Factor V Leiden does not affect bleeding in aprotinin recipients after cardiopulmonary bypass.

BACKGROUND: Carriers of the factor V Leiden mutation (FVL) are resistant to activated protein C proteolysis. Therefore, they are at increased risk of thromboembolic events. Aprotinin is an unspecific proteinase inhibitor frequently used during cardiac surgery procedures to reduce bleeding. However, aprotinin may cause thromboembolic complications after cardiopulmonary bypass (CPB). The primary endpoint of this study was the amount of blood loss after CPB in aprotinin recipients, and secondary endpoints were thromboembolic complications. METHODS: A total of 1,447 consecutive patients who underwent cardiac surgery with CPB were prospectively enrolled. All patients were screened for FVL by a fluorescence-based polymerase chain reaction method. Linear and logistic regression analyses were performed to assess associations of FVL on bleeding and thromboembolic complications. RESULTS: One hundred seven individuals (7.4%) were heterozygous FVL carriers. No difference was found between FVL carriers and noncarriers regarding age, sex, CPB, type of operation, EuroSCORE, antiplatelet treatment, and reoperation. FVL was not significantly associated with postoperative blood loss, whereas a significant influence was found for female sex (P < 0.0001), duration of CPB (P < 0.0001), reoperation (P = 0.001), and preoperative antiplatelet treatment (P < 0.002). Multiple linear regression analysis for total blood loss had an observed power of at least 99%. FVL carriers faced the same risk for postoperative transfusion (P = 0.391), reoperation (P = 0.675), myocardial infarction (P = 0.44), stroke (P = 0.701), and 30-day mortality (P = 0.4) as did noncarriers. CONCLUSIONS: These data suggest that FVL carriers do not have reduced blood loss compared with noncarriers. Furthermore, the combination of aprotinin and FVL does not enhance the risk for thromboembolic complications.

Calcineurin and matrix protein expression in cardiac hypertrophy: evidence for calcineurin B to control excessive hypertrophic signaling.

In the compensatory state of human left ventricular hypertrophy (LVH), the remodeling processes in the extracellular matrix and the role of calcineurin (Cn) are not completely understood. The present work aimed to analyze the expression and activity of matrix metalloproteinases (MMPs), their endogenous inhibitors (TIMPs), and of Cn in patients with compensated LVH. By semiquantitative RT-PCR, Western blotting, and gelatine zymography, we determined mRNA, protein, and/or enzyme activity levels of MMPs, TIMPs, atrial natriuretic peptide (ANP), Cn subunits, and of the modulatory calcineurin-interacting protein (MCIP) 1. Myocardial samples from patients showing severe aortic stenosis, normal ejection fraction, and compensated LVH were compared with autopsy samples from healthy hearts. LVH patients showed upregulation of CnA-beta mRNA but downregulation of both CnB-alpha mRNA and protein. Total Cn activity (as determined through NF-AT phosphorylation and MCIP1 mRNA expression) was unchanged. There were no differences in gene expression and activities of MMP-2, MMP-9, and of TIMPs 1-4 between LVH patients and controls. As expected, ANP mRNA expression was high in LVH patients. We propose a prominent role for CnB in controlling Cn activity in compensated LVH. At this stage of the disease, MMP and TIMP activities are balanced.

Transcriptional regulation of alpha5beta1 integrin, fibronectin, VCAM-1, MCSF-1/c-fms, and MCP-1 in atrioventricular valves after valvular surgery and Staphylococcus aureus bacteremia.

OBJECTIVE: The primary event in the development of infective endocarditis (IE) is bacterial adherence to damaged heart valves. This includes capture, adhesion and internalization of bacteria into host cells. METHODS: We determined in an experimental rabbit model for IE whether a transient bacteremia caused by Staphylococcus aureus and/or endothelial heart valve lesions induce transcriptional regulation of alpha(5)beta(1) integrin, fibronectin, vascular cell adhesion molecule-1 (VCAM-1), macrophage colony-stimulating factor-1 (MCSF-1), c-fms proto-oncogene (MCSF-1 receptor), and macrophage chemoattractant protein-1 (MCP-1) in mitral and tricuspid valves. RESULTS: No significant upregulation was found after isolated bacteremia. Six hours after surgical manipulation valvular endothelial lesions led to a distinct modulation in the mRNA expression of proinflammatory cytokines (MCSF-1 and MCP-1), VCAM-1 and alpha(5)beta(1) integrin. The most evident differences between the mitral and tricuspid valves were seen in the significant upregulation of VCAM-1 mRNA on the tricuspid valve in the surgical groups, whereas there was no effect on the mitral valve. MCSF-1 and MCP-1 were dramatically upregulated in both valves after surgery. CONCLUSIONS: During the host defence mechanisms in the development of IE proinflammatory cytokines, cellular adhesion molecules, and molecules of the fibronectin/integrin axis are activated, showing distinct differences in right- and left-sided heart valves.

Atrial fibrosis in heart surgery patients Decreased collagen III/I ratio in postoperative atrial fibrillation.

In chronic atrial fibrillation, increased expression of angiotensinconverting enzyme (ACE) promotes upregulation of profibrotic proteins. Atrial fibrillation early after cardiac surgery (poAF) is common but unpredictable, and is regarded as a different entity. Therefore, the present study tested whether atrial expression of ACE, osteopontin (OPN), and collagen is elevated in patients with no history of AF but who develop poAF. Thus, 19 patients (66 +/- 9 years) with postoperative sinus rhythm (poSR) were compared to 14 patients (68 +/- 10) who experienced poAF. mRNA and protein expression were determined by RT-PCR and Western blotting. Picrosirius red was used to stain collagen. The medians for ACE, OPN, type I collagen (Col I), and type III collagen (Col III) mRNA and protein expression did not significantly differ between poSR and poAF (U-test). However, the Col III/I protein ratio was significantly lower in patients with poAF (2.62 vs. 1.09; poSR vs. poAF; p < 0.05). Our data suggest that the occurrence of poAF is not dependent on increased ACE and OPN expression, rendering the determination of preoperative OPN plasma levels inadequate to estimate the risk for the occurrence of poAF. Contrarily, a shift in atrial collagen expression levels in favor of Col I is linked to the occurrence of poAF.