Sandrine Pierre

Ginkgo biloba extract (EGb 761) protects Na, K-ATPase activity during cerebral ischemia in mice

Neuroprotective drugs such as Ginkgo biloba extract (EGb 761) could prevent the ischemia-induced impairment of the Na,K-ATPase activity. In this study, Na,K-ATPase activity and expression, contents in fatty acids and malondialdehyde, an index of lipoperoxidation, were compared in the ipsilateral (ischemic) and the contralateral (unlesioned) cortices after 1 h of unilateral focal cortices cerebral ischemia in the mouse. EGb 761 (110 mg/kg) was administered daily to half of the animals for 10 days before ischemia. Ischemia significantly reduced Na,K-ATPase activity by about 40% and increased malondialdehyde content; EGb 761 pretreatment abolished these effects. The free radical scavenger properties of EGb 761 are a potential mechanism by which Na,K-ATPase injury and lipoperoxidation are prevented.

Protective effect of an acute oral loading dose of trimetazidine on myocardial injury following percutaneous coronary intervention

Objective: To evaluate the effect of pre-procedural acute oral administration of trimetazidine (TMZ) on percutaneous coronary intervention (PCI)-induced myocardial injury. Design: Single-centre, prospective, randomised evaluation study. Setting: Patients with stable angina pectoris and single-vessel disease undergoing PCI. Patients: 582 patients were prospectively randomised. Patients who underwent more than one inflation during PCI were excluded, resulting in 266 patients randomly assigned to 2 groups. Interventions: Patients were randomly assigned to receive or not an acute loading dose of 60 mg of TMZ prior to intervention. Main outcome: The frequency and the increase in the level of cardiac troponin Ic (cTnI) after successful PCI. cTnI levels were measured before and 6, 12, 18 and 24 h after PCI. Results: 136 patients were assigned to the TMZ group and 130 to the control group. Although no statistically significant difference was observed in the frequency of cTnI increase between the two groups, post-procedural cTnI levels were significantly reduced in the TMZ group at all time points (6 h: mean (SD) 4.2 (0.8) vs 1.7 (0.2), p<0.001; 12 h: 5.5 (1.5) vs 2.3 (0.4), p<0.001; 18 h: 9 (2.3) vs 3 (0.5), p<0.001; and 24 h: 3.2 (1.2) vs 1 (0.5), p<0.001). Moreover, the total amount of cTnI released after PCI, as assessed by the area under the curve of serial measurement, was significantly reduced in the TMZ group (p<0.05). Conclusion: Pre-procedural acute oral TMZ administration significantly reduces PCI-induced myocardial infarction.

Specific Up-Regulation of Mitochondrial F0F1-ATPase Activity after Short Episodes of Atrial Fibrillation in Sheep

ATPase Activity and Atrial Fibrillation. Introduction: Ventricular fibrillation induced by either digitalis intoxication or electrical stimulation is reported to alter myocardial energy by impairing the sarcolemmal Na,K‐ATPase or the receptor for digitalis and the mitochondrial ATPase synthase or F0,F1‐ATPase. However, little is known about these membrane functions during atrial fibrillation (AF).

A Quantitative Immunocytochemical Study of Na+, K+-ATPase in Rat Hepatocytes After STZ-induced Diabetes and Dietary Fish Oil Supplementation

Because diabetes causes alterations in hepatic membrane fatty acid content, these changes may affect the Na+, K+-ATPase. In this study we documented the effects of streptozotocin (STZ)-induced diabetes on hepatic Na+, K+-ATPase catalytic α1-subunit and evaluated whether these changes could be normalized by fish oil supplementation. Two groups of diabetic rats received fish oil or olive oil supplementation. Both groups had a respective control group. We studied the localization of catalytic α1-subunit on bile canalicular and basolateral membranes using immunocytochemical methods and confocal laser scanning microscopy, and the Na+, K+-ATPase activity, membrane fluidity, and fatty acid composition on isolated hepatic membranes. A decrease in the α1-subunit was observed with diabetes in the bile canalicular membranes, without changes in basolateral membranes. This decrease was partially prevented by dietary fish oil. Diabetes induces significant changes as documented by enzymatic Na+, K+-ATPase activity, membrane fluidity, and fatty acid content, whereas little change in these parameters was observed after a fish oil diet. In conclusion, STZ-induced diabetes appears to modify bile canalicular membrane integrity and dietary fish oil partly prevents the diabetes-induced alterations.

REMODELING OF Na,K-ATPase, AND MEMBRANE FLUIDITY AFTER ATRIAL FIBRILLATION IN SHEEP

ABSTRACT Atrial fibrillation (AF) is accompanied by various changes in ion channels that cause atrial electrophysiological remodeling. The enzyme Na,K-ATPase is also a major cellular mechanism for the regulation of ion homeostasis. During AF, Na,K-ATPase may be regulated by synthesis of its α- and β-subunits as well as changes in membrane fluidity. To test this hypothesis, we studied the effect of pacing-induced AF in sheep on atrial Na,K-ATPase α- and β-subunits and on membrane fluidity as well. Methods: A group of six sheep (AF group) was subjected to overdrive electrical stimulation of the right atrium in order to induce AF. A group of six sham operated sheep served as control. All paced sheep developed multiple episodes of sustained AF with a mean total duration of 110u2005min over a 2-hours period. Protein expression of Na,K-ATPase α- and β-subunits in atrial microsomal membranes was assayed by Western blotting analysis. When significant changes in membrane expression were observed, transcriptional regulation was analysed by Northern blotting. Membrane fluidity was assessed on atrial microsomal fractions by anisotropy measurements using the fluorescent probe diphenylhexatriene. Results: Atrial fibrillation enhanced the expression of the Na,K-ATPase β1-subunit at both membrane and mRNA levels. Anisotropy values were higher in AF group than in control group, indicating a decreased fluidity of the membranes isolated from paced sheep atria. Conclusion: These data are the first evidence for an enhanced Na,K-ATPase β1-subunit expression in membrane during AF. Membrane rigification represents a new factor of tachycardia-induced atrial remodeling.

Immunological Identification of Na,K-ATPase Isoforms in Nonfailing and Failing Myocardium

Digitalis therapies are widely used in the treatment of congestive heart failure. The myocardial effect of digitalis to improve contractility results from specific binding and inhibition of the Na,K-ATPase. Failing hearts respond differently to digitalis than do healthy myocardiums, which may be related to a change in expression of the cardiac isoform of Na,K-ATPase. The Na,K-ATPase consists of two subunits, a catalytic a subunit bearing the digitalis binding site and a glycosylated P subunit. We investigated the relative levels of expression of aand P-subunit isoforms in patients with end-stage heart failure and whether these changes in humans could be predicted from experimental failing heart models.