitation fluxes, but also the factors responsible for those changes.

There are many properties of convection that can change as the atmosphere warms, each of which could produce deviations from CC scaling. These properties include the effective water-vapor gradient, cloud pressure depth, and cloud velocity. A simple theory is developed that predicts the changes in these properties consistent with CC scaling. Convection in the cloud-resolving simulations is found to change as predicted by this theory, leading to an ∼20% increase in local precipitation fluxes when the CO2 concentration is doubled. Overall, an increase in CO2 leads to more vigorous convection, composed of clouds that are wider, taller, and faster.