Estrogen Receptors and Chronic Venous Disease.

OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is a common and relevant problem affecting Western people. The role of estrogens and their receptors in the venous wall seems to support the major prevalence of CVD in women. The effects of the estrogens are mediated by three estrogen receptors (ERs): ERα, ERß, and G protein-coupled ER (GPER). The expression of ERs in the vessel walls of varicose veins is evaluated. METHODS: In this prospective study, patients of both sexes, with CVD and varicose veins undergoing open venous surgery procedures, were enrolled in order to obtain vein samples. To obtain control samples of healthy veins, patients of both sexes without CVD undergoing coronary artery bypass grafting with autologous saphenous vein were recruited (control group). Samples were processed in order to evaluate gene expression. RESULTS: Forty patients with CVD (10 men [25%], 30 women [75%], mean age 54.3 years [median 52 years, range 33-74 years]) were enrolled. Five patients without CVD (three men, two women [aged 61-73 years]) were enrolled as the control group. A significant increase of tissue expression of ERα, ERß and GPER in patients with CVD was recorded (p < .01), which was also related to the severity of venous disease. CONCLUSION: ERs seem to play a role in CVD; in this study, the expression of ERs correlated with the severity of the disease, and their expression was correlated with the clinical stage.

Extensive endovascular repair of thoracic aorta: observational analysis of the results and effects on spinal cord perfusion.

AIM: The study aims to analyze retrospective results of extensive endovascular repair of the descending thoracic aorta with special attention to spinal cord malperfusion. METHODS: From April 2002 through November 2011, 21 patients underwent stent-graft coverage of the thoracic aorta from the aortic arch at the origin of the left subclavian artery to the celiac trunk, 6 (mean age =72.3±8.1) for aneurysm disease, 13 (mean age =74.3±8.4) for type B aortic dissection and 2 (mean age =52.1±6.5) for aortic rupture. The mean of aortic diameter in cases with aneurysm disease was 7.1±1.6 cm and the causes of aortic rupture were post-traumatic and aneurysm pathology respectively. In all cases needing coverage of the left subclavian artery duplex ultrasonography and flowmetry were performed to evaluate patency and flow of both the vertebral arteries. RESULTS: Technical success was 100% with 0% in-hospital mortality. The left subclavian artery was crossed with the uncovered portion of the stent-graft in 11 cases (52.4%) and the covered segment in the other 10 patients (47.6%) without subclavian revascularization because no pre-operative hemodynamic alterations of vertebral arteries were revealed by duplex ultrasonography. The incidence of paraplegia was 9.5% in 2 patients who had prior abdominal aortic aneurysm repair: the first case with preoperative type B aortic dissection presented significant lower extremity paresis within 24 hours after the procedure and in the second patient with a large thoracic aneurysm the signs of paraplegia were evident 3 weeks after discharge from Hospital probably due to delayed occlusion of a major medullary artery. The cumulative survival rate after 1, 3 and 9 years was 91%, 81%, and 71%. CONCLUSIONS: The coverage of the entire thoracic aorta is an effective procedure with high probability of success. Spinal cord malperfusion remains a serious complication especially in patients with prior aortic surgery but if collateral blood supply is maintained the occlusion of intercostal arteries do not determine paraplegia or paraparesis. In order to consider acute or chronic occlusion of subclavian, lumbar or hypogastric arteries so preventing spinal cord ischemia, strong preoperative evaluation including analysis of previous surgery for abdominal aortic aneurysm repair and avoidance of T12 aortic segment coverage if feasible is mandatory.

Valve preservation in acute type A aortic dissection: 13-year experience.

AIM: Aortic dissection is frequently complicated by regurgitation of the aortic valve resulting from leaflet prolapse or tearing of the annulus or leaflet. The authors have evaluated the results using the technique of aortic valve preservation in patients with acute type A aortic dissection (AAD). METHODS: In a consecutive series of 79 AAD observed from January 1994 to September 2007, 51 (64.6%) presented aortic valve insufficiency (AI). All patients were emergency operated on via median sternotomy and femoral (46/79, 58.2%) or axillary artery-right atrium (33/79, 41.8%) cardiopulmonary bypass with 60 cases (75.9%) of antegrade selective cerebral perfusion. The dissected aorta was resected and the aortic valve was replaced in 2 patients/51 (3.9%) and was preserved in the remaining 49 cases as follows: 42 (85.7%) commissural resuspensions due to commissural prolapse, 3 (6.1%) resuspensions due to cusp prolapse, 3 (6.1%) commissural plication and 1 (2.1%) circumclusion due to annular dilatation. RESULTS: The overall hospital mortality was 20.3% (16/79) with a percentage of 19.6% (10/51) in the AI group. 1 patient presented a type B dissection at 1 months and died after reoperation. The remaining 40 patients with a preserved native valve were followed by echocardiography and computed tomography (CT) (follow-up ranged from 3 to 165 months) with 4 late deaths. Twenty-six patients had absent or grade I AI (72.2%), 8 had grade II AI (22.2%) and 2 presented grade III or IV AI (5.6%). Actuarial freedom from significant AI was 96.2+/-2.4% and 94.2+/-2.3% at 5 and 10 years respectively. CONCLUSION: The experience with this technique demonstrates the effectiveness of valve conservative treatment within a vascular graft. The reconstruction of the sinotubular junction reducing annular dilatation with appropriated sized graft is obviously mandatory. Although this procedure is not applicable to every patient, we firmly believe that is a valid option when a morphologically intact valve is present.

Aortic tube grafts wrapping with hemostatic fleeces reduces postoperative pericardial effusions.

Pericardial effusions often complicate the postoperative course of ascending aortic surgery. We evaluated whether an unconventional use of hemostatic fleeces (TachoSil, Nycomed; Austria), wrapped around aortic tube grafts, may reduce such complication. Twenty-nine consecutive patients undergoing button-Bentall were submitted - according to surgeon's choice - to 360 degrees wrapping of the aortic grafts with hemostatic fleeces immediately before sternal wiring (11 patients - group A) or sternal wiring without any wrapping of the prosthesis (18 patients - group B). Hospital outcome was recorded. No differences were recorded in hospital mortality and major organ morbidity. When pericardial complications were considered, group A showed lower chest drains (P=0.0001), time of chest drainage (P=0.002), pretamponade/tamponade with need for pericardiocentesis (P=0.039), predischarge echocardiographic amount of pericardial effusion (P=0.026), fever (P=0.029), need for anti-inflammatory (P=0.05) or antibiotic drugs (P=0.007), hospital stay (P=0.010) and white blood cell count (P=0.016 on postoperative day 3; P=0.014 on day 6). Wrapping of aortic tube grafts with hemostatic fleeces is effective in reducing pericardial effusion and its deleterious effects following aortic surgery.

Usefulness of the axillary artery as vascular access for cardiopulmonary bypass.

AIM: In this paper we report our clinical experience with extended utilization of axillary artery cannulation for cardiopulmonary bypass (CPB) and discuss the indications and the results of the procedure in terms of complications and usefulness. METHODS: Between January 1999 and May 2004, 26 patients underwent right axillary artery cannulation for CPB. Fifteen patients presented acute type A aortic dissection and were operated urgently. Axillary cannulation was also used in 11 elective cases: 3 reoperative coronary surgery, 3 valve redo-operations and 5 cases of aortic valve regurgitation+aneurysm of the ascending aorta. RESULTS: All axillary artery cannulations were successful (21 direct and 5 with a side graft) without neurologic or vascular injuries to the right upper extremities. Hospital mortality was 7.7% and included 2 patients operated in an emergency procedure because of acute type A aortic dissection. In all cases, this cannulation site provided adequate perfusion, with a range of peak flows from 4.1 to 5.7 L/min. CONCLUSION: Our preliminary results demonstrate that the right axillary artery may be considered an alternative cannulation site for achieving full CPB and providing antegrade flow, thus avoiding complications related to retrograde flow when femoral artery perfusion is performed. This safe and useful method may be used not only in aortic surgery but in other such complex cardiac procedures as redo-operations.

Myocardial protection in diabetics with left main stem disease: which is the best strategy?

AIM: Diabetes mellitus is a well known risk factor for extensive coronary disease. The optimal route for cardioplegia administration in patients with severe ischaemic heart disease undergone surgery, especially with left main stem disease (LMSD) is still under debate. Aim of the study is to compare 2 different strategies of myocardial protection in diabetics with LMSD. METHODS: Between January 2000 and June 2003 90 consecutive patients with type II diabetes mellitus and LMSD undergoing isolated myocardial revascularization were divided into 2 groups according to the route of cardioplegia delivery: antegrade in 45 patients (group A), antegrade followed by intermittent retrograde in 45 (group B). ECG, Troponin I, MB-CPK, MB-CPK mass were performed at 12, 24, 48, and 72 hours postoperatively. Echocardiography was performed preoperatively and before hospital discharge. RESULTS: Groups were homogeneous in preoperative and intraoperative variables, apart from higher incidence of unstable angina and longer cardiopulmonary bypass time in Group B and hypertension in Group A. Hospital deaths, in intensive care units (ITU) stay, perioperative acute myocardial infarction, intra-aortic balloon pump support, postoperative recovery of left ventricle ejection fraction and wall motion score index were similar in both groups. In hospital stay proved shorter in group B (p=0.002), whereas postoperative atrial fibrillation was higher in group A (p<0.001), as postoperative inotropic support (p=0.006). Troponin I proved significantly higher in group A from the 12 degrees to the 72 degrees postoperative hour (p<0.0001). CONCLUSIONS: Despite major in hospital end-points did not differ with strategy of cardioplegia administration, combined route of intermittent blood cardioplegia allows better biochemical and perioperative results in diabetics with LMSD.

Intermittent warm blood cardioplegia induces the expression of heat shock protein-72 by ischemic myocardial preconditioning.

OBJECTIVE: Recent studies have demonstrated that the induction of heat shock protein-72 (HSP72) by different stimuli preserves the heart function after cardioplegic arrest. Based on these findings, we investigated whether intermittent warm blood cardioplegia would induce changes in the myocardial expression of HSP72. METHODS: Forty patients scheduled for aortocoronary bypass were randomly assigned to receive either cold or warm intermittent blood cardioplegia. In all patients HSP72 and HSP72 mRNA were assayed in biopsies from the right atrium at baseline, and during the reperfusion period. Plasma CK-MB and troponin-T, and myocardial oxygen extraction and lactate release were also measured. RESULTS: In both groups, myocardial expression of HSP72 increased throughout the reperfusion period, but the values of HSP72 band lengths were significantly higher in the warm group. Correspondingly, HSP72 mRNA levels increased progressively in both groups, with significant difference between groups observed in biopsies at the reperfusion. Warm blood cardioplegia was associated with lower levels of CK-MB and troponin-T. Myocardial oxygen extraction and lactate release were higher during intermittent warm cardioplegia, indicating a more profound ischemic anaerobic metabolism in the warm group. CONCLUSIONS: Intermittent warm blood cardioplegia induces an increased expression of HSP72 and it is associated with a better myocardial protection, by a mechanism involving a variant of the classical ischemic preconditioning model.

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass.

OBJECTIVE: To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass. DESIGN: Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions. SETTING: University hospital (tertiary referral centre). PATIENTS: Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls. MAIN OUTCOME MEASURES: Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium. RESULTS: Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin. CONCLUSIONS: Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.

Pseudoaneurysm of the thoracic aorta in patients with human immunodeficiency virus infection.

Arterial pseudoaneurysm has been reported as a possible complication of immunodeficiency virus infection. We report two cases of HIV-positive patients with a pseudoaneurysm at the level of the descending thoracic aorta. The first patient refused surgery and has been followed up to 14 months, whereas the second patient underwent successful surgical repair. The importance of magnetic resonance imaging in the diagnosis of thoracic aorta pseudoaneurysm is also discussed.

Prognostic significance of endothelial dysfunction in hypertensive patients.

BACKGROUND: Forearm endothelial dysfunction, characterized by an impaired vasodilating response to acetylcholine (ACh), may be associated with several cardiovascular risk factors, including essential hypertension. Although the prognostic value of coronary endothelial dysfunction has been demonstrated, that of forearm endothelial dysfunction is still unknown. Methods and Results-- Endothelium-dependent and -independent vasodilation was investigated in 225 never-treated hypertensive patients (age, 35 to 54 years) by intra-arterial infusion of increasing doses of ACh and sodium nitroprusside. Patients were divided into tertiles on the basis of their increase in ACh-stimulated forearm blood flow (FBF) from basal: group 1, from 30% to 184%; group 2, from 185% to 333%; and group 3, from 339% to 760% increase from basal. During a mean follow-up of 31.5 of months (range, 4 to 84 months), there were 29 major adverse events at the cardiac (n=19), cerebrovascular (n=9), or peripheral vascular (n=1) level. Events included myocardial infarction, angina, coronary revascularization procedures, stroke, transient cerebral ischemic attack, and aortoiliac occlusive disease. Event rate per 100 patient-years was 8.17, 4.34, and 2.02 in the first, second, and third tertiles of peak percent increase in FBF during ACh infusion. The excess risk associated with an FBF increase in the first tertile was significant (relative risk, 2.084; 95% CI, 1.25 to 3.48; P=0.0049) after controlling for individual risk markers, including 24-hour ambulatory blood pressure. CONCLUSIONS: Our data suggest that forearm endothelial dysfunction is a marker of future cardiovascular events in patients with essential hypertension.

Plasma levels of atrial and brain natriuretic peptides as indicators of recovery of left ventricular systolic function after coronary artery bypass.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of atrial and brain natriuretic peptides (ANP and BNP, respectively) as indicators of recovery of left ventricular (LV) function after coronary surgery. METHODS: We measured the concentrations of these peptides in 31 patients with poor LV function (ejection fraction, EF<35%) undergoing coronary artery bypass, and evaluated their correlation with the echocardiographic indexes of LV function. RESULTS: Pre-operatively, the plasma levels of both ANP and BNP were markedly higher in coronary patients than in normal control subjects, and strongly correlated with both EF (BNP: r=-0.8, P<0.001; ANP: r=-0.6, P<0.001) and wall motion score index (WMSI). At post-operative follow up, plasma levels of both natriuretic peptides were markedly reduced compared with pre-operative values in 21 patients. In addition, the post-operative-pre-operative differences of BNP (Delta(BNP)) and ANP (Delta(ANP)) plasma levels strongly correlated with the differences of both EF (r=-0.7, P<0.0001 vs. Delta(BNP); r=-0.6, P=0.0003 vs. Delta(ANP)) and WMSI (r=0.6, P=0.002 vs. Delta(BNP); r=0.6, P=0.04 vs. Delta(ANP)). Finally, by logistic regression analysis, BNP appeared a significant predictor of LVEF recovery after surgery. CONCLUSION: Plasma levels of ANP and BNP might be used in routine clinical practice as a support to echocardiography in detecting recovery of the LV function after coronary surgery.

Duromedics original prosthesis: what do we really know about diagnosis and mechanism of leaflet escape?

The Edwards-Duromedics (ED) is a bileaflet pyrolitic carbon mechanical valve introduced by Hemex Scientific Inc in 1982, subsequently acquired by Baxter Healthcare Corp, withdrawn from the market in 1988, and modified and reintroduced in 1990. From 1982 to date, 46 cases of leaflet escape have been registered by the manufacturer of an estimated total of 20,000 valves implanted. Disc embolization 12 years after an ED mitral prosthesis implantation is reported in a 45-year-old man operated on when he was in cardiogenic shock because a preliminary transthoracic Doppler echocardiography did not show malfunction of the valve. A correct diagnosis was made four days after the onset of the symptoms by transesophageal echocardiography. During the operation, the posterior leaflet of the ED valve was not found, a 29 mm St Jude Medical bileaflet mechanical prosthesis was implanted and the patient died in the intensive care unit because of low cardiac output syndrome. Cavitation damage is generally considered the most frequent mechanism in cases of such fracture. Thus, any patient with a mechanical valve presenting with acute pulmonary edema must be immediately transferred to a surgical unit; cinefluoroscopy or transesophageal echocardiography may be performed rapidly to achieve successful management of patients with leaflet embolization.

Effects of atorvastatin and vitamin C on endothelial function of hypercholesterolemic patients.

We tested the effects of vitamin C and atorvastatin treatment on endothelium-dependent and endothelium-independent vasodilation in 18 hypercholesterolemic patients (ten men and eight women, aged 20-46 years) in comparison with 12 normal volunteers (seven men and five women, aged 20-45 years). The responses of the forearm blood flow (FBF) to acetylcholine (ACh) (7.5, 15 and 30 microg/min), sodium nitroprusside (SNP) (0.8, 1.6, 3.2 microg/min) and L-NMMA (2, 4, 8 micromol/min) were evaluated at baseline and after 1 month of atorvastatin (10 mg/day) treatment. Drugs were infused into the brachial artery and FBF was measured by strain-gauge plethysmography. At baseline, the response to ACh was significantly attenuated in hypercholesterolemics versus controls: at the highest dose (30 microg/min), FBF was 27.0+/-3.4 versus 11.5+/-1.9 ml.100 ml tissue(-1).min(-1) respectively (P<0.0001). No significant differences were found between groups during SNP infusion. The atorvastatin treatment significantly improved ACh-stimulated FBF: at highest dose the FBF increased to 14.9+/-1.5 ml.100 ml tissue(-1). min(-1) (P<0.0001). Similarly, the L-NMMA endothelial effects were significantly enhanced by lipid-lowering treatment, supporting the improvement of basal nitric oxide. Vitamin C increased ACh-vasodilation in the same way before and after atorvastatin treatment. In conclusion, the endothelial dysfunction in hypercholesterolemics is due to an oxidative stress and atorvastatin rapidly improves both basal and stimulated endothelium-dependent vasodilation.

Hypertensive left ventricular remodeling and ACE-gene polymorphism.

OBJECTIVE: To evaluate the relationship between ACE-gene polymorphism and left ventricular geometry in never treated hypertensives. METHODS: We enrolled 200 hypertensive outpatients that underwent clinical and ambulatory blood pressure measurements, echocardiographic evaluation and analysis for insertion (I)/deletion (D) polymorphism by PCR. Patients with normal or increased (> 125 g/m2 in males and > 110 g/m2 in females) left ventricular mass were considered to have concentric remodeling or concentric left ventricular hypertrophy if their relative wall thickness was > or = 0.45. RESULTS: The left ventricular mass index values (g/m2) were 136 +/- 30 in DD genotype, 124 +/- 26 in ID genotype, and 116 +/- 20 in II genotype (DD vs. ID P < 0.005; DD vs. II P < 0.05), and were unrelated to blood pressure. Ninety-six patients presented left ventricular hypertrophy (48.0%): 51 with concentric and 45 with eccentric hypertrophy. The eccentric left ventricular hypertrophy was detected in 32 (36.8%) DD patients, in ten (10.5%) ID patients (P < 0.05), and in three (16.6%) II patients. The relative septal thickness was 0.43 +/- 0.09 in DD genotype, 0.45 +/- 0.08 in ID genotype, and 0.43 +/- 0.10 in II genotype. In DD and ID genotypes, the relative posterior wall thickness (0.37 +/- 0.07 vs. 0.41 +/- 0.07; P < 0.0001) and the end-diastolic left ventricular internal dimension (52.8 +/- 3.3 mm vs. 48.3 +/- 2.8 mm; P < 0.0001) were statistically different. CONCLUSIONS: The DD genotype of the ACE-gene is associated with an increased left ventricular mass and with a significantly higher prevalence of eccentric left ventricular hypertrophy, when compared to ID genotype.

Emergency thoracoabdominal aortic aneurysm repair: clinical outcome.

OBJECTIVE: Emergency repair of thoracoabdominal aortic aneurysm remains a formidable operation with high morbidity and mortality. Although advanced surgical and perioperative care techniques have reduced the risks in elective repair of these aneurysms, the mortality rate has remained high when emergency surgery is performed. We have evaluated the outcome of patients undergoing emergency repair of thoracoabdominal aortic aneurysm. METHODS: Of 47 consecutive patients with thoracoabdominal aortic aneurysm observed from January 1993 to September 1998, 19 required an emergency operation. Twelve had a ruptured aneurysm and 7 an acute dissection. Twelve type I, 3 type II, 1 type III, and 3 type IV thoracoabdominal aortic aneurysms (Crawford's classification) were diagnosed. All patients were operated on via a thoracolaparotomy with partial femoral-femoral extracorporeal circulation. The cerebrospinal fluid pressure was monitored, and the aorta was replaced with a vascular graft. Patent intercostal arteries were reimplanted when feasible. RESULTS: The early (30-day) mortality was 42.1%; there were 2 late deaths. Complications in the 11 surviving patients are summarized as follows: paraplegia/paraparesis, 3 cases; renal, 4 cases; pulmonary, 4 cases; cardiac, 1 case; cerebrovascular, 1 case; and reexploration for bleeding, 1 case. Hemodialysis and aortic dissection were predictive factors of hospital mortality. CONCLUSIONS: Our surgical experience in emergency repair of thoracoabdominal aortic aneurysm must be considered encouraging in terms of late outcome despite the in-hospital mortality of 42.1% and serious postoperative complications in the surviving patients. Moreover, our results show that acute aortic dissection and the need for hemodialysis are predictive factors for mortality.

Inhibition by dipyridamole of neutrophil adhesion to vascular endothelium during coronary bypass surgery.

BACKGROUND: Release of reactive oxygen radicals by activated neutrophils and neutrophil adhesion to endothelial cells have been observed after cardiopulmonary bypass. The aim of the present study was to evaluate the effects of preoperative dipyridamole treatment on neutrophil superoxide anion generation and endothelial cell-neutrophil interactions. METHODS: Two groups of patients scheduled for elective coronary artery bypass grafting were randomized to receive oral dipyridamole or a placebo. Nitro blue tetrazolium scores of circulating neutrophils, neutrophil CD11b/CD18 expression, and their adhesion to human umbilical vein endothelial cells were assayed before anesthesia, 30 minutes after the beginning of cardiopulmonary bypass, at the end of bypass, and 60 minutes postoperatively. RESULTS: In both groups, cardiopulmonary bypass resulted in a significant increase in nitro blue tetrazolium scores in circulating neutrophils as well as a significant increase in both neutrophil CD11b/CD18 expression and neutrophil adhesion to endothelial cells. The extent of neutrophil superoxide anion generation was higher in the control group; a significant (p < 0.01) reduction in neutrophil adhesion to endothelial cells was observed 1 hour postoperatively in the dipyridamole group. In 5 patients treated with dipyridamole, the incubation of activated polymorphonuclear leukocytes with adenosine deaminase significantly increased their adhesion to endothelial cells (p < 0.05). CONCLUSIONS: Our study demonstrated that preoperative treatment with oral dipyridamole significantly reduces both neutrophil superoxide anion generation and extent of neutrophil adhesion to endothelial cells after coronary bypass grafting procedures with cardiopulmonary bypass. The mechanism is probably mediated by endogenous adenosine.