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Biomedical subjects

George Dangas

Publications and source records attributed to George Dangas.

At least 73 records · Page 4Linked to original sources
PubMed2003

Deferoxamine enhances neovascularization and recovery of ischemic skeletal muscle in an experimental sheep model.

BACKGROUND: Iron chelators have been reported to interfere with inflammatory cells and possibly enhance vascular growth factor expression. The objective of this study was to investigate the efficacy of the iron chelator deferoxamine mesylate in preventing skeletal muscle ischemia. METHODS: The latissimus dorsi muscle (LDM) was mobilized in 20 adult sheep. Two separate pockets were created in each sheep. Autologous fibrin sealant with or without 100 mg/mL of deferoxamine mesylate (10 pockets) was added to the pockets. Deferoxamine mesylate alone was also applied to another 10 pockets, whereas the 10 other pockets served as controls. RESULTS: Conventional, indirect immunofluorescent enface staining showed that in nonmobilized, nonischemic LDM the capillary density was 196 +/- 14 capillaries/mm2 in the distal and 207 +/- 19 capillaries/mm2 in the middle part. After severe ischemic shock (subtotal mobilization), the muscle did not recover completely even after 2 months (149 +/- 15 capillaries/mm2 in the distal part and 177 +/- 16 capillaries/mm2 in the middle part of the LDM). Fibrin application only increased muscle neovascularization. The number of capillaries per mm2 of muscle increased to 250 +/- 25 in the distal part and to 271 +/- 24 in the middle part of the LDM. However, when fibrin was applied with added deferoxamine mesylate, the capillary density increased to 361 +/- 25 capillaries/mm2 in the distal part (p < 0.05 vs fibrin only; controls) and to 401 +/- 20 capillaries/mm2 in the middle part of the LDM (p < 0.05 vs fibrin only and p < 0.001 vs controls). The data are concordant with the blood flow estimation before and after mobilization (severe ischemic shock) in the different parts of the LDM. CONCLUSIONS: Local application of deferoxamine mesylate enhances neovascularization and recovery of surgically induced skeletal muscle ischemia in a sheep model.

Animals↗
PubMed2003

Transplantation of autologous endothelial cells induces angiogenesis.

This study examined the feasibility and efficacy of autologous endothelial cell (EC) transplantation using a fibrin matrix in the ischemic myocardium of sheep. Four weeks after placing an ameroid constrictor in the circumflex artery of 12 adult sheep, four animals (EC group) were subjected to EC transplantation. In four others (saline [SAL] group) saline with added inactivated cells was injected and four animals served as controls. Eight weeks after treatment the animals were sacrificed to assess histology and ultrastructure. Eight weeks after injection, ventricular function was markedly improved in the EC transplant group, but had deteriorated in the SAL and control groups. Myocardial blood flow was also increased in the EC group. Histology and electron microscopy revealed extensive neovascularization after EC transplantation and improved myocardial appearance. Heterotopic transplantation of EC within a fibrin matrix enhances neovascularization, increases myocardial blood flow, and improves left ventricular function.

Animals↗
PubMed2003

Fibrinolytic activity and bleeding after cardiac surgery with cardiopulmonary bypass and low-dose aprotinin therapy.

Low-dose aprotinin inhibits hyperfibrinolysis in cardiac surgery. However, excessive postoperative bleeding and increased fibrinolysis may occur despite low dose-aprotinin administration. We investigated (i) whether fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) whether this is associated with excessive postoperative bleeding (> or = 1000 ml/24 h). In a prospective single-blind trial, 120 consecutive patients were randomized to receive 280 mg aprotinin or no aprotinin before skin incision. D-dimer levels increased significantly to the end of surgery, reaching higher levels in the control group. The risk for excessive bleeding was lower in the aprotinin group (12 versus 37%, = 0.001). Fifteen minutes after heparin reversal, patients were at risk for excessive bleeding, when enhanced fibrinolysis was documented (aprotinin group, D-dimer > or = 1.0 micro g/ml, odds ratio = 9.1, = 0.047; control group, D-dimer > or = 3.0 micro g/ml, odds ratio = 4.6, = 0.014). Ninety-seven per cent of the aprotinin group and 81% of control group patients had no excessive bleeding when the D-dimer plasma level was below these values. We conclude that (i) fibrinolytic activity significantly rises under low-dose aprotinin administration, and (ii) plasma D-dimer levels at end of surgery may help to identify patients who are unlikely to develop excessive postoperative bleeding.

Adult↗
PubMed2003

Impact of gender on the incidence and outcome of contrast-induced nephropathy after percutaneous coronary intervention.

BACKGROUND: Contrast-induced nephropathy (CIN) is a recognized complication after percutaneous interventions (PCI). We sought to determine the impact of gender on incidence and clinical outcome of CIN. METHODS AND RESULTS: Of a total 8,628 patients who underwent PCI, there were 1,431 (16.5%) who developed CIN (defined as > 25% rise in creatinine after PCI). Patients were followed clinically for one year. CIN was present in 23.6% of female versus 17.4% of male patients (p < 0.0001). Multivariate analysis showed that female gender (OR = 1.4, 95% CI = 1.25 1.60; p < 0.0001), pre-PCI chronic renal failure (CRF) (OR= 1.8, 95% CI = 1.53 2.10, p < 0.0001), diabetes mellitus (OR = 1.5, 95% CI = 1.34 1.70; p < 0.0001), age (OR = 1.01, 95% CI = 1.01 1.02, p < 0.0001), and hypertension (OR = 1.2, 95% CI = 1.06 1.36, p = 0.0035) were independent predictors of CIN. Clinical outcomes after CIN were examined in patients with or without CRF. Among patients without CRF who developed CIN, females (n = 465) had higher rates of one-year mortality, and MACE comparing to males (n = 710) without CRF (14% vs. 10% mortality, 36% vs. 30% MACE; p = 0.05 and 0.06, respectively). In patients with CRF who developed CIN, we found no significant gender differences in one-year clinical events (37% vs. 36% mortality, 42% vs. 45% MACE; p = 0.8 and 0.6, respectively). By multivariate analysis only baseline CRF, diabetes, age, functional NYHA IV class were identified as independent predictors of one-year mortality in patients with CIN after PCI. CONCLUSIONS: Female gender is an independent predictor of CIN development after PCI and a marker of worse 1-year mortality after CIN in patients without baseline CRF. After CIN is developed, pre-PCI CRF, diabetes mellitus, age, severe heart failure (not gender) are independent predictors of one-year mortality.

Aged↗
PubMed2003

Radiocontrast nephropathy: identifying the high-risk patient and the implications of exacerbating renal function.

Radiographic procedures using contrast media are widely performed throughout the world. This necessitates physicians' awareness of radiocontrast nephropathy-the disorder that develops as a result of exposure to contrast agents. Although in the general population the risk of radiocontrast nephropathy is rather low, it may be very high in selected subsets of patients. This article focuses on the incidence, pathogenesis, risk factors, and prognosis of radiocontrast nephropathy and provides important insights on its prevention.

Contrast Media↗
PubMed2003

Premature coronary artery disease in systemic lupus erythematosus with extensive reocclusion following coronary artery bypass surgery.

A 21-year-old woman with a history of systemic lupus erythematosus (SLE) presented to the emergency room with a chief complaint of substernal chest pain and palpitations. She had undergone a four-vessel coronary artery bypass graft operation with separate saphenous vein grafts to the left anterior descending (LAD), obtuse marginal (OM) 1 and 2, and distal right coronary arteries (RCA) 8 months prior to admission. The patient underwent angiography of the coronary vessels, which showed severe diffuse disease with a long, 90% narrowing of the vein graft to the LAD and closed vein grafts to OM1 and OM2. The RCA graft showed mild diffuse disease. An intervention was done in which the LAD was stented twice with subsequent TIMI 3 flow. Advances in medical therapy and a better understanding of the disease have contributed to a dramatic improvement in the long-term survival of patients with SLE. However, despite the overall long-term improvement, coronary artery disease remains a major cause of morbidity and mortality with an incidence of approximately nine-fold greater than would be expected for this population.

Adult↗
PubMed2002

Comparison of clinical outcomes using stents versus no stents after percutaneous coronary intervention for proximal left anterior descending versus proximal right and left circumflex coronary arteries.

Previous studies have demonstrated that proximal left anterior descending (LAD) stenoses have higher rates of restenosis after angioplasty than stenoses in other coronary segments. Stenting strategies may reduce this high rate of LAD restenosis. The study population included 1,289 patients with proximal coronary artery stenoses treated with percutaneous coronary interventions (PCI) with or without stents for single-vessel coronary disease between 1994 and 1999. Patients were divided into 4 groups: non-stent PCI in the proximal LAD artery (n = 168), non-stent PCI in proximal right/circumflex artery (n = 217), stent in the proximal LAD artery (n = 364), and stent to proximal right/circumflex artery (n = 540). Procedural success was higher in the stenting groups, but there were no significant differences in the major in-hospital events between the different lesion locations among the groups. At 1-year follow-up, there was no difference in mortality or myocardial infarction between the groups. There was no significant difference in the rate of target lesion revascularization (TLR) in the patients with proximal LAD stents compared with the patients with proximal right/circumflex coronary artery stents (10.1% vs 13.8%, p = 0.11). In the patients who did not receive stents with proximal narrowings, there was a significant increase in TLR in the LAD group compared with the right/circumflex group (21.1% vs 12.5%, p = 0.04). Thus, patients with proximal stenoses treated with non-stenting strategies have lower procedural success than those treated with stenting strategies; the patients with proximal LAD non-stent PCI have significantly higher rates of clinical restenosis than patients with proximal right and circumflex stenoses. A stenting strategy for proximal LAD stenoses appears to attenuate the differences of clinical restenosis noted after non-stent PCI.

Aged↗
PubMed2002

Intramural coronary delivery of advanced antisense oligonucleotides reduces neointimal formation in the porcine stent restenosis model.

OBJECTIVES: We evaluated the long-term influence of intramural delivery of advanced c-myc neutrally charged antisense oligonucleotides (Resten-NG) on neointimal hyperplasia after stenting in a pig model. BACKGROUND: Neointimal hyperplasia after percutaneous coronary interventions is one of the key components of the restenotic process. The c-myc is a critical cell division cycle protein involved in the formation of neointima. METHODS: In short-term experiments, different doses (from 500 microg to 5 mg) of Resten-NG or saline were delivered to the stent implantation site with an infiltrator delivery system (Interventional Technologies, San Diego, California). Animals were euthanized at 2, 6 and 18 h after interventions, and excised vessels were analyzed for c-myc expression by Western blot. In long-term experiments, either saline or a dose of 1, 5 or 10 mg of Resten-NG was delivered in the same fashion, and animals were euthanized at 28 days after the intervention. RESULTS: Western blot analysis demonstrated inhibition of c-myc expression and was dose dependent. Morphometry showed that the intimal area was 3.88 +/- 1.04 mm(2) in the control. There was statistically significant reduction of intimal areas in the 5 and 10 mg groups (2.01 +/- 0.66 and 1.95 +/- 0.91, respectively, p < 0.001) but no significant reduction in the 1 mg group (2.81 +/- 0.56, p > 0.5) in comparison with control. CONCLUSIONS: This study demonstrated that intramural delivery of advanced c-myc neutrally charged antisense morpholino compound completely inhibits c-myc expression and dramatically reduces neointimal formation in a dose dependent fashion in a porcine coronary stent restenosis model, while allowing for complete vascular healing.

Angioplasty, Balloon, Coronary↗
PubMed2002

Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction.

OBJECTIVES: We sought to evaluate and validate the ability of the angiographic myocardial blush grade to risk stratify patients after successful angioplasty in acute myocardial infarction (AMI). BACKGROUND: Although epicardial Thrombolysis In Myocardial Infarction (TIMI)-3 flow is restored in >90% of patients undergoing primary percutaneous coronary intervention (PCI), normal myocardial perfusion may be present less frequently and may detrimentally impact survival. METHODS: A cohort of 173 consecutive patients undergoing intervention within 24 h of AMI onset were studied. High-risk features of this population included failed thrombolysis in 39%, cardiogenic shock in 17% and saphenous vein graft culprit in 11% of patients. RESULTS: Despite the restoration of TIMI-3 flow in 163 (94.2%) patients, myocardial perfusion, as evidenced by normal contrast opacification of the myocardial bed subtended by the infarct artery (myocardial blush), was normal in only 29.4% of patients with TIMI-3 flow following PCI, and in no patient with TIMI 0 to 2 flow. In patients in whom TIMI-3 flow was restored, survival was strongly dependent on the myocardial perfusion grade; one-year cumulative mortality was 6.8% with normal myocardial blush, 13.2% with reduced myocardial blush and 18.3% in patients with absent myocardial blush (p = 0.004). CONCLUSIONS: Abnormal myocardial perfusion is present in most patients following primary or rescue PCI in AMI, despite restoration of brisk epicardial coronary flow. In high risk patients achieving TIMI-3 flow after intervention, the myocardial blush score may be used to stratify prognosis into excellent, intermediate and poor survival. Further study is warranted to examine whether adjunctive mechanical or pharmacologic strategies can further improve myocardial perfusion and survival of patients with acute myocardial infarction undergoing intervention.

Aged↗
PubMed2002

Quantitative angiographic methods for appropriate end-point analysis, edge-effect evaluation, and prediction of recurrent restenosis after coronary brachytherapy with gamma irradiation.

OBJECTIVES: The study was done to investigate the relationship between clinical restenosis and the relative angiographic location of the recurrent restenotic lesion, after treatment of in-stent restenosis with vascular brachytherapy in the Washington Radiation for In-Stent Restenosis Trial (WRIST). BACKGROUND: Intracoronary radiation therapy reduces recurrence of in-stent restenosis. We investigated the above objective in patients enrolled in WRIST. METHODS: The WRIST study randomized 130 patients to double-blinded therapy with gamma irradiation (iridium-192 [(192)Ir]) versus placebo after interventional treatment of diffuse in-stent restenosis. After the intervention and at follow-up, three vessel segments were individually analyzed with quantitative coronary angiography: 1) the "stent," 2) the "radiation ribbon," and 3) the "ribbon+margin" segment (including 5 mm on either end of the injured or radiation-ribbon segment). Receiver operator curves (ROC) were used to assess the value of the follow-up percent diameter stenosis (DS) for each of the three analyzed segments in predicting target vessel revascularization (TVR). RESULTS: (192)Ir reduced recurrent restenosis (23.7% vs. 60.7%, p < 0.001) and the length of recurrent restenosis (8.99 +/- 4.34 mm vs. 17.54 +/- 10.48 mm, p < 0.001) at follow-up compared to placebo. Isolated stent edge (3.4%) and ribbon edge (1.7%) restenoses were infrequent in both groups. The best angiographic surrogate of TVR was the 50% follow-up DS obtained from the ribbon+margin analysis (ROC area 0.806). CONCLUSIONS: In WRIST, not only was (192)Ir therapy effective in reducing restenosis, but it also reduced the lesion length of treatment failures by 50%, and it was not associated with edge proliferation. The restenosis rate obtained from the vessel segment inclusive of the dose fall-off zones was the best correlate of TVR and should become a standard analysis site in all vascular brachytherapy trials.

Brachytherapy↗