An Overview of Current Methods for Real-world Applications to Generalize or Transport Clinical Trial Findings to Target Populations of Interest.

It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant-or target-populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose.

SAR340835, a Novel Selective Na/Ca Exchanger Inhibitor, Improves Cardiac Function and Restores Sympathovagal Balance in Heart Failure.

In failing hearts, Na/Ca exchanger (NCX) overactivity contributes to Ca depletion, leading to contractile dysfunction. Inhibition of NCX is expected to normalize Ca mishandling, to limit afterdepolarization-related arrhythmias, and to improve cardiac function in heart failure (HF). SAR340835/SAR296968 is a selective NCX inhibitor for all NCX isoforms across species, including human, with no effect on the native voltage-dependent calcium and sodium currents in vitro.

GTP-cyclohydrolase deficiency induced peripheral and deep microcirculation dysfunction with age.

The present study assessed the impact of impaired tetrahydrobiopterin (BH) production on vasoreactivity from conduit and small arteries along the vascular tree as seen during aging. For this purpose, the mutant hyperphenylalaninemic mouse (hph-1) was used. This model is reported to be deficient in GTP cyclohydrolase I, a rate limiting enzyme in BH biosynthesis.

Regional and temporal heterogeneity of postsystolic wall thickening is associated with left ventricular asynchrony in normal and experimental stunned myocardium.

Aims: Postsystolic wall thickening (PSWT) occurs after aortic valve closure. We investigated the influence of ischemia location and wall interactions on PSWT in normal and stunned myocardium.

Methods And Results: Twenty-two dogs were studied.

Conversion of post-systolic wall thickening into ejectional thickening by selective heart rate reduction during myocardial stunning.

Aims: Post-systolic wall thickening (PSWT) occurs after aortic valve closure. This waste of thickening does not participate in ejection. PSWT increases with myocardial ischaemia and stunning but the effects of anti-anginal drugs on PSWT during myocardial dysfunction remain unknown.

The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6.

Unlabelled: The inotropic adaptation during late preconditioning against myocardial stunning is associated with an increase in FKBP12.6. by Laurence Lucats, Laurent Vinet, Alain Bizé, Xavier Monnet, Didier Morin, Jin Bo Su, Patricia Rouet-Benzineb, Olivier Cazorla, Jean-Jacques Mercadier, Luc Hittinger, Alain Berdeaux, Bijan Ghaleh.

Reduction in postsystolic wall thickening during late preconditioning.

Brief coronary artery occlusion (CAO) and reperfusion induce myocardial stunning and late preconditioning. Postsystolic wall thickening (PSWT) also develops with CAO and reperfusion. However, the time course of PSWT during stunning and the regional function pattern of the preconditioned myocardium remain unknown.

Differential effects of postconditioning on myocardial stunning and infarction: a study in conscious dogs and anesthetized rabbits.

Postconditioning, i.e., brief intermittent episodes of myocardial ischemia-reperfusion performed at the onset of reperfusion, reduces infarct size after prolonged ischemia.

Rapid ventricular pacing induces delayed cardioprotection against myocardial stunning.

Tachycardia with rapid ventricular pacing induces delayed preconditioning against arrhythmias secondary to coronary artery occlusion (CAO) and reperfusion (CAR) but its effects on myocardial stunning remains unknown. Accordingly, we investigated whether delayed preconditioning with ventricular pacing develops against myocardial stunning and whether this phenomenon is triggered by reactive oxygen species. Eight chronically instrumented conscious dogs underwent three experimental sequences in a random order a week apart: (a) 10-min CAO (coronary occluder) followed by CAR, i.

Phenotypic adaptation of the late preconditioned heart: myocardial oxygen consumption is reduced.

Objectives: Although the signalling pathways of late preconditioning have been extensively investigated, its consequence for myocardial metabolism remains unknown. Thus, myocardial oxygen consumption (MVO2) was evaluated before and under late preconditioning.

Methods: In 7 chronically instrumented dogs, we measured MVO2 in vivo at baseline and during inotropic stimulation with dobutamine (10 and 20 microg/kg/min, i.