Endocarditis after mitral valve repair

Background. Native valve endocarditis is frequently managed with antibiotics alone, but prosthetic valve endocarditis usually requires an early operation. What is the best treatment of endocarditis after mitral valve repair?

Methods. From 1986 to 2000, 22 patients were treated for endocarditis affecting a previously repaired mitral valve. Causes of mitral valve dysfunction that led to repair were degenerative (11 patients), ischemic (5 patients), endocarditic (3 patients), rheumatic (2 patients), and functional (1 patient). Endocarditis was active in 21 patients and healed in 1. Interval from initial mitral valve repair to onset of endocarditis ranged from 1 week to 10.3 years (median, 6 months). Pathology included leaflet vegetation (15), annuloplasty vegetation (4), leaflet perforation (5), and abscess (3). Mean follow-up was 3.9 ± 3.3 years.

Results. Fifteen patients underwent repeat mitral valve operations with freedom from mitral valve reoperation of 65%, 41%, and 26% at 30 days, 1 year, and 5 years after onset of endocarditis. After a high early hazard, risk of reoperation fell to 10.8% per year. Seven patients, all with a leaflet vegetation, were treated with antibiotics alone. Antibiotics eradicated infection in all; however all had mitral regurgitation 2+ to 4+. Survival was 96%, 74%, and 68% at 30 days, 1 year, and 5 years. Endocarditis recurred in 1 patient (92% free of event).

Conclusions. Most patients that have endocarditis develop after mitral valve repair require reoperation. However if infection is limited to a leaflet, early reoperation may be unnecessary because antibiotics alone can eradicate infection.     

Reoperative cryopreserved root and ascending aorta replacement for acute aortic prosthetic valve endocarditis

BACKGROUND: Prosthetic aortic valve endocarditis (PVE) is an important complication of aortic valve replacement (AVR) and is a particularly difficult situation after an operation combining AVR with ascending aortic replacement. METHODS: From 1988 through 2000, 27 patients with aortic valve PVE after previous ascending aortic replacement (aortic root replacement in 13, aortic valve replacement with a supracoronary graft in 14) underwent reoperation for aortic root replacement with a cryopreserved aortic allograft and prolonged intravenous antibiotic therapy. All patients were considered to have active PVE (25 with positive cultures); root abscess formation was present in 89% and aortoventricular discontinuity in 41%. RESULTS: One patient (3.7%) died in-hospital, and permanent pacemakers were required in 10 patients (37%). Mean postoperative follow-up interval was 3.9 +/- 3.0 years, and survival at 1, 2, 5, and 7.5 years was 92%, 88%, 70%, and 56%, respectively. One patient underwent reoperation for recurrent PVE 8 months after operation. CONCLUSIONS: Radical debridement of infected prosthetic material and tissue, and allograft aortic root and ascending aorta replacement, combined with intravenous antibiotic therapy, appears to achieve a low hospital mortality and a high degree of freedom from recurrent infection for patients with PVE after AVR and ascending aortic replacement.     

High mobility group proteins 1 and 2 recognize chromium-damaged DNA

Chromium (Cr) is a human carcinogen and a potent DNA damaging agent. Incubation of DNA with CrCl3 resulted in dose-dependent binding of Cr to DNA and, at concentrations >20 microM, altered the electrophoretic mobility of a 100 bp oligonucleotide. We also demonstrate that high mobility group (HMG) proteins 1 and 2 bind Cr-damaged DNA (Cr-DNA). Protein binding was lesion density-dependent, with maximal binding to DNA treated with 100 microM CrCl3. HMG2 binds to Cr-DNA with a calculated Kd of approximately 10(-9) M. These proteins also bound DNA obtained from chromate-treated cells. These results suggest that the covalent attachment of Cr to DNA induces alterations in DNA structure which are recognized by HMG1 and HMG2. Therefore, these proteins may function as Cr-damaged DNA recognition proteins in vivo and as a consequence of binding, may play a role in directing the cellular response to Cr-DNA adduct formation.      

Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

Interleukin-1 alpha, soluble interleukin-2 receptor, and IgG concentrations in cystic fibrosis treated with prednisolone

The cytokines interleukin-1 and interleukin-2 participate in the inflammatory response, and may contribute to hypergammaglobulinaemia G and the development of lung injury in cystic fibrosis. Anti-inflammatory treatment with corticosteroids may attenuate this response. The effect of a 12 week course of oral prednisolone on spirometry and serum concentrations of interleukin-1 alpha (IL-1 alpha), soluble interleukin-2 receptor (sIL-2R), and IgG was investigated in 24 children with cystic fibrosis. Prednisolone was administered, in a double blind and placebo controlled manner, at an initial dose of 2 mg/kg daily for 14 days and tapered to 1 mg/kg on alternate days for 10 weeks. The treated group (n = 12) experienced an increase in forced expiratory volume in one second and forced vital capacity at 14 days, however, these changes were smaller at 12 weeks. In the treated group, change in pulmonary function was associated with decreased serum IgG and cytokine concentrations. Prednisolone suppresses serum concentrations of these cytokines, which may participate in the inflammatory response, the excessive synthesis of IgG, and airflow obstruction observed in cystic fibrosis patients.     

Peripheral α2-adrenoceptor-mediated sympathoinhibitory effects of mivazerol

Summary— Mivazerol is a new compound that could potentially reduce perioperative cardiovascular morbidity and mortality in patients with or at risk of coronary disease and submitted to surgery. This action of mivazerol depends on a well documented centrally mediated reduction in sympathetic nerve activity, but a direct peripheral decrease in sympathetic neurotransmitter release induced by activation of prejunctional α₂-adrenoceptors located on sympathetic nerve endings could also contribute. To investigate this issue, the effects of mivazerol on the pressor, systemic and regional hemodynamic (pulsed Doppler technique) as well as on the cardiac responses to electrical stimulation of the spinal cord (SCS) were measured in pithed rats in the absence and in the presence of mivazerol. Mivazerol exerted strong sympathoinhibitory effects: SCS-induced increases in blood pressure, total peripheral resistance and heart rate were dose-dependently reduced by mivazerol, but among the regional vascular beds investigated, only the hindlimb vasoconstrictor responses were significantly drug-affected. All these sympathoinhibitory effects of mivazerol were abolished by prior yohimbine administration. Simultaneously, mivazerol did not induce any postjunctional adrenoceptor blockade as it did not affect noradrenaline cardiac and hemodynamic effects. On the contrary, through postjunctional α₂-adrenoceptor stimulation, mivazerol, in this pithed preparation, dose-dependently increased blood pressure, total peripheral and hindlimb vascular resistances, but heart rate was not affected. We conclude that, in the pithed rat, mivazerol exerts strong peripheral sympathoinhibitory effects. The mechanism involved is prejunctional α₂-adrenoceptor activation as i) mivazerol does not display any postsynaptic α-adrenoceptor blocking effect — it even behaves as a postsynaptic α₂-adrenoceptor agonist — and ii) yohimbine abolishes mivazerol's sympathoinhibitory effects. Thus, direct peripheral together with central mechanisms contribute to mivazerol's sympathoinhibitory effects and ultimately to its cardioprotective action.