Flow cytometric analysis of intraplatelet VASP phosphorylation for the detection of clopidogrel resistance in patients with ischemic cardiovascular diseases.

Interindividual variability of the inhibitory effect of clopidogrel on platelet functions leading to clopidogrel resistance has been described in some patients with ischemic cardiovascular disease. A reliable laboratory test is therefore needed to identify patients insufficiently protected by this antiplatelet treatment. The phosphorylation of vasodilator-stimulated phosphoprotein (VASP), an intraplatelet actin regulatory protein, is dependent on the level of activation of the platelet P2Y12 receptor, which is targeted by clopidogrel. The aim of this study was to use a flow cytometric VASP phosphorylation assay to evaluate the efficacy of clopidogrel therapy. The platelet reactivity index (PRI), expressed as a percentage, is the difference in VASP fluorescence intensity between resting (+PGE1) and activated (+ADP) platelets. In vitro, the PRI was strongly correlated with the inhibition of platelet aggregation induced by specific blockade of the P2Y12 receptor by the competitive antagonist AR-C69931MX (R = 0.72, P < 0.0001). Ex vivo, the PRI was 78.3 +/- 4.6% in 47 healthy donors, 79.0 +/- 4.1% in 34 patients not receiving clopidogrel and 61.1 +/- 17.0% in 33 patients treated with clopidogrel (P < 0.0001). In the clopidogrel group, the PRI values were widely dispersed (from 6.6 to 85.8%) and more than 30% of these patients had a PRI equivalent of values in patients not receiving clopidogrel. The flow cytometric analysis of VASP phosphorylation seems to be a suitable test to evaluate the efficacy of clopidogrel treatment. This assay demonstrated a wide interindividual variability of the inhibitory response of platelets to clopidogrel and showed that one-third of the patients treated appeared to be 'unprotected' by this therapy.

[Enoximone, vasodilator and/or inotropic agent in congestive cardiac insufficiency? Hemodynamic and ventriculographic study of 20 cases]. / Enoximone, vasodilatateur et/ou inotrope dans l'insuffisance cardiaque congestive? Etude hémodynamique et ventriculographique à propos de 20 cas.

The aim of this study was to document the effects of enoximone in congestive cardiac failure. The haemodynamic data (aortic pressure, pulmonary pressures, left ventricular pressure, cardiac output, isovolumic contractility index: Vmax) and left ventricular kinetics of 20 patients with dilated cardiomyopathy (11 ischemic and 9 idiopathic in Stages III or IV of the NYHA Classification before recompensation) were recorded under basal conditions, after 30 minutes infusion of dobutamine (10 micrograms/kg/mn) and after 3 hours infusion of enoximone (total dose: 3.6 mg/kg). The two drugs had an equivalent inotropic effect: ejection fraction + 4 +/- 22% with dobutamine and + 16 +/- 39% with enoximone; Vmax increased from 1.53 +/- 0.5 c/sec to 2.49 +/- 0.8 c/sec with dobutamine and to 1.82 +/- 0.5 c/sec with enoximone. Enoximone induced a greater degree of vasodilation (systemic resistances - 14 +/- 21% with dobutamine and - 21 +/- 27% with enoximone) and a more pronounced fall in ventricular filling pressures (- 35 +/- 42% with dobutamine and - 58 +/- 24% with enoximone). Enoximone was less effective than dobutamine in increasing cardiac output (+ 46 +/- 42% with dobutamine and 16 +/- 33% with enoximone) and stroke volume (+ 23 +/- 47% with dobutamine and + 2 +/- 41% with enoximone). This difference in efficacy may be explained by the major reduction in ventricular preload which enoximone induced after that observed with dobutamine. "Responders" (12 patients) had basal cardiac outputs of less than 2.3 l/mn/m2; the peripheral vasodilatation caused by enoximone was greater. Finally, the reduction in left ventricular end diastolic pressure and the increase in Vmax were significantly less in the 11 patients with ischemic cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of heart rate increase by transesophageal stimulation on the left ventricular filling in the normal subject. A pulsed echo-Doppler study]. / Effets de l'accroissement de la fréquence cardiaque par stimulation transoesophagienne sur le remplissage ventriculaire gauche chez le sujet normal. Etude par écho-Doppler pulsé.

The effects of increasing the heart rate on left ventricular filling were studied by Doppler echocardiography in 12 mildly sedated normal subjects. The heart rate was increased by 10, 20 and 30 bpm with respect to the basal rhythm by transoesophageal pacing. Four stages were thereby defined: S0, S1, S2 and S3. The principal results were: absence of variation of the isovolumic relaxation period in absolute values (92 +/- 14, 86 +/- 16, 87 +/- 16, 78 +/- 11 ms); absence of variation of the duration of the rapid filling period (246 +/- 36 at 50 vs 220 +/- 28 ms at 53); no change in peak filling velocity (72 +/- 11 at 50 vs 61 +/- 11 ms at 53) or in the timing of peak velocity (77 +/- 12 at 50 vs 72 +/- 13 ms at 53); increased contribution of atrial systole during tachycardia (Vmax 43 +/- 7 at 50 vs 76 +/- 17 cm/s at 53). Therefore, of these Doppler echo parameters, only atrial systole changed during the range of tachycardia rates which were studied. Its increase compensated the loss of diastolic diastasis. These changes should be born in mind in Doppler echocardiographic studies of left ventricular diastolic function.

[Ventricular arrhythmia in moderate essential arterial hypertension. Review of the literature apropos of 2 cases]. / Les troubles du rythme ventriculaire dans l'hypertension artérielle essentielle modérée. Revue de la littérature à propos de deux observations.

The authors report two observations of severe ventricular arrhythmias is two hypertensive patients without coronary disease. In the light of these observations and of a literature review, they recall the frequency of these arrhythmias, their possible role in the event of the sudden death of the hypertensive subject without coronary disease and their physiopathology, where the left ventricular hypertrophy is predominant. They also try to draw the practical guidelines for the management of the hypertensive patient.

[Isolated ST-segment depression in precordial leads V2 to V4. An early electrocardiographic sign of posterolateral myocardial infarction]. / Sous-Décalage isolé du segment ST dans les dérivations précordiales V2 à V4. Un signe électrocardiographique précoce d'infarctus postéro-latéral du myocarde.

The authors report the cases of two men, 62 and 66 years-old, who both presented a posterolateral myocardial infarction which, in the first two days, as only electrocardiographic sign, consisted in a baseline offset of the ST segment in precordial leads V2 to V4. Necrosis and its topography were confirmed in each case by elevated myocardial enzymes, the progression of the electrocardiogram and bidimensional ultrasound cardiography exploration. Coronary angiography performed in both cases, revealed, in the first case, an isolated narrow stenosis of a first marginal artery, and in the second case, significant stenoses of the circumflex and right coronary artery without lesion of the anterior interventricular artery. These cases, along with those recently published in the literature, suggest that such alterations of ventricular repolarization which represent the reciprocal projection of a high posterior sub-epicardiac lesion current, could complete the electrocardiographic criteria of really thrombolysis in a context of prolonged precordial pain.