Efficiency of amifostine as a protection against doxorubicin toxicity in rats during a 12-day treatment.

BACKGROUND: Our purpose was to determine the effects of amifostine, a cytoprotective agent, on doxorubicin tolerance and cardiotoxicity in rats. MATERIALS AND METHODS: Male Wistar rats were treated every other day with an intraperitoneal injection of amifostine or saline 30 minutes before intraperitoneal injection of doxorubicin or saline. Weight change was recorded, and contractile function was evaluated after 11 injections by means of the isolated heart. RESULTS: Weight evolution and cardiac function were significantly improved by 7 and 20 mg/kg amifostine (p < 0.001) but not by 50 mg/kg. The final weight were: controls 349 +/- 16 g; doxorubicin alone 258 +/- 54 g; with amifostine: 7 mg/kg 314 + 28 g; 20 mg/kg 312 +/- 32 g; 50 mg/kg 250 +/- 34 g. Left ventricular developed pressure were: controls 137 +/- 15 mmHg; doxorubicin alone 119 +/- 20 mmHg; with amifostine: 7 mg/kg 140 +/- 20 mmHg; 20 mg/kg 137 +/- 25 mmHg; 50 mg/kg 124 +/- 20 mmHg. CONCLUSION: Seven and 20 mg/kg amifostine protected rats from the toxicity of doxorubicin at the cumulative dose of 18 mg/kg during a 12-day treatment, with regard to weight loss and heart contraction.

[Biochemical markers of myocardial ischemia and necrosis]. / Marqueurs biochimiques d'ischémie et de nécrose myocardique.

The biochemical markers of myocardial ischaemia have to be interpreted according to their kinetics; their interests depend on the clinical presentation. They are helpful to orient to a myocardial ischaemia in front of undefined chest pain, to stratify the outcome of acute coronary syndrome without ST segment elevation, to evaluate the amount of myocardial damage following infarction, to detect the failure of thrombolysis therapy and probably to stratify the post percutaneous coronary intervention outcome.

[Value of pulsed Doppler tissue imaging for early detection of myocardial dysfunction with anthracyclines]. / Intérêt du Doppler tissulaire pulsé pour le dépistage précoce de l'altération de la fonction myocardique aux anthracyclines.

The cumulative and definitive nature of chronic cardiotoxicity of anthracyclines requires a preventive strategy of early diagnosis. The authors undertook a prospective study of the association of echocardiography, mitral Doppler and pulsed Doppler tissue imaging of the left ventricular lateral and posterior walls in the context of this problem in 20 patients without cardiac disease undergoing cancer chemotherapy including anthracyclines. Doppler echocardiography was performed before the first session of chemotherapy and at the end of treatment, 6 +/- 4 months later. After a total cumulative dose of 227 +/- 91 mg/m2 of doxorubicine, there were no changes in left ventricular ejection fraction but a significant decrease in mitral E wave velocity (p = 0.04) and in E/A ratio (p = 0.01), suggesting early changes in left ventricular relaxation. The Doppler tissue examination confirmed the presence of radial and longitudinal abnormalities in myocardial relaxation (decreases in myocardial E wave velocities of the posterior and lateral walls of the left ventricle, p = 0.02 and p = 0.01, respectively). The peak velocity of the myocardial systolic wave (Sm) was significantly decreased in the lateral wall (p = 0.02) and approached statistical significance in the posterior wall (p = 0.07). These results suggest concomitant changes in myocardial systolic and diastolic function with moderate doses of anthracyclines. Therefore, pulsed Doppler tissue examination enables earlier detection of left ventricular cardiotoxicity with anthracyclines than classical echocardiographic parameters.

[One center's experience of coronary angioplasty with a 5 French catheter guide by a femoral approach at the same time as coronary angiography]. / Expérience monocentrique de l'angioplastie coronaire par cathéter guide 5 French menée par voie fémorale dans le même temps que l'examen coronarographique.

The object of this study was to assess the feasibility of so-called ad hoc 5 F percutaneous transluminal coronary angioplasty (PTCA). This monocentric register included 200 consecutive procedures (233 lesions) of 5F PTCA by a femoral approach after a bolus of standard heparin (50 to 70 IU/kg). The population included 15.4% of stable angina, 29.4% of unstable angina, 11% acute phase, 13.5% post-revascularisation angina and 30.7% post-infarction cases. A successful procedure was defined as a good angiographic result without ischaemic complications. A failed 5F procedure was defined by the need to fall back on a 6F PTCA. The peripheral vascular complications were recorded. The lesions were stented in 77.4% of cases including 13.4% of direct stenting. There were 200 successful procedures (87%). The failures (N = 26) were mainly explained by the inability to cross chronic obstruction (N = 11). The ischaemic complications included 2 coronary bypasses (2 retrograde dissections of the left anterior descending artery) and 7 enzymatic increases without ECG changes. Fall back to 6F PTCA was required in 4 cases (1.7%) always because of the instability of the 5F catheter guide before the procedure. The quality of coronary contrast was estimated to be good. The vascular complication rate was low with 2% of communicating haematomas (N = 4). Therefore, 5F PTCA is feasible with failure and complication rates comparable to those reported with catheters of larger dimensions. One of its principal advantages is "ad hoc" angioplasty after 5F coronary angiography.

[A rare cause of stroke in a patient with a cardiac pacemaker]. / Etiologie rare d'accident vasculaire cérébral ischémique chez un patient ayant un stimulateur cardiaque.

The authors report the case of a 78 year old woman admitted to hospital for recurrent cerebrovascular accidents, the initial investigation of which was normal. This pacemaker patient had a displacement of the definitive ventricular pacing catheter which was positioned in the left ventricle through a patent foramen ovale. The diagnosis was suspected on clinical and echocardiographic examination and confirmed by transthoracic and transoesophageal echocardiography. In view of the risk of systemic embolism, the pacing catheter was repositioned by an endovascular approach in the right ventricle.

[Prediction of improvement of left ventricular systolic function by dobutamine echocardiography after recent myocardial infarction]. / Prédiction de l'amélioration de la fonction systolique ventriculaire gauche par échographie à la dobutamine après infarctus du myocarde récent.

Left ventricular ejection fraction is a major prognostic factor of ischaemic heart disease. In the early phase of myocardial infarction, part of the myocardium may be stunned and responsible for marked segmental wall dysfunction which is potentially reversible. The authors studied the potential of low dose dobutamine echocardiography to predict secondary improvement of left ventricular systolic function in 21 patients with recent inaugural myocardial infarction without primary angioplasty. All patients were treated and the investigation was carried out up to 20 micrograms/Kg/min of dobutamine without unwanted side-effects or myocardial ischaemia. The detection of viability by this method was associated with improved wall motion of the affected segments in 74% of cases, most of which had benefited from myocardial revascularisation at control echocardiography performed 8 weeks later. If 4 or more segments were estimated to be viable initially, the left ventricular ejection fraction improved to a value comparable to that obtained at a dosage of 20 micrograms/Kg/min of dobutamine. On the other hand, there was no secondary improvement in 76% of segments estimated to be non-viable whether or not they had been revascularised. The sensitivity, specificity, positive and negative predictive values of low dose dobutamine echocardiography for prediction of myocardial recovery after recent infarction were respectively 71, 79, 74 and 76%. The results of this investigation show prognostic value and could be an aid to the decision concerning revascularisation of patients not having undergone primary angioplasty.

[Vascular effects of neurokinins in humans]. / Effets vasculaires des neurokinines chez l'homme.

Neurokinins (mainly substance P and neurokinin A) are released by sensitive nerve fibres. These fibres have been found in the vascular wall of arteries and veins of many vascular regions, particularly in nasal mucosa vessels, temporal and coronary arteries and saphenous veins. Substance P causes vascular relaxation by stimulating NK1 endothelial receptors. This relaxant effect is mediated, according to the vessels, by nitric oxide (NO), prostanoids or endothelium-dependent hyperpolarizing factor (EDHF). Capsaïcin, which induces the release of neurokinins, and neurokinin A can cause contractions of some vascular preparations, suggesting the existence of smooth muscle NK2 receptor associated with contraction. The vasodilatation induced by substance P injection appears reduced in patients with cardiovascular risk factors. The clinical development of specific neurokinin receptor antagonists may give the opportunity to specify the role of neurokinins in systemic vascular diseases. The results already obtained after repeated local applications of capsaïcin (to reduce local levels of neurokinins) in vasomotor rhinitis and urticaria suggest that the vascular effects of neurokinins may participate in the clinical expression of these diseases.

[Pulmonary embolism in the child: diagnostic and therapeutic particularities]. / Embolie pulmonaire de l'enfant: particularités diagnostiques et thérapeutiques.

BACKGROUND: Pulmonary embolism in children is an overlooked pathology. Yet the first description dates back to the end of the 19th century and this specific pathology is not seldom observed. The main risk factors are trauma, surgery, and foreign bodies. DIAGNOSIS: Thrombophilia can be diagnosed when a thromboembolic event occurs. The initial thrombosis may be found anywhere in the venous network. Venous sonography usually gives the diagnosis. Pulmonary embolism usually has a poor clinical expression. An unexplained situation can be the first manifestation. Echocardiography guides diagnosis confirmed by ventilation-perfusion scintigraphy. TREATMENT: Prophylaxis is achieved with small doses of heparin. Treatment is based on the use of hypocoagulant doses of heparin, potentially after systemic thrombolysis and followed by oral anticoagulation.

Use of the PFA-100 apparatus to assess platelet function in patients undergoing PTCA during and after infusion of c7E3 Fab in the presence of other antiplatelet agents.

The PFA-100 (Dade) is a new functional whole blood analyzer, the accuracy and reliability of which have been evaluated in von Willebrand disease and during acetyl salicylate acid therapy. This new test has the advantages of rapidity and simplicity. It may be useful to monitor new antiplatelet agents, such as GPIIb/IIIa receptor antagonists. The objective of this study was to assess the PFA-100 in comparison with aggregometry and with the percentage of blockaded receptors GPIIb/IIIa during and after c7E3 Fab infusion in fifteen patients undergoing PTCA. Our results showed a change of closure time values from normal to abnormal within a small margin of flow cytometric values (60-75% of blockaded receptors), and moreover a variable platelet response to long-term low dose aspirin treatment in agreement with aggregometry. No influence with heparin was observed. In conclusion, this study shows that PFA-100 may be helpful in the decision making for additional antiaggregant therapy before PTCA or in monitoring long-term GPIIb/IIIa receptor antagonist treatment.

[Comparative evaluation of hydrophilic and standard guide wires for retrograde catheterization of severe aortic stenosis]. / Evaluation comparative des guides hydrophiles versus guides standards dans le franchissement rétrograde des rétrécissements aortiques serrés.

The feasibility and safety of using hydrophilic guide wires were compared with those of standard guide wires for retrograde catheterization of aortic stenosis in a prospective randomised study. The performances of the guide wires were assessed by the time taken to catheterize the aortic valve (minutes) and the duration of radioscopy (minutes: grays). The success of the procedure was defined as presence of the guide in the left ventricle in less than 8 minutes. The two patient groups were comparable with respect to the severity of the aortic stenosis. Two failures of catheterisation were observed in the "standard guide wire" group compared with three failures with the hydrophilic guide wire. The mean catheterisation time of the "standard" group was 2.56 minutes compared with 3.12 minutes with the hydrophilic guide wire (p = 0.35 NS). This result was correlated with the duration of radioscopy and number of groups (respectively p = 0.18 NS and p = 0.5 NS). One case of tamponade and a transient ischaemic cerebral attack were observed in the "standard" group. This study does not show the hydrophilic guide wire to be superior to the standard guide wire for catheterisation of aortic stenosis. However, the hydrophilic guide wires were perfectly innocuous for this procedure.

[Cardiac lymphoma disclosed by ischemic accident. A case report]. / Lymphome cardiaque révélé par un accident ischémique. A propos d'un cas.

We report on the detection of a primitive cardiac lymphoma revealed by a cerebral vascular accident in a context of deterioration of the general state with fever. The diagnosis of the cerebral vascular accident was verified by the brain scan. The echocardiography, in particular the transesophageal ultrasound, suggested the diagnosis of cardiac lymphoma due to the existence of an inhomogeneous multilobar mass invading the right ventricle and largely encompassing the right auricle. The histologic diagnosis of a malignant non-Hodgkin's lymphoma of type B malignancy was confirmed by anatomopathology. The evolution was, unfortunately, rapidly unfavorable, with the patient dying in a state of cerebral suffering despite a combination treatment of chemotherapy and radiotherapy.

[Early postoperative constrictive pericarditis: value of echocardiography. Report of 4 cases]. / Péricardite constrictive postopératoire précoce: intérêt de l'échocardiographie. A propos de quatre observations.

In the present study, four cases of early postoperative constrictive pericarditis have been described which serve as a basis for recalling the current main echographic features of this disorder: pericardial thickening, abnormal septal movement with inspiratory expansion of the right ventricle, respiratory variations in ventricular filling, characteristic modifications in the supra-hepatic pulmonary venous flow, and pulmonary insufficiency. Some hypotheses have also been presented on the possible etiology of this disease. The necessity of making a precise and rapid diagnosis, which should also be confirmed by catheterization to ensure the appropriateness of therapy, has been emphasized. Pericardectomy can determine the long-term prognosis.

[Acute aortic insufficiency]. / Insuffisance aortique aiguë.

Acute aortic insufficiency can now be diagnosed rapidly and accurately thanks to Doppler echocardiography. The etiologies include infectious endocarditis, aortic dissection, bioprosthesis degeneration and thoracic injury. The clinical diagnosis is substantiated by the particular etiological context, dyspnea and pulmonary edema being the main factors involved. Examination includes finding out whether there is a reduction in the first sound, S1 a generally brief apical diastolic murmur. Echocardiography detects the presence of aortic leakage, the acute character of which is confirmed by the findings of a premature closure of the mitral valve, the existence of telediastolic mitral leakage, a restriction in the transmitral flow, and finally, the absence of left ventricular dilatation. An emergency operation is recommended by most authors in the case of acute aortic leakage due to the major risk or mortality resulting from pulmonary edema, ventricular arrhythmias, electromechanical dissociation or cardiogenic shock.

[Dobutamine doppler echocardiography in severe aortic stenosis with left ventricular dysfunction. Comparison with postoperative examination]. / Apport de l'échocardiographie Doppler sous dobutamine dans le rétrécissement aortique serré avec dysfonction ventriculaire gauche. Comparaison aux données postopératoires.

The association of left ventricular dysfunction with aortic stenosis worsens the spontaneous prognosis and increases operative mortality. The aim of this prospective study was to assess the predictive value of dobutamine Doppler echocardiography on the indices of left ventricular contractile function in patients with aortic stenosis and left ventricular dysfunction (LVEF < 0.45) undergoing aortic valve replacement. Eighteen patients, including 9 with coronary artery disease, were included in a protocol consisting of analysis of left ventricular function and of the severity of aortic stenosis before, during dobutamine infusion, and after valvular replacement. The dobutamine was given in progressive increments of 5 micrograms/Kg up to a maximum of 20 micrograms/Kg. During pharmacological stress, the functional aortic valve area increased from 0.46 +/- 0.15 to 0.56 +/- 0.23 cm2. Tolerance of the procedure was good. All but 2 patients improved their postoperative ejection fraction with values equivalent to those observed during the last increment of dobutamine (r = 0.73; p < 0.003). The patients with initial mean pressure gradients > 50 mmHg normalised their LVEF after valve replacement. The authors conclude that dobutamine echocardiography is useful for predicting the values of postoperative left ventricular contractile indices when severe aortic stenosis is associated with systolic dysfunction. It allows evaluation of the expected short term benefits to these indices after aortic valve replacement.

[Extensive mycotic coronary aneurysm detected by echocardiography. Apropos of a case]. / Volumineux anévrisme mycotique coronaire de découverte échographique. A propos d'un cas.

The authors report the case of a large mycotic right coronary aneurysm detected at echocardiography in a 45 year old patient with AIDS. Although emergency surgery was planned, the patient died of rupture of the aneurysm with cardiogenic shock and sudden pericardial tamponade. This case underlines the diagnostic value of echocardiography, by the transthoracic approach for para-cardiac masses and with the transoesophageal probe for accurate localisation and demonstration of the coronary origin. In this case, the CT scan was less useful than transthoracic echocardiography. Coronary angiography confirmed the strongly suggestive echocardiographic diagnosis and helped decide management strategy. Atheromatous coronary aneurysms may be treated by stenting but mycotic aneurysms require surgical management.

Free and total platelet glycoprotein IIb/IIIa measurement in whole blood by quantitative flow cytometry during and after infusion of c7E3 Fab in patients undergoing PTCA.

A quantitative flow cytometry assay was used to evaluate the ex vivo kinetics of c7E3 Fab platelet effect in 16 patients undergoing PTCA treated with abciximab and compared with aggregometry assay. Immunolabeling of platelets was directly assessed on whole blood, using in parallel two monoclonal antibodies (Mabs) raised against GPIIIa, Mab1, the binding of which is inhibited by c7E3 Fab, and Mab2, the binding of which is not affected by c7E3 Fab. We found a severe and sustained inhibition of both GPIIb/IIIa receptors and platelet functions. The inter-individual variation in response to abciximab was low. A significant transient increase at H24 and H48 in the binding of Mab2 was found as an unexpected result, and confirmed in vitro. Results demonstrate that flow cytometry is a reliable method in agreement with aggregation. In addition, our results show that it is a standardized tool and a time-saving technique.

[Incidence and predictive factors of mitral insufficiency in surgically treated aortic stenosis. Transthoracic and transesophageal ultrasonographic evaluation]. / Incidence et facteurs prédictifs de l'insuffisance mitrale dans le rétrécissement aortique chirurgical. Evaluation échographique transthoracique et transoesophagienne.

Mitral regurgitation is common in adults with aortic stenosis. When severe, it may aggravate the clinical condition and pose an additional therapeutic problem. The authors studied 40 consecutive patients with severe surgical aortic stenosis prospectively by transthoracic echocardiography and pre-operative transoesophageal echocardiography to determine the incidence, mechanism and degree of mitral regurgitation and its eventual relationship to the aortic stenosis. Mitral regurgitation was detected in all cases when both investigations were taken into consideration. It was usually mild, evaluated grade 2 by measuring the surface of the colour Doppler regurgitant jet, or mild to minimal of transoesophageal echocardiography in 35/40 patients (87.5% of cases). Rarely, a case of significant, autonomous mitral regurgitation (2 cases of valvular dystrophy, 1 pure severe mitral stenosis). On the other hand, calcification of the mitral annulus is common (14/40 patients, 35% of cases). The severity of the regurgitation in univariate analysis was significantly correlated mainly to the age of the patients (p = 0.027). The severity of the aortic stenosis (p = 0.0082) and the parameters related to the effects of stenosis, such as ventricular wall thickness and left atrial size. In multivariate analysis, the severity of the aortic stenosis and of its consequences were confirmed to play a role in the genesis of mitral regurgitation, the severity of which was correlated on transthoracic echocardiography to the aortic valve surface area and the left ventricular ejection fraction and, on transoesophageal echocardiography, to the transvalvular pressure gradient.

Immediate femoral sheath removal after 6 French routine coronary angioplasty with a weight-adjusted low-dose heparin: results of a prospective registry.

This study assesses the feasibility and safety of immediate sheath removal after coronary angioplasty with the use of 6 French (Fr) guiding catheters by the femoral route and weight-adjusted low-dose heparin (100 IU/kg). We prospectively evaluated such a strategy among a single-center cohort of 261 consecutive patients undergoing routine percutaneous transluminal coronary angioplasty (PTCA). Immediate sheath withdrawal was performed in cases when post-PTCA residual coronary stenosis was less than 30%, with or without stenting. One hundred eighty-two (70%) of the enrolled patients were eligible for immediate sheath removal. When compared with non-eligible patients (sheath removal 4 hours or more post-PTCA), we observed a reduction of hematoma occurrence (15% vs. 30%; p < 0.01), time to manual hemostasis of the puncture site (13.8 +/- 7 vs. 19.7 +/- 12 minutes; p < 0.0001), and time to hospital discharge (2.2 +/- 1.9 vs. 2.8 +/- 1.8 days; p < 0.02), while ischemic event rate was similar (1 vs. 2 non-Q wave myocardial infarction; 2 vs. 1 repeat PTCA for out-of-lab acute vessel closure). In conclusion, a good angiographic result at completion of PTCA using a 6 Fr sheath, even without stenting, makes an immediate sheath removal feasible at no increased risk and with a potential reduction in minor bleeding complications.

[Werner's disease presenting as ischemic mitral incompetence]. / Fuite mitrale ischémique révélant une maladie de Werner.

Werner's syndrome or progeria, described for the first time in 1886, is a rare disease with autosomal recessive transmission, characterized by premature ageing of connective tissues. About 200 cases have since been reported in the literature. Most patients die young, generally from heart failure due to early coronary atherosclerosis [1]. The authors report the case of a 46-year-old woman presenting with cardiovascular abnormalities, unusual for her age, associated with a particular morphotype belonging to Werner's syndrome.