A S Wechsler

University at Albany, The State University of New York, New York City, New York, United States

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Publications (235)1056.17 Total impact

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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.
    The Journal of thoracic and cardiovascular surgery 02/2013; · 3.41 Impact Factor
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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.
    The Annals of thoracic surgery 02/2013; · 3.45 Impact Factor
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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.
    The Annals of thoracic surgery 01/2013; · 3.45 Impact Factor
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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.
    The Annals of thoracic surgery 11/2012; · 3.45 Impact Factor
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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.
    JAMA The Journal of the American Medical Association 07/2012; 308(2):157-64. · 29.98 Impact Factor
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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.
    Circulation 04/2012; 125(20):2423-30. · 15.20 Impact Factor
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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.
    The Journal of thoracic and cardiovascular surgery 02/2012; 144(1):250-5. · 3.41 Impact Factor
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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.
    The Journal of thoracic and cardiovascular surgery 02/2012; 144(1):243-9. · 3.41 Impact Factor
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    ABSTRACT: 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. 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. The difference in long-term mortality between on-pump and off-pump coronary artery bypass graft surgery is not statistically significant.
    Circulation Cardiovascular Quality and Outcomes 01/2012; 5(1):76-84. · 5.66 Impact Factor
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    ABSTRACT: 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. 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. 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. Coronary artery bypass grafting is associated with a lower risk of death than is stenting with bare metal stents for multivessel coronary disease.
    The Annals of thoracic surgery 12/2011; 92(6):2132-8. · 3.45 Impact Factor
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    ABSTRACT: The aim of this study was to identify reasons for and predictors of readmission. Short-term readmissions have been identified as an important cause of escalating health care costs, and coronary artery bypass graft (CABG) surgery is 1 of the most expensive procedures. We retrospectively analyzed 30-day readmissions for 33,936 New York State patients who underwent CABG surgery between January 1, 2005, and November 30, 2007. The main reasons for readmission (principal diagnoses) and the significant independent predictors of readmission were identified. The hospital-level relationship between risk-adjusted mortality rate and risk-adjusted readmission rate was explored to determine the value of readmission rate as a complementary measure of quality. The most common reasons for readmission were post-operative infection (16.9%), heart failure (12.8%), and "other complications of surgical and medical care" (9.8%). Increasing age, female sex, African-American race, higher body mass index, numerous comorbidities, 2 post-operative complications (renal failure and unplanned cardiac reoperation), Medicare or Medicaid status, discharges to a skilled nursing facility, saphenous vein grafts, and longer lengths of stay were all associated with higher rates of readmission. The correlation between the risk-adjusted 30-day readmission rate of hospitals and risk-adjusted in-hospital/30-day mortality rate was 0.32 (p = 0.047). The range across hospitals in the readmission rate was from 8.3% to 21.1%. The 30-day readmission rate for CABG surgery remains high, despite decreases in short-term mortality. Patients with any of the numerous risk factors for readmission should be closely monitored. Hospital readmission rates are not highly correlated with mortality rates and might serve as an independent quality measure.
    JACC. Cardiovascular Interventions 05/2011; 4(5):569-76. · 1.07 Impact Factor
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    ABSTRACT: To determine predictors of low intensive care unit (ICU) admission hematocrit, and to determine if low hematocrit is associated with postoperative outcomes for coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass. We performed a retrospective study of 8417 patients who underwent CABG surgery on cardiopulmonary bypass in New York in 2007. Patients with very low ICU admission hematocrit (≤ 21.9%) and low ICU admission hematocrit (22.0% to 25.9%) were identified. Significant independent predictors of low and very low ICU admission hematocrit, and the independent impact of each of these states on adverse outcomes were identified. A total of 1.1% had very low hematocrit and 8.3% had low hematocrit. Significant independent predictors for either low or very low hematocrit included older age, females, lower body surface area, lower ventricular function, Hispanic ethnicity, non-Caucasian race, high creatinine, previous cardiac surgery, absence of left main disease, and emergency transfer to the operating room following catheterization or percutaneous coronary intervention. Patients with hematocrit ≤ 21.9% had significantly higher risk-adjusted rates of postoperative bleeding (adjusted OR = 4.37, 95% CI [1.97, 9.68, respiratory failure (adjusted OR = 2.85, 95% CI [1.45, 5.63]), and one or more complications than patients with normal hematocrit. Patients with hematocrit between 22.0% and 25.9% also had higher complication rates. It is important for cardiovascular surgical teams to be aware of risk factors that predispose patients to unacceptable hematocrit values, to monitor values closely, and to treat accordingly in the operating room when low values occur. 
    Journal of Cardiac Surgery 10/2010; 25(6):638-46. · 1.35 Impact Factor
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    ABSTRACT: The study objective was to determine predictors of hypothermia and hyperthermia, and the impact of hypothermia and hyperthermia on postoperative outcomes for off-pump coronary artery bypass grafting. We performed a retrospective study of 2294 patients who underwent off-pump coronary artery bypass grafting in New York in 2007. Patients were classified as moderately to severely hypothermic (< or = 34.5 degrees C), mildly hypothermic (34.6 degrees C-35.9 degrees C), or mildly hyperthermic (37.5 degrees C-38.8 degrees C) after leaving the operating room. Significant independent predictors of these temperature states and the independent impact of each of these states on in-hospital mortality and complications were identified. A total of 37.7% of patients were mildly hypothermic, 9.0% of patients were moderately to severely hypothermic, and 5.6% of patients were mildly hyperthermic. Significant independent predictors for postoperative hypothermia included older age, female gender, lower body surface area, congestive heart failure, higher ventricular function, non-Hispanic ethnicity, single/double-vessel disease, low postoperative hematocrit, previous cardiac surgery, race other than white or black, and organ transplant. Patients with moderate to severe hypothermia had significantly higher risk-adjusted in-hospital mortality than patients with normothermia (adjusted odds ratio 3.00; 95% confidence interval, 1.11-8.08). Patients with mild hyperthermia also had significantly higher mortality (adjusted odds ratio 5.04; 95% confidence interval,1.18-21.55). Patients with either mild or moderate to severe hypothermia had significantly higher rates of respiratory failure and unplanned operations, and patients with mild hyperthermia had a significantly higher rate of respiratory failure than normothermic patients. It is important to maintain normal postsurgical core temperatures in patients who have undergone cardiac surgery to minimize or avoid death and complications.
    The Journal of thoracic and cardiovascular surgery 02/2010; 139(6):1568-1575.e1. · 3.41 Impact Factor
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    ABSTRACT: In patients with multivessel coronary artery disease, performing multiple internal mammary artery (MIMA) grafts to two coronary systems during coronary artery bypass grafting (CABG) improves clinical outcome. Few databases have decades of follow-up, however, and the optimal configuration is still in question. The purpose of this study was to assess 20-year clinical benefits of MIMA grafting and to evaluate the possible effects of two different MIMA configurations. From 1984 to 1986, 867 patients with multivessel coronary disease underwent CABG. Single (SIMA) IMA grafts were used in 490 and multiple (MIMA) IMA grafts in 377, along with concomitant saphenous veins. Generally, MIMAs were placed to the two largest coronary systems. Among baseline characteristics, only smoking, diabetes, and hypertension were significantly higher for MIMA versus SIMA. Multivariable Cox model analysis was used to assess outcome differences between groups. During a median follow-up of 20 years, the composite of mortality, myocardial infarction, percutaneous coronary intervention, and redo CABG was significantly reduced after MIMA versus SIMA (p = 0.013). Event-free survival was extended by almost 1 year (p = 0.018), and redo CABG was reduced by 59% (p = 0.005). A comparison within the MIMA group was made between 235 patients receiving IMA grafts to left anterior descending/left circumflex territories versus 122 with grafts to left anterior descending/right coronary artery systems. No significant difference in composite outcome was observed between these configurations (p = 0.88). These data confirm the clinical benefits of MIMA grafting in multivessel coronary disease to 20 years of follow-up. As long as MIMAs are placed to the two largest coronary systems, no significant differences in long-term results are evident between left anterior descending/left circumflex and left anterior descending/right coronary artery configurations.
    The Annals of thoracic surgery 04/2007; 83(3):1008-14; discussion 1014-5. · 3.45 Impact Factor
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    ABSTRACT: The long-term clinical advantages of using routine multiple internal mammary artery (IMA) grafts for coronary artery bypass (CAB) are not clear. This study was designed to test the hypothesis that multiple IMA grafts would provide better 15-year outcomes when compared with single IMA and vein grafts. Between 1984 and 1987, 1067 consecutive patients undergoing isolated CAB were referred to 1 surgeon practicing primarily single and another surgeon maximizing multiple IMA grafts (clinical practice trial). A 207-patient subset with multiple IMAs underwent postoperative graft angiography at 1 to 32 weeks to define initial IMA patency. Patients were followed-up yearly, and the groups were analyzed as (I) surgical strategy (surgeon operating) (single=413 versus multiple=654), (II) ultimate operation performed (single=418 versus multiple=449), or (III) single versus multiple coronary systems revascularized with IMAs (single=490 versus multiple=377). Advantages of this study design were that an entire referral population was examined, multiple IMAs were applied to the entire spectrum of baseline patient risk, 15-year follow-up provided a complete prognostic picture, and the subgroups were potentially comparable at baseline. In all 3 analyses, single and multiple groups were statistically similar with respect to baseline, operative, and immediate postoperative variables. Early IMA patency was 98.5% (333/338 grafts patent), validating the quality of IMA procedures. Unadjusted and adjusted 15-year outcome analyses for I, II, and III for death, myocardial infarction, percutaneous coronary intervention, redo coronary bypass, and the composite of all events identified multiple versus single as a significant predictor of outcome for the composite end point in adjusted analysis III (hazard ratio=0.808; 95% CI, 0.689 to 0.948; P=0.009), because of a 5% to 10% absolute reduction in each of the outcome variables at 15 years. Moreover, >50% reduction in reoperation rate was observed at 15 years in every analysis. At 15-year follow-up, multiple IMA grafting was associated with a 19.2% adjusted risk reduction in death and cardiac events, caused by decreases in all adverse end points and fewer reoperations. These data indicate that the clinical advantages of maximizing IMA conduits are significant. Based on this information, it is suggested that multiple IMA grafting to 2 coronary systems should be applied liberally to patients with noncardiac risk profiles predictive of long-term survival.
    Circulation 09/2004; 110(11 Suppl 1):II27-35. · 15.20 Impact Factor
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    ABSTRACT: Brain death results in cardiac injury and hemodynamic instability. After brain death, catecholamine levels surge in concert with increased expression of select myocardial gene products. Sympathetic blockade was used to investigate the effects of the adrenergic nervous system on myocardial gene expression in a rabbit model of brain death. A balloon expansion model of brain death in rabbits (n = 42) was used with and without sympathetic blockade (xylazine, acetylpromazine, and ketamine). Sham-operated and naive rabbits served as control animals. Over 4 hours, mean arterial pressure, heart rate, electrocardiographic results, catecholamine levels, myocardial histology, and messenger RNA levels were assessed. Sympathetic blockade decreased basal catecholamine levels and blocked the catecholamine surge accompanying brain death. The typical hemodynamic instability, adverse electrocardiographic changes, and myocellular injury associated with brain death were all significantly decreased. Sympathetic blockade not only suppressed the previously reported increases in myocardial gene expression (cardiac and skeletal alpha-actin, egr-1, and heat shock protein 70) but also suppressed the expression of multiple other genes (alpha and beta myosin heavy chain, calcium ATPase [sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase pump, SERCA-2a], phospholamban [ryanodine receptor], and c-jun). Central sympathetic blockade minimizes the hemodynamic instability associated with brain death and neutralizes the increased expression of multiple myocardial gene products associated with brain death.
    Journal of Thoracic and Cardiovascular Surgery 01/2003; 124(6):1087-98. · 3.53 Impact Factor
  • T Yeh, A S Wechsler
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    ABSTRACT: One of the concerns in using radial artery as coronary artery bypass grafts centers around its unusual propensity for vasospasm when experimentally exposed to norepinephrine. This case report demonstrates an absence of vasospasm in a radial artery graft on high dose norepinephrine and may provide reassurance when alpha-agonists are required in this setting.
    The Annals of Thoracic Surgery 12/1999; 68(6):2349-50. · 3.45 Impact Factor
  • K Baghelai, L J Graham, A S Wechsler, E R Jakoi
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    ABSTRACT: Alpha-adrenergic stimulation induces protection in reperfused ischemic (I/R) myocardium 24 hours later. We tested the hypothesis that phenylephrine improves dysfunction after global I/R by limiting cell death not stunning. Rabbits were pretreated with either phenylephrine or vehicle. Twenty-four hours later, isolated hearts underwent either 45 (infarction protocol) or 20 minutes (stunning protocol) of global ischemia before 2 hours of reperfusion (n = 6 per group). Cell death was determined by triphenyl tetrazolium chloride staining (infarction) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (apoptosis). Compared with vehicle, phenylephrine pretreatment improved post-I/R-developed pressures in hearts after infarction (53.2 +/- 4.0 vs 35.8 +/- 4.1 mm Hg, p = 0.01) but not stunning protocol (64.3 +/- 8.9 vs 57.7 +/- 6.2 mm Hg, p = NS). The improved developed pressure was due to better diastolic recovery. Systolic pressures were similar between groups. Phenylephrine markedly decreased infarction (9.0 +/- 1.9% vs 40.8 +/- 1.8% for vehicle, p < 0.001) and TUNEL-positive staining. Stunned hearts of either group had less than 3% infarction and no apoptosis. Phenylephrine pretreatment 24 hours before global I/R improves function by limiting infarction but not stunning.
    The Annals of Thoracic Surgery 10/1999; 68(4):1219-24. · 3.45 Impact Factor
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    ABSTRACT: Chronic arteriovenous fistulae (AVF) create sustained hyperdynamic circulation. It is not known whether hyperdynamic circulation alters myocardial sensitivity to ischemia and reperfusion injury. We tested the hypothesis that AVF activate molecular responses that increase tolerance to infarction in dogs. Twelve dogs were divided into two groups: 1) AVF group, where an AVF in the femoral region was done; and 2) sham-operated group (each n = 6). After 8 weeks, left ventricular performance was determined from stroke work/end-diastolic length relationship. Myocardial biopsy was obtained to determine heat-shock protein 70 and adenosine triphosphate (ATP) pool. Left anterior descending coronary artery was occluded for 90 minutes at 37 degrees C, followed by 4 hours of reperfusion. Coronary blood flow was determined using different colored microspheres. The fistula group showed improvement of left ventricular performance (p = 0.03). The infarct size was significantly lower in the fistula group; it was 9.2+/-2.0% in the fistula group versus 28.4+/-5.2% in the sham group (p < 0.05). ATP depletion during ischemia was less in the fistula group (p = 0.02). Regional myocardial blood flow was significantly higher in the fistula group (p = 0.03). Peripheral AVF improve the left ventricular performance, and decrease infarct size and ATP depletion. This protective effect is caused by the development of collaterals in the coronary circulation without expression of heat-shock protein 70.
    The Annals of Thoracic Surgery 07/1999; 68(1):22-8. · 3.45 Impact Factor
  • K Baghelai, L J Graham, A S Wechsler, E R Jakoi
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    ABSTRACT: Previous studies have demonstrated that alpha1-adrenoceptor activation increases myocardial resistance to ischemic injury 24 hours later. Here we tested the hypothesis that delayed protection is associated with limited infarction and involves altered expression of pro-apoptotic and/or anti-apoptotic proteins. Rabbits were treated with phenylephrine or an equivalent volume of vehicle (n = 6 per group). Twenty-four hours after pretreatment, isolated hearts were perfused with a bovine erythrocyte suspension in modified Krebs solution, subjected to 45 minutes of global ischemia (37 C), and reperfused for 120 minutes. Infarct size was determined by triphenyltetrazolium chloride staining. Apoptosis was quantified by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. Left ventricular tissue from separate groups of animals (n = 5 per group), 24 hours after pretreatment with phenylephrine or vehicle but without ischemia and reperfusion, was analyzed by Western blotting for content of the anti-apoptotic protein, bclx, and pro-apoptotic protein, bax. Isolated hearts after phenylephrine pretreatment had increased end-reperfusion developed pressures (56.8 +/- 4.9 vs 36.2 +/- 3.9 mm Hg for vehicle, P =.008) and decreased elevated end-diastolic pressures (26.7 +/- 4.5 vs 42.3 +/- 5.0 mm Hg for vehicle, P =.04). Phenylephrine pretreatment abrogated infarction (9.9 +/- 2.4% vs 42.6 +/- 6.3% for vehicle, P =.002) and reduced the number of apoptotic nuclei (24 +/- 4.8 vs 51 +/- 4.6 for vehicle, P = .038). Analysis by Western blotting showed that the ratio of bclx to bax protein increased in phenylephrine-pretreated hearts (2.65 +/- 0.5 vs 1.0 +/- 0.1 for vehicle, P =.008). Delayed myocardial protection to infarction mediated by alpha1-adrenoceptor activation involves an increased bclx/bax ratio, thereby limiting apoptotic cell death.
    Journal of Thoracic and Cardiovascular Surgery 06/1999; 117(5):980-6. · 3.53 Impact Factor

Publication Stats

2k Citations
1,056.17 Total Impact Points

Institutions

  • 2013
    • University at Albany, The State University of New York
      • Department of Health Policy, Management, and Behavior
      New York City, New York, United States
    • Richmond VA Medical Center
      Richmond, Virginia, United States
  • 2011–2013
    • Penn State Hershey Medical Center and Penn State College of Medicine
      • Public Health Sciences
      Hershey, Pennsylvania, United States
  • 2010–2013
    • Drexel University College of Medicine
      • Department of Cardiothoracic Surgery
      Philadelphia, Pennsylvania, United States
  • 2010–2012
    • State University of New York
      New York City, New York, United States
  • 1991–2012
    • Virginia Commonwealth University
      • • Department of Surgery
      • • Division of Cardiothoracic Surgery
      Richmond, VA, United States
  • 2007
    • Drexel University
      Philadelphia, Pennsylvania, United States
  • 1999
    • University of Louisville
      • Department of Surgery
      Louisville, KY, United States
  • 1989
    • SickKids
      Toronto, Ontario, Canada
  • 1973–1989
    • Duke University Medical Center
      • Department of Surgery
      Durham, NC, United States
  • 1987
    • University of Massachusetts Medical School
      • Department of Surgery
      Worcester, MA, United States