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In human atrial myocytes, serotonin rather than sympathetic, stimulation is more frequently associated with atrial fibrillation. So does the arrhythmogenic effect of serotonin result from the mechanism of action of the receptor or the context of its action upon cardiac myocytes? The capacity of agonists to produce cAMP followed the sequence 5-HT [ABSTRACT FROM AUTHOR]

Heparin-induced thrombocytopenia (HIT) is due primarily to IgG antibodies specific to platelet factor 4/heparin complexes (PF4/Hs) that activate platelets via FC&ggr;RIIA. CD148 is a protein tyrosine phos-phatase that regulates Src kinases and collagen-induced platelet activation. Three polymorphisms affecting CD148 (Q276P, R326Q, and D872E) were studied in HIT patients and 2 control groups, with or without antibodies to PF4/Hs. Heterozy-gote status for CD148 276P or 326Q alleles was less frequent in HIT patients, suggesting a protective effect of these polymorphisms. Aggregation tests performed with collagen, HIT plasma, and monoclonal antibodies crosslinking FC&ggr;RIIA showed consistent hyporespon-siveness of platelets expressing the 276P/ 326Q alleles. In addition, platelets expressing the 276P/326Q alleles exhibited a greater sensitivity to the Src family kinases inhibitor dasatinib in response to collagen or ALB6 cross-linking Fc-&ggr;RIIA receptors. Moreover, the activatory phos-phorylation of Src family kinases was considerably delayed as well as the phos&ggr;phorylation of Linker for activation of T cells and phospholipase C&ggr;2, 2 major signaling proteins downstream from FC&ggr;RIIA. In conclusion, this study shows that CD148 polymorphisms affect platelet activation and probably exert a protective effect on the risk of HIT in patients with antibodies to PF4/HS. [ABSTRACT FROM AUTHOR]

Background and Aim of the Study: Currently, valve thrombosis, thromboembolic events and bleeding events account for 75% of all complications that occur after mechanical heart valve replacement. The study aim was to determine the main risk factors for valve-related complications in patients undergoing mechanical heart valve replacement., Methods: Data were available from the systematic follow up of patients who had received a CarboMedics bileaflet mechanical heart valve replacement at the authors' institution. Follow up examinations were conducted prospectively at two-year intervals, via questionnaires sent to the patients' general practitioners, or by telephone calls., Results: Between January 1988 and December 2005, a total of 505 consecutive patients (300 males, 205 females; mean age 52 years; range: 5 to 77 years) underwent heart valve replacement using a CarboMedics mechanical prosthesis. Aortic valve replacement (AVR) was performed in 308 patients, mitral valve replacement (MVR) in 134 patients, and double-valve replacement (DVR) in 62 patients. The follow up was 95.4% complete; the mean follow up was 7.5 years, and the total follow up 3,718 patient-years. Thromboembolic and bleeding complications represented the leading cause of valve-related events (104/195), of valve-related mortality (15/25), and of the need for repeat surgery (9/16). Valve thrombosis occurred in 12 patients. Implantation in the mitral position was identified as a risk factor (HR = 15.07; CI: 8.41-23.07; p 0.0001). Thromboembolism occurred in 32 patients; the use of antiplatelet agents was found to be a protective factor (HR = 0.23; CI: 0.08-0.70; p = 0.01). Bleeding events occurred in 52 patients; risk factors for bleeding events included a history of thromboembolic or bleeding complications (HR = 2.70; CI: 1.33-5.26; p = 0.006) and an unstable International Normalized Ratio (INR) (HR = 2.86; CI: 1.01-8.08; p = 0.05)., Conclusion: After mechanical heart valve replacement, the only risk factors for bleeding complications were an unstable INR and a history of thromboembolic or bleeding events. The use of antiplatelet agents proved to be a protective factor against thromboembolic events.

Background and Aim of the Study: Aortic stenosis (AS) is the most important cause of aortic valve disease, its prevalence increasing with patient age. The present study formed part of a long-term evaluation on use of the Perimount pericardial valve for aortic calcified stenosis., Methods: A total of 1133 consecutive patients who underwent aortic valve replacement (AVR) with a Perimount pericardial bioprosthesis for degenerative AS between July 1984 and December 2003 at the authors' institution, was followed up in 2004. Among the patients (716 males, 417 females; mean age 72.6 years), 997 were in sinus rhythm, and the mean NYHA functional class was 2.3. Preoperative echocardiography indicated a mean gradient of 56 mmHg, a peak gradient of 89 mmHg, and an effective orifice area of 0.6 cm2. Associated procedures were required in 336 patients., Results: All patients but 18 (1.5%) were followed up for an average of 5.5 years postoperatively; thus, the total follow up was 6,180 patient-years. Operative mortality was 2.8% (n=32), and there were 330 late deaths. At 18 years the actuarial survival rate was 22 +/- 4%. Among the 725 patients followed, 80% were in sinus rhythm and 98% in NYHA classes I or II. Valve-related complications included 39 thromboembolic episodes, 24 endocarditis, 22 anticoagulant-related hemorrhage, 28 reoperations, and 19 structural valve failures. A total of 54 patients died from valve-related causes (13 embolic events, two endocarditis, two hemorrhage, one structural failure, 36 unknown causes), and 57 died from cardiac failure. Neither thrombosis nor hemolysis was observed. At 18 years, freedom from embolism was 92 +/- 2%, from endocarditis 93 +/- 4%, from hemorrhage 95 +/- 2%, from reoperation 62 +/- 11%, from valve failure 68 +/- 12%, and from all complications 47 +/- 8%. Among patients aged >60 years, the 18-year actuarial freedom from reoperation was 76 +/- 14%, and from valve failure 85 +/- 8%., Conclusion: With a low rate of valve-related events at 18 years, and an especially low rate of structural failure, the Perimount pericardial prosthesis is a reliable choice for patients with aortic calcified stenosis.

In human atrial myocytes, serotonin rather than sympathetic, stimulation is more frequently associated with atrial fibrillation. So does the arrhythmogenic effect of serotonin result from the mechanism of action of the receptor or the context of its action upon cardiac myocytes? The capacity of agonists to produce cAMP followed the sequence 5-HT < Iso < Forskolin to increase ICaL with 5-HT = Iso = Forskolin. The simultaneous application of threshold concentrations of 5-HT and Iso maximally increased ICaL. We will show that the effect of 5-HT upon human atrial myocytes is an imbalance between low production of cAMP and maximal activation of ICaL.