[Unusual cause of Takotsubo cardiomyopathy after pacemaker implantation]. / Un cas inhabituel de cardiomyopathie de Takotsubo après implantation de pacemaker.

Since its first description in Japan in 1990, Takotsubo (stress) cardiomyopathy has gained worldwide recognition. The disease is characterized by transient systolic and diastolic left ventricular dysfunction with a variety of wall-motion abnormalities. She predominantly affects elderly women and she is often preceded by an emotional or physical trigger. In the acute phase, the clinical presentation, electrocardiographic findings and biomarker profiles are often similar to those of an acute coronary syndrome. Although, the cause of Takotsubo cardiomyopathy remains unknown, the role of the brain-heart axis in the pathogenesis of the disease has been described. The potential role of catecholamine excess in the pathogenesis of Takotsubo cardiomyopathy has been long debated, and as such beta-blockers have been proposed as a therapeutic strategy. Currently, the treatment is not codified and it adapts according to clinical symptomatology. It seems difficult to summarize all the factors to provoque the cardiomyopathy, we describe a case of Takotsubo after a pacemaker (PM) implantation and to give a recent progress on this heart disease.

[Unusual cause of acute coronary syndrome: Horton's disease]. / Un syndrome coronaire aigu particulier : maladie de Horton.

The pathophysiology of acute coronary syndromes is in most cases due to the erosion or rupture of a plaque with consequent thrombotic obstruction of coronary artery. In a few cases, the mechanism is different, this not modifying the initial management but imposing special techniques for diagnosis and therapeutic management. We report a clinical case of a patient supported for an acute coronary syndrome, in a context of impaired general condition and biological inflammatory syndrome revealing a Horton's disease.

[Coronary artery fistulas, a current problem: Clinical and therapeutic considerations]. / Les fistules coronaires, un problème d'actualité : approche clinique et considérations thérapeutiques.

The coronary fistula is a link between one or more of the coronary arteries and cardiac cavity or great vessel. The exact occurrence is unknown. The majority of these fistulas are congenital in origin. However, they may occasionally be detected after cardiac surgery. For a long time, fistulas are asymptomatic, especially if they are small; the frequency of the symptoms and especially the complications rise with age. The potential complications are: cardiac failure, endocarditis, endarteritis, atrial fibrillation, ventricular arrhythmias, rupture, and thrombosis. The main differential diagnosis is patent arterial duct, while other congenital arteriovenous shunts need to be excluded. Even though echocardiography Doppler can help to differentiate shunts, the coronary angiography remains the main diagnostic tool for the description of the anatomy. For a long time, the surgery was the only therapeutic means, up till now, percutaneous occlusion is the first line therapy of coronary fistulas and that the different devices can be tailored to meet different anatomic and functional characteristics.

Involvement of both G protein alphas and beta gamma subunits in beta-adrenergic stimulation of vascular L-type Ca(2+) channels.

1. Previous data have shown that activation of beta(3)-adrenoceptors stimulates vascular L-type Ca(2+) channels through a G alphas-induced stimulation of the cyclic AMP/PKA pathway. The present study investigated whether beta-adrenergic stimulation also uses the G beta gamma/PI3K/PKC pathway to modulate L-type Ca(2+) channels in rat portal vein myocytes. 2. Peak Ba(2+) current (I(Ba)) measured using the whole-cell patch clamp method was maximally increased by application of 10 microm isoprenaline after blockade of beta(3)-adrenoceptors by 1 microM SR59230A. Under these conditions, the isoprenaline-induced stimulation of I(Ba) was reversed by ICI-118551 (a specific beta(2)-adrenoceptor antagonist) but not by atenolol (a specific beta(1)-adrenoceptor antagonist). The beta(2)-adrenoceptor agonist salbutamol increased I(Ba), an effect which was reversed by ICI-118551 whereas the beta(1)-adrenoceptor agonist dobutamine had no effect on I(Ba). 3. Application of PKA inhibitors (H-89 and Rp 8-Br-cyclic AMPs) or a PKC inhibitor (calphostin C) alone did not affect the beta(2)-adrenergic stimulation of I(Ba) whereas simultaneous application of both PKA and PKC inhibitors completely blocked this stimulation. 4. The beta(2)-adrenergic stimulation of L-type Ca(2+) channels was blocked by a pre-treatment with cholera toxin and by intracellular application of an anti-G alphas antibody (directed against the carboxyl terminus of G alphas). In the presence of H-89, intracellular infusion of an anti-Gss(com) antibody or a beta ARK(1) peptide as well as a pre-treatment with wortmannin (a PI3K inhibitor) blocked the beta(2)-adrenergic stimulation of I(Ba). 5. These results suggest that the beta(2)-adrenergic stimulation of vascular L-type Ca(2+) channels involves both G alphas and G beta gamma subunits which exert their stimulatory effects through PKA and PI3K/PKC pathways, respectively.

Beta-3 adrenergic stimulation of L-type Ca(2+) channels in rat portal vein myocytes.

1. The effects of beta(3)-adrenergic stimulation were studied on the L-type Ca(2+) channel in single myocytes from rat portal vein using the whole-cell mode of the patch-clamp technique. 2. Reverse transcription-polymerase chain reaction showed that beta(1)-, beta(2)- and beta(3)-adrenoceptor subtypes were expressed in rat portal vein myocytes. Application of both propranolol (a non-selective beta(1)- and beta(2)-adrenoceptor antagonist) and SR59230A (a beta(3)-adrenoceptor antagonist) were needed to inhibit the isoprenaline-induced increase in L-type Ca(2+) channel current. 3. L-type Ca(2+) channels were stimulated by CGP12177A (a beta(3)-adrenoceptor agonist with potent beta(1)- and beta(2)-adrenoceptor antagonist property) in a manner similar to that of isoprenaline. The CGP12177A-induced stimulation of Ca(2+) channel current was blocked by SR59230A, cyclic AMP-dependent protein kinase inhibitors, H-89 and Rp 8-Br-cyclic AMPs, but was unaffected by protein kinase C inhibitors, GF109203X and 19-31 peptide. This stimulation was mimicked by forskolin and 8-Br-cyclic AMP. In the presence of okadaic acid (a phosphatase inhibitor), the beta(3)-adrenoceptor-induced stimulation was maintained after withdrawal of the agonist. 4. The beta(3)-adrenoceptor stimulation of L-type Ca(2+) channels was blocked by a pretreatment with cholera toxin and by the intracellular application of an anti-Galpha(s) antibody. This stimulation was unaffected by intracellular infusion of an anti-Gbeta(com) antibody and a betaARK(1) peptide. 5. These results show that activation of beta(3)-adrenoceptors stimulates L-type Ca(2+) channels in vascular myocytes through a Galpha(s)-induced stimulation of the cyclic AMP/protein kinase A pathway and the subsequent phosphorylation of the channels.

[Experimental study of changes in the pressure of the posterior segment of the eye under general anesthesia. Consequences for surgery of the anterior segment]. / Etude expérimentale des variations de la pression du segment postérieur de l'oeil sous anesthésie générale. Conséquence pour la chirurgie du segment antérieur.

Animal studies were conducted to compare variations in intraocular (IOP) and posterior segment pressure (PSP) during general anesthesia to assess the role of PSP in the development of anesthesia for ophthalmological procedures. Anesthetic agents appear to have a marked effect on IOP during operations involving opening of hypertonic globe or examinations of children under general anesthesia, but their action on IOP has no significance during procedures requiring opening of the anterior chamber because of alteration of aqueous humor physiology. The PSP, defined as pressure in the posterior segment when the anterior segment is at atmospheric pressure, is the main factor affecting surgical conditions, a rise in PSP possibly resulting in typical complications of cataract surgery but having beneficial effects in corneal grafts for example. Posterior segment pressure cannot be studied in humans and an experimental model using rabbits under artificial ventilation following tracheotomy after general anesthesia was developed. Pressure gauges recorded arterial and central venous pressures and were connected to needles inserted in both eyes to monitor IOP and PSP, the latter from a needle passed into the anterior chamber through the cornea, which was incised over the needle to enable permanent drainage of aqueous humor. All pressures were recorded simultaneously and no correlations were observed between IOP and PSP after pentobarbitone, neosynephrine, succinylcholine, or asphyxia (interruption of ventilation and curarization). These findings suggest that IOP is not a valid measurement for assessment of anesthetic techniques, whereas PSP provides a better guideline for development of ophthalmological anesthesia.

[Acute thrombosis of the aortic bifurcation caused by heparin allergy. Apropos of 5 cases]. / Les thromboses aiguës du carrefour aortique par allergie à l'héparine. A propos de 5 observations.

Five patients with humoral intolerance to heparin developed acute thromboses, with a fatal outcome in two cases from failure to establish the diagnosis, marked sequelae in one case, and recovery without complications in the other two. Accidents of this type may occur in 0.6 p. cent of patients on heparin therapy and are almost always fatal if administration is not discontinued. They result from a severe immunoallergic. Thrombocytopenia which may lead to the formation of arterial clots. Arterial thrombosis during heparin therapy is suggestive of the diagnosis and tests for diminished platelet counts are necessary. Apart from surgery, treatment involves the immediate cessation of heparin therapy.

A betagamma dimer derived from G13 transduces the angiotensin AT1 receptor signal to stimulation of Ca2+ channels in rat portal vein myocytes.

A G protein composed of alpha13, beta1, and gamma3 subunits selectively couples the angiotensin AT1A receptors to increase cytoplasmic Ca2+ concentration ([Ca2+]i) in rat portal vein myocytes (Macrez-Leprêtre, N., Kalkbrenner, F., Morel, J. L., Schultz, G., and Mironneau, J. (1997) J. Biol. Chem. 272, 10095-10102). We show here that Gbetagamma transduces the signal leading to stimulation of L-type Ca2+ channels. Intracellular dialysis through the patch pipette of a carboxyl-terminal anti-betacom antibody and a peptide corresponding to the Gbetagamma binding region of the beta-adrenergic receptor kinase 1 inhibited the stimulation of Ca2+ channels and the increase in [Ca2+]i evoked by angiotensin II. The Gbetagamma binding peptide did not prevent the dissociation of the heterotrimeric G protein into its subunits, as it did not block activation of phospholipase C-beta by Galphaq in response to stimulation of alpha1-adrenoreceptors. Transient overexpression of the beta-adrenergic receptor kinase 1 fragment and of Galpha subunits also inhibited the angiotensin II-induced increase in [Ca2+]i. Both anti-alpha13 antibody and carboxyl-terminal alpha13 peptide abrogated the angiotensin II-induced stimulation of Ca2+ channels. We conclude that activation of angiotensin AT1 receptors requires all three alpha, beta, and gamma subunits of G13 for receptor-G protein interaction, whereas the transduction of the signal to L-type Ca2+ channels is mediated by Gbetagamma.

Effects of hindlimb suspension on cytosolic Ca2+ and [3H]ryanodine binding in cardiac myocytes.

Effects of a 14-day hindlimb suspension were examined on [3H]ryanodine binding to rat ventricular microsomes and on cytosolic Ca2+ concentration ([Ca2+]i) and voltage-dependent Ca2+ channels in isolated ventricular myocytes. In suspended rats, the amplitude of the twitch [Ca2+]i transient was increased without significant modifications of the basal [Ca2+]i and sarcoplasmic reticulum content. Because cell capacitance, L-type Ca2+-current density, and Ca2+-channel gating were not significantly modified after suspension, the increase in [Ca2+]i was expected to reside in a change in ryanodine receptors. Scatchard analysis of [3H]ryanodine binding revealed that suspension enhanced binding by increasing the affinity of the receptors for [3H]ryanodine without affecting the maximal binding capacity. Both Ca2+-release channel activity and [3H]ryanodine binding are modulated by Ca2+. However, the Ca2+ sensitivity of [3H]ryanodine binding remained unchanged after suspension. Taken together, these results suggest that the increase in twitch [Ca2+]i transients after suspension may result from a change in the intrinsic properties of the ryanodine receptors but not from a change in the expression level of these receptors.

Gbetagamma dimers stimulate vascular L-type Ca2+ channels via phosphoinositide 3-kinase.

We have previously reported that, in venous myocytes, Gbetagamma scavengers inhibit angiotensin AT1A receptor-induced stimulation of L-type Ca2+ channels (1). Here, we demonstrate that intracellular infusion of purified Gbetagamma complexes stimulates the L-type Ca2+ channel current in a concentration-dependent manner. Additional intracellular dialysis of GDP-bound inactive Galphao or of a peptide corresponding to the Gbetagamma binding region of the beta-adrenergic receptor kinase completely inhibited the Gbetagamma-induced stimulation of Ca2+ channel currents. The gating properties of the channel were not affected by intracellular application of Gbetagamma, suggesting that Gbetagamma increased the whole-cell calcium conductance. In addition, both the angiotensin AT1A receptor- and the Gbetagamma-induced stimulation of L-type Ca2+ channels were blocked by pretreatment of the cells with wortmannin, at nanomolar concentrations. Correspondingly, intracellular infusion of an enzymatically active purified recombinant Gbetagamma-sensitive phosphoinositide 3-kinase, PI3Kgamma, mimicked Gbetagamma-induced stimulation of Ca2+ channels. Both Gbetagamma- and PI3Kgamma-induced stimulations of Ca2+ channel currents were reduced by protein kinase C inhibitors suggesting that the Gbetagamma/PI3Kgamma-activated transduction pathway involves a protein kinase C. These results indicate for the first time that Gbetagamma dimers stimulate the vascular L-type Ca2+ channels through a Gbetagamma-sensitive PI3K.

[Severe Epstein-Barr virus infection in an infant]. / Infection grave à virus d'Epstein-Barr chez un nourrisson.

A 11 month-old boy, without any informative familial pedigree, was admitted for peritonitis after intestinal perforation, associated with signs of pseudolymphoma and histiocytic activation. He developed later unexplained gastrointestinal bleeding and interstitial pneumonitis, which spontaneously improved. All infectious and immunologic studies were negative. Epstein-Barr Virus was found in throat, lungs and blood, whereas the specific antibodies production was delayed. No abnormality was detected 18 months later, except for a disappearance of vaccinal antibodies.