Biomedical subjects

Elad Anter

Publications and source records attributed to Elad Anter.

8 recordsLinked to original sources

PubMed2006

Endoscopic versus conventional radial artery harvest for coronary artery bypass grafting: functional and histologic assessment of the conduit.

BACKGROUND: The radial artery's propensity for vasospasm and vulnerability to surgical trauma are well known. A less invasive endoscopic method to harvest the radial artery was recently introduced, but its effect on radial artery integrity is unknown. METHODS: To compare the effects of harvest method on radial artery function, we prospectively randomized 54 patients undergoing coronary artery bypass grafting with the radial artery into 3 groups on the basis of harvest techniques: endoscopic, conventional with cautery, and conventional with harmonic scalpel. We assessed endothelium-dependent and endothelium-independent relaxation of radial artery segments to sequential doses of acetylcholine and nitroglycerin, respectively, using standard organ-chamber methodology. Vasospasm was assessed as the vasoconstrictor response to the thromboxane analog U46619. We assessed endothelial integrity using light and electron microscopy and by rating intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and P-selectin expression by means of immunohistochemistry on a semiquantitative 0- to 3-point scale. Harvest procedures were performed by a single surgeon, and data analyses were blinded to the harvesting method. RESULTS: Maximal relaxation-contraction responses to acetylcholine, nitroglycerin, and U46619 and effective drug concentration yielding 50% response were similar in the 3 groups. Adhesion molecule expression and histologic changes, as assessed by means of light and electron microscopy, were similar in the 3 groups. CONCLUSIONS: Endoscopic harvest does not alter radial artery vasoreactivity or endothelial integrity compared with conventional harvest techniques. Because the endoscopic technique is less invasive, it might prove to be the technique of choice to harvest the radial artery.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2005

Estradiol-mediated endothelial nitric oxide synthase association with heat shock protein 90 requires adenosine monophosphate-dependent protein kinase.

BACKGROUND: Estradiol activates endothelial nitric oxide synthase (eNOS) by mechanisms that involve estrogen receptor-alpha (ERalpha), protein kinase B/Akt, mitogen-activated protein kinases, and heat shock protein 90 (HSP90). Recently, AMP-activated protein kinase (AMPK), an enzyme that plays a crucial role in cellular adaptation to metabolic stress, has been implicated in physiological eNOS activation by the hormones adiponectin and insulin. We therefore investigated whether AMPK is activated by estradiol in endothelial cells and plays a role in estradiol-induced eNOS activation. METHODS AND RESULTS: Porcine aortic endothelial cells exhibited time- and concentration-dependent AMPK activation as determined by phosphorylation of AMPK and its downstream target acetyl coenzyme A carboxylase in response to estradiol (1 nmol/L to 10 micromol/L, 1 to 30 minutes). AMPK activation by estradiol was independent of both AMP levels and ERalpha but required estradiol conversion to its catechol metabolites. Estradiol treatment increased eNOS catalytic activity, an effect that was largely reversed when endothelial cells were infected with an AMPK dominant-negative adenovirus. However, inhibition of AMPK did not alter estradiol-induced eNOS phosphorylation at serine 1177 or threonine 495 but decreased eNOS interaction with HSP90. Consistent with this observation, blood vessels from alpha1-AMPK-null mice exhibited defective eNOS-mediated NO production in response to estradiol. CONCLUSIONS: Taken together, these data indicate that AMPK activity is essential for estradiol-induced eNOS activation via the promotion of eNOS interaction with HSP90. These data point to a novel role for AMPK in modulating endothelial cell NO bioactivity and HSP90 function.

Adenylate Kinase↗

PubMed2005

p38 mitogen-activated protein kinase activates eNOS in endothelial cells by an estrogen receptor alpha-dependent pathway in response to black tea polyphenols.

Black tea has been shown to improve endothelial function in patients with coronary artery disease and recent data indicate the polyphenol fraction of black tea enhances endothelial nitric oxide synthase (eNOS) activity through p38 MAP kinase (p38 MAPK) activation. Because the mechanisms for this phenomenon are not yet clear, we sought to elucidate the signaling events in response to black tea polyphenols. Bovine aortic endothelial cells (BAECs) exposed to black tea polyphenols demonstrated eNOS activation that was inhibited by the estrogen receptor (ER) antagonist ICI 182,780, and siRNA-mediated silencing of ER expression. Consistent with this observation, black tea polyphenols induced time-dependent phosphorylation of ERalpha on Ser-118 that was inhibited by ICI 182,780. Phosphorylation of ERalpha on Ser-118 was due to p38 MAP kinase (p38 MAPK) as, it was inhibited by SB203580 and overexpression of dominant-negative p38alpha MAPK. Conversely, constitutively active MKK6 induced p38 MAPK activation that recapitulated the effects of polyphenols by inducing ERalpha phosphorylation and downstream activation of Akt, and eNOS. The key role of ERalpha Ser-118 phosphorylation was confirmed in eNOS-transfected COS-7 cells, as polyphenol-induced eNOS activation required cotransfection with ERalpha subject to phosphorylation at Ser-118. This residue appeared critical for functional association of ERalpha with p38 MAPK as ERalpha with Ser-118 mutated to alanine could not form a complex with p38 MAPK. These findings suggest p38 MAP kinase-mediated eNOS activation requires ERalpha and these data uncover a new mechanism of ERalpha activation that has broad implications for NO bioactivity and endothelial cell phenotype.

Animals↗

PubMed2004

Activation of endothelial nitric-oxide synthase by the p38 MAPK in response to black tea polyphenols.

Black tea improves endothelial function in patients with coronary artery disease. We sought to determine the responsible components of black tea and elucidate the underlying cell signaling mechanisms. We exposed porcine aortic endothelial cells to components of black tea and found that the polyphenol fraction acutely enhanced nitric oxide bioactivity. This effect involved endothelial nitric-oxide synthase (eNOS) phosphorylation at Ser-1177 and dephosphorylation at Thr-495, consistent with increased eNOS activity. These effects were calcium-dependent, as removal of extracellular calcium prevented eNOS phosphorylation at Ser-1177, whereas inhibition of intracellular calcium mobilization with TMB-8 blunted Thr-495 dephosphorylation. Black tea polyphenol-induced eNOS activation appeared dependent upon the phosphatidylinositol 3-kinase-Akt pathway, as it was significantly inhibited by LY294002 and a dominant negative Akt, respectively. Pharmacological inhibition of p38 mitogen-activated protein kinase (p38 MAPK) with either SB202190 or SB203580 as well as overexpression of a dominant negative p38 MAPKalpha attenuated both eNOS activation and phosphorylation changes in response to black tea polyphenols. Inhibition of p38 MAPKalpha also blunted Akt activation in response to black tea polyphenols, suggesting that p38alpha MAPK is upstream of Akt in this pathway. Finally, a constitutively active mutant of MKK6bE, an upstream kinase for p38 MAPK, enhanced both the basal and stimulated activity of Akt, leading to increased eNOS activity. Taken together, these data identify the p38 MAPK as an upstream component of Akt-mediated eNOS activation.

Adenoviridae↗

PubMed2004

Endoscopic radial artery harvest for coronary artery bypass grafting: initial clinical experience.

BACKGROUND: Recently, an endoscopic technique was developed to harvest the radial artery (RA) via a 3-cm wrist incision in patients undergoing coronary artery bypass graft (CABG). The aim of this study was to evaluate our initial clinical experience with this technology. METHODS: Data were prospectively collected on 75 consecutive patients undergoing CABG with endoscopic RA harvest using the Ultra-Retractor (CardioVations, Somerville, NJ, USA) and the harmonic scalpel (Ethicon Endo-Surgery, Cincinnati, OH, USA). RESULTS: There were 66 men (88%) and 9 women (12%) with a mean age of 60 years (range, 31-77 years). Forty-eight (64%) of cases had non-elective surgery. Thirty-one (41%) of patients had diabetes. Sixty seven percent of the operations were performed on pump and 33% off pump. Average RA harvest time was 66 minutes (range, 25-120 minutes) with a significant learning curve (75 minutes for the first 20 cases and 63 minutes for the last 50 cases). Two (2.6 %) radial arteries were discarded, one because of extensive calcifications and the other because of damage to the conduit. No patients suffered death, perioperative myocardial infarction, or stroke. There was one reexploration of the forearm for a tunnel hematoma. Follow-up was achieved in 100% of patients and averaged 3.6 months (range, 0.5-13 months). Two patients died during the follow-up. There were no myocardial infarctions or reinterventions, with 96% of patients in functional class I /II. There were no motor deficits. There were no sensory deficits in the distribution of the lateral antebrachial cutaneous nerve, but transient mild dorsal thenar numbness or paresthesias were observed in 86% of patients. Cosmetic results were defined as good to excellent in 82% of patients. CONCLUSIONS: Short-term results of endoscopic RA harvest are excellent. There is a significant learning curve. Longterm follow-up as well as structural and functional assessments of the conduit are indicated.

Adult↗

PubMed2004

Oxidative stress, antioxidants, and endothelial function.

Endothelial dysfunction, characterized by a loss in nitric oxide bioactivity, is an early event in the development of atherosclerosis and determines future vascular complications. Emerging evidence suggests a causal role for oxidative stress in this process. Reactive oxygen species can directly inactivate nitric oxide, modulate protein function and act as cellular signaling molecules. These events contribute to the initiation and progression of endothelial dysfunction. Considerable data also indicates that antioxidant compounds limit oxidative damage and restore endothelial function. The purpose of this review is to discuss these data and suggest novel approaches for lowering the oxidative stress in the vasculature.

Animals↗

PubMedDate not supplied

Coronary artery bypass grafting in patients with severe left ventricular dysfunction--early and mid-term outcomes.

BACKGROUND: The prevalence of patients with severe left ventricular dysfunction (LVD) referred for coronary artery bypass grafting (CABG) is increasing. The aim of the present study was to assess the outcomes of patients with severe LVD undergoing CABG. METHODS: Outcomes of 115 consecutive patients with severe LVD (left ventricular ejection fraction [LVEF]</= 30%, mean 22 +/- 6%) undergoing isolated CABG between 1995 and 2000 were compared to 2335 patients with LVEF >30% (HEF). To further evaluate the LVD patients, they were divided into three subgroups base on LVEF: 0% to 10%, 11% to 20%, and 21% to 30%. Data were collected prospectively and entered into the departmental database of the Society of Thoracic Surgeons. RESULTS: Patients in the LVD group had increased incidence of diabetes, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, prior myocardial infarction (MI), congestive heart failure, and less elective procedures compared to the HEF group. Despite this greater risk profile, operative mortality (LVD 2.6% vs. HEF 1.2%, p = 0.19), the incidence of stroke (2.6% vs. 1.0%, p = 0.13), and perioperative MI (0.9% vs. 0.7%) were not statistically different between the groups. The incidence of respiratory (14.8% vs. 1.9%, p < 0.001), renal (5.2% vs. 1.0%, p < 0.001), and vascular (5.2% vs. 0.5%, p < 0.001) complications was significantly higher in the LVD group, resulting in a longer hospital length of stay (8 +/- 8 vs. 6 +/- 4 days, p < 0.0001). In a multivariate analysis, advanced age was as an independent predictor of hospital mortality. Average follow-up in 108 (94%) LVD patients was 36 +/- 22 months (range 2 to 78 months). Twenty-one patients expired during the follow-up, for nine the causes were cardiac-related. Three- and 5-year survival rates were 91 +/- 3% and 76 +/- 6%, respectively. Independent predictors of mid-term mortality in the LVD group by a multivariate analysis included female gender, renal failure, respiratory complications, and grade I/II mitral regurgitation (MR). At the time of follow-up, 72% of LVD patients were in functional class I/II. There were no statistically significant differences in short- and mid-term outcomes among the LVD subgroups. CONCLUSION: CABG in patients with severe LVD can be performed with a low mortality, albeit with higher morbidity and longer length of hospital stay, than patients with LVEF >30%. Low ejection fraction per se was not a predictor of hospital mortality. CABG should be considered a safe and effective therapy for low ejection fraction patients with ischemic heart disease. Mitral valve repair/replacement in the presence of moderate degree of MR should be considered at the time of the initial operation.

Aged↗

PubMedDate not supplied

Endoscopic versus conventional radial artery harvest--is smaller better?

BACKGROUND: We sought to assess our initial experience with the recently introduced technique of endoscopic radial artery harvest (ERH) for coronary artery bypass grafting (CABG). METHODS: Data were prospectively collected on 108 consecutive patients undergoing isolated CABG with ERH, and compared to 120 patients having conventional harvest (CH). Follow-up was achieved in 227 patients (99%). At the time of follow-up the severity of motor and sensory symptoms, as well as cosmetic result in the harvest forearm, were subjectively graded using a 5-point scale. Grade 1-- high intensity deficits, poor cosmetic result. Grade 5 -- no deficits, excellent cosmetic result. RESULTS: Hospital mortality, myocardial infarction, and stroke rates were similar between the groups. Follow-up mortality, reintervention rate, and average angina class were also similar. Harvest time was longer in the ERH group (61 +/- 24 min vs. 45 +/- 11 min, p < 0.001). Three patients in the ERH group were converted to CH and one radial artery was discarded. There were no vascular complications of the hand in either group. Average score of motor (ERH 4.4 +/- 0.9, CH 4.2 +/- 1.0) or sensory symptoms (ERH 3.7 +/- 1.1, CH 3.8 +/- 1.2) were similar. In the CH group sensory deficits were observed in the distribution of both the lateral antebrachial cutaneous and the superficial radial nerves (SRN). In contrast, sensory deficits in the ERH group were limited to the distribution of the SRN. Cosmetic result score was higher in the ERH group (ERH 4.2 +/- 1.0, CH 3.1 +/- 1.4, p < 0.0001). CONCLUSIONS: ERH is safe. It is technically demanding with a significant learning curve. Motor and sensory symptoms are not completely eliminated by using a smaller incision, but cosmetic results are clearly superior.

Adult↗