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1.
Ann Thorac Surg ; 112(2): e123-e126, 2021 08.
Article in English | MEDLINE | ID: mdl-33444578

ABSTRACT

The Revivent TC System (BioVentrix Inc, San Ramon, CA) enables a less invasive approach for left ventricular reshaping and scar exclusion in selected patients with ischemic cardiomyopathy. Although the system is designed to improve quality of life and to promote reverse remodeling, patients can still progress to end-stage heart failure requiring advanced therapies. This report describes a case of left ventricular assist device surgery in a patient 16 months after Revivent System implantation. The planning process and surgical technique proved to be complex. This case report can help provide guidance to advanced heart failure teams who encounter patients with the Revivent System who require left ventricular assist device support.


Subject(s)
Cardiac Surgical Procedures/methods , Heart Failure/surgery , Heart Ventricles/surgery , Heart-Assist Devices , Ventricular Function, Left/physiology , Ventricular Remodeling/physiology , Aged , Echocardiography , Heart Failure/diagnosis , Heart Failure/physiopathology , Heart Ventricles/physiopathology , Humans , Male , Quality of Life , Tomography, X-Ray Computed
2.
Ann Thorac Surg ; 100(6): 2227-36, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26294345

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Drug-Eluting Stents , Postoperative Complications/epidemiology , Registries , Aged , Aged, 80 and over , Confidence Intervals , Coronary Artery Disease/mortality , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Incidence , Male , Middle Aged , New York/epidemiology , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex Distribution , Sex Factors , Survival Rate/trends , Time Factors , Treatment Outcome
3.
J Thorac Cardiovasc Surg ; 148(6): 2720-6.e1-2, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25218533

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.


Subject(s)
Cardiopulmonary Bypass , Coronary Artery Bypass , Age Factors , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/therapeutic use , Aspirin/therapeutic use , Cardiopulmonary Bypass/adverse effects , Cardiopulmonary Bypass/mortality , Cardiovascular Agents/therapeutic use , Chi-Square Distribution , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Double-Blind Method , Heart Failure/complications , Heart Failure/physiopathology , Humans , Logistic Models , Multivariate Analysis , Odds Ratio , Patient Selection , Peripheral Arterial Disease/complications , Protective Factors , Ribonucleosides/therapeutic use , Risk Assessment , Risk Factors , Stroke/etiology , Stroke Volume , Time Factors , Treatment Outcome , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy , Ventricular Function, Left
4.
J Thorac Cardiovasc Surg ; 148(1): 225-31, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24084284

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Cardiac Surgical Procedures , Heart Aneurysm/surgery , Heart Ventricles/surgery , Pericardium/surgery , Plastic Surgery Procedures , Ventricular Function, Left , Animals , Biomechanical Phenomena , Disease Models, Animal , Heart Aneurysm/diagnosis , Heart Aneurysm/physiopathology , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Pericardium/diagnostic imaging , Pericardium/physiopathology , Recovery of Function , Sheep , Stroke Volume , Systole , Time Factors , Torsion, Mechanical , Ultrasonography , Ventricular Remodeling
6.
Interact Cardiovasc Thorac Surg ; 17(6): 915-22, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23985410

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Anterior Wall Myocardial Infarction/surgery , Cardiac Catheterization/instrumentation , Cardiac Catheters , Cardiac Surgical Procedures/instrumentation , Heart Aneurysm/surgery , Heart Failure/surgery , Heart Ventricles/surgery , Animals , Anterior Wall Myocardial Infarction/complications , Anterior Wall Myocardial Infarction/diagnosis , Anterior Wall Myocardial Infarction/physiopathology , Disease Models, Animal , Equipment Design , Feasibility Studies , Heart Aneurysm/complications , Heart Aneurysm/diagnosis , Heart Aneurysm/physiopathology , Heart Failure/diagnosis , Heart Failure/etiology , Heart Failure/physiopathology , Heart Ventricles/pathology , Heart Ventricles/physiopathology , Recovery of Function , Sheep , Thoracotomy , Time Factors , Ventricular Function, Left , Ventricular Remodeling
7.
Eur J Cardiothorac Surg ; 44(3): e189-92; discussion e192, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23739293

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.


Subject(s)
Cardiac Surgical Procedures/instrumentation , Cardiac Surgical Procedures/methods , Heart Ventricles/surgery , Animals , Cardiac Output/physiology , Echocardiography , Heart Failure , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Myocardial Ischemia , Sheep , Surgical Fixation Devices
8.
J Thorac Cardiovasc Surg ; 146(4): 961-970.e3, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23422047

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.


Subject(s)
Adenine/analogs & derivatives , Adenosine Triphosphate/metabolism , Equilibrative Nucleoside Transporter 1/antagonists & inhibitors , Heart Arrest, Induced , Myocardial Ischemia/therapy , Myocardial Reperfusion Injury/prevention & control , Myocardial Stunning/prevention & control , Myocardium/metabolism , Thioinosine/analogs & derivatives , Adenine/administration & dosage , Animals , Cold Ischemia , Disease Models, Animal , Dogs , Equilibrative Nucleoside Transporter 1/metabolism , Female , Heart Arrest, Induced/adverse effects , Hypothermia, Induced/adverse effects , Male , Myocardial Ischemia/metabolism , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/etiology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardial Stunning/etiology , Myocardial Stunning/metabolism , Myocardial Stunning/physiopathology , Recovery of Function , Thioinosine/administration & dosage , Time Factors , Ventricular Function, Left/drug effects , Warm Ischemia
9.
Ann Thorac Surg ; 95(4): 1297-305, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23391171

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.


Subject(s)
Coronary Artery Bypass/mortality , Coronary Disease/surgery , Drug-Eluting Stents , Risk Assessment/methods , Aged , Aged, 80 and over , Coronary Artery Bypass/methods , Coronary Disease/mortality , Female , Follow-Up Studies , Humans , Male , Middle Aged , New York/epidemiology , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , Time Factors
10.
JAMA ; 308(2): 157-64, 2012 Jul 11.
Article in English | MEDLINE | ID: mdl-22782417

ABSTRACT

CONTEXT: 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. OBJECTIVE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOME MEASURE: Composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD during and following CABG surgery through postoperative day 28. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00872001.


Subject(s)
Adenosine/metabolism , Aminoimidazole Carboxamide/analogs & derivatives , Coronary Artery Bypass/adverse effects , Coronary Artery Bypass/mortality , Reperfusion Injury/prevention & control , Ribonucleosides/therapeutic use , Aged , Aminoimidazole Carboxamide/adverse effects , Aminoimidazole Carboxamide/therapeutic use , Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Double-Blind Method , Female , Humans , Male , Middle Aged , Perioperative Period , Ribonucleosides/adverse effects , Stroke , Ventricular Dysfunction, Left
11.
Circulation ; 125(20): 2423-30, 2012 May 22.
Article in English | MEDLINE | ID: mdl-22547673

ABSTRACT

BACKGROUND: No simplified bedside risk scores have been created to predict long-term mortality after coronary artery bypass graft surgery. METHODS AND RESULTS: 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. CONCLUSION: 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.


Subject(s)
Coronary Artery Bypass/mortality , Coronary Disease/mortality , Coronary Disease/surgery , Aged , Aged, 80 and over , Databases, Factual/statistics & numerical data , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Risk Assessment/methods , Risk Factors
12.
J Thorac Cardiovasc Surg ; 144(1): 243-9, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22325325

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Adenine/analogs & derivatives , Adenosine Deaminase Inhibitors/pharmacology , Ischemic Preconditioning/methods , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/prevention & control , Myocardial Stunning/prevention & control , Nucleoside Transport Proteins/pharmacology , Receptor, Adenosine A1/metabolism , Thioinosine/analogs & derivatives , Adenine/pharmacology , Animals , Chromatography, High Pressure Liquid , Constriction , Disease Models, Animal , Dogs , Myocardial Reperfusion Injury/physiopathology , Myocardial Stunning/physiopathology , Theophylline/analogs & derivatives , Theophylline/pharmacology , Thioinosine/pharmacology , Xanthines/pharmacology
13.
J Thorac Cardiovasc Surg ; 144(1): 250-5, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22329983

ABSTRACT

OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Adenosine Deaminase Inhibitors/pharmacology , Equilibrative Nucleoside Transporter 1/pharmacology , Ischemic Preconditioning/methods , Myocardial Reperfusion Injury/prevention & control , Myocardial Stunning/prevention & control , Thioinosine/analogs & derivatives , Ventricular Fibrillation/prevention & control , Adenosine Triphosphate/metabolism , Analysis of Variance , Animals , Coronary Circulation , Dogs , Least-Squares Analysis , Myocardial Contraction/drug effects , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/metabolism , Myocardial Reperfusion Injury/physiopathology , Myocardial Stunning/metabolism , Myocardial Stunning/physiopathology , Thioinosine/pharmacology , Ventricular Fibrillation/physiopathology
14.
Circ Cardiovasc Qual Outcomes ; 5(1): 76-84, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22235063

ABSTRACT

BACKGROUND: The survival difference between off-pump and on-pump coronary artery bypass graft surgery for follow-up longer than 5 years is not well-understood. The objective of this study is to examine the difference in 7-year mortality after these 2 procedures. METHODS AND RESULTS: The state of New York's Cardiac Surgery Reporting System was used to identify the 2640 off-pump and 5940 on-pump patients discharged from July through December 2000. The National Death Index was used to ascertain patients' vital statuses through 2007. A logistic regression model was fit to predict the probability of receiving an off-pump procedure using baseline patient characteristics. Off-pump and on-pump patients were matched with a 1:1 ratio based on the probability of receiving an off-pump procedure. Kaplan-Meier survival curves for the 2 procedures were compared using the propensity-matched data, and the hazard ratio for death for off-pump in comparison with on-pump procedures was obtained. In subgroup analyses, the significance of interactions between type of surgery and baseline risk factors was tested. In this study, 2631 pairs of off-pump and on-pump patients were propensity matched. The 7-year Kaplan-Meier survival rates were 71.2% and 73.4% (P=0.07) for off-pump and on-pump surgery, respectively. The hazard ratio for death (off-pump versus on-pump) was 1.10 (95% confidence interval: 0.99 to 1.21, P=0.07). No statistical significance was detected for the interaction terms between the type of surgery and a number of different baseline risk factors. CONCLUSIONS: The difference in long-term mortality between on-pump and off-pump coronary artery bypass graft surgery is not statistically significant.


Subject(s)
Coronary Artery Bypass , Coronary Artery Disease/therapy , Intra-Aortic Balloon Pumping , Aged , Aged, 80 and over , Coronary Artery Bypass/mortality , Coronary Artery Disease/epidemiology , Female , Follow-Up Studies , Humans , Intra-Aortic Balloon Pumping/mortality , Male , Middle Aged , New York , Prevalence , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome
15.
J Biomech ; 45(5): 824-31, 2012 Mar 15.
Article in English | MEDLINE | ID: mdl-22196970

ABSTRACT

The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range 10 kPa-30 kPa, near those of the healthy tissue. On stiffer substrates (>60 kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (<1 kPa) PAA gels myocytes exhibit disorganized actin networks and sarcomeres. However, when the polyacrylamide matrix is replaced by hyaluronic acid (HA) as the gel network to which integrin ligands are attached, robust development of functional neonatal rat ventricular myocytes occurs on gels with elastic moduli of 200 Pa, a stiffness far below that of the neonatal heart and on which myocytes would be amorphous and dysfunctional when cultured on polyacrylamide-based gels. The HA matrix by itself is not adhesive for myocytes, and the myocyte phenotype depends on the type of integrin ligand that is incorporated within the HA gel, with fibronectin, gelatin, or fibrinogen being more effective than collagen I. These results show that HA alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter the response of cells that bind the ECM through integrins. The integration of HA with integrin-specific ECM signaling proteins provides a rationale for engineering a new class of soft hybrid hydrogels that can be used in therapeutic strategies to reverse the remodeling of the injured myocardium.


Subject(s)
Biocompatible Materials/metabolism , Hyaluronic Acid/metabolism , Integrins/metabolism , Myocytes, Cardiac/physiology , Receptor Cross-Talk , Acrylic Resins/metabolism , Actins/metabolism , Actins/physiology , Animals , Bioengineering/methods , Biomechanical Phenomena/physiology , Cell Culture Techniques/methods , Collagen Type I/metabolism , Elastic Modulus/physiology , Extracellular Matrix/metabolism , Extracellular Matrix/physiology , Extracellular Matrix Proteins/metabolism , Fibrinogen/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Fibroblasts/physiology , Fibronectins/metabolism , Gelatin/metabolism , Hydrogels/metabolism , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Rats , Rats, Sprague-Dawley , Sarcomeres/metabolism , Sarcomeres/physiology , Tissue Engineering/methods
16.
Ann Thorac Surg ; 92(6): 2132-8, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22014747

ABSTRACT

BACKGROUND: There is little information on relative survival with follow-up longer than 5 years in patients undergoing coronary artery bypass grafting (CABG) and patients undergoing percutaneous coronary intervention (PCI) with stenting. This study tested the hypothesis that CABG is associated with a lower risk of long-term (8-year) mortality than is stenting with bare-metal stents for multivessel coronary disease. METHODS: We identified 18,359 patients with multivessel disease who underwent isolated CABG and 13,377 patients who received bare-metal stenting in 1999 to 2000 in New York and followed their vital status through 2007 using the National Death Index (NDI). We matched CABG and stent patients on the number of diseased coronary vessels, proximal left anterior descending (LAD) artery disease, and propensity of undergoing CABG based on numerous patient characteristics and compared survival after the 2 procedures. RESULTS: In the 7,235 pairs of matched patients, the overall 8-year survival rates were 78.0% for CABG and 71.2% for stenting (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.64 to 0.74; p < 0.001). For anatomic groups classified by the number of diseased vessels and proximal LAD involvement, the HRs ranged from 0.53 (p < 0.001) for patients with 3-vessel disease involving proximal LAD artery disease to 0.78 (p = 0.05) for patients with 2-vessel disease but no disease in the LAD artery. A lower risk of death after CABG was observed in all subgroups stratified by a number of baseline risk factors. CONCLUSIONS: Coronary artery bypass grafting is associated with a lower risk of death than is stenting with bare metal stents for multivessel coronary disease.


Subject(s)
Angioplasty, Balloon, Coronary/mortality , Coronary Artery Bypass/mortality , Stents , Adult , Aged , Female , Humans , Male , Middle Aged , Survival Rate
17.
Blood Coagul Fibrinolysis ; 22(5): 362-8, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21346555

ABSTRACT

The objective of the present study was to determine if a new procoagulant molecule, carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) would improve coagulation following cardiopulmonary bypass (CPB). Plasma was obtained from patients undergoing elective cardiac surgery requiring CPB. Whole blood was collected and anticoagulated with sodium citrate after induction of anesthesia and again after CPB and heparin neutralization with protamine. Blood samples were centrifuged for 15 min, with plasma collected and stored at -80°C prior to analysis. Samples were subsequently exposed to 0 or 100 µmol/l CORM-2, with coagulation activated with tissue factor. Data were collected with thrombelastography until clot strength stabilized. Patients underwent CPB for 133 ± 61 min (mean ± SD). The velocity of thrombus formation was significantly decreased (52%) by CPB, as was clot strength (53%). Addition of CORM-2 to plasma samples obtained after CPB significantly increased the velocity of clot formation (75%) and strength (52%) compared to matched unexposed samples. The lesion of plasmatic coagulation associated with CPB was significantly improved in vitro by addition of CORM-2. If preclinical assessments of efficacy and safety of CORM-2 are favorable, future clinical trials involving CORM-2 or other CORMs as a hemostatic intervention in the setting of CPB are justified.


Subject(s)
Blood Coagulation/drug effects , Cardiopulmonary Bypass/adverse effects , Organometallic Compounds/therapeutic use , Thrombosis/prevention & control , Adult , Anesthesia , Cardiopulmonary Bypass/methods , Female , Humans , Male , Middle Aged , Organometallic Compounds/pharmacology , Protamines , Thrombelastography , Thrombosis/etiology , Young Adult
18.
Innovations (Phila) ; 6(4): 276-82, 2011 Jul.
Article in English | MEDLINE | ID: mdl-22437990

ABSTRACT

Multiple ablation technologies are used to treat atrial fibrillation during cardiac operations. All such ablation technologies use locally induced temperature extremes (>50°C or <-20°C) to kill tissue and create a lesion pattern in the atria which blocks activation pathways that initiate and sustain atrial fibrillation. The technologies used to heat tissue have included radiofrequency (RF), microwave, high-intensity focused ultrasound, and infrared laser. RF accounts for more than 95% of the heating-based ablation technology used by cardiac surgeons. Energy delivery with RF is easier to control than with some other technologies, the heating produced by the energy source is well understood, and manufacturing costs are not excessive. Whichever heating technology is used, control of energy delivery is required to ensure both safe and effective heating of the targeted tissue. All targeted tissue needs to be heated above 50°C to achieve cell death. However, the targeted tissue should not be heated above 100°C, as this can cause perforation due to a steam pop. In addition, adjacent noncardiac tissues must not be damaged during the ablation procedure. The best method to achieve this control uses direct measurement of tissue temperature, because the tissue temperature defines both the safe and effective limits for the ablative process.

19.
Ann Thorac Surg ; 90(5): 1698-9, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20971297

ABSTRACT

Ventricular fibrillation is a common arrhythmia encountered after the termination of cardiopulmonary bypass. Risk is augmented in patients who are undergoing repeat cardiac procedures with most documented complications occurring during repeat sternotomy. Aortic valve surgery is more complex after coronary artery bypass grafting using internal mammary arteries, and it compounds the increased risk of repeat sternotomy. This case report describes a low-flow state artificially created by sternal retraction applying tension on a right internal mammary artery to posterior descending artery anastomosis, with resultant unrecognized myocardial ischemia yielding refractory ventricular fibrillation during aortic valve replacement.


Subject(s)
Aortic Valve/surgery , Heart Valve Prosthesis Implantation/adverse effects , Internal Mammary-Coronary Artery Anastomosis/adverse effects , Sternotomy/adverse effects , Ventricular Fibrillation/etiology , Aged , Humans , Male , Reoperation
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