Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction.

Following the acute phase of a myocardial infarction, a set of structural and functional changes evolves in the myocardium, collectively referred to as cardiac remodeling. This complex set of processes, including interstitial fibrosis, inflammation, myocyte hypertrophy and apoptosis may progress to heart failure. Analogs of the incretin hormone glucagon-like peptide 1 (GLP-1) have shown some promise as cardioprotective agents.

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage.

Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI).

Design, Setting, And Participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning.

A post hoc analysis of long-term prognosis after exenatide treatment in patients with ST-segment elevation myocardial infarction.

Aims: We aimed to assess the effect of exenatide treatment as an adjunct to primary percutaneous coronary intervention (PCI) on long-term clinical outcome.

Methods And Results: We performed a post hoc analysis in 334 patients with a first STEMI included in a previous study randomised to exenatide (n=175) or placebo (n=159) as an adjunct to primary PCI. The primary endpoint was a composite of all-cause mortality and admission for heart failure during a median follow-up of 5.

Increased myocardial vulnerability to ischemia-reperfusion injury in the presence of left ventricular hypertrophy.

Objective: Despite its high prevalence among patients suffering myocardial infarction, the significance of left ventricle hypertrophy for infarct size is not known. We asked whether infarct size might be increased by this condition, and whether any such increase might be associated with an increased mitochondrial damage following coronary occlusion.

Methods: Occlusion of the left descending artery in isolated, perfused hearts of SHR-SP (spontaneously hypertensive rat stroke-prone) (left ventricular hypertrophy) or Wistar-Kyoto (WKY) (control) rats was used, followed by reperfusion with or without exendin-4 (Exe-4), a glucagon-like peptide-1 receptor agonist.

Predictors and prognostic value of left atrial remodelling after acute myocardial infarction.

Purpose: Left atrial (LA) volume is a strong prognostic predictor in patients following ST-segment elevation myocardial infarction (STEMI). However, the change in LA volume over time (LA remodelling) following STEMI has been scarcely studied. We sought to identify predictors for LA remodelling and to evaluate the prognostic importance of LA remodelling.

Impact of acute hyperglycemia on myocardial infarct size, area at risk, and salvage in patients with STEMI and the association with exenatide treatment: results from a randomized study.

Hyperglycemia upon hospital admission in patients with ST-segment elevation myocardial infarction (STEMI) occurs frequently and is associated with adverse outcomes. It is, however, unsettled as to whether an elevated blood glucose level is the cause or consequence of increased myocardial damage. In addition, whether the cardioprotective effect of exenatide, a glucose-lowering drug, is dependent on hyperglycemia remains unknown.

In situ Raman study of redox state changes of mitochondrial cytochromes in a perfused rat heart.

We developed a Raman spectroscopy-based approach for simultaneous study of redox changes in c-and b-type cytochromes and for a semiquantitative estimation of the amount of oxygenated myoglobin in a perfused rat heart. Excitation at 532 nm was used to obtain Raman scattering of the myocardial surface of the isolated heart at normal and hypoxic conditions. Raman spectra of the heart under normal pO2 demonstrate unique peaks attributable to reduced c-and b-type cytochromes and oxymyoglobin (oMb).

Mapping of redox state of mitochondrial cytochromes in live cardiomyocytes using Raman microspectroscopy.

This paper presents a nonivasive approach to study redox state of reduced cytochromes c, c1 and b of complexes II and III in mitochondria of live cardiomyocytes by means of Raman microspectroscopy. For the first time with the proposed approach we perform studies of rod- and round-shaped cardiomyocytes, representing different morphological and functional states. Raman mapping and cluster analysis reveal that these cardiomyocytes differ in the amounts of reduced cytochromes c, c1 and b.

ST peak during primary percutaneous coronary intervention predicts final infarct size, left ventricular function, and clinical outcome.

Background And Purpose: One third of patients treated with primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction develop a secondary increase in electrocardiographic ST segment (ST peak) during reperfusion. The purpose was to determine the clinical importance of ST peak during primary PCI.

Methods: A total of 363 patients with ST-elevation myocardial infarction were stratified to no ST peak or ST peak.

Postconditioning with curaglutide, a novel GLP-1 analog, protects against heart ischemia-reperfusion injury in an isolated rat heart.

Aim: GLP-1(7-36)amide (GLP-1) is an intestinal hormone with effects on glucose metabolism and feeding behavior, including insulinotropic, insulinomimetic, glucagonostatic and anorectic actions. In experimental settings, GLP-1 has also been shown to diminish infarct size following heart ischemia-reperfusion. GLP-1 analogs with extended half-lives are continuously being developed against type 2 diabetes mellitus.

Exenatide reduces final infarct size in patients with ST-segment-elevation myocardial infarction and short-duration of ischemia.

Background: Exenatide has been demonstrated to be cardioprotective as an adjunct to primary percutaneous coronary intervention in patients with ST-segment-elevation myocardial infarction (STEMI). The aim of the post hoc analysis study was to evaluate the effect of exenatide in relation to system delay, defined as time from first medical contact to first balloon.

Methods And Results: Patients with STEMI and Thrombolysis In Myocardial Infarction flow 0/1 were randomly assigned to intravenous exenatide or placebo continuous infusion.

Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction.

Aims: Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI).

Methods And Results: A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously.

ST-Segment resolution and clinical outcome with ischemic postconditioning and comparison to magnetic resonance.

Background: Ischemic postconditioning (IPost) during primary percutaneous coronary intervention (PPCI) is suggested to reduce myocardial damage. However, the association with ST-segment resolution (STR) and clinical outcome is not determined. The primary aim of this study was to evaluate the association of IPost with STR and clinical outcome.

[Glucagon-like peptide-1: a cardiological perspective].

Increasing experimental evidence points to direct effects of glucagon-like peptide-1 (GLP-1) and its analogs on the heart and circulatory system, in addition to the well-established, antidiabetic actions of these agents on glucose and on the energy metabolism. These effects are primarily vasodilation, diminished heart muscle loss after myocardial infarction and a contractility increase of a weak left ventricle. A few, small patient trials appear to support the latter effect.

Glucagon-like peptide 1--a cardiologic dimension.

Recent experimental data suggest glucagon-like peptide 1 (GLP-1) and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. These direct effects may be cardioprotective, contractility augmenting, and vasorelaxant. A few preliminary clinical trials appear to support a mechanical function improvement after GLP-1 administration to patients with a weakened left ventricle.

Cardioprotective effects of ischemic postconditioning in patients treated with primary percutaneous coronary intervention, evaluated by magnetic resonance.

Background: Postconditioning has been suggested to reduce myocardial damage during primary percutaneous coronary intervention (PPCI) in patients with ST-segment-elevation myocardial infarction. However, because clinical experience is limited, we examined the cardioprotective effects of postconditioning, using cardiac MRI in patients treated with PPCI.

Methods And Results: One hundred eighteen patients with ST-segment-elevation myocardial infarction referred for PPCI were randomly assigned to have either conventional PPCI or PPCI with postconditioning.

The cardioprotective and inotropic components of the postconditioning effects of GLP-1 and GLP-1(9-36)a in an isolated rat heart.

GLP-1 and its metabolite GLP-1(9-36)a have been shown to exert cardiotropic effects, and were demonstrated to be cardioprotective agents in isolated, postischemic rat or mouse hearts. An agent's total effect on myocardial performance in a postconditioning paradigm is a sum of its myocyte-preserving (cardioprotective) and contractility-affecting (negative or positive inotropic) action components. These components may not always be explicitly separated by the experimental protocol.

Fluorescence assay for mitochondrial permeability transition in cardiomyocytes cultured in a microtiter plate.

Mitochondrial permeability transition pore (MPTP) is a voltage-dependent, large-conductance channel of the inner mitochondrial membrane with an important role in a range of pathophysiological conditions. To facilitate studies of pharmacological pore modulation, we describe an assay in a model using neonatal cardiomyocytes in a 96-well microtiter plate format. In the presence of mitochondrial membrane potential Delta Psi m, accumulation of rhodamine-123 in mitochondria (40,000 cells/well, 2.

Protective effects of GLP-1 analogues exendin-4 and GLP-1(9-36) amide against ischemia-reperfusion injury in rat heart.

Glucagon-Like Peptide-1 (GLP-1) is an incretin peptide secreted from intestinal L-cells, whose potent plasma glucose-lowering action has prompted intense efforts to develop GLP-1 receptor-targeting drugs for treatment of diabetic hyperglycemia. More recently, GLP-1 and its analogues have been shown to exert cardiovascular effects in a number of experimental models. Here we tested exendin-4 (Exe-4), a peptide agonist at GLP-1 receptors, and GLP-1(9-36) amide, the primary endogenous metabolite of GLP-1 (both in the concentration range 0.

Protection by 6-aminonicotinamide against oxidative stress in cardiac cells.

Oxidative stress at the time of reperfusion is a major aspect of ischemia-reperfusion injury in heart as well as in other organs. There is a continuing interest in development of pharmacological approaches to alleviate this injury. 6-Aminonicotinamide (6AN) has been shown to diminish myocardial necrosis following global ischemia in an isolated rat heart, apparently by limiting the oxidative injury component.

Calcium pumps of plasma membrane and cell interior.

Calcium entering the cell from the outside or from intracellular organelles eventually must be returned to the extracellular milieu or to intracellular storage organelles. The two major systems capable of pumping Ca2+ against its large concentration gradient out of the cell or into the sarco/endoplasmatic reticulum are the plasma membrane Ca2+ ATPases (PMCAs) and the sarco/endoplasmic reticulum Ca2+ ATPases (SERCAs), respectively. In mammals, multigene families code for these Ca2+ pumps and additional isoform subtypes are generated via alternative splicing.

Regulation of the endoplasmic reticulum calcium storage during the unfolded protein response--significance in tissue ischemia?

Endoplasmic reticulum (ER) is an organelle intimately involved in control of cell activities through Ca(2+) signaling, as well as in post-translational protein folding and maturation. Ca(2+) storage within the ER is required for both of these functions. Several of the ER-resident proteins essential for the protein folding pathway require Ca(2+) binding for their activity.