Andrew S. Wechsler

Drexel University, Filadelfia, Pennsylvania, United States

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Publications (322)1542.88 Total impact


  • No preview · Article · Oct 2015 · Journal of the American College of Cardiology
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    ABSTRACT: Several randomized controlled trials and observational studies have compared outcomes for coronary artery bypass graft (CABG) surgery and drug-eluting stents (DES), but these studies have not thoroughly investigated the relative difference in outcomes by sex. We aimed to compare 3-year outcomes (mortality, mortality/myocardial infarction/stroke, and repeat revascularization) for CABG surgery and percutaneous coronary interventions with DES by sex. A total of 4,532 women (2,266 pairs of CABG and DES patients) and 11,768 men (5,884 pairs) were propensity matched separately using multiple patient risk factors and were compared with respect to 3-year outcomes. Both women and men receiving DES had significantly higher mortality rates (adjusted hazard ratio, 1.28; 95% confidence interval, 1.06 to 1.54 and adjusted hazard ratio, 1.22; 95% confidence interval, 1.06 to 1.41, respectively) and myocardial infarction/mortality/stroke rates (adjusted hazard ratio, 1.40; 95% confidence interval, 1.19 to 1.64 and adjusted hazard ratio, 1.36; 95% confidence interval, 1.20 to 1.54, respectively) with DES. The advantage for CABG surgery was also present for several preselected patient subgroups. Men had consistently lower adverse outcome rates than women for both procedures. For example, the mortality rates for CABG and DES for men were 8.0% and 9.1%, compared with respective rates of 11.8% and 13.7% for women. For women, the advantage of CABG surgery over DES is very similar to what was found for men, and this advantage persisted for patients with and without high-risk characteristics. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · The Annals of thoracic surgery
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    ABSTRACT: Several studies have compared short-term and medium-term mortality rates for patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR), but no studies have compared short-term readmission rates for the 2 procedures. New York's Cardiac Surgery Reporting System was used to propensity match 617 TAVI and 1981 SAVR patients using numerous patient risk factors contained in the registry. The 389 propensity-matched pairs were then used to analyze differences in readmission rates between the 2 groups. TAVI and SAVR readmission rates were also compared for patients with a history of congestive heart failure and for patients aged ≥80. Also, reasons for readmission for TAVI and SAVR patients were examined and compared. Readmission rates were not statistically different for all propensity-matched TAVI and SAVR patients (respective rates, 18.8% and 19.3%; P=0.86). After further adjustment using a logistic regression model, there was still no significant difference (adjusted odds ratio, 0.97; 95% confidence interval [0.68-1.39]). For patients aged ≥80, the 30-day readmission rates were 19.9% and 22.0% (P=0.59), and when further adjusted using the logistic regression model, adjusted odds ratio=0.89 (0.55-1.45). For patients with a history of congestive heart failure, the respective rates were 22.8% and 20.4% (P=0.56), and with further adjustment, adjusted odds ratio became 1.15 (0.72-1.82). There are no statistically significant differences between TAVI and SAVR patients in short-term readmission rates. © 2015 American Heart Association, Inc.
    No preview · Article · Aug 2015 · Circulation Cardiovascular Interventions
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    ABSTRACT: To test the feasibility of a thoracoscopically assisted, off-pump, transcatheter ventricular reconstruction (TCVR) approach in an ovine model of left ventricular (LV) anteroapical aneurysm. Myocardial infarction (MI) was induced by coil occlusion of the middle left anterior descending artery and diagonals. Two months after MI creation, TCVR was performed via a minimal thoracotomy in eight sheep. Under endoscopic and fluoroscopic guidance, trans-interventricular septal puncture was performed from the LV epicardial scar. A guidewire was externalised via a snare placed in the right ventricle from the external jugular vein. An internal anchor was inserted over the wire and positioned on the right ventricular septum and an external anchor was deployed on the LV anterior epicardium. Serial pairs of anchors were placed and plicated together to exclude the scar completely. Immediately after TCVR, echocardiography showed LV end-systolic volume decreased from pre-procedure 58.8±16.6 ml to 25.1±7.6 ml (p<0.01) and the ejection fraction increased from 32.0±7.3% to 52.0±7.5% (p<0.01). LV twist significantly improved (3.83±2.21 vs. pre-procedure -0.41±0.94, p=0.01) and the global peak-systolic longitudinal strain increased from -5.64% to -10.77% (p<0.05). TCVR using minimally invasive access techniques on the off-pump beating heart is feasible and resulted in significant improvement in LV performance.
    No preview · Article · Apr 2015 · EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

  • No preview · Article · Sep 2014 · Journal of the American College of Cardiology
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    ABSTRACT: Objectives: The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes. Methods: The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates. Results: The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes. Conclusions: Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes.
    No preview · Article · Aug 2014 · Journal of Thoracic and Cardiovascular Surgery
  • Andrew S Wechsler

    No preview · Article · Dec 2013 · The Annals of thoracic surgery
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    ABSTRACT: The loss of normal apical rotation is associated with left ventricular (LV) remodeling and systolic dysfunction in patients with congestive heart failure after myocardial infarction. The objective of the present study was to evaluate the effect of epicardial ventricular reconstruction, an off-pump, less-invasive surgical reshaping technique, on myocardial strain, LV twist, and the potential alteration of myocardial fiber orientation in an ovine model of LV anteroapical aneurysm. LV anteroapical myocardial infarction was induced by coil embolization of the left anterior descending artery. Eight weeks after occlusion, epicardial ventricular reconstruction was performed using left thoracotomy under fluoroscopic guidance in 8 sheep to completely exclude the scar. The peak systolic longitudinal/circumferential strains and LV twist were evaluated using speckle tracking echocardiography before (baseline), after device implantation, and at 6 weeks of follow-up. Epicardial ventricular reconstruction was completed in all sheep without any complications. Immediately after device implantation, LV twist significantly increased (4.18 ± 1.40 vs baseline 1.97 ± 1.92; P = .02). The ejection fraction had increased 17% and LV end-systolic volume had decreased 40%. The global longitudinal strain increased from -5.3% to -9.1% (P < .05). Circumferential strain increased in both middle and apical LV segments, with the greatest improvement in the inferior lateral wall (from -11.4% to -20.6%, P < .001). These effects were maintained ≥6 weeks after device implantation without redilation. Less invasive than alternative therapies, epicardial ventricular reconstruction on the off-pump beating heart can restore LV twist and systolic strain and reverse LV remodeling in an ovine anteroapical aneurysm model.
    No preview · Article · Sep 2013 · The Journal of thoracic and cardiovascular surgery

  • No preview · Article · Sep 2013 · Interactive Cardiovascular and Thoracic Surgery
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    ABSTRACT: Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P = 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P = 0.02). The circumferential strain in the anterior septum (-7.67 ± 5.12% vs baseline -0.96 ± 2.22%, P = 0.03) and anterior wall (-9.01 ± 3.51% vs baseline -4.15 ± 1.36%, P = 0.01) were significantly improved. The longitudinal strain in apex was reversed (-3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P = 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm.
    Preview · Article · Aug 2013 · Interactive Cardiovascular and Thoracic Surgery

  • No preview · Article · Aug 2013 · Journal of Cardiac Failure
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    ABSTRACT: Objectives: We previously presented early results employing a technique designed for beating heart, ventricular volume reduction (surgical ventricular restoration, SVR) without ventriculotomy for patients with antero-septal scar and dilated ischaemic cardiomyopathy. Significant volume reduction and clinical improvement were achieved. We now report durability in the first 11 patients available for assessment at 6 and 12 months after operation. Methods: After the Ethics Committee approval, 31 symptomatic patients with left ventricular (LV) dilatation and antero-septal scars underwent operation. The scarred lateral LV wall was apposed to the septal scar with serial paired anchors placed through epicardial transmural catheters, excluding non-viable portions of the chamber. Patients were followed at 1, 3, 6 and 12 months postoperatively with echocardiograms. Data are presented for the first 11 patients for whom core lab echocardiographic data were available at 12 months of follow-up. Results: LV end-systolic index (LVESVI), percent decreases from baseline at 6 and 12 months were 36.2 ± 18.3 (P < 0.001) and 39.6 ± 14.8 (P < 0.001). LV end-diastolic volume index (LVEDVI) percent decreases from baseline at 6 and 12 months were 28.6 ± 18.8 (P < 0.001) at 6 months and 32.2 ± 14.9 (P < 0.005) at 12 months. All comparisons were by one-tailed t-tests using paired data. Conclusions: These results demonstrate the persistence of volume reduction employing a technique designed to be used on beating hearts without ventriculotomy or cardiopulmonary bypass. The extent of volume reduction was consistent with results of conventional SVR in experienced centres. These early data validate the further development of technical iterations leading to a clinical study employing a closed chest endovascular platform.
    Full-text · Article · Jun 2013 · European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery
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    ABSTRACT: Objective: Simultaneous inhibition of the cardiac equilibrative-p-nitrobenzylthioinosine (NBMPR)-sensitive (es) type of the equilibrative nucleoside transport 1 (ENT1) nucleoside transporter, with NBMPR, and adenosine deaminase, with erythro-9-[2-hydroxy-3-nonyl]adenine (EHNA), prevents release of myocardial purines and attenuates myocardial stunning and fibrillation in canine models of warm ischemia and reperfusion. It is not known whether prolonged administration of hypothermic cardioplegia influences purine release and EHNA/NBMPR-mediated cardioprotection in acutely ischemic hearts. Methods: Anesthetized dogs (n = 46), which underwent normothermic aortic crossclamping for 20 minutes on-pump, were divided to determine (1) purine release with induction of intermittent antegrade or continuous retrograde hypothermic cardioplegia and reperfusion, (2) the effects of postischemic treatment with 100 μM EHNA and 25 μM NBMPR on purine release and global functional recovery, and (3) whether a hot shot and reperfusion with EHNA/NBMPR inhibits purine release and attenuates ventricular dysfunction of ischemic hearts. Myocardial biopsies and coronary sinus effluents were obtained and analyzed using high-performance liquid chromatography. Results: Warm ischemia depleted myocardial adenosine triphosphate and elevated purines (ie, inosine > adenosine) as markers of ischemia. Induction of intermittent antegrade or continuous retrograde hypothermic (4°C) cardioplegia releases purines until the heart becomes cold (<20°C). During reperfusion, the levels of hypoxanthine and xanthine (free radical substrates) were >90% of purines in coronary sinus effluent. Reperfusion with EHNA/NBMPR abolished ventricular dysfunction in acutely ischemic hearts with and without a hot shot and hypothermic cardioplegic arrest. Conclusions: Induction of hypothermic cardioplegia releases purines from ischemic hearts until they become cold, whereas reperfusion induces massive purine release and myocardial stunning. Inhibition of cardiac es-ENT1 nucleoside transporter abolishes postischemic reperfusion injury in warm and cold cardiac surgery.
    No preview · Article · Feb 2013 · The Journal of thoracic and cardiovascular surgery
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    ABSTRACT: Background: Few studies have examined differences in long-term mortality between coronary artery bypass graft surgery and stenting with drug-eluting stents (DES) for multivessel disease without left main coronary artery stenosis. This study compares the risks of long-term mortality between these 2 procedures during a follow-up of up to 5 years. Methods: Patients who underwent isolated bypass surgery (n=13,212) and stenting with DES (n=20,161) between October 2003 and December 2005 in New York State were followed for their vital status through 2008. To control for treatment selection bias, bypass and stenting patients were matched on age, number of diseased coronary vessels, presence of proximal or nonproximal left anterior descending (LAD) artery disease, and propensity of undergoing bypass surgery. Five-year survival rates for the 2 procedures were compared and hazard ratios for death of bypass surgery compared with stenting were obtained. Results: The respective 5-year survival rates in the 8,121 pairs of matched bypass and stenting patients were 80.4% and 73.6% (p<0.001), and the risk of death after bypass surgery was 29% lower than for stenting (hazard ratio = 0.71, 95% confidence interval: 0.67 to 0.77, p<0.001). Significantly lower risks of death for bypass surgery were observed in patients with LAD artery disease but not in patients without LAD artery disease. Significantly lower risks of death for bypass surgery were also found in all patient subgroups defined by the presence of selected baseline risk factors. Conclusions: Bypass surgery is associated with lower risk of death than stenting with DES for multivessel disease without left main stenosis.
    No preview · Article · Feb 2013 · The Annals of thoracic surgery
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    ABSTRACT: Background: Risk scores are simplified linear formulas for predicting mortality or other adverse outcomes at the bedside without personal digital assistants or calculators. Although risk scores are available for valve surgery, they do not predict short-term mortality (within 30 days of surgery) after hospital discharge. Methods: New York's Cardiac Surgery Reporting System 2007 to 2009 data were matched to vital statistics data to identify valve surgery with and without concomitant coronary artery bypass graft (CABG) surgery deaths occurring in the index admission or within 30 days after the procedure in any location. Risk scores were created to easily predict these outcomes by modifying more complicated logistic regression models. Results: There were 13,455 isolated valve surgery patients and 8,373 valve/CABG surgery patients in the study. The respective in-hospital/30-day mortality rates were 4.03% and 6.60%. There are 11 risk factors comprising the isolated valve surgery score, with risk factor scores ranging from 1 to 8, and the highest observed total score is 28. There are 14 risk factors comprising the valve/CABG surgery score, with risk factor scores ranging from 1 to 6, and the highest observed total score is 19. The scores accurately predicted mortality in 2007 to 2009 as well as in 2004 to 2006, and were strongly correlated with complications and length of stay. Conclusions: The risk scores that were developed provide quick and accurate estimates of patients' chances of short-term mortality after cardiac valve surgery.
    No preview · Article · Jan 2013 · The Annals of thoracic surgery
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    ABSTRACT: Background: Simplified risk scores for coronary artery bypass graft surgery are frequently in lieu of more complicated statistical models and are valuable for informed consent and choice of intervention. Previous risk scores have been based on in-hospital mortality, but a substantial number of patients die within 30 days of the procedure. These deaths should also be accounted for, so we have developed a risk score based on in-hospital and 30-day mortality. Methods: New York's Cardiac Surgery Reporting System was used to develop an in-hospital and 30-day logistic regression model for patients undergoing coronary artery bypass graft surgery in 2009, and this model was converted into a simple linear risk score that provides estimated in-hospital and 30-day mortality rates for different values of the score. The accuracy of the risk score in predicting mortality was tested. This score was also validated by applying it to 2008 New York coronary artery bypass graft data. Subsequent analyses evaluated the ability of the risk score to predict complications and length of stay. Results: The overall in-hospital and 30-day mortality rate for the 10,148 patients in the study was 1.79%. There are seven risk factors comprising the score, with risk factor scores ranging from 1 to 5, and the highest possible total score is 23. The score accurately predicted mortality in 2009 as well as in 2008, and was strongly correlated with complications and length of stay. Conclusions: The risk score is a simple way of estimating short-term mortality that accurately predicts mortality in the year the model was developed as well as in the previous year. Perioperative complications and length of stay are also well predicted by the risk score.
    No preview · Article · Nov 2012 · The Annals of thoracic surgery
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    ABSTRACT: Ischemia/reperfusion injury remains an important cause of morbidity and mortality after coronary artery bypass graft (CABG) surgery. In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery. To assess the efficacy and safety of acadesine administered in the perioperative period in reducing all-cause mortality, nonfatal stroke, and severe left ventricular dysfunction (SLVD) through 28 days. The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate- to high-risk patients (median age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. Enrollment occurred from May 6, 2009, to July 30, 2010. Eligible participants were randomized 1:1 to receive acadesine (0.1 mg/kg per minute for 7 hours) or placebo (both also added to cardioplegic solutions) beginning just before anesthesia induction. Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. Because results of a prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, the trial was stopped after 3080 of the originally projected 7500 study participants were randomized. The primary outcome occurred in 75 of 1493 participants (5.0%) in the placebo group and 76 of 1493 (5.1%) in the acadesine group (odds ratio, 1.01 [95% CI, 0.73-1.41]). There were no differences in key secondary end points measured. In this population of intermediate- to high-risk patients undergoing CABG surgery, acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or SLVD. clinicaltrials.gov Identifier: NCT00872001.
    Full-text · Article · Jul 2012 · JAMA The Journal of the American Medical Association
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    ABSTRACT: No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. The New York State Cardiac Surgery Reporting System was used to identify 8597 patients who underwent isolated coronary artery bypass graft surgery in July through December 2000. The National Death Index was used to ascertain patients' vital statuses through December 31, 2007. A Cox proportional hazards model was fit to predict death after CABG surgery using preprocedural risk factors. Then, points were assigned to significant predictors of death on the basis of the values of their regression coefficients. For each possible point total, the predicted risks of death at years 1, 3, 5, and 7 were calculated. It was found that the 7-year mortality rate was 24.2 in the study population. Significant predictors of death included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular disease, peripheral arterial disease, congestive heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes mellitus, renal failure, and history of open heart surgery. The points assigned to these risk factors ranged from 1 to 7; possible point totals for each patient ranged from 0 to 28. The observed and predicted risks of death at years 1, 3, 5, and 7 across patient groups stratified by point totals were highly correlated. The simplified risk score accurately predicted the risk of mortality after coronary artery bypass graft surgery and can be used for informed consent and as an aid in determining treatment choice.
    Full-text · Article · Apr 2012 · Circulation
  • Anwar Saad Abd-Elfattah · Hamdy Aly · Scott Hanan · Andrew S Wechsler
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    ABSTRACT: To determine the role of the p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 (es-ENT1) in postmyocardial infarction reperfusion injury-mediated ventricular fibrillation and regional dysfunction. We used erythro-9 (2-hydroxy-3-nonyl)-adenine and p-nitrobenzylthioinosine to inhibit both adenosine deamination and transport in a canine model of off pump acute myocardial infarction. Anesthetized adult dogs (n = 37), instrumented to monitor the percentage of systolic segmental shortening and wall thickening using sonomicrometry, underwent 90 minutes of left anterior descending coronary artery occlusion and 120 minutes of reperfusion. Myocardial coronary blood flow, adenosine triphosphate pool, infarct size, and the incident of ventricular fibrillation and cardioversion were also measured. The dogs received an intravenous infusion of the vehicle (control) or 100 μM of erythro-9 (2-hydroxy-3-nonyl)-adenine and 25 μM p-nitrobenzylthioinosine before ischemia (preconditioning group) or just before reperfusion (postconditioning group). In the control group, adenosine triphosphate depletion was associated with the accumulation of more inosine than adenosine during ischemia and washed out during reperfusion. Myocardial adenosine and inosine were the major nucleosides in the pre- and postconditioning groups during ischemia and remained detectable during reperfusion. In both groups, recovery of systolic segmental shortening and wall thickening and a reduction in the incidence of ventricular fibrillation (P < .05 vs the control group) coincided with retention of myocardial nucleosides. The infarct size in the 3 groups was not significantly different, independent of myocardial blood flow during ischemia. Preconditioning or postconditioning with erythro-9 (2-hydroxy-3-nonyl)-adenine/p-nitrobenzylthioinosine significantly reduced the incidence of ventricular fibrillation and cardioversion and attenuated regional contractile dysfunction mediated by postmyocardial infarction reperfusion injury. It is concluded that p-nitrobenzylthioinosine-sensitive equilibrative nucleoside transporter 1 played a major role in these events.
    No preview · Article · Feb 2012 · The Journal of thoracic and cardiovascular surgery
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    ABSTRACT: The inhibition of adenosine deaminase with erythro-9 (2-hydroxy-3-nonyl)-adenine (EHNA) and the es-ENT1 transporter with p-nitro-benzylthioinosine (NBMPR), entraps myocardial intracellular adenosine during on-pump warm aortic crossclamping, leading to a complete recovery of cardiac function and adenosine triphosphate (ATP) during reperfusion. The differential role of entrapped intracellular and circulating adenosine in EHNA/NBMPR-mediated protection is unknown. Selective (8-cyclopentyl-1,3-dipropyl-xanthine) or nonselective [8-(p-sulfophenyl)theophyline] A1 receptor antagonists were used to block adenosine A1-receptor contribution in EHNA/NBMPR-mediated cardiac recovery. Anesthetized dogs (n = 45), instrumented to measure heart performance using sonomicrometry, were subjected to 30 minutes of warm aortic crossclamping and 60 minutes of reperfusion. Three boluses of the vehicle (series A) or 100 μM EHNA and 25 μM NBMPR (series B) were infused into the pump at baseline, before ischemia and before reperfusion. 8-Cyclopentyl-1,3-dipropyl-xanthine (10 μM) or 8-(p-sulfophenyl)theophyline (100 μM) was intra-aortically infused immediately after aortic crossclamping distal to the clamp in series A and series B. The ATP pool and nicotinamide adenine dinucleotide was determined using high-performance liquid chromatography. Ischemia depleted ATP in all groups by 50%. The adenosine/inosine ratios were more than 10-fold greater in series B than in series A (P < .001). ATP and function recovered in the EHNA/NBMPR-treated group (P < .05 vs control group). 8-Cyclopentyl-1,3-dipropyl-xanthine and 8-(p-sulfophenyl)theophyline partially reduced cardiac function in series A and B to the same degree but did not abolish the EHNA/NBMPR-mediated protection in series B. In addition to the cardioprotection mediated by activation of the adenosine receptors by extracellular adenosine, EHNA/NBMPR entrapment of intracellular adenosine provided a significant component of myocardial protection despite adenosine A1 receptor blockade.
    No preview · Article · Feb 2012 · The Journal of thoracic and cardiovascular surgery

Publication Stats

5k Citations
1,542.88 Total Impact Points

Institutions

  • 2002-2015
    • Drexel University
      • • Department of Surgery
      • • Department of Cardiothoracic Surgery
      Filadelfia, Pennsylvania, United States
  • 2003-2013
    • Drexel University College of Medicine
      • • Department of Cardiothoracic Surgery
      • • Department of Anesthesiology
      Filadelfia, Pennsylvania, United States
  • 2002-2004
    • Philadelphia University
      Filadelfia, Pennsylvania, United States
  • 1999-2003
    • University of Louisville
      • Department of Surgery
      Louisville, Kentucky, United States
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 1998-1999
    • Allegheny University
      Filadelfia, Pennsylvania, United States
  • 1992-1999
    • Virginia Commonwealth University
      • • Division of Cardiothoracic Surgery
      • • Department of Surgery
      Richmond, Virginia, United States
  • 1974-1993
    • Duke University Medical Center
      • • Department of Surgery
      • • Department of Medicine
      Durham, North Carolina, United States
  • 1990
    • Richmond VA Medical Center
      Ричмонд, Virginia, United States
  • 1980-1990
    • Duke University
      • Department of Surgery
      Durham, North Carolina, United States
  • 1989
    • SickKids
      Toronto, Ontario, Canada