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Biomedical subjects

P Dos Santos

Publications and source records attributed to P Dos Santos.

At least 19 recordsLinked to original sources

[Direct thrombin inhibitors in coronary angioplasty. Value of bivalirudin ].

During coronary angioplasty, the association of platelet inhibitors and antithrombin agents is required to prevent myocardial infarction. Bivalirudine, a synthetic direct thrombin inhibitor, has been widely validated in this context and has shown its efficacy and safety in several comparative studies. It is officially recommended as a replacement of NFH and LMWH associated or not with anti-GPIIb/IIIa agents because at comparable efficacy it causes fewer bleeding complications. In acute coronary syndromes without ST elevation, anti GPIIb/IIIa agents reduce angioplasty-related complications and mortality, especially in high risk patients in salvage situations. In the REPLACE-2 trial the clinical efficacy of bivalirudine (associated only when necessary with anti-GPIIb/IIIa agents) was no less than that of NFH associated systematically with anti-GPIIb/IIIa agents at the time of intervention. The incidents of serious adverse events at 30 days (death, infarctus, emergency revascularisation, major bleeding) in the bivalirudine group was 9.2% versus 10.2% in the NFH group. In a retrospective analysis, these results did not seem to be influenced by the prior administration of clopidogrel. Finally, the one year follow-up results showed a lower mortality in patients treated with bivalirudine (1.9% versus 2.5%), essentially in the high risk sub-groups such as the elderly, the diabetic or the renal failure patients. Clinical trials are underway (ACUITY) to study the interaction of anti GPIIb/IIIa agents with bivalirudine in the first hours of acute coronary syndromes and should confirm a major role of direct anti-thrombin drugs in the safety of angioplasty.

Angioplasty, Balloon, Coronary↗

[Placement of an implantable defibrillator via the endocavitary route in a patient presenting with a univentricular heart and a Glenn anastomosis].

We report the observation of a female 45 year old patient presenting with a post-surgery complex congenital cardiopathy, associated with serious ventricular rhythm disorders necessitating the placement of an implantable defibrillator. The palliative surgery performed (cavo-pulmonary Glenn anastomosis) does not allow the usual access to the right ventricle via the superior vena cava. The different possibilities for defibrillator implantation are discussed. These include associating a surgical approach to introduce the bipolar probe with subcutaneous tunnelling to connect the probe to the box.

Arrhythmias, Cardiac↗

[Ebstein's anomaly].

Since Ebstein's first description in 1866 and the first surgical attempts at treatment in the 1950's, the natural history of this condition remains obscure. The anatomical description contrasts with the clinical and prognostic variability of this malformation. The form observed in the foetal or prenatal periods has a very different prognosis to that observed in adults. The risk factors are not the same even though the anatomical entity is comparable. The difficulty in managing these patients is due to the problems of diagnosis and determination of these prognostic factors. Advances in echocardiography, the key investigation which facilitates diagnosis, and in surgical and ablation techniques, have improved our understanding of this condition and its prognosis.

Adult↗

Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase.

M. N. Laclau, S. Boudina, J. B. Thambo, L. Tariosse, G. Gouverneur, S. Bonoron-Adèle, V. A. Saks, K. D. Garlid and P. Dos Santos. Cardioprotection by Ischemic Preconditioning Preserves Mitochondrial Function and Functional Coupling Between Adenine Nucleotide Translocase and Creatine Kinase. Journal of Molecular and Cellular Cardiology (2001) 33, 947-956. This study investigates the effect of ischemic preconditioning on mitochondrial function, including functional coupling between the adenine nucleotide translocase and mitochondrial creatine kinase, which is among the first reactions to be altered in ischemia. Three groups of Langendorff-perfused rat hearts were studied: a control group, a group subjected to 30 min ischemia followed by 15 min reperfusion, and a group subjected to ischemic preconditioning prior to 30 min ischemia and 15 min reperfusion. Ischemic preconditioning significantly delayed the onset and amplitude of contracture during ischemia, decreased enzymatic release, and improved the recovery of heart contractile function after reperfusion. Mitochondrial function was assessed in permeabilized skinned fibers. The protective effect of preconditioning was associated with preservation of mitochondrial function, as evidenced by maintenance of the high K(1/2)for ADP in regulation of mitochondrial respiration and V(max)of respiration, the near absence of respiratory stimulation by exogenous cytochrome c, and preservation of functional coupling between mitochondrial creatine kinase and adenine nucleotide translocase. These data suggest that ischemic preconditioning preserves the structure-function of the intermembrane space, perhaps by opening the mitochondrial ATP-sensitive K(+)channel. The consequence is preservation of energy transfer processes from mitochondria to ATP-utilizing sites in the cytosol. Both of these factors may contribute to cardioprotection and better functional recovery of preconditioned hearts.

Adenosine Diphosphate↗

Improved reliability for echocardiographic measurement of left ventricular volume using harmonic power imaging mode combined with contrast agent.

Harmonic power imaging (HPI) is a new echocardiographic modality that enhances the detection of contrast agents in the left ventricle. The endocardium can be delineated by conventional echocardiography using ultrasound contrast agents, although the images tend to be faint. The present study was designed to assess left ventricular volume using HPI after intravenous injection of the contrast agent Levovist (Schering SA, Berlin, Germany) in 25 unselected patients. End-diastolic volume, end-systolic volume, and ejection fraction were determined for each patient with angiography and with 4 different ultrasound modalities: (1) conventional mode without contrast, (2) contrast conventional mode, (3) contrast harmonic intermittent imaging mode, and (4) contrast triggered HPI. The use of HPI improved correlations between the echographic and angiographic measurements for all parameters as well as precision and bias determined by Bland and Altman analysis. The relative errors for interobserver variability were also lower with HPI. This study demonstrates that echocardiographic determination of left ventricular volumes and ejection fraction is more accurate and reproducible using HPI combined with Levovist.

Angiography↗

Metabolic control of contractile performance in isolated perfused rat heart. Analysis of experimental data by reaction:diffusion mathematical model.

The intracellular mechanisms of regulation of energy fluxes and respiration in contracting heart cells were studied. For this, we investigated the workload dependencies of the rate of oxygen consumption and metabolic parameters in Langendorff-perfused isolated rat hearts.(31)P NMR spectroscopy was used to study the metabolic changes during transition from perfusion with glucose to that with pyruvate with and without active creatine kinase system. The experimental results showed that transition from perfusion with glucose to that with pyruvate increased the phosphocreatine content and stability of its level at increased workloads. Inhibition of creatine kinase reaction by 15-min infusion of iodoacetamide decreased the maximal developed tension and respiration rates by a factor of two.(31)P NMR data were analyzed by a mathematical model of compartmentalized energy transfer, which is independent from the restrictions of the classical concept of creatine kinase equilibrium. The analysis of experimental data by this model shows that metabolic stability-constant levels of phosphocreatine, ATP and inorganic phosphate-at increased energy fluxes is an inherent property of the compartmentalized system. This explains the observed substrate specificity by changes in mitochondrial membrane potential. The decreased maximal respiration rate and maximal work output of the heart with inhibited creatine kinase is well explained by the rise in myoplasmic ADP concentration. This activates the adenylate kinase reaction in the myofibrillar space and in the mitochondria to fulfil the energy transfer and signal transmission functions, usually performed by creatine kinase. The activity of this system, however, is not sufficient to maintain high enough energy fluxes. Therefore, there is a kinetic explanation for the decreased maximal respiration rate of the heart with inhibited creatine kinase: i.e. a kinetically induced switch from an efficient energy transfer pathway (PCr-CK system) to a non-efficient one (myokinase pathway) within the energy transfer network of the cell under conditions of low apparent affinity of mitochondria to ADP in vivo. This may result in a significant decrease in the thermodynamic affinity of compartmentalized ATPase systems and finally in heart failure.

Animals↗

Can power motion imaging mode combined with contrast agent assess myocardial contraction and perfusion? In vitro and in vivo studies.

Power motion imaging (PMI) is a new Doppler imaging technology that can enhance contrast agent visualization. We hypothesized that PMI combined with Albunex injection (CPMI) could provide new insights into myocardial contractility and perfusion. In a first step, PMI signal was studied with an in vitro phantom. In a second step, PMI signal was studied in 10 rabbits at different workloads. In a third step, 10 rabbits were studied before and after ischemia produced by coronary ligation and finally during reperfusion. During the latter protocol, epicardial echocardiography analyzed by PMI and fundamental mode was performed before and after Albunex injection. PMI signal was well correlated with phantom velocity. PMI signal and myocardial wall thickening were well correlated, particularly in the septal area. On the coronary occlusion model, ischemia was associated with a significant decrease in PMI and CPMI signals, whereas reperfusion was associated with a significant decrease in PMI signals only, indicating stunning. We conclude that PMI combined with CPMI is a powerful tool to assess myocardial contractility and perfusion.

Albumins↗

[Superiority of second harmonic imaging for echocardiographic measurement of lef ventricular volumes. Comparison with angiocardiography].

Analysis of left ventricular volumes is a prognostic factor in cardiovascular disease. Echocardiography is a means of obtaining these parameters but is limited by poor reproducibility. Recently, a new echocardiographic technique, second harmonic imaging (SHI), developed through contrast agent methods, significantly improved the quality of imaging. The aim of this study was to demonstrate the value of SHI for assessing left ventricular volumes. Thirty patients admitted for cardiovascular evaluation and requiring angiocardiography underwent echocardiography with calculation of end diastolic (EDV) and end systolic volumes (ESV) of the left ventricle in fundamental (FI) and second harmonic (SHI) imaging. These measurements were compared with those of angiocardiography. The reproducibility of SHI was calculated after repetition of the measurements by two independent observers for both echocardiographic modes. There was a significant improvement of the parameters of linear regression in SHI compared with FI both for EDV (r = 0.93 versus 0.76) and for ESV (r = 0.94 versus 0.83), the reproducibility was also significantly improved in SHI (relative error of 5% versus 12% for intra-observer error and 6% versus 13% for inter-observer error). The authors conclude that SHI significantly improves two-dimensional imaging and provides a reliable and reproducible measurement of left ventricular volumes.

Adult↗

Quantitative studies of enzyme-substrate compartmentation, functional coupling and metabolic channelling in muscle cells.

Some historical aspects of development of the concepts of functional coupling, metabolic channelling, compartmentation and energy transfer networks are reviewed. Different quantitative approaches, including kinetic and mathematical modeling of energy metabolism, intracellular energy transfer and metabolic regulation of energy production and fluxes in the cells in vivo are analyzed. As an example of the system with metabolic channelling, thermodynamic aspects of the functioning the mitochondrial creatine kinase functionally coupled to the oxidative phosphorylation are considered. The internal thermodynamics of the mitochondrial creatine kinase reaction is similar to that for other isoenzymes of creatine kinase, and the oxidative phosphorylation process specifically influences steps of association and dissociation of MgATP with the enzyme due to channelling of ATP from adenine nucleotide translocase. A new paradigm of muscle bioenergetics-the paradigm of energy transfer and feedback signaling networks based on analysis of compartmentation phenomena and structural and functional interactions in the cell is described. Analysis of the results of mathematical modeling of the compartmentalized energy transfer leads to conclusion that both calcium and ADP, which concentration changes synchronously in contraction cycle, may simultaneously activate oxidative phosphorylation in the muscle cells in vivo. The importance of the phosphocreatine circuit among other pathways of intracellular energy transfer network is discussed on the basis of the recent data published in the literature, with some experimental demonstration. The results of studies of perfused rat hearts with completely inhibited creatine kinase show significantly decreased work capacity and respectively, energy fluxes, in these hearts in spite of significant activation of adenylate kinase system (Dzeja et al. this volume). These results, combined with those of mathematical analysis of the energy metabolism of hearts of transgenic mice with switched off creatine kinase isoenzymes confirm the importance of phosphocreatine pathway for energy transfer for cell function and energetics in mature heart and many other types of cells, as one of major parts of intracellular energy transfer network and metabolic regulation.

Adenine Nucleotides↗

[Double stenosing valve disease after mediastinal radiotherapy: a case report of a 31 year-old man].

Cardiac complications of radiotherapy for cancer, especially lymphoma and breast cancer, are well documented. The three tunics of the heart can be affected. However, valvular disease is rare and, when present, is usually regurgitant. Stenosis is very rare. The authors report the case of a 31 year old man who developed double mitro-aortic valvular stenosis 20 years after mediastinal radiotherapy associated with aortic regurgitation, right coronary stenosis and inflammatory epicardo-pericarditis with effusion. Surgery was undertaken and associated double aortic and mitral valve replacement and right coronary by pass grafting.

Adult↗

Impact of restenosis after optimal directional coronary atherectomy on regional left ventricular function.

To assess the effect of optimal directional coronary atherectomy (DCA) on restenosis and left ventricular (LV) function, 95 patients who underwent DCA and adjunctive balloon angioplasty for de novo lesions were prospectively followed for 6 months. Absolute and relative coronary lumen measurements were analyzed with online quantitative coronary angiography. LV volumes, ejection fraction, and segmental wall motion were measured off-line according to the radial method for LV cineangiograms acquired in a right anterior oblique projection. Target vessels were the left anterior descending artery in 63 patients and right coronary artery in 32. Mean (+/- SD) reference diameter was 3.58 +/- 0.65 mm. Mean lumen diameter improved significantly after DCA from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, yielding a 14 +/- 10% residual stenosis. Overall angiographic restenosis rate (> 50% stenosis in diameter) at control was 23%. In patients without restenosis, there were no significant changes in LV volumes or in LV pressures. In this subgroup, ejection fraction improved significantly in the left anterior descending group (mean difference 3 +/- 10%, p < 0.04). Moreover, there was an increase in fractional shortening of all anterior segments (mean difference 11 +/- 16%, p < 0.005). Improvement in fractional shortening was less marked in the right coronary artery group even without restenosis. We conclude that: (1) optimal DCA can achieve a low restenosis rate in selected large vessels, (2) long-term beneficial effects on regional LV function are possible, particularly in patients with left anterior descending disease and in the absence of coronary restenosis.

Angioplasty, Balloon, Coronary↗

[Predictive factors of coronary restenosis after optimal directional atherectomy. A multivariate analysis apropos of 102 patients].

The authors studied 102 patients prospectively who were undergoing coronary atherectomy optimised by balloon dilatation in order to assess the restenosis rate at 6 months. The coronary lesions were measured in a reproducible manner by quantitative angiography. The vessels dilated were the left anterior descending in 66 patients and the right coronary artery in 36 patients. The reference diameter was on average of 3.57 +/- 0.64 mm. Atherectomy increased the minimal diameter of the lesion of 1.20 +/- 0.44 to 3.01 +/- 0.44 mm giving a residual stenosis of 15 +/- 11%. At six months, 25% of patients had developed a restenosis (> 50% stenosis) with a residual lumen of 2.15 +/- 0.77 mm. The predictive factors of restenosis were the initial absolute gain, the length of the lesion, the reference diameter of the vessel and the presence of an endoluminal thrombus. In multivariate analysis, a small initial gain (p < 0.02) and length of stenosis (p < 0.02) were independently correlated with restenosis. The authors conclude: 1) that optimal atherectomy is associated with acceptable restenosis rates in selected vessels, 2) that short stenoses of large diameter arteries may be a privileged indication of the technique if the best results are obtained.

Adult↗

[Cerebral abscess and cyanotic congenital heart disease].

Cerebral abscess is a classical complication of cyanotic congenital heart disease. The authors report 7 cases of cerebral abscess diagnosed since 1982. One asymptomatic patient died of a postoperative cerebral haemorrage. The child was repatriated from Africa for complete correction of his cardiac lesion. The presentation of the other 6 cases was quite typical : headaches, pyrexia and vomiting with a neurological deficit in 4 cases : two hemiparesias and two homonymous lateral hemianopsia. These 6 patients recovered without sequeilae. Four underwent surgical drainage of the abscess with antibiotic therapy. Two recovered with antibiotic therapy alone. The causal organism was only identified in patients undergoing surgical drainage and then only in 3 cases. They were gram positive cocci, in particular the streptococcus. The association ampicillin-chloramphenicol has often been proposed as the treatment of first intention. Adaptation of antibiotic therapy then depends on clinical, biological, bacteriological (CSF, blood cultures, portal of entry) outcomes and the results of CT scanning. The association of a third generation cephalosporin and an imidazole may be proposed as treatment of second intention. The minimal duration of treatment is generally acknowledged to be 4 weeks for intravenous therapy in cases of medical therapy alone, and 2 to 3 weeks in cases with surgical drainage. The age of apparition of this complication seems to be increasing as the average age was 16 in this series (cerebral abscess is classically described as occurring between 8 and 12 years of age). This may be due to palliative surgery which reduces systemic hypoxia and polycythaemia. It also appears that neurological drainage is not systematic now because of early diagnosis of this complication. Finally, in the last few years, a new population of patients is becoming more common : patients repatriated by humanitary organisations in the third world, which should incite great vigilance in the preoperative period in this pathology.

Adolescent↗

[Restenosis after optimal coronary atherectomy and influence on left ventricular function].

The authors prospectively assessed 95 patients undergoing optimal guided atherectomy to assess the incidence of restenosis at 6 months. The coronary lesions were measured by a system of quantitative angiography to ensure reproducibility. Ventricular volumes, ejection fraction and segmental wall motion were assessed by ventriculography performed in the right anterior oblique projection. Sixty-three patients underwent atherectomy of the left anterior descending artery and 32 patients of the right coronary artery. The reference diameter was 3.58 +/- 0.65 mm. Atherectomy increased the minimal diameter of the lesion from 1.19 +/- 0.44 to 3.03 +/- 0.45 mm, with a residual stenosis of 14 +/- 10% of the diameter. At 6 months, 23% of patients had restenosed (> 50% stenosis) with a residual lumen at 1.16 +/- 0.39 mm. In the absence of restenosis, there was no significant change in left ventricular volumes or pressures and the global ejection fraction increased by +4 +/- 9% (p < 0.01), mainly in the group undergoing left anterior descending atherectomy. Moreover, fractional shortening increased in the anterior segments (+11 +/- 18%; p < 0.001). The authors conclude that optimal atherectomy is associated with acceptable rates of restenosis and that medium-term benefits of segmental wall motion are observed in patients without angiographic restenosis, mainly in those undergoing the procedure on the left anterior descending artery.

Adult↗

[Local progression of atherosclerosis after optimal directional atherectomy. Endocoronary ultrasonography of 17 patients].

In vivo endovascular ultrasonography has confirmed the extension of atheroma to angiographically normal segments. The authors set out to determine by endocoronary ultrasonography if the introduction of the atherotome changed the intimal thickness 20 mm proximal and distal to the site treated. The area circumscribed by the external elastic layer (EEL) and the surface area of the lumen was measured in 17 patients: 1) before atherectomy; 2) after atherectomy; 3) at control 6 months later. Atherectomy immediately increased the luminal area at the site dilated from 1.9 + 0.9 to 8.1 +/- 2mm (p < 0.001). At the proximal segment, the surface area of the lumen was unchanged (mean + 0.6 +/- 1.5 mm2; p = 0.13). Similarly the procedure did not change the surface circumscribed by the EEL (mean + 0.8 +/- 3.2 mm2; p = 0.32) in this zone. The same results were observed at the distal site. At 6 months, the areas under the EEL and those of the lumen were unchanged at the unoperated sites. The mean of the differences (+/- 1 SD) for the area under the EEL was respectively -0.2 +/- 1.5 mm2 proximally and +0.7 +/- 2.5 mm2 distally. The means for the luminal area were 0.2 +/- 1 mm2 proximally and -0.01 +/- 1.1 mm2; distally. At the site of atherectomy, the luminal surface increased (+2.0 +/- 2.6 mm2; p < 0.01) as did the area under the EEL (+2.0 +/- 3.5 mm2; p < 0.05). This preliminary series shows no significant progression of atherosclerosis at the sites not affected by atherectomy.

Adult↗

[Percutaneous dilatation of the pulmonary tract in tetralogy of Fallot].

When palliative treatment is indicated in tetralogy of Fallot, percutaneous endoluminal dilatation of the valvular pulmonary stenosis may represent an alternative to palliative surgery (systemico-pulmonary shunt) and its disadvantages. This paper sets out the clinical outcome and growth of the pulmonary arterial circulation after dilatation of the valvular pulmonary stenosis in children with tetralogy of Fallot. Twenty-five children (average age: 8 +/- 5.8 week; average weight: 6.7 +/- 2.4 kg) were included in this study. The dilatation resulted in an immediate decrease in the patients' cyanosis and a significant increase (+10%) in arterial oxygen saturation. However, this technique did not suppress the risk of anoxic malaise. Only 5 children (20%) required a palliative surgical shunt for persistence of anoxic malaise. From the anatomical point of view, the dilatation induced significant growth of the pulmonary annulus (7.6 mm vs 11.3 mm; p < 0.0001), of the main pulmonary artery (6.8 mm vs 10 mm); p = 0.008) and left pulmonary artery (7 mm vs 11 mm; p = 0.02). The need for a procedure to widen the right ventricular outflow tract at the time of complete correction was also reduced. The perioperative mortality of complete correction and postoperative pulmonary insufficiency were decreased. Percutaneous dilatation of the right ventricular outflow tract is therefore a valuable palliative alternative to surgical sytemico-pulmonary shunt.

Blood Gas Monitoring, Transcutaneous↗