1079-102 Correlation between norepinephrine and epinephrine myocardial spillover and tumor necrosis factor-alpha in conventional versus off-pump coronary artery bypass surgery

Background: Complete revascularization obtained by coronary artery bypass surgery does not prevent long term left ventricular remodeling and heart failure development. Periprocedural events linked to different surgical techniques, such as cardiopulmonary bypass with cardioplegic arrest (CABG) versus off-pump procedures may trigger an irreversible microvascular dysfunction or myocytes necrosis and apoptosis. Methods: To test this hypothesis we measured norepinephrine and epinephrine coronary sinus and aortic spillover before and after surgery, simultaneously with Tumor Necrosis Factor-alpha (TNF-alpha) measurements in 30 patients randomized to CABG (n=15), or off-pump (n=15) coronary surgery. Plasma catecholamines were assessed by high performance liquid chromatography and TNF-alpha by ELISA. Results: Norepinephrine and epinephrine spillover was similar in the two groups before surgery, being 1.38\ub10.62 and 1.08\ub10.45, respectively. After surgery norepinephrine spillover was 1.43\ub10.56, 0.72\ub10.49 in CABG and off-pump, respectively (P<0.05 CABG versus off-pump, means \ub1SD ). Epinephrine spillover was 1.27\ub10.16 and 0.65\ub10.15 respectively (P<0.05, CABG versus off-pump). TNF-alpha significantly increased only in CABG patients being 22.17\ub16.79 and 35.4\ub15.98, pg/mL, before and after surgery (P<0.05), respectively. After surgery norepinephrine spillover correlated with TNF-alpha levels (P=0.01, R=0.553). Conclusions: Patients undergoing off-pump interventions showed significantly lower catecholamines spillover as compared to CABG, suggesting that the off-pump technique may result less invasive, not only for a lower local and whole body inflammatory response but also for a lower sympathetic drive. For the first time in humans we have detected an increase in epinephrine-spillover after cardiac surgery. Further studies are necessary to evaluate if the short-term advantages observed after off-pump coronary surgery translate into a long-term attenuation of left ventricular remodeling and in the prevention of heart failure progression

Non infective severe aortic paravalvular leakage 7 years after surgery: the role of suture technique

We report a case of redo aortic prosthesis replacement for a severe paravalvular leak (PVL) in a man operated with continuous suture technique 7 years earlier. The severe aortic regurgitation was due to the rupture of the suture. In spite of operations to replace malfunctioning heart valves are common procedures and performed all over the world from more than 50 years, there is still an open debate about the most suitable suture technique. In this case report, we'll discuss if the suture technique has a role in preventing or leading complications as severe PVL

Proteomics Reveals Novel Oxidative and Glycolytic Mechanisms in Type 1 Diabetic Patients' Skin Which Are Normalized by Kidney-Pancreas Transplantation

Background: In type 1 diabetes (T1D) vascular complications such as accelerated atherosclerosis and diffused macro-/microangiopathy are linked to chronic hyperglycemia with a mechanism that is not yet well understood. End-stage renal disease (ESRD) worsens most diabetic complications, particularly, the risk of morbidity and mortality from cardiovascular disease is increased several fold. Methods and Findings: We evaluated protein regulation and expression in skin biopsies obtained from T1D patients with and without ESRD, to identify pathways of persistent cellular changes linked to diabetic vascular disease. We therefore examined pathways that may be normalized by restoration of normoglycemia with kidney-pancreas (KP) transplantation. Using proteomic and ultrastructural approaches, multiple alterations in the expression of proteins involved in oxidative stress (catalase, superoxide dismutase 1, Hsp27, Hsp60, ATP synthase δ chain, and flavin reductase), aerobic and anaerobic glycolysis (ACBP, pyruvate kinase muscle isozyme, and phosphoglycerate kinase 1), and intracellular signaling (stratifin-14-3-3, S100-calcyclin, cathepsin, and PPI rotamase) as well as endothelial vascular abnormalities were identified in T1D and T1D+ESRD patients. These abnormalities were reversed after KP transplant. Increased plasma levels of malondialdehyde were observed in T1D and T1D+ESRD patients, confirming increased oxidative stress which was normalized after KP transplant. Conclusions: Our data suggests persistent cellular changes of anti-oxidative machinery and of aerobic/anaerobic glycolysis are present in T1D and T1D+ESRD patients, and these abnormalities may play a key role in the pathogenesis of hyperglycemia-related vascular complications. Restoration of normoglycemia and removal of uremia with KP transplant can correct these abnormalities. Some of these identified pathways may become potential therapeutic targets for a new generation of drugs

Ticlopidine and Aspirin Pretreatment Reduces Coagulation and Platelet Activation During Coronary Dilation Procedures

AbstractObjectives. It is unknown whether a therapeutic combination of aspirin (ASA) and ticlopidine might effectively decrease activation of hemostasis.Background. Percutaneous transluminal coronary angioplasty (PTCA), rotational atherectomy and stent implantation are procedures that fracture or ablate endothelium and plaque, a situation that activates hemostasis.Methods. In 85 patients undergoing PTCA for a 77.8 ± 1% stenosis, we measured markers of coagulation and platelet activation (thrombin-antithrombin complexes [TAT], prothrombin fragment 1 + 2 [F1+2] serotonin and the presence of circulating activated platelets reacting with monoclonal antibodies against glycoproteins exposed on platelet membranes). Blood samples were drawn from a peripheral vein and from the coronary ostium before the procedures. Both immediately and 10 min after angioplasty, and 10 min afterward, samples were collected from a probing catheter (0.018 in. [0.46 cm]) positioned beyond the stenosis. All patients were being treated with antianginal drugs and ASA, 250 mg/day. Seventy of them had taken ticlopidine, 250 mg, twice daily for ≤1 day (≤24 h) (n = 28) or for ≥3 days (≥72 h) (n = 42). Heparin (150 U/kg) was administered before angioplasty. Thirty patients underwent PTCA; 15 of them were not treated with ticlopidine and 15 were given ticlopidine (≥72 h). Thirty-five patients had stent implantation, 20 rotational atherectomy.Results. Before and during the procedures, there was greater thrombin generation (expressed by higher TAT and F1+2plasma levels) in patients not taking ticlopidine or taking it for ≤24 h (p < 0.05). Platelet activation and plasma serotonin levels were also significantly higher in the no ticlopidine or ≤24-h ticlopidine groups.Conclusions. The combined use of ticlopidine, ASA and heparin effectively controls activation of coagulation in patients with stable or unstable angina undergoing coronary dilation.(J Am Coll Cardiol 1997;29:13–20)

Psychiatric and psychological evaluation in living donor kidney transplantation: a single center experience

Background: Living donor kidney transplantation (LDKT) is the treatment of choice for end stage renal disease. LDKT involves complex psychosocial issues, which remain partially unexplored. Methods: The study involved all potential living donors and recipient pairs consecutively referred for psychosocial evaluation from the nephrologist. Clinical and sociodemographic variables including prior psychiatric history, previous and current use of psychopharmacological therapy, motivation and information about the transplant procedure were collected. Study participants completed the Symptom Checklist-90-R (SCL-90-R) to assess psychopathological distress. Results: Fifty-three donor/recipient pairs underwent psychiatric and psychological evaluation. Seven subjects (13%) in the recipient group and 13 subjects (25%) in the donor group reported a history of psychological distress and/or psychiatric conditions. A psychiatric diagnosis was confirmed in 4 recipients (7.5% of the study sample, including autism spectrum disorder, histrionic personality disorder, and anxiety-depressive disorders) and 5 donors (9%, including narcissistic personality disorder in one case and anxiety-depressive disorders). SCL-90-R GSI mean scores were 0.3 ±0.3 and 0.2 ±0.2 for the recipient and donor groups, respectively. Overall, 8 couples (15%) suspended the living donation pathway before transplantation. Four couples were excluded for a new onset medical condition. The psychological and psychiatric evaluation excluded one candidate. One couple dropped out before completing the scheduled exams. One recipient refused to undergo crossover renal transplantation, while 1 donor candidate withdrew her consent for transplantation at the end of the evaluation process. Conclusions: Limited but significant psychopathological distress in donors and recipients supports the usefulness of psychiatric and psychological competencies within the transplant team