Surgical ventricular remodeling: a balancing act on systolic and diastolic properties.
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Cardiomyopathy, Dilated↗
Biomedical subjects
Andrew S Wechsler
Publications and source records attributed to Andrew S Wechsler.
Single versus multiple internal mammary artery grafting for coronary artery bypass: 15-year follow-up of a clinical practice trial.
BACKGROUND: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.
Aged↗
Does off-pump coronary artery bypass reduce the incidence of clinically evident renal dysfunction after multivessel myocardial revascularization?
In this prospective, observational trial, we determined whether off-pump coronary artery bypass (OPCAB) was associated with less postoperative renal dysfunction (RD) compared with coronary bypass surgery with cardiopulmonary bypass (CABG). All patients undergoing primary, isolated coronary surgery at our institution in the year 2000 participated. Data collected on each patient included demographics, preoperative risk factors for RD, perioperative events, and serum creatinine concentrations from date of admission until discharge or death. The criteria for RD was both a >or=50% increase from preoperative creatinine and an absolute postoperative creatinine >or=2.0 mg/dL (177 microM). Student's t-test or the Fisher's exact test was used to compare groups. Stepwise multiple logistic regression identified determinants of RD; P < 0.05 significant. The CABG group (n = 119) differed from the OPCAB group (n = 220) with respect to age (64 +/- 13 versus 67 +/- 10 yr, P = 0.0074) and number of distal grafts (median 4 versus 3, P = 0.0003). Type of operation did not associate with the presence of postoperative RD: 18 (8.2%) of 220 OPCAB patients versus 12 (10%) of 119 CABG patients (P = 0.55). Our data suggest that choice of operative technique (OPCAB versus CABG) is not associated with reduced renal morbidity.
Aged↗
Cardiomyocyte-mediated contact programs human mesenchymal stem cells to express cardiogenic phenotype.
BACKGROUND: Intercellular crosstalk and cellular plasticity are key factors in embryogenesis and organogenesis. The microenvironment plays a critical role in directing the progression of stem cells into differentiated cells. We hypothesized that intercellular interaction between adult human mesenchymal stem cells and adult human cardiomyocytes would induce stem cells to acquire the phenotypical characteristics of cardiomyocytes, and we tested the role that direct cell-to-cell contact plays in directing this differentiation process. Human mesenchymal stem cells were cultured in the presence of human cardiomyocytes ("coculture") or in the presence of media conditioned by separate cultures of human cardiomyocytes ("conditioned media"). METHODS: Human cardiomyocytes were labeled with chloromethyl derivatives of fluorescein diacetate. In the coculture experiments, human mesenchymal stem cells and human cardiomyocytes were mixed at a 1:1 ratio in smooth muscle 2 media and seeded at a cell density of 10,000 cells/cm(2). Cells were cocultured in an incubator at 37 degrees C for 48 hours. Subsequently, fluorescence-activated cell sorting was used to extract the differentiating human mesenchymal stem cells. In the conditioned media experiments, human mesenchymal stem cells were incubated in media previously conditioned by cardiomyocytes, in the presence and absence of serum (+/-serum). The conditioned media was changed 3 times, at intervals of 48 hours. Total RNA was isolated and reverse transcriptase-polymerase chain reaction was performed for expression of contractile proteins and cardiac specific genes. Immunostaining against myosin heavy chain, beta-actin troponin-T, and troponin-I was performed. RESULTS: Fluorescence-activated cell sorting analysis identified 66% of the human mesenchymal stem cells in the G1 phase. Differentiated hMSCs from the coculture experiments expressed myosin heavy chain, beta-actin, and troponin-T by reverse transcriptase-polymerase chain reaction. Immunostaining was also positive against myosin heavy chain and troponin-T. In contrast, only beta-actin expression was observed in the human mesenchymal stem cells incubated with conditioned media +/- serum. CONCLUSION: In addition to soluble signaling molecules, direct cell-to-cell contact is obligatory in relaying the external cues of the microenvironment controlling the differentiation of adult stem cells to cardiomyocytes. These data indicate that human mesenchymal stem cells are plastic and can be reprogrammed into a cardiomyogenic lineage that may be used in cell-based therapy for treating heart failure.
Actins↗
The gender initiative.
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Cardiovascular Surgical Procedures↗
Mechanical support of the unrepaired postinfarction ventricular septal defect with the Abiomed BVS 5000 ventricular assist device.
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Heart Rupture, Post-Infarction↗
Cecilie Greig memorial lecture 2002. Myocardial protection: an expanding or contracting discipline?
For the past thirty years cardiac surgeons have had a unique opportunity to study the consequences of myocardial ischemia and reperfusion. With the advent of an ability to intervene in acute myocardial syndromes, cardiologists have vigorously joined that effort as have fundamental scientists. Exogenous myocardial protective strategies have emerged as have novel strategies that take advantage of endogenous mechanisms of myocardial protection. As a consequence of improved myocardial protection, operative mortality and morbidity, in particular the low output syndrome, have diminished. However, despite important increases in the knowledge base referable to myocardial ischemia and reperfusion, major advances in myocardial protection have slowed in the past several years. This article explores potential untapped options for augmenting myocardial protection and focuses on the potential adverse interactions between cardiopulmonary bypass and myocardial protection as a prime target for future investigations leading to improved myocardial management during heart operations.
Cardiology↗
Central sympathetic blockade ameliorates brain death-induced cardiotoxicity and associated changes in myocardial gene expression.
OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Animals↗