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Biomedical subjects

G D Angelini

Publications and source records attributed to G D Angelini.

At least 19 recordsLinked to original sources
PubMed2006

Reactive oxygen species and erectile dysfunction: possible role of NADPH oxidase.

Erectile dysfunction (ED) is a widespread condition, the incidence of which is increasing globally. ED is also indicative of underlying vasculopathy and represents a predictor of more serious cardiovascular disorders. Understanding the aetiology of ED may therefore provide invaluable pointers to the pathobiology of other cardiovascular diseases (CVDs) and syndromes. It follows, too, that therapeutic interventions that are successful in treating ED may, ipso facto, be effective in treating the early stages of conditions that include atherosclerosis, angina, plaque rupture and diabetic angiopathy. One common pathological denominator in both CVD and ED is oxidative stress, that is, the overproduction of reactive oxygen species (ROS), in particular, superoxide (O(2)(*-)) and hydrogen peroxide (H(2)O(2)). In this review, therefore, we consider the aetiology and pathobiology of O(2)(*-) in promoting ED and focus on NADPH oxidase as an inducible source of O(2)(*-) and H(2)O(2). Therapeutic strategies aimed at reducing oxidative stress to improve erectile function are also discussed.

Animals↗
PubMed2006

Influence of concomitant coronary artery bypass graft on outcome of surgery of the ascending aorta/arch.

BACKGROUND: Surgery of the ascending aorta with or without arch is being performed in an increasingly elderly population with risks of coexisting coronary artery disease. AIM: To define specific groups requiring coronary artery bypass graft (CABG) and to analyse the influence of concomitant CABG on outcome. DESIGN: Over a 10-year period in a single institution, 296 consecutive procedures on the ascending aorta with or without arch were carried out in 291 patients. CABG was required in 42 (14.2%) procedures. In 24 (57%) patients, CABG was planned preoperatively and in 18 (43%) patients, on a salvage basis. RESULTS: In-hospital mortality for patients undergoing concomitant CABG was higher (21.4% v 11%, p<0.06). Adjusting for baseline and operative characteristics, this was attributable to operative priority, and was not a consequence of concomitant CABG (adjusted OR 0.30, 95% CI 1.1 to 8.31; p = 0.48). However, in-hospital mortality was significantly higher when CABG was performed as salvage rather than as a planned procedure (38.9% v 8.9%, p = 0.025), and this difference remained after adjusting for confounding variables (adjusted OR 16.2, 95% CI 1.03 to >200; p = 0.047). The 3-year survival was significantly lower with concomitant CABG (59% v 81.9%, p<0.001). CONCLUSIONS: In association with surgery of the ascending aorta with or without arch planned concomitant CABG did not entail any added operative risk. However, salvage CABG, which occurred almost exclusively in association with emergency cases, was associated with a higher early mortality. Patients needing concomitant CABG had worse survival at 3 years compared with those requiring isolated surgery of the ascending aorta with or without arch.

Aged↗
PubMed2005

Postoperative chest radiographic changes after on- and off-pump coronary surgery.

AIM: A variety of chest radiograph abnormalities are recognized after coronary artery bypass grafting (CABG). This study analyzes the appearance of preoperative and postoperative chest radiographs in two groups of patients undergoing myocardial revascularization with or without the use of cardiopulmonary bypass (CPB). METHODS: Chest radiographs (preoperative and at 1 day, 6 days and 6 to 8 weeks post operatively) were analyzed according to a detailed protocol in cases of conventional CABG on CPB (n=60) or off-pump coronary artery bypass (OPCAB) (n=60) surgery. On each film 17 different major potential postoperative abnormalities were analyzed. RESULTS: Clinical findings were similar in the two groups. Patients undergoing OPCAB surgery had decreased blood loss, decreased red cell and platelet transfusion, significantly lower intubation time and required less postoperative inotropic support compared with patients undergoing CPB. The CPB group had a significantly higher incidence of left band atelectasis than the OPCAB group (37.6% vs 17.5%, p=0.01) at 6 days postoperatively. There was no other statistically significant difference in any of the 16 remaining major chest radiograph findings between the two groups. CONCLUSION: Although OPCAB surgery is associated with improved clinical outcome compared with conventional CABG surgery, the analysis of postoperative chest radiographs demonstrated only a minor benefit as shown by a reduced degree of left band atelectasis in the OPCAB group.

Aged↗
PubMed2005

Safety, efficacy, and cost of intraoperative cell salvage and autotransfusion after off-pump coronary artery bypass surgery: a randomized trial.

OBJECTIVE: We evaluated, in a randomized controlled trial, the safety and effectiveness of intraoperative cell salvage and autotransfusion of washed salvaged red blood cells after first-time coronary artery bypass grafting performed on the beating heart. METHODS: Sixty-one patients undergoing off-pump coronary artery bypass grafting surgery were prospectively randomized to autotransfusion (n = 30; receiving autotransfused washed blood from intraoperative cell salvage) or control (n = 31; receiving homologous blood only as blood-replacement therapy). Homologous blood was given according to unit protocols. RESULTS: The groups were well matched with respect to demographic and comorbid characteristics. Patients in the autotransfusion group had a significantly higher 24-hour postoperative hemoglobin concentration (11.9 g/dL; SD, 1.41 g/dL) than those in the control group (10.5 g/dL; SD, 1.37 g/dL) (mean difference, 1.02 g/dL; 95% confidence interval, 1.60-0.44 g/dL; P = .0007), as well as a 20% reduction in the frequency of homologous blood product use (11/31 vs 5/30; P = .095). Autotransfusion of washed red blood cells was not associated with any derangement of thromboelastograph values or laboratory measures of clotting pathway function (prothrombin time, activated partial thromboplastin time, and fibrinogen levels), increased postoperative bleeding, fluid requirements, or adverse clinical events. There was no statistical difference between groups in the total operation, hospitalization, and management costs per patient (median difference, USD 1015.90; 95% confidence interval, -USD 2260 to USD 206; P = .11). Conclusions Intraoperative cell salvage and autotransfusion was associated with higher postoperative hemoglobin concentrations, a modest reduction in transfusion requirements, no adverse clinical or coagulopathic effects, and no significant increase in cost compared with controls. This study supports its routine use in off-pump coronary artery bypass grafting surgery.

Adult↗
PubMed2005

Risk factors for and economic implications of prolonged ventilation after cardiac surgery.

OBJECTIVE: The study's objective was to identify predictors of prolonged ventilation and assess clinical and cost implications in patients undergoing cardiac surgery. METHODS: Patients undergoing cardiac surgery were classified as (1) ventilated less than 96 hours or (2) ventilated 96 hours or more. Multivariate modeling was used to identify predictors of prolonged ventilation and to ascertain the impact of prolonged ventilation on in-hospital mortality and bed occupancy costs and 5-year survival. RESULTS: A total of 7553 patients were studied; 197 (2.6%) had prolonged ventilation. Median ventilation times were 8 and 192 hours, and in-hospital mortality was 1.0% and 22.2% in the control and prolonged ventilation groups, respectively (P < .001). In-hospital mortality remained higher in the prolonged ventilation group after adjustment and when comparing propensity-matched patients (odds ratio 8.06; 95% confidence interval [CI] 4.27-15.2; P < .001 for propensity-matched groups). Independent predictors of prolonged ventilation were as follows: older age, New York Heart Association class, ejection fraction less than 50%, creatinine greater than 200 micromol/L, multiple valve replacements, aortic procedures, operative priority, reoperation for bleeding, inotropes, and preoperative intra-aortic balloon pump. Five-year survival was lower in the prolonged ventilation group (56.1% [95% CI 46.6%-64.6%] vs 88.8% [95% CI 87.9%-89.6%]) also after adjustment for imbalances and when comparing propensity-matched patients (hazard ratio 2.39; 95% CI 1.75-3.27; P < .001 for propensity-matched groups). Mean bed occupancy costs were 14,286 dollars (95% CI 12,731 dollars-15,690 dollars) and 2761 dollars (95% CI 2705 dollars-2814 dollars) in the prolonged ventilation and control groups, respectively (P < .001). CONCLUSION: Prolonged ventilation is associated with high in-hospital mortality and costs, and poor 5-year survival. Identified predictors of prolonged ventilation might help to optimize the clinical management of these patients.

Aged↗
PubMed2005

Acute hypoxia simultaneously induces the expression of gp91phox and endothelial nitric oxide synthase in the porcine pulmonary artery.

BACKGROUND: The effect of hypoxia on the formation of superoxide (O2-), the expression of gp91phox and endothelial NO synthase (eNOS) were studied in pig intact pulmonary artery (PA) segments and PA vascular smooth muscle cells (PAVSMCs) and PA endothelial cells (PAECs). METHODS: Segments and cells were incubated under hypoxic conditions for 2 hours (with or without enzyme inhibitors) and the formation of O2- measured spectrophotometrically. Protein expression was assessed using Western blotting and immunocytochemistry. RESULTS: Hypoxia promoted the formation of O2- in PA segments, PAVSMCs and PAECs, an effect inhibited by diphenylene iodonium and apocynin (NAD[P]H oxidase inhibitors). Hypoxia induced O2- formation was enhanced by inhibition of eNOS and augmented by endotoxin and cytokines and re-oxygenation. Hypoxia also promoted the expression of gp91phox and eNOS. In intact PA segments hypoxia induced the expression of nitrotyrosine and eNOS in the endothelium. CONCLUSIONS: The simultaneous upregulation of NAD[P]H oxidase and eNOS in response to hypoxia in the PA results in the simultaneous formation of O2-, NO, and ONOO-. This may represent either a protective mechanism designed to counter the pro-oxidant effect of hypoxia or a novel pathological mechanism underlying the progression of acute respiratory distress syndrome (ARDS).

Animals↗
PubMed2004

Early and mid-term outcomes of surgery of the ascending aorta/arch: is there a relationship with caseload?

OBJECTIVES: The relationship between caseload and early outcome remains a subject for debate in cardiac surgery. Surgery of the thoracic aorta is an area of specialist expertise within the adult cardiac surgical field. There is, however, a conflict between the concentration of expertise and the provision of effective emergency cover. This study evaluates the early and mid-term outcomes of patients undergoing surgery of the ascending aorta/aortic arch in a single institution and compares the results of a single higher volume surgeon with lower volume operators. METHODS: From March 1992 till August 2003, 296 procedures were carried out on 291 patients (aged 17-80, median 62) who underwent operations for replacement of the ascending aorta/aortic arch. One hundred and thirty procedures were carried out by the higher volume surgeon and 160 by one of the six lower volume surgeons (range 10-57). Emergency operation was performed in 138 (47%) patients. One or more other associated cardiac procedures were carried out in 65 patients (22%). RESULTS: The overall early mortality was 37 (12.5%). After adjustment for baseline differences, era and surgical risk/complexity, the risk of in-hospital death was lower in the higher volume group, but not significantly so. For survival to 3 years the overall risk of death was significantly lower for patients in the higher volume group (hazard ratio 0.72; 95% CI 0.54-0.95) Apart from post-operative renal failure no other significant differences between the two groups were observed. CONCLUSIONS: Elective surgery of the ascending aorta/arch was associated with low mortality. Outcomes after emergency surgery conformed to contemporary expectations. Only limited differences were identified both with respect to the case profile and early clinical outcomes. Better outcomes in the mid-term in the higher volume group persisted despite adjustment for differences in caseload and are worthy of further study. We believe that these data support our hypothesis that dissemination of appropriate techniques among a group of surgeons represents the most practical method of service provision.

Adolescent↗
PubMed2004

Coronary artery bypass grafting in the awake patient: combined thoracic epidural and lumbar subarachnoid block.

High thoracic epidural anaesthesia has recently been proposed to perform surgical revascularisation with arterial grafts in awake patients. However, in high-risk patients with associated co-morbidity it is not always possible to perform complete arterial revascularisation. A technique which combines thoracic epidural and selective lumbar subarachnoid block is described, allowing harvesting of saphenous vein and complete surgical revascularisation in awake patients.

Aged↗
PubMed2004

Myocardial metabolic changes during pediatric cardiac surgery: a randomized study of 3 cardioplegic techniques.

BACKGROUND: Blood cardioplegia and terminal warm blood cardioplegic reperfusion ("hot shot") reduce myocardial injury and improve metabolic recovery in hypoxic but not normoxic experimental models. However, there is little evidence of a benefit of either technique in pediatric clinical practice compared with crystalloid cardioplegia. METHODS: Pediatric patients undergoing cardiac surgery were randomized to receive intermittent antegrade cold crystalloid cardioplegia, cold blood cardioplegia, or cold blood cardioplegia with a hot shot. Right ventricular biopsy specimens were collected before ischemia, at the end of ischemia, and 20 minutes after reperfusion. Cellular metabolites were analyzed. In acyanotic patients postoperative serum troponin I levels were also measured at 1, 4, 12, 24, and 48 hours. RESULTS: Of 103 patients recruited, 32 (22 acyanotic and 10 cyanotic), 36 (24 acyanotic and 12 cyanotic), and 35 (25 acyanotic and 10 cyanotic), respectively, were allocated to the groups receiving cold crystalloid cardioplegia, cold blood cardioplegia, and cold blood cardioplegia with a hot shot. Cyanotic patients were younger, with longer crossclamp times. There were no significant differences in clinical outcomes between cardioplegic methods. The cardioplegic method had no overall effect in terms of adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), or ln(glutamate) in acyanotic patients (P =.11, P =.66, and P =.30, respectively). Also, there was no significant difference between groups in troponin I release. However, in cyanotic patients cold blood cardioplegia with a hot shot significantly reduced the decrease in adenosine triphosphate, ln(adenosine triphosphate/adenosine diphosphate), and glutamate observed at the end of ischemia and after reperfusion compared with the decrease seen in those receiving cold crystalloid cardioplegia (P =.002, P =.003, and P =.008, respectively), with cold blood cardioplegia representing an intermediate. CONCLUSIONS: For cyanotic patients (younger, with longer crossclamp times), cold blood cardioplegia with a hot shot is the best method of myocardial protection. For acyanotic patients (older, with shorter crossclamp times), cardioplegic technique is not critical.

Adenosine Diphosphate↗
PubMed2004

Low micromolar concentrations of copper augment the impairment of endothelium-dependent relaxation of aortae from diabetic rabbits.

Both diabetes mellitus (DM) and elevated plasma copper concentrations are risk factors for cardiovascular disease (CVD). DM is associated with impaired endothelial nitric oxide (NO) and with excess superoxide (O2*-) formation. Copper is also elevated in DM and is also associated with the generation of O2*-. To explore possible interactions between DM and copper, the effect of exogenous copper (CuCl2) on endothelium-dependent relaxation and cyclic guanosine monophosphate (GMP) formation was investigated in aortae from diabetic rabbits. Rabbits were rendered diabetic by intravenous injection of alloxan. Six months after induction of DM, the aortae were excised, cut into rings, and mounted in an organ bath for isometric measurement of acetylcholine (Ach)-evoked relaxation in rings precontracted with phenylephrine (PE). In parallel studies, cyclic (c)GMP formation by aortic rings following stimulation with Ach, calcium ionophore A23187 (A23187) and sodium nitroprusside (SNP) was assessed using radioimmunoassay. The effect of copper on these parameters was then studied using the same methods. Ach-evoked relaxation and Ach- and A23187-evoked cGMP formation were significantly impaired in aortae from diabetic rabbits compared to controls, effects that were reversed with superoxide dismutase (SOD) and catalase (CAT). In contrast, there were no significant differences in SNP-stimulated relaxation or cGMP formation in aortae from diabetic rabbits compared to controls. Copper (1 to 10 micromol/L) promoted a further significant inhibition of Ach-stimulated relaxation in aortae from diabetic but not control rabbits. This reduction by copper was again reversed by SOD and CAT. We conclude that copper augments the reduction of NO bioavailability, which is already impaired in aortae from diabetic rabbits due to excess production of O2*- and H2O2. These results indicate that patients with DM may be susceptible to copper-mediated vasculopathy at much lower concentrations than those that promote vasculopathy in nondiabetic patients.

Acetylcholine↗
PubMed2004

A multi-centre randomised controlled trial of minimally invasive direct coronary bypass grafting versus percutaneous transluminal coronary angioplasty with stenting for proximal stenosis of the left anterior descending coronary artery.

OBJECTIVES: To compare the clinical- and cost-effectiveness of minimally invasive direct coronary artery bypass grafting (MIDCAB) and percutaneous transluminal coronary angioplasty (PTCA) with or without stenting in patients with single-vessel disease of the left anterior descending coronary artery (LAD). DESIGN: Multi-centre randomised trial without blinding. The computer-generated sequence of randomised assignments was stratified by centre, allocated participants in blocks and was concealed using a centralised telephone facility. SETTING: Four tertiary cardiothoracic surgery centres in England. PARTICIPANTS: Patients with ischaemic heart disease with at least 50% proximal stenosis of the LAD, suitable for either PTCA or MIDCAB, and with no significant disease in another vessel. INTERVENTIONS: Patients randomised to PTCA had local anaesthetic and underwent PTCA according to the method preferred by the operator carrying out the procedure. Patients randomised to MIDCAB had general anaesthetic. The chest was opened through an 8-10-cm left anterior thoracotomy. The ribs were retracted and the left internal thoracic artery (LITA) harvested. The pericardium was opened in the line of the LAD to confirm the feasibility of operation. The distal LITA was anastomosed end-to-side to an arteriotomy in the LAD. All operators were experienced in carrying out MIDCAB. MAIN OUTCOME MEASURES: The primary outcome measure was survival free from cardiac-related events. Relevant events were death, myocardial infarction, repeat coronary revascularisation and recurrence of symptomatic angina or clinical signs of ischaemia during an exercise tolerance test at annual follow-up. Secondary outcome measures were complications, functional outcome, disease-specific and generic quality of life, health and social services resource use and their costs. RESULTS: A total of 12,828 consecutive patients undergoing an angiogram were logged at participating centres from November 1999 to December 2001. Of the 1091 patients with proximal stenosis of the LAD, 127 were eligible and consented to take part; 100 were randomised and the remaining 27 consented to follow-up. All randomised participants were included in an intention-to-treat analysis of survival free from cardiac-related events, which found a non-significant benefit from MIDCAB. Cumulative hazard rates at 12 months were estimated to be 7.1 and 9.2% for MIDCAB and PTCA, respectively. There were no important differences between MIDCAB and PTCA with respect to angina symptoms or disease-specific or generic quality of life. The total NHS procedure costs were 1648 British pounds and 946 British pounds for MIDCAB and PTCA, respectively. The costs of resources used during 1 year of follow-up were 1033 British pounds and 843 British pounds, respectively. CONCLUSIONS: The study found no evidence that MIDCAB was more effective than PTCA. The procedure costs of MIDCAB were observed to be considerably higher than those of PTCA. Given these findings, it is unlikely that MIDCAB represents a cost-effective use of resources in the reference population. Recent advances in cardiac surgery mean that surgeons now tend to carry out off-pump bypass grafting via a sternotomy instead of MIDCAB. At the same time, cardiologists are treating more patients with multi-vessel disease by PTCA. Future primary research should focus on this comparison. Other small trials of PTCA versus MIDCAB have now finished and a more conclusive answer to the original objective could be provided by a systematic review.

Aged↗
PubMed2003

Treatment of an aortic fungal false aneurysm by composite stentless porcine/pericardial conduit: a case report.

Fungal prosthetic valve endocarditis is an uncommon but serious condition with high early and long-term mortality. The majority of these cases occur after aortic valve surgery and are caused by Candida species. Radical debridement of all infected tissues, valve replacement with perioperative and long-term anti-fungal agents is the recommended treatment. Choice of prosthesis varies widely among surgeons, but present recommendations favour biological prostheses. We report for the first time the case of a fungal PVE with false aneurysm after composite aortic root replacement with a dacron composite conduit treated successfully with aortic root replacement using a Shelhigh (Shelhigh Inc., Millburn, NJ) stentless porcine pericardial valved conduit.

Adult↗
PubMed2003

Operative factors that contribute to post-operative atrial fibrillation: insights from a prospective randomized trial.

Atrial fibrillation (AF) is the most common complication following cardiac surgery and is associated with significant increases in postoperative morbidity, length of stay and cost of care. In a randomized study we assessed the impact of coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) (off-pump, n = 100), compared to conventional (on-pump, n = 100) CABG, on the frequency of postoperative AF. Arrhythmias were detected using an automated arrhythmia detector for the first 72 hours following surgery and by four hourly clinical observations thereafter. AF was defined as an irregular narrow complex rhythm (in the absence of bundle branch block) with absence of discrete P waves lasting greater then 10 minutes. There was a significant reduction in the incidence of postoperative AF in the off-pump group (11% versus 45%, P < 0.001) in addition to significant reductions in blood usage, postoperative pneumonia, inotrope requirements, and hospital and intensive care unit stay. Univariate analysis identified all these variables as risk factors for AF, however multivariate regression analysis identified CPB and cardioplegic arrest as the only independent predictor of postoperative AF (OR 7.4; 95% CI 3.4 to 17.9). This study therefore suggests that the inflammatory response to bypass, myocardial ischaemia and atrial cannulation are significant contributory factors to the development of AF following cardiac surgery. In the light of more recent trials it is apparent that this benefit may be most marked in patients with multiple perioperative risk factors for postoperative AF.

Adrenergic beta-Antagonists↗