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Biomedical subjects

Paolo Biglioli

Publications and source records attributed to Paolo Biglioli.

At least 19 recordsLinked to original sources
PubMed2007

Resection and end-to-end anastomosis for ascending aortic aneurysms associated with a bicuspid valve: case reports.

Ascending aortic aneurysms associated with a bicuspid valve are generally treated by replacement with a tubular graft because the aortic wall is claimed to be genetically pathological. We describe 9 cases in which patients with an ascending aortic aneurysm and an associated diseased bicuspid valve underwent aneurysmal resection and end-to-end anastomosis. This technique permitted us to remove the entire aneurysmal wall, avoiding graft interposition.

Adult↗
PubMed2006

17Beta-estradiol effects on human coronaries and grafts employed in myocardial revascularization: a preliminary study.

BACKGROUND: This study was undertaken to compare the in vitro effects of 17beta-estradiol on human epicardial coronary arteries, resistance coronary arteries and on arterial vessels usually employed as grafts in surgical myocardial revascularization. METHODS: Coronary artery rings (descending coronary artery, right coronary artery, circumflex coronary artery, first septal branch) and arterial graft rings (internal thoracic artery, gastro-epiploic artery) obtained from human heart donors with heart not suitable to cardiac transplantation were connected to force transducer for isometric force recording. Precontracted specimens with and without endothelium were exposed to increasing concentration of 17beta-estradiol (3-30-300-3000 nmol/l) and to vehicle (0.1% v/v ethanol). We also evaluated the effects of 17beta-estradiol on vessels before and 20 minutes after exposure to L-monomethyl-arginine and indomethacin. RESULTS: 17beta-estradiol induced a significant relaxation in all precontracted vessels (mean maximum effect: 78,6% +/- 8,5). This effect was not different among the different rings and was not related to the presence of endothelium. N-monomethyl-L-arginine and indomethacin did not modify 17beta-estradiol relaxant effect. CONCLUSION: The vasodilator action of the 17beta-estradiol is similar on coronary arteries, resistance coronary arteries and arterial vessels usually employed as grafts in myocardial revascularization.

Journal Article↗
PubMed2006

Cyclin D1 degradation enhances endothelial cell survival upon oxidative stress.

The understanding of endothelial cell responses to oxidative stress may provide insights into aging mechanisms and into the pathogenesis of numerous cardiovascular diseases. In this study, we examined the regulation and the functional role of cyclin D1, a crucial player in cell proliferation and survival. On H2O2 treatment, endothelial cells showed a rapid down-modulation of cyclin D1. Other D-cyclins were similarly regulated, and this decrease was also observed after exposure to other oxidative stress-inducing stimuli, namely 1,3-bis (2 chloroethyl)-1 nitrosourea treatment and ischemia. H2O2 treatment induced cyclin D1 ubiquitination followed by proteasome degradation. Phospholipase C inhibition prevented cyclin D1 degradation, and its activation triggered cyclin D1 down-modulation in the absence of oxidative stress. Activated phospholipase C generates inositol-1,4,5-trisphosphate (IP3) and Ca2+ release from internal stores. We found that both IP3-receptor inhibition and intracellular Ca2+ chelation prevented cyclin D1 degradation induced by oxidative stress. Furthermore, Ca2+ increase was transduced by Ca2+/calmodulin-dependent protein kinase (CaMK). In fact, H2O2 stimulated CaMK activity, CaMK inhibitors prevented H2O2-induced cyclin D1 down-modulation, and CaMK overexpression induced cyclin D1 degradation. Finally, overriding of cyclin D1 down-modulation via its forced overexpression or via CaMK inhibition increased cell sensitivity to H2O2-induced apoptotic cell death. Thus, cyclin D1 degradation enhances endothelial cell survival on oxidative stress.

Apoptosis↗
PubMed2006

Isoprostanes and oxidative stress in off-pump and on-pump coronary bypass surgery.

BACKGROUND: Conventional on-pump coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response and by an increased production of reactive oxygen species, whereas off-pump coronary artery bypass grafting (OPCAB) is thought to be accompanied by less oxidative stress. Urinary isoprostane iPF2alpha-III is a new marker reflecting oxidative stress; it has emerged as the most reliable marker of oxidative stress status in vivo. This study was designed to ascertain whether OPCAB compared with CABG represents a surgical strategy that avoids oxidative stress. To this end urinary isoprostanes and other established oxidative stress markers were measured during the first 24 hours after CABG and OPCAB. METHODS: Fifty low-risk coronary patients were randomly assigned to CABG or OPCAB. Urinary isoprostane iPF2alpha-III levels, plasma levels of free malondialdehyde, and total antioxidant status were measured before, during, and up to 24 hours after surgery. RESULTS: In OPCAB iPF2alpha-III excretion remained unchanged throughout the study. As expected, in CABG iPF2alpha-III levels significantly increased during surgery and returned at baseline 24 hours later. Free malondialdehyde behaved similarly, with no change in OPCAB and sharp increases during CABG. Conversely, total antioxidant status showed a sharp drop during CABG, followed by a slow recovery, whereas a significantly lower drop occurred in OPCAB. CONCLUSIONS: In this randomized study in low-risk coronary patients, OPCAB revealed less perioperative oxidative stress, as reflected by lack of excretion of iPF2alpha-III in urine, by lack of increase of plasma free malondialdehyde, and by lower decreases in plasma total antioxidant status.

Aged↗
PubMed2006

Reduction ascending aortoplasty: midterm follow-up and predictors of redilatation.

BACKGROUND: Reduction ascending aortoplasty is an alternative procedure to the replacement of the ascending aorta in case of ascending aorta aneurysm without aortic root involvement. This study was designed to evaluate the midterm follow-up of aortoplasty and to determine predictors of redilatation. METHODS: From January 1, 1998, to April 30, 2005, 68 patients with dilatation of the ascending aorta underwent unsupported reduction aortoplasty in combination with other cardiac procedures. All patients underwent associated surgical procedures. Sixty patients (88.2%) underwent associated aortic valve replacement. Cumulative follow-up time was 191.4 patient-years and was 100% complete. Median follow-up time was 2.5 years, and mean follow-up time was 2.9 +/- 1.7 years (range, 0.4 to 6.3 years). RESULTS: The overall perioperative mortality rate was 1.5%. Overall survival estimates at 3 and 6 years were 93.3% +/- 4.5% and 89.3% +/- 5.9%, respectively. The actuarial freedom from cardiac-related death at 3 and 6 years was 100% and 95.7% +/- 4.3%, respectively. Ascending aorta redilatation occurred in 5 patients (7.5%). The actuarial freedom from redilatation at 3 and 6 years was 97.7% +/- 2.3% and 79.8% +/- 8.4%, respectively. The actuarial freedom from reoperation at 3 and 6 years was 100% and 86.3% +/- 7.5%, respectively. Only preoperative diameter was a significant predictor of redilatation using multivariate stepwise logistic regression analysis. CONCLUSIONS: Unsupported reduction aortoplasty is a safe and effective technique with low mortality, low morbidity, and rare late complications for selected chronic aneurysm of the ascending aorta with diameter less than 55 mm.

Adult↗
PubMed2006

Left common carotid artery as inflow site in coronary artery bypass grafting.

Porcelain aorta is associated to significantly increased risk of atheromatous embolization in patients who undergo cardiac surgery. We described three cases in which coronary artery bypass grafting was performed off-pump and the saphenous vein graft was anastomosed proximally to the left common carotid artery. This technique permitted avoidance of ascending aortic manipulation and reduce the risk of atheromatous embolization.

Aged↗
PubMed2006

Effect of cryopreservation techniques on aortic valve glycosaminoglycans.

This study was designed to evaluate the effect of cryopreservation on the glycosaminoglycan (GAG) content of the aortic allografts. Twenty-one porcine aortic valves were obtained. Five aortic roots were immediately analyzed without cryopreservation, eight were cryopreserved in closed leaflet position, and eight in open leaflet position. The groups were compared in terms of GAG concentration and subclass proportion in three different zones including the aortic root wall, the commissures, and the leaflets. GAG content at the commissures was significantly lower in the closed leaflet group than in the other groups (P = 0.001). The electrophoretic analysis did not show any significant difference in the zonal distribution of GAG classes between groups. Quantitative analysis in various aortic valve zones suggests that cryopreservation can alter the GAG content. Cryopreservation of the aortic valve in an open leaflet position can preserve the matrix more efficiently and might prolong the durability of the aortic allograft.

Animals↗
PubMed2006

[Off-pump coronary bypass surgery: pros and cons].

Off-pump coronary artery bypass surgery is a well established surgical option for patients candidate to coronary artery bypass. Current evidence suggests that there are no differences between off-pump and on-pump coronary surgery in terms of major perioperative outcomes such as perioperative mortality, myocardial infarction, stroke, and renal failure, whereas off-pump coronary surgery seems to reduce some minor complications like atrial fibrillation, transfusion requirements, and postoperative hospital stay. However, some recent papers suggest that graft patency may be lower for grafts performed with the off-pump technique. In this paper we review current knowledge about pros and cons of off-pump and on-pump coronary bypass surgery.

Atrial Fibrillation↗
PubMed2005

P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFalpha and potential role in myocardial cell death.

ATP acts as a neurotransmitter via seven P2X receptor-channels for Na(+) and Ca(2+), and eight G-protein-coupled P2Y receptors. Despite evidence suggesting roles in human heart, the map of myocardial P2 receptors is incomplete, and their involvement in chronic heart failure (CHF) has never received adequate attention. In left myocardia from five to nine control and 5-12 CHF subjects undergoing heart transplantation, we analyzed the full repertoire of P2 receptors and of 10 "orphan" P2Y-like receptors. All known P2Y receptors (i.e. P2Y(1,2,4,6,11,12,13,14)) and two P2Y-like receptors (GPR91 and GPR17) were detected in all subjects. All known P2X(1-7) receptors were also detected; of these, only P2X(6) was upregulated in CHF, as confirmed by quantitative real time-PCR. The potential significance of this change was studied in primary cardiac fibroblasts freshly isolated from young pigs. Exposure of cardiac fibroblasts to ATP or its hydrolysis-resistant-analog benzoylATP induced apoptosis. TNFalpha (a cytokine implicated in CHF progression) exacerbated cell death. Similar effects were induced by ATP and TNFalpha in a murine cardiomyocytic cell line. In cardiac fibroblasts, TNFalpha inhibited the downregulation of P2X(6) mRNA associated to prolonged agonist exposure, suggesting that, by preventing ATP-induced P2X(6) desensitization, TNFalpha may abolish a defense mechanism meant at avoiding Ca(2+) overload and, ultimately, Ca(2+)-dependent cell death. This may provide a basis for P2X(6) upregulation in CHF. In conclusion, we provide the first characterization of P2 receptors in the human heart and suggest that the interaction between TNFalpha and the upregulated P2X(6) receptor may represent a novel pathogenic mechanism in CHF.

Adenosine Triphosphate↗
PubMed2005

Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress.

Experimental evidence indicates that shear stress (SS) exerts a morphogenetic function during cardiac development of mouse and zebrafish embryos. However, the molecular basis for this effect is still elusive. Our previous work described that in adult endothelial cells, SS regulates gene expression by inducing epigenetic modification of histones and activation of transcription complexes bearing acetyltransferase activity. In this study, we evaluated whether SS treatment could epigenetically modify histones and influence cell differentiation in mouse embryonic stem (ES) cells. Cells were exposed to a laminar SS of 10 dyne per cm2/s(-1), or kept in static conditions in the presence or absence of the histone deacetylase inhibitor trichostatin A (TSA). These experiments revealed that SS enhanced lysine acetylation of histone H3 at position 14 (K14), as well as serine phosphorylation at position 10 (S10) and lysine methylation at position 79 (K79), and cooperated with TSA, inducing acetylation of histone H4 and phosphoacetylation of S10 and K14 of histone H3. In addition, ES cells exposed to SS strongly activated transcription from the vascular endothelial growth factor (VEGF) receptor 2 promoter. This effect was paralleled by an early induction of cardiovascular markers, including smooth muscle actin, smooth muscle protein 22-alpha, platelet-endothelial cell adhesion molecule-1, VEGF receptor 2, myocyte enhancer factor-2C (MEF2C), and alpha-sarcomeric actin. In this condition, transcription factors MEF2C and Sma/MAD homolog protein 4 could be isolated from SS-treated ES cells complexed with the cAMP response element-binding protein acetyltransferase. These results provide molecular basis for the SS-dependent cardiovascular commitment of mouse ES cells and suggest that laminar flow may be successfully applied for the in vitro production of cardiovascular precursors.

Acetylation↗
PubMed2005

Preoperative assessment of the radial artery for coronary artery bypass grafting: is the clinical Allen test adequate?

BACKGROUND: The clinical Allen test (AT) is widely adopted as the only preoperative assessment of the hand collateral circulation before radial artery (RA) harvest as a coronary artery bypass graft. Nevertheless, in some cases it may be misleading because of clinically undetectable anatomic anomalies of the forearm arteries. METHODS: We evaluated the nondominant forearm arterial circulation by echo color Doppler (ECD) technique and by performing static and dynamic tests such as the AT, snuffbox test (SBT), and palmar arch test (PAT) in 150 patients who underwent elective coronary artery revascularization with a RA graft. RESULTS: Although the clinical AT was normal in all patients, in 8 patients (5.3%) preoperative ECD AT, SBT, and PAT did contraindicate RA harvesting. We did not harvest the RA in these patients. In the remaining 142 patients the RA was harvested. We did not observe any case of postoperative forearm or hand ischemia. We examined the blood flow to the hand in all patients at both 5 days and 24 months after surgery. In all patients ECD showed adequate hand perfusion and a significant increase of the peak flow velocity in the ulnar artery at both follow-up times. CONCLUSIONS: The clinical AT may be not sufficient to assess the hand collateral flow and the quality of the RA as a coronary artery bypass graft in at least 5% of patients. The ECD technique, performed during static and dynamic tests, does offer a safer and more objective preoperative noninvasive evaluation and it may have an important role also from the medicolegal point of view.

Blood Flow Velocity↗
PubMed2005

Long-term results after aortic valve replacement with the Bravo 400 stentless xenograft.

BACKGROUND: This study was undertaken to evaluate the long-term clinical and echocardiographic outcome after aortic valve replacement with the Bravo Cardiovascular Model 400 stentless xenograft. METHODS: Between February 1992 and January 1994, 67 patients underwent aortic valve replacement with the Bravo 400 bioprosthesis. The valvular pathology was aortic stenosis in 36 patients (53.7%), aortic insufficiency in 17 patients (25.4%), and mixed lesion in 14 patients (20.9%). Mean follow-up time was 9.8 +/- 2.73 years and median follow-up time was 11 years. Cumulative follow-up time was 659 patients-years and was 94% complete. RESULTS: No early deaths were observed. Overall survival estimates at 11 years were 74.71% +/- 5.47%. The actuarial freedom from valve-related death at 11 years was 91.04% +/- 3.84%; from cardiac-related death at 11 years it was 87.95% +/- 4.29%; and from noncardiac death at 11 years it was 85.14% +/- 4.58%. Eleven-year Kaplan-Meier survival of patients younger than 65 years was 90.91% +/- 6.13% versus 66.08% +/- 7.38% for older patients (p = 0.0307, log-rank test). The actuarial freedom from all valve-related morbidity and mortality at 11 years was 80.3% +/- 5.4%. The mean transvalvular gradient decreased significantly after aortic valve replacement with a corresponding increase in effective orifice area. Left ventricular mass index at 10-year follow-up was 68.5% of the preoperative value. CONCLUSIONS: The Bravo Cardiovascular Model 400 stentless xenograft has provided good clinical and hemodynamic results up until 11 years of follow-up.

Adult↗
PubMed2005

Meta-analysis of randomized trials comparing off-pump with on-pump coronary artery bypass graft patency.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) is increasingly becoming a widely used technique and challenges conventional on-pump coronary artery bypass grafting as the standard surgical therapy for coronary artery disease. Little information, however, is available concerning postoperative performance of bypass grafts done with this new technique. The aim of this study is to assess differences in graft patency between OPCAB and coronary artery bypass grafting by meta-analysis of data published in randomized trials. METHODS: A literature search for the period beginning January 1990 until December 2004 supplemented with manual bibliographic review was performed for all peer-reviewed English-language publications. A systematic overview (meta-analysis) of randomized trials was conducted to assess differences between OPCAB and coronary artery bypass grafting in graft occlusion rates. RESULTS: Literature search yielded five comparable randomized studies, for a total of 872 and 998 grafts performed during OPCAB and coronary artery bypass grafting procedures, respectively. Meta-analysis of these studies showed an increased risk of graft occlusion in the OPCAB group of patients, both when all the studies were analyzed together (odds ratio, 1.51; 95% confidence intervals, 1.15 to 1.99; p = 0.003), and when low-quality (odds ratio, 1.46; 95% confidence intervals, 1.05 to 2.03; p = 0.02) and high-quality (odds ratio, 1.65; 95% confidence intervals, 0.99 to 2.75; p = 0.05) studies were analyzed separately. CONCLUSIONS: Cumulative analysis of the few prospective randomized studies currently available in the literature documents a reduction in postoperative patency of coronary artery bypass grafts performed during OPCAB procedures. The risk of reduced graft patency needs to be considered when choosing OPCAB as tailored strategy for selected patients.

Coronary Artery Bypass↗