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Biomedical subjects

G D Angelini

Publications and source records attributed to G D Angelini.

At least 55 records · Page 3Linked to original sources
PubMed2001

Off-pump coronary artery bypass surgery for critical left main stem disease: safety, efficacy and outcome.

OBJECTIVES: To determine whether patients with critical left main stem (LMS) coronary artery disease can undergo off-pump coronary artery bypass (OPCAB) surgery safely and successfully. METHODS: From May 1996 to March 2000 data for patients with critical (> or =50%) LMS stenosis who underwent conventional coronary artery bypass surgery with cardiopulmonary bypass (CCAB) or without (OPCAB) were collected prospectively using the Patient Analysis & Tracking System. A reusable pressure stabilizer, intra-coronary shunts and a single posterior pericardial stitch exposure technique were used in all OPCAB cases. Non-randomized, retrospective data analysis included demographic and preoperative risk factors, operative details, clinical outcome and early follow-up. RESULTS: During the study period 387 patients with LMS stenosis underwent surgery (OPCAB n=75, CCAB n=312). Groups were similar in terms of preoperative and intraoperative variables although CCAB patients received significantly more grafts per patient (3.1+/-0.73 vs. 2.6+/-0.76, P< or =0.001). Mortality was similar in both groups (OPCAB 1.3% vs. CCAB 2.6%). OPCAB patients when compared to CCAB patients had a lower requirement for postoperative inotropes (12.0% vs. 38.1%, P=0.0001), temporary postoperative pacing (2.7% vs. 10.1%, P=0.02), and blood product transfusion (6.7% vs. 31.4%, P<0.0001), a lower incidence of postoperative chest infection (0% vs. 6.7%, P=0.02) and a slightly reduced postoperative length of stay (7.9+/-5.46 vs. 8.3+/-5.11 days, P=0.01). At 24 months follow-up, CCAB and OPCAB actuarial survival was 94.1+/-1.7% and 97.7+/-2.3%, respectively. CONCLUSIONS: OPCAB surgery is safe and effective in patients with critical LMS disease.

Aged↗
PubMed2001

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis.

Patency of autologous human saphenous vein coronary artery bypass grafts (CABG) is compromised by intimal thickening and superimposed atherosclerosis, caused by migration of vascular smooth muscle cells (SMC) to the intima where they proliferate. Here, using adenoviral transfer, we have targeted SMCs using wild-type p53 (wt p53) overexpression. Initial in vitro analyses demonstrated that wt p53 overexpression had no effect on SMC proliferation but promoted apoptosis, which was inhibited by co-expression of bcl2 or crmA. Wt p53 inhibited SMC invasion through reconstituted matrices, a phenotype not affected by bcl2 or crmA. Overexpression of wt p53 in human saphenous vein before organ culture significantly induced apoptosis (P < 0.01, Student's t test) without affecting proliferation rates either in the media or in the intima. SMC migration was, however, significantly reduced by wt p53 (P < 0.01, Student's t test). Intimal thickening and the number of neointimal cells were reduced by 89% and 73%, respectively, after 14 days (P < 0.01 and P < 0.001, respectively, Student's t test). This study demonstrates that overexpression of wt p53 promotes apoptosis and inhibits migration of SMC leading to reduced intimal thickening. This maybe a useful approach for increasing patency rates in CABG procedures in the clinic.

Adenoviridae↗
PubMed2001

Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study.

OBJECTIVE: Coronary artery bypass grafting on the beating heart through median sternotomy is a relatively new treatment, which allows multiple revascularization without the use of cardiopulmonary bypass. A prospective randomized study was designed to investigate the effect of coronary bypass with or without cardiopulmonary bypass on postoperative blood loss and transfusion requirement. METHODS: Two hundred patients with coronary artery disease were prospectively randomized to (1) on-pump treatment with conventional cardiopulmonary bypass and cardioplegic arrest and (2) off-pump treatment on the beating heart. Postoperative blood loss identified as total chest tube drainage, transfusion requirement, and related costs together with hematologic indices and clotting profiles were analyzed. RESULTS: There was no difference between the groups with respect to preoperative and intraoperative patient variables. The mean ratio of postoperative blood loss and 95% confidence interval between groups was 1.64 and 1.39 to 1.94, respectively, suggesting on average a postoperative blood loss 1.6 times higher in the on-pump group compared with the off-pump group. Seventy-seven patients in the off-pump group required no blood transfusion compared with only 48 in the on-pump group (P <.01). Furthermore, less than 5% of patients in the on-pump group required fresh frozen plasma and platelet transfusion compared with 30% and 25%, respectively, in the on-pump group (both P <.05). Mean transfusion cost per patient was higher in the on-pump compared with that in the off-pump group ($184.8 +/- $35.2 vs $21.47 +/- $6.9, P <.01). CONCLUSIONS: Coronary artery bypass grafting on the beating heart is associated with a significant reduction in postoperative blood loss, transfusion requirement, and transfusion-related cost when compared with conventional revascularization with cardiopulmonary bypass and cardioplegic arrest.

Blood Transfusion↗
PubMed2001

Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein.

Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure.

Caseins↗
PubMed2000

Predictors of atrial fibrillation after conventional and beating heart coronary surgery: A prospective, randomized study.

BACKGROUND: Atrial fibrillation (AF) increases the morbidity of CABG. The pathophysiology is uncertain, and its prevention remains suboptimal. This prospective, randomized study was designed to define the role of cardiopulmonary bypass (CPB) and cardioplegic arrest in the pathogenesis of this complication. METHODS AND RESULTS: Two hundred patients were prospectively randomized to (1) on-pump conventional surgery [(100 patients, 79 men, mean age 63 (40 to 77) years)] with normothermic CPB and cardioplegic arrest of the heart or (2) off-pump surgery [(100 patients, 82 men, mean age 63 (38 to 86) years)] on the beating heart. Heart rate and rhythm were continuously monitored with an automated arrhythmia detector during the first 72 hours after surgery. Thereafter, routine clinical observation was performed and continuous monitoring restarted in the case of arrhythmia. The association of perioperative factors with AF was investigated by univariate analysis. Significant variables were then included into a stepwise logistic regression model to ascertain their independent influence on the occurrence of AF. There were no significant baseline differences between groups. Thirty-nine patients in the on-pump group and 8 patients in the off-pump group had postoperative sustained AF (P:=0.001). Univariate analysis showed that CPB inclusive of cardioplegic arrest, postoperative inotropic support, intubation time, chest infection, and hospital length of stay were predictors of AF (all P:<0.05). However, stepwise multivariate regression analysis identified CPB inclusive of cardioplegic arrest as the only independent predictor of postoperative AF (OR 7.4; CI 3.4 to 17.9). CONCLUSIONS: CPB inclusive of cardioplegic arrest is the main independent predictor of postoperative AF in patients undergoing coronary revascularization.

Adult↗
PubMed2000

Inhibition of late vein graft neointima formation in human and porcine models by adenovirus-mediated overexpression of tissue inhibitor of metalloproteinase-3.

BACKGROUND: Autologous saphenous vein coronary artery bypass graft surgery is complicated by late graft failure due to neointima formation and subsequent atherosclerosis. Growth factors and metalloproteinases (MMPs) act in concert to promote neointima formation. Tissue inhibitor of metalloproteinase-3 (TIMP-3), an extracellular matrix-associated MMP inhibitor, uniquely promotes apoptosis of isolated vascular smooth muscle cells. Here, we overexpressed TIMP-3 at the luminal surface of human saphenous veins before organ culture and in pig saphenous veins before interposition grafting into carotid arteries in vivo to assess neointima formation. METHODS AND RESULTS: In both models, high TIMP-3 immunoreactivity occurred in the luminal and upper medial extracellular matrix after adenovirus delivery. MMP activity measured by in situ zymography was reduced throughout the veins, confirming a bystander effect. By use of 3 independent techniques, apoptosis levels in the neointima and medial layer were significantly elevated by TIMP-3 overexpression. Neointima formation was reduced by 84% in 14-day human organ cultures and by 58% in 28-day pig vein grafts (both P<0.05). In contrast, TIMP-2 overexpression had no effect on neointima formation in vivo. CONCLUSIONS: Our results highlight the potential therapeutic benefit for TIMP-3 overexpression to reduce neointima formation associated with late vein graft failure.

Adenoviridae↗
PubMed2000

Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition.

OBJECTIVE: Diminishing oxidative stress may protect the heart against ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest. METHOD: Isolated perfused Wistar rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working heart mode) in the presence or absence of propofol. MPT pore opening was determined using [3H]-2-deoxyglucose-6-phosphate ([3H]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress. RESULTS: Propofol (2 micrograms/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4 +/- 6.2 to 53.3 +/- 7.3 mmHg and left ventricular end diastolic pressure from 52.9 +/- 4.3 to 37.5 +/- 3.9 mmHg). Recovery was also improved in propofol (4 micrograms/ml) treated working hearts following cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42 +/- 0.05 to 0.60 +/- 0.03 J/s, representing 45-64% of baseline values, when compared to controls (P < 0.05). Propofol inhibited MPT pore opening during reperfusion, [3H]-DOG-6P entrapment being 16.7 vs. 22.5 ratio units in controls (P < 0.05). Mitochondria isolated from non-ischaemic, propofol-treated hearts exhibited increased respiratory chain activity and were less sensitive to calcium-induced MPT pore opening. CONCLUSION: Propofol confers significant protection against global normothermic ischaemia and during cold cardioplegic arrest. This effect is associated with less opening of mitochondrial MPT pores, probably as a result of diminished oxidative stress. Propofol may be a useful adjunct to cardioplegic solutions in heart surgery.

Analysis of Variance↗
PubMed2000

Inflammatory response after coronary revascularization with or without cardiopulmonary bypass.

BACKGROUND: We sought to investigate the effect of multiple coronary artery bypass grafting (CABG) with or without cardiopulmonary bypass (CPB) on the perioperative inflammatory response. METHODS: Sixty patients undergoing CABG were randomly assigned to one of two groups: (A) on pump with conventional CPB and cardioplegic arrest, and (B) off pump on the beating heart. Serum samples were collected for estimation of neutrophil elastase, interleukin 8 (IL-8), C3a, and C5a preoperatively and at 1, 4, 12, and 24 hours postoperatively. Furthermore, white blood cell (WBC), neutrophil, and monocyte counts were carried out preoperatively and at 1, 12, 36 and 60 hours postoperatively. Overall incidence of infection and perioperative clinical outcome were also recorded. RESULTS: The groups were similar in terms of age, weight, gender ratio, extent of coronary disease, left ventricular function, and number of grafts per patient. Neutrophil elastase concentration peaked early after CPB in the on-pump group, with a decline with time. Repeated-measures analysis of variance between groups and comparisons at each time point (modified Bonferroni) showed elastase concentrations were significantly higher in the on-pump than the off-pump group (both p < 0.0001). IL-8 increased significantly after surgery in the on-pump group, with no decline during the observation period (p = 0.01 vs off pump). C3a and C5a rose early after surgery in both groups when compared with baseline values. Postoperative WBC, neutrophil, and monocyte counts were significantly higher in the on-pump than the off-pump group (p < 0.01). Finally, the incidence of postoperative overall infections was significantly higher in the on-pump group (p < 0.0001 vs off pump). CONCLUSIONS: CABG on the beating heart is associated with a significant reduction in inflammatory response and postoperative infection when compared with conventional revascularization with CPB and cardioplegic arrest.

Aged↗
PubMed2000

Effect of cardiopulmonary bypass on pulmonary gas exchange: a prospective randomized study.

BACKGROUND: Conventional coronary artery bypass surgery is associated with postoperative pulmonary dysfunction. Inflammation due to cardiopulmonary bypass has been regarded as one of the main causes. In this study, we investigated the effect of coronary revascularization with or without cardiopulmonary bypass on pulmonary function. METHODS: Fifty-two patients (40 male, mean age 60.1 years) were prospectively randomized to undergo coronary revascularization via median sternotomy, with or without normothermic cardiopulmonary bypass. Alveolar-arterial oxygen gradients were measured before and after induction of anesthesia, postoperatively in the intensive care unit during mechanical ventilation and 6 hours after tracheal extubation. The techniques of anesthesia and mechanical ventilation were standardized throughout. RESULTS: Patient characteristics were similar in the two groups. The alveolar-arterial oxygen gradients increased progressively throughout the perioperative period, with no significant differences in the two groups at any time during the study. CONCLUSIONS: Myocardial revascularization with or without cardiopulmonary bypass caused a similar degree of pulmonary dysfunction, as assessed by alveolar-arterial oxygen gradient. Our study suggests that the deterioration in pulmonary gas exchange associated with cardiac surgery is due to factors other than the use of cardiopulmonary bypass.

Body Temperature↗
PubMed2000

Neural reorganisation in porcine vein grafts: a potential role for endothelin-1.

Vein grafts are associated with adventitial remodelling which may influence innervation of the graft. Since there is also evidence that endothelin-1 (ET-1) plays a role in the adventitial remodelling process, we investigated neural distribution in porcine vein grafts 1 and 6 months after implantation, as well as the localisation of immunoreactive ET-1 and its receptors in the same tissues. Saphenous vein-carotid artery interposition grafting was performed in Landrace pigs. One and 6 months after surgery, vein grafts and ungrafted saphenous veins were excised; neural tissue and ET-1 were identified by immunocytochemistry and ET receptors were identified using in vitro autoradiography. In ungrafted saphenous veins, abundant perivascular nerves were located in the outer region of the media with only a few paravascular nerves in the adventitia. In vein grafts at 1 month after implantation, there was almost complete depletion of perivascular nerves in the media. In contrast, in the neoadventitia, there was an emphatic appearance of large paravascular nerve bundles and a marked increase in small paravascular nerves. These changes were more pronounced at 6 months after surgery, although the principal changes had occurred within 1 month. Immunoreactive ET-1 (index of ET-1 content) was associated with paravascular nerve bundles, appearing as a dark, dense ring at the perineurium. Furthermore, within the nerve bundles, positive ET-1 immunoreactivity was associated with positive alpha-actin staining, indicating that ET-1 is associated with (neural) microvessels. Also, dense 125I-labelled BQ3020 (ET(B)-selective) binding to nerve bundles was observed, indicating the presence of ET(B) receptor subtypes. ET(A) receptor subtypes were not detected in neural tissue. These data demonstrate neural reorganisation in vein grafts and indicate that ET-1 content and binding may play a role in this process. The functional consequences of these changes on neointima formation, a major cause of vein graft failure, remain to be determined.

Animals↗
PubMed2000

Serum S-100 protein release and neuropsychologic outcome during coronary revascularization on the beating heart: a prospective randomized study.

OBJECTIVES: Our purpose was to establish whether coronary revascularization on the beating heart without cardiopulmonary bypass is less harmful to the brain than conventional surgery with cardiopulmonary bypass as indicated by measures of cognitive function or by changes in serum concentrations of S-100 protein, a recognized biochemical marker of cerebral injury. METHODS: We conducted a prospective randomized trial in which the assessors of the outcome measures were blind to the treatment received. Sixty patients without known neurologic abnormality, undergoing coronary revascularization, were prospectively randomized to 1 of 2 groups: (1) cardiopulmonary bypass (32 degrees C-34 degrees C) and cardioplegic arrest (on pump) with intermittent antegrade warm blood cardioplegia or (2) surgery on the beating heart (off pump). Neuropsychologic performance was assessed before and 12 weeks after the operation. Serum S-100 protein concentration was measured at intervals up to 24 hours after the operation. RESULTS: The groups had similar preoperative characteristics. There were no deaths or major neurologic complications in either group, nor was there any difference between groups in the chosen index of neurologic deterioration. Serum S-100 protein concentrations were higher in the on-pump group at 30 minutes, but any such difference between groups had disappeared 4 hours later. The extent of the changes in S-100 protein was unrelated to the index of neuropsychologic deterioration. CONCLUSIONS: The changes in S-100 protein concentration suggest that the brain and/or blood-brain barrier may be more adversely affected during coronary artery surgery with cardiopulmonary bypass than during surgery on the beating heart, but that this may not be reflected in detectable neuropsychologic deterioration at 12 weeks.

Aged↗
PubMed2000

Emergency repair of type A aortic dissection in type IV Ehlers-Danlos syndrome.

Ehlers-Danlos syndrome type IV is a distinctive syndrome in which thin and fragile skin, premature ageing, bruising and scarring are combined with lethal or life-threatening arterial weakness. Aortic rupture either at the aortic root and arch, or sometimes lower down the artery, are particularly characteristic. Even quite minor injury can produce dangerous vascular tearing and damage. Technical difficulties encountered in arterial repair or venous ligature are particularly worrying. The authors report the treatment of a ruptured type A aortic dissection associated with Ehlers-Danlos syndrome where the extreme fragility of the tissues and tendency to bleed posed a difficult task for the surgeon.

Adult↗
PubMed2000

Reduced cerebral embolic signals in beating heart coronary surgery detected by transcranial Doppler ultrasound.

Cerebral emboli detected by transcranial Doppler imaging were recorded in 20 patients undergoing multiple-vessel coronary artery bypass surgery, either with or without cardiopulmonary bypass, in a prospective unblinded comparative study. Emboli were recorded continuously from the time of pericardial incision until 10 min after the last aortic instrumentation. The numbers of coronary grafts and of aortic clampings were also documented. Patients undergoing revascularization with cardiopulmonary bypass had more emboli (median 79, range 38-876) per case compared with patients having off-pump surgery (median 3, range 0-18). No clinically detectable neurological deficits were seen in either group. Beating heart surgery is associated with fewer emboli than coronary surgery with cardiopulmonary bypass. Further research is necessary to determine whether a smaller number of emboli alters the incidence of neurological deficit after cardiac surgery.

Aged↗
PubMed2000

Coronary artery bypass graft outcome: the Trinidad and Tobago experience.

The study is retrospective review of the demographic, clinical, angiographic, and operative data of the first 205 consecutive CABG operations performed by Caribbean Heart Care at the Eric Williams Medical Sciences Complex (EWMSC), Trinidad and Tobago, between November 1993 and December 1997. The aim of the study was to determine the in-hospital and intermediate-term follow-up results. The mean age of patients was 59 +/- 10 years and 78% were male. Sixty-four per cent were of East Indian descent, whereas 16% were of African descent. Forty-eight per cent of the patients were hypertensive, 46% were diabetic, 33% had hyperlipidaemia, 20% had a recent history of cigarette smoking and 16% were obese. Sixty-five per cent had a positive family history of ischaemic heart disease. The average time interval between angiography and surgery was 2.3 months. At the time of angiography, 63.5% of patients had Canadian Cardiac Society (CCS) class 3 or 4 angina. The mean ejection fraction was 61 +/- 15%. Wall motion abnormalities were seen in 67% of patients. Significant stenoses of the left anterior descending artery, right circumflex artery, circumflex and ramus coronary arteries were present in 91%, 78%, 54% and 5%, respectively. Many patients (67%) had severe diffuse disease on angiography. The mean intensive care stay was 2.2 +/- 0.8 days. In-hospital mortality was 3.9% (8/205). The most frequent post-operative complication was haemorrhage (2.6%). Acute renal failure occurred in 2.1%; pulmonary collapse, 1.6%; stroke, 1% and cardiac arrest, 1%. Both sternal wound infections and systemic sepsis occurred in 0.5%. Intermediate-term follow-up data were obtained for 92% (189/205). The duration of follow-up ranged from 1 to 5 years (mean 3.7 years). During the follow-up period, 7 patients (3.4%) died. Angina severity was reduced from a mean CCS score of 2.61 +/- 0.95 before CABG to 1.22 +/- 0.55 at the time of follow-up (p < 0.0001). Overall 4-year mortality compared favourably with data from international studies. Among survivors, quality of life improved as evidenced by the reduction in the mean angina score.

Angina Pectoris↗