Telomere length in vascular tissues from patients with atherosclerotic disease.

OBJECTIVES: The present study was aimed at evaluating telomere length in blood and in different vascular tissues with or without atheroma, in 3 groups of subjects: a group of atherosclerotic subjects who underwent surgery (Atherosclerosis-Surgery), a second group of subjects with asymptomatic atherosclerotic carotid plaques but who did not undergo cardiovascular surgery (Atherosclerosis-No surgery), and a third group of subjects without atherosclerotic disease (Controls). The main objective was to determine if there is in vivo regulation of telomere length in situ by atherosclerotic lesions. METHODS: A total of 84 subjects (mean age 69 ± 8 years) were studied. Blood and arterial tissue telomere lengths were determined by Southern blotting. Personal medical history (diabetes, hypertension, cardiovascular disease, dyslipidemia), family medical history, drug intake, and lifestyle were evaluated in the entire population through the use of a questionnaire. RESULTS AND CONCLUSION: Arterial segments which did not develop atherosclerosis such as the saphenous vein and internal mammary artery, had longer telomere length than aortic segments. On the other hand, telomere length was shorter in aortic tissues which presented atherosclerotic lesions compared to corresponding tissues without atherosclerotic lesions. These results also suggest tissue regulation of telomere size by local factors likely related to oxidative stress responses.

[Evaluation of the benefit of early valve surgery in the treatment of infective endocarditis. Contribution of propensity analyses]. / Evaluation du bénéfice de la chirurgie valvulaire précoce dans le traitement de l'endocardite infectieuse. Apport des analyses de propension.

Early valve surgery for infective endocarditis, that is surgery performed during the course of antibiotic therapy, is widely used. However, this intervention has never been proven effective in any clinical trial. Five recently published observational studies, using propensity analysis, analyzed the relationship between surgery and mortality. But they gave conflicting results, mainly because of their methodological limitations. Thus, to date, there is no reliable estimation of early valvular surgery impact on mortality. In addition, this example allows for discussing the interest of propensity analyses and to emphasizing their limitations.

[Staphylococcus aureus bacteremia and endocarditis]. / Bactériémies et endocardites àStaphylococcus aureus.

The prevalence of Stapylococcus bacteriaemia is increasing worldwide, because of the increasing use of invasive procedures leading to nosocomial infections, but also of a changing way of life (increasing fashion for tattoos or piercing, use of intravenous drugs). Infective endocarditis develops in 10-30% of the cases of staphylococcus bacteriaemia. Staphylococcus aureus endocarditis must be suspected when it develops in the year following heart surgery or implantation of permanent devices. In drug users, it usually involves the tricuspid valve. According to the resistance of the germ to meticillin, antibiotic therapy uses a combination of intravenous penicillin or glycopeptide and an aminoside. Other antibiotics such as fosfomycin, rifampicin, fusidic acid, or clindamycin can be used when aminosides are contra-indicated. The role of newer antibiotic agents, such as daptomycin or linezolide, remains to be established.

[Non-valvular cardiac devices endocarditis]. / L'endocardite sur matériel de stimulation intracardiaque.

The risk of infective endocarditis on pacemaker or ICD is not negligible and has increased in recent years. Several host-related, procedure-related, or device-related risk factors have been recognized. Owing to its potential severity, the possibility of infective endocarditis should be envisaged in patients with repeated pulmonary infections or documented bacteremia and transesophageal echocardiography should then be used. The most common germs causing pacemaker endocarditis are staphylococci. Treatment requires prolonged antibiotic therapy and retrieval of the pacemaker and leads.

[Mortality prognostic factors of cardiogenic shock complicating an acute myocardial infarction and treated by percutaneous coronary intervention]. / Facteurs pronostiques de mortalité chez les patients en etat de choc cardiogénique primaire traités par angioplastie en phase aiguë d'infarctus.

OBJECTIVE: To determine the in-hospital prognosis and late outcome of cardiogenic shock complicating acute myocardial infarction treated by early (< 24 hours) percutaneous coronary intervention (PCI). METHODS: Retrospective monocentric study of a consecutive cohort of patients undergoing early PCI (< 24 heures) for cardiogenic shock complicating acute myocardial infarction from 1994 to 2004. RESULTS: The cohort included 175 patients (mean age = 65 +/- 14 years, 68% male). A successful PCI was obtained in 69% of patients. The in-hospital mortality was 43%. Independent risk factors associated with an increased mortality were: absence of TIMI three flow (P < 0.0001), absence of smoking (P < 0.009) and the need for mechanical ventilation (P < 0.002). Nor stent use or anti GP IIb/IIa infusions were predictors of a better outcome. At hospital discharge, mean left ventricular ejection fraction (LVEF) was 38 +/- 12%. Kaplan-Meier estimate of survival was 63% for in-hospital survivors (maximum follow-up = 9 years). Independent predictors of an impaired long-term outcome were: a LVEF < 0.3 (P < 0.028) and 3-vessel disease on coronary angiography (P < 0.004). CONCLUSION: In-hospital mortality of patients suffering cardiogenic shock complicating acute myocardial infarction and treated by PCI remains high despite PCI improvement. The long-term survival appears, however, to be better than that of patients with coronary artery disease and low LVEF.

[Use of ecarin clotting time in whole blood for monitoring recombinant hirudine treatment during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia]. / Utilisation du temps de coagulation par l'écarine en sang total pour la surveillance d'un traitement anticoagulant par lépirudine (Refludan au cours de circulation extracorporelle dans un contexte de thrombopénie induite par l'héparine.

Lepirudin (Refludan is a recombinant hirudin, approved for anticoagulation treatment of heparin-induced thrombocytopenia patients with thrombosis. We report here our method for laboratory monitoring with ecarin clotting time (ECT) of hirudin therapy as anticoagulation for cardiac surgery. Ecarin is extracted from the Echis carinatus snake venom and directly converts prothrombin to its intermediate, meizothrombin. This one binds in a stoechiometric way to hirudin to be proportioned in whole blood. The activation of coagulation starts up only when the totality of the hirudin is bound to the meizothrombin. To minimize the effect of dilution related to the CEC on the prothrombin and fibrinogen levels, thus lengthening the ECT, the specimen to be tested is diluted with normal whole blood. In 1997, when we have performed our first surgery with cardiopulmonary bypass, only one team (Pötzsch et al., 1997) had described the use of the ECT in whole blood. We describe in this work our assay to dose hirudin with ECT after dilution in whole blood. This assay was used during 8 CEC among 7 patients affected with HIT (n = 6) or potentially sensitized with heparin (n = 1). Experimental conditions and interpretation of the assay are reported here. This test is fast enough to provide useful information for adjusting the dose during cardiopulmonary bypass.

Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence.

OBJECTIVES: This study aimed to determine whether the myocardial T2 relaxation time, determined using a black-blood magnetic resonance imaging (MRI) sequence, could predict acute heart transplant rejection. BACKGROUND: The use of black-blood MRI sequences allows suppression of the confusing influence of blood signal when myocardial T2 is calculated to detect myocardial edema. METHODS: A total of 123 investigations, including cardiac MRI and myocardial biopsy, were performed 8 +/- 11 months after heart transplantation. Myocardial T2 was determined using an original inversion-recovery/spin-echo sequence. RESULTS: A higher than normal T2 (> or = 56 ms) allowed an accurate detection of the moderate acute rejections evidenced at baseline biopsy (> or = International Society for Heart and Lung Transplantation grade 2): sensitivity, 89% and specificity, 70% (p < 0.0001). T2 was increased in grade 2 (n = 11) compared with grade 0 (n = 49, p < 0.05), grade 1A (n = 34, p < 0.05) and grade 1B (n = 21, p < 0.05); T2 was further increased in grade 3 (n = 8) compared with grade 2 (p < 0.05). In addition, in patients without rejection equal to or greater than grade 2 at baseline, a T2 higher than normal (> or = 56 ms) was correlated with the subsequent occurrence of equal or greater than grade 2 rejection within the next three months: sensitivity 63% (12/19) and specificity 78% (64/82) (p = 0.001). CONCLUSIONS: Myocardial T2 determined using a black-blood MRI sequence, is sufficiently sensitive to identify most of the moderate acute rejections documented with biopsy at the same time, but is also a predictor of the subsequent occurrence of such biopsy-defined rejections.

Activation of metalloproteinase-2, loss of matrix scleroprotein content and coronary artery calcification.

Plaques from the coronary arteries of explanted hearts showed massive calcification (15-fold increase) with a loss of scleroproteins (-36%), an increase in the collagen to elastin ratio (twofold) and activation (+15%) of matrix metalloproteinase-2 (MMP-2). Plaque-free portions of the coronary artery gave results similar to those obtained with the internal mammary artery. There was a significant correlation between plaque calcification and MMP-2 activation, suggesting that the two processes may be linked.

Investigation of 3-D mechanical properties of blood vessels using a new in vitro tests system: results on sheep common carotid arteries.

In order to investigate the three-dimensional (3-D) mechanical properties of blood vessels, a new experimental device is described allowing in vitro static and dynamic measurements on segments of arteries with high technical performances. Static tests are applied to sheep common carotid arteries. Considering a thick-walled cylindrical model of orthotropic material under large deformations, a classical 3-D approach based on strain energy density is used to calculate the resulting mechanical behavior law in radial and circumferencial directions and stresses distribution throughout the wall thickness. Results are presented with reference to unloaded and zero-stress initial state thanks to simple measurements of inner and outer circumferences. A particular ratio relating the two main stresses (circumferential and longitudinal) is calculated that put into the forth the progressive modifications in the direction of the predominant stress in the wall and the specific radial location where these changes occur. We observe that this point location is a function of the test conditions of the specimen, i.e., stretching length and level of pressure.

Consequences of inspired oxygen fraction manipulation on myocardial oxygen pressure, adenosine and lactate concentrations: a combined myocardial microdialysis and sensitive oxygen electrode study in pigs.

Adenosine is a potent vasodilator whose concentration has been shown to increase in cardiac tissue in response to hypoxia. However, the time-dependent relationship between the levels of myocardial interstitial adenosine and tissue oxygenation has not yet been completely established. Therefore, the purpose of this study was to investigate the complex relationship between tissue myocardial oxygen tension (PtiO(2)) and interstitial myocardial adenosine and lactate concentrations by developing a new technique which combines a cardiac microdialysis probe and a Clark-type P O(2)electrode. The combined and the single microdialysis probes were implanted in the left ventricular myocardium of anesthetized pigs. The consequences of the combined use of microdialysis and P O(2)probes on myocardial PtiO(2)and microdialysis performances against glucose were evaluated. A moderate but significant reduction in the relative recovery against glucose of the combined probe was observed when compared to that of the single microdialysis probe (42+/-2 v 32+/-1%, mean+/-S.E. M.n=5 P<0.05), at 2microl/min microdialysis probe perfusion flow. Similarly, myocardial oxygen enrichment, measured by the P O(2)electrode, was negligible when microdialysis probe perfusion flow was 2microl/min. Systemic hypoxia (FiO(2)=0.08) resulted in a significant decrease in PtiO(2)from 30+/-4 to 11+/-2 mmHg, limited increase in coronary blood flow (CBF), and a significant increase in myocardial adenosine and lactate concentrations from 0.34+/-0.05 to 0.98+/-0.06micromol/l and from 0.45+/-0.05 to 0.97+/-0.06 mmol/l respectively (P<0.05). Increasing the FiO(2)to 0.3 restored the PtiO(2)and hemodynamic parameters to baseline values with no changes in interstitial adenosine and lactate concentrations. Nevertheless, myocardial interstitial adenosine remained significantly higher than baseline values. In conclusion, this study demonstrates the ability of a combined probe to measure simultaneously regional myocardial PtiO(2)and metabolite concentration during hypoxia. The hypoxia-induced increase in myocardial adenosine persists after correction of hypoxia. The physiological significance of this observation requires further studies.

[Advanced cardiac failure. New surgical approaches]. / L'insuffisance cardiaque avancée. Approches chirurgicales actuelles.

THERAPEUTIC OPTIONS: Prognosis of advanced heart failure is ominous since survival rate is less than 65% one year after an acute and severe cardiac episode. Medical therapy has proven to be efficient in reducing fatal complications and in delaying critical evolution. Depending on the etiology and the myocardial status, new surgical approaches can also be proposed for repair or substitution. SURGICAL REPAIR: The beneficial effect of myocardial revascularization on severe ischemic cardiomyopathy, the relevance of mitral valve repair in dilated cardiomyopathy, and the advantage of ventricular remodeling in patients with major ventricular dyskinesia has been clearly demonstrated. All these surgical techniques improve ventricular function and enhance survival rate by about 70% after three years. SUBSTITUTION PROCEDURES: The best therapeutic option to recover heart function for normal life and reduced mortality remains, when possible, cardiac transplantation. Ventricular cardiac assist devices are planned as a temporary option to bridge the waiting period to transplantation or for myocardial recovery but can also be proposed as a chronic implantation in an outpatient care scheme. Cardiomyoplasty for therapeutic management of advanced cardiac failure is still a controversial surgical approach. Other clinical strategies such as transmyocardial laser revascularization, myocardial angiogenesis and myocardial cell therapy are being investigated or developed. ADAPTED TREATMENT: Optimal management of each patient with advanced heart failure requires an adequate treatment selected among a wide range of medical and/or surgical strategies.

Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin.

BACKGROUND: Acute pulmonary hypertension occurring after cardiopulmonary bypass can be a cause of post-operative morbidity and mortality. The purpose of this study was to investigate whether bosentan, a non-peptidic mixed endothelin antagonist affected the pulmonary hypertension induced by experimental cardiopulmonary bypass. METHODS: Pigs were anesthetized and instrumented to determine hemodynamic measurements. Pigs were randomized to receive either 3 mg/kg bolus + 7 mg/kg per h bosentan (n = 8) or saline (n = 7). All pigs underwent 90 min of cardiopulmonary bypass and were further observed for a 120-min period. RESULTS: In the control group, cardiopulmonary bypass induced a dramatic pulmonary hypertension (+78 +/- 13%, P < 0.005) and accompanied an increase of pulmonary vascular resistance (+228 +/- 50%, P < 0.005), whereas, in the treated group, bosentan completely prevented these deleterious effects of cardiopulmonary bypass with only a moderate decrease of systemic vascular resistance (-19 +/- 14.6%, P < 0.05). CONCLUSIONS: The present findings support the hypothesis that endogenous endothelin is a mediator of acute pulmonary hypertension occurring after cardiopulmonary bypass. Bosentan, a mixed endothelin antagonist completely prevented pulmonary hypertension after cardiopulmonary bypass and may, therefore, have therapeutic applications in the management of patients following cardiac surgery.

Aortic valve surgery in osteogenesis imperfecta: report of two cases and review of the literature.

Aortic insufficiency is a well known but uncommon valvular dysfunction in patients with osteogenesis imperfecta. In such cases, aortic valve surgery has rarely been performed, and carries a high risk of perioperative complications. We report two patients with osteogenesis imperfecta, who underwent elective successful aortic valve replacement. The surgical problems encountered in this connective tissue disorder are also reviewed.