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Biomedical subjects

Alessandro Parolari

Publications and source records attributed to Alessandro Parolari.

At least 19 recordsLinked to original sources

Head-to-head comparison of two- and three-dimensional transthoracic and transesophageal echocardiography in the localization of mitral valve prolapse.

OBJECTIVES: The aim of this study, undertaken in patients who underwent mitral valve (MV) repair surgery, was to evaluate the feasibility and accuracy of 3-dimensional (3D) transthoracic (TTE) and transesophageal (TEE) echocardiography in the evaluation of MV pathology. BACKGROUND: A pre-operative assessment of MV anatomy is essential to surgical design in patients undergoing MV repair. Although 2-dimensional (2D) echocardiography provides precise information regarding MV anatomy, 3D TTE and 3D TEE could increase the understanding of MV apparatus and individual scallop identification. METHODS: One-hundred-twelve consecutive patients with severe mitral regurgitation due to MV prolapse underwent a complete 2D and 3D TTE the day before surgery and a complete 2D and 3D TEE in the operating room. Echocardiographic data obtained by the different techniques were compared with surgical inspection. RESULTS: Three-dimensional techniques were feasible in a relatively short time (3D TTE: 7 +/- 4 min; 3D TEE: 8 +/- 3 min), with good (3D TTE 55%; 3D TEE 35%) and optimal (3D TTE 21%; 3D TEE 45%) imaging quality in the majority of cases. Three-dimensional TEE allowed more accurate identification (95.6% accuracy) of all MV lesions in comparison with other techniques. Three-dimensional TTE and 2D TEE had similar accuracies (90% and 87%, respectively), whereas the accuracy of 2D TTE (77%) was significantly lower. CONCLUSIONS: Three-dimensional TTE and TEE are feasible and useful methods in identifying the location of MV prolapse. They were superior in the description of pathology in comparison with the corresponding 2D techniques and should be regarded as an important adjunct to standard 2D examinations in decisions regarding MV repair.

Aged↗

Proteomic analysis of membrane microdomains derived from both failing and non-failing human hearts.

Eukaryotic cells plasma membranes are organized into microdomains of specialized function such as lipid rafts and caveolae, with a specific lipid composition highly enriched in cholesterol and glycosphingolipids. In addition to their role in regulating signal transduction, multiple functions have been proposed, such as anchorage of receptors, trafficking of cholesterol, and regulation of permeability. However, an extensive understanding of their protein composition in human heart, both in failing and non-failing conditions, is not yet available. Membrane microdomains were isolated from left ventricular tissue of both failing (n = 15) and non-failing (n = 15) human hearts. Protein composition and differential protein expression was explored by comparing series of 2-D maps and subsequent identification by LC-MS/MS analysis. Data indicated that heart membrane microdomains are enriched in chaperones, cytoskeletal-associated proteins, enzymes and protein involved in signal transduction pathway. In addition, differential protein expression profile revealed that 30 proteins were specifically up- or down-regulated in human heart failure membrane microdomains. This study resulted in the identification of human heart membrane microdomain protein composition, which was not previously available. Moreover, it allowed the identification of multiple proteins whose expression is altered in heart failure, thus opening new perspectives to determine which role they may play in this disease.

Adult↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery.

OBJECTIVE: This study investigated whether the activation of coagulation, fibrinolysis, and endothelium occurring during the first postoperative month after on-pump coronary artery bypass surgery differs from that after off-pump coronary artery bypass grafting. METHODS: Thirty-five patients candidates to coronary surgery were randomized to undergo on-pump (n = 18) or off-pump (n = 17) coronary artery bypass grafting. Blood samples were collected before the intervention and to 1 month after surgery. RESULTS: Prothrombin fragment F1.2, thrombin-antithrombin complex, and D-dimer increased after surgery and were persistently higher than preoperative values as late as 30 postoperative days in both on- and off-pump groups; higher levels of these variables were detected after on-pump surgery relative to off-pump surgery only at the time point after termination of cardiopulmonary bypass (fragment F1.2 and thrombin-antithrombin complex) or from bypass end to 8 postoperative days (D-dimer). Fibrinogen levels decreased after surgery and then increased in parallel in both groups to 8 days after surgery. The von Willebrand factor level increased postoperatively in both groups and returned to baseline 30 days after surgery; it was higher after on-pump surgery from bypass end to 8 postoperative days. Soluble vascular cell adhesion molecule 1 was increased significantly from baseline in both groups 30 days after surgery, with no difference between groups. CONCLUSION: Patients undergoing off-pump surgery showed protection against activation of coagulation and fibrinolysis and against endothelial injury only during the intraoperative period; this was followed by the development of a prothrombotic pattern comparable to that of patients undergoing on-pump surgery lasting at least as late as 30 days after surgery.

Blood Coagulation↗

The role of tissue factor and P-selectin in the procoagulant response that occurs in the first month after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: It has been previously shown that a persistent (up to 1 month) prothrombotic status occurs after coronary bypass surgery performed both on pump and off pump. To assess the pathways involved in the occurrence of postoperative prothrombotic state, in this study we evaluated plasma, monocyte-bound, and platelet-bound tissue factor expression, as well as platelet and soluble P-selectin expression, up to 1 month after off-pump and on-pump coronary artery bypass grafting. METHODS: Thirty patient candidates for coronary surgery were randomized to undergo off-pump coronary artery bypass grafting (n = 15) or on-pump coronary artery bypass grafting (n = 15). Blood samples were collected before the intervention, after protamine administration, and 4, 8, and 30 days after surgical intervention. RESULTS: Plasma tissue factor levels were significantly higher than baseline both in the on-pump coronary artery bypass grafting group (from protamine administration up to 4 postoperative days) and in the off-pump coronary artery bypass grafting group (at 4 postoperative days), with no differences between groups. Basal and lipopolysaccharide-stimulated monocyte tissue factor expression, as well as basal and adenosine diphosphate-stimulated platelet tissue factor expression, did not show significant variations over time and were similar in the on-pump and off-pump coronary artery bypass grafting groups throughout the course of the study. Platelet expression of P-selectin, both basal and after adenosine diphosphate stimulation, did not significantly change over time and was not different in the on-pump and off-pump coronary artery bypass grafting groups. Soluble P-selectin levels in plasma were significantly higher in patients receiving on-pump coronary artery bypass grafting only at the time point after protamine administration, whereas this variable behaved similarly in the on-pump and off-pump coronary artery bypass grafting groups for the whole postoperative period. CONCLUSIONS: The postoperative tissue factor and P-selectin expression did not differ between the on-pump and off-pump coronary artery bypass grafting groups. The distinct increase of plasma tissue factor occurring after both surgical procedures might represent a mechanism that might explain, in part, the early postoperative prothrombotic state occurring after on-pump and off-pump coronary artery bypass grafting.

Aged↗

The stimulation of arginine transport by TNFalpha in human endothelial cells depends on NF-kappaB activation.

In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-alpha (TNFalpha) and bacterial lipopolysaccharide (LPS), but neither interferon gamma (IFNgamma) nor interleukin 1beta (IL-1beta), stimulate arginine transport. The effects of TNFalpha and LPS are due solely to the enhancement of system y+ activity, whereas system y+L is substantially unaffected. TNFalpha causes an increased expression of SLC7A2/CAT-2B gene while SLC7A1/CAT-1 expression is not altered by the cytokine. The suppression of PKC-dependent transduction pathways, obtained with the inhibitor chelerytrhine, the inhibitor peptide of PKCzeta isoform, or chronic exposure to phorbol esters, does not prevent TNFalpha effect on arginine transport. Likewise, ERK, JNK, and p38 MAP kinases are not involved in the cytokine effect, since arginine transport stimulation is unaffected by their specific inhibitors. On the contrary, inhibitors of NF-kappaB pathway hinder the increase in CAT2B mRNA and the stimulation of arginine uptake. These results indicate that in human endothelial cells the activation of NF-kappaB pathway mediates the TNFalpha effects on arginine transport.

Amino Acid Transport Systems, Basic↗

Upper and lower spinal cord blood supply: the continuity of the anterior spinal artery and the relevance of the lumbar arteries.

OBJECTIVE: Thoracic and thoracoabdominal aortic repair are still complicated by spinal cord ischemia and paraplegia. The aim of the present article is to present the results of an anatomical study conducted by means of both postmortem injection of the vertebral artery and perfusion of the abdominal aorta. METHODS: The spinal cord blood supply was investigated in 51 Caucasian cadavers: in 40 cases a methylene blue solution was hand-injected into the vertebral artery, whereas in the remaining 11 cases the abdominal aorta was perfused with a methylene blue solution by means of a roller pump. The level and side of the arteria radicularis magna and the continuity of the anterior spinal artery were recorded. RESULTS: The anterior spinal artery was a continuous vessel without interruptions along the spinal cord in all 51 cases. The arteria radicularis magna level was variable, ranging from T9 to L5. The arteria radicularis magna arose from a lumbar artery in 36 cases (70.5%) and it was left-sided in 32 cases (62.7%). CONCLUSIONS: The anterior spinal artery constitutes an uninterrupted pathway between the vertebral arteries, the arteria radicularis magna, and the posterior intercostal and lumbar arteries. Moreover, the arteria radicularis magna arises from a lumbar artery in most of cases. Therefore, the sacrifice of the intercostal arteries during a thoracic aorta repair could be justified, at least from an anatomical standpoint. However, if an extended thoracoabdominal aortic repair is planned, it may be prudent to preserve the blood flow from the lumbar arteries.

Aged↗

Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs.

OBJECTIVE: Tissue factor (TF) is the main activator of the coagulation cascade occurring in physiologic and pathologic conditions. Recent data suggest that human platelets might contain TF that is possibly derived from leukocytes. In this study, we investigated whether intraplatelet TF can be exposed on the membrane by platelet agonists. The modulation of this process by antiplatelet drugs has been evaluated as well. METHODS AND RESULTS: Flow cytometric analysis of unstimulated platelets showed a small amount of membrane-associated immunoreactive TF (irTF) in whole blood, platelet-rich plasma, and washed platelets isolated from healthy subjects. ADP, thrombin receptor-activating peptide, and epinephrine significantly increased functionally active, membrane-associated irTF. ADP induced irTF exposure in a concentration- and time-dependent fashion. Agonist-induced irTF expression was completely inhibited by iloprost but not by aspirin. Interestingly, glycoprotein IIb/IIIa antagonists did not inhibit but rather potentiated the stimulatory effect of ADP on platelet irTF expression. Real-time polymerase chain reaction experiments showed detectable amounts of TF mRNA in unstimulated platelets. CONCLUSIONS: These findings indicate that platelet agonists and antiplatelet drugs might modulate platelet-associated irTF expression. Regulated TF expression establishes the potential for a previously unrecognized role for platelets in sustaining thrombus formation and growth via coagulation-mediated mechanisms.

Antigens, Surface↗