Myocardial infarct size and area at risk assessment in mice.

Mouse models of myocardial ischemia and infarction are important in cardiovascular research. Reliable and reproducible assessment of the area at risk (AAR) and infarct size (IS) in mice is vital for deciphering mechanisms behind these common diseases, and for developing and evaluating treatment strategies. The present review will briefly describe and discuss the most common methods for determining the AAR and IS in mouse models of cardiovascular disease.

YKL-40 levels are independently associated with albuminuria in type 2 diabetes.

Objective And Design: YKL-40 is involved in inflammation and endothelial dysfunction, and is increased in patients with type 1 diabetes, with an independent association between increasing YKL-40 levels and increasing levels of albuminuria. YKL-40 is associated with atherosclerosis and an increased cardiovascular mortality in the general population. In the present study YKL-40 levels were examined in patients with type 2 diabetes (T2D) with increasing levels of albuminuria, known to be associated with an increased risk of cardiovascular disease.

The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction.

Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins.

Unfractionated heparin administration in patients treated with bivalirudin during primary percutaneous coronary intervention is associated lower mortality and target lesion thrombosis: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

Background: Bivalirudin reduces bleeding events and is associated with a lower mortality than the combination of unfractionated heparin (UFH) and glycoprotein IIb/IIIa inhibitor during primary percutaneous coronary intervention (PCI). However, the effect of adding UFH in patients with ST elevation myocardial infarction (STEMI) treated with bivalirudin during primary PCI is unknown.

Methods: Patients enrolled in the national Swedish Coronary Angiography and Angioplasty Registry who underwent primary PCI due to STEMI with bivalirudin as anticoagulant were evaluated.

How to think about stress-induced cardiomyopathy?--Think "out of the box"!

Stress-induced cardiomyopathy (SIC) is a novel syndrome with a substantial morbidity and mortality rate. It has become an important differential diagnosis in patients with acute chest pain. The characteristic hallmark of SIC is a development of extensive but reversible left ventricular dysfunction which may cause fulminant heart failure, cardiogenic shock and literally heart rupture leading to death.

Is pre-hospital treatment of chest pain optimal in acute coronary syndrome? The relief of both pain and anxiety is needed.

Background: Many patients who suffer from acute chest pain are transported by ambulance. It is not known how often treatment prior to hospital admission is optimal and how optimal pain-relieving treatment is defined. It is often difficult to delineate pain from anxiety.

Levosimendan neither improves nor worsens mortality in patients with cardiogenic shock due to ST-elevation myocardial infarction.

Background: The aim of this study was to evaluate the effect of levosimendan on mortality in cardiogenic shock (CS) after ST elevation myocardial infarction (STEMI).

Methods And Results: Data were obtained prospectively from the SCAAR (Swedish Coronary Angiography and Angioplasty Register) and the RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) about 94 consecutive patients with CS due to STEMI. Patients were classified into levosimendan-mandatory and levosimendan-contraindicated cohorts.

Overexpression of apolipoprotein-B improves cardiac function and increases survival in mice with myocardial infarction.

Background: The heart produces apolipoprotein-B containing lipoproteins (apoB) whose function is not well understood. The aim of this study was to evaluate importance of myocardial apoB for cardiac function, structure and survival in myocardial infarction (MI) and heart failure (HF).

Methods And Results: MI was induced in mice (n=137) and myocardial apoB content was measured at 30 min, 3, 6, 24, 48, 120 h and 8 weeks post-MI.

Silent myocardial infarction in women with type II diabetes mellitus and microalbuminuria.

Introduction: The aim of this study was to investigate whether asymptomatic women with diabetes mellitus (DM) without previous history of ischemic heart disease (IHD) and normal electrocardiogram (ECG) have suffered silent myocardial infarction (MI).

Methods: The study population consisted of 64-years old women with DM and albuminuria (n = 15) and aged- and body mass index-matched controls (n = 16). The patients were selected after screening of 240 women with previously known or unknown DM.

Aqueous fish extract increases survival in the mouse model of cytostatic toxicity.

Background: Treatment of cancer patients with anthracycline antibiotic doxorubicin (DOX) may be complicated by development of acute and chronic congestive heart failure (CHF), malignant arrhythmias and death. The aim of this study was to test whether an aqueous low molecular weight (LMW) extract from cod muscle decreases acute mortality in the mouse model of acute CHF caused by DOX.

Methods: A LMW fraction (<500 Da) of the aqueous phase of cod light muscle (AOX) was used for treatment of male BALB/c mice (approximately 25 g, n = 70).

Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal models of acute myocardial infarction and invasive electrophysiology.

Introduction: A growing body of evidence suggests a possible role for growth hormone (GH) in the treatment of congestive heart failure (CHF) and myocardial infarction (MI). The aim of this study was to investigate in vivo the effects of GH treatment on incidence and severity of ventricular arrhythmias normal and MI rats.

Methods: Male Sprague-Dawley rats weighing approximately 350 g were randomized into 3 groups.

In vivo effects of myocardial creatine depletion on left ventricular function morphology and lipid metabolism: study in a mouse model.

Background: The failing heart is characterized by disturbed myocardial energy metabolism and creatine depletion. The aims of this study were to evaluate in vivo the effects of creatine (Cr) depletion on 1) left ventricular (LV) function, morphology, and lipid metabolism and 2) to test whether functional, morphologic, and metabolic disturbances induced by Cr depletion are reversible.

Methods And Results: Male Balb/c mice approximately 20 g were used.

Native cardiac reserve predicts survival in acute post infarction heart failure in mice.

Unlabelled: Cardiac reserve can be used to predict survival and outcome in patients with heart failure. The aim of this study was to investigate if native cardiac reserve could predict survival after myocardial infarction (MI) in mice.

Method: We investigated 27 healthy C57Bl6 mice (male symbol10-12 weeks old) with echocardiography using a high-frequency 15-MHz linear transducer.

Effects of complete heart block on myocardial function, morphology, and energy metabolism in the rat.

Aims: Severe sustained bradycardia may cause acute and possibly chronic congestive heart failure (CHF). The aim of this study was to investigate acute and chronic effects of complete heart block (CHB) on cardiac function, morphology, and creatine (Cr) metabolism.

Methods And Results: CHB was induced in male Sprague-Dawley rats (approximately 250 g, n = 11) by means of electrocautery applied to the region of AV node and were compared with controls (n = 15).

Effects of neuropeptide Y2 receptor blockade on ventricular arrhythmias in rats with acute myocardial infarction.

Excessive sympathetic activity is believed to be the key arrhythmogenic factor both in the setting of acute myocardial infarction and during chronic heart failure. The aim of this study was to evaluate the effect of neuropeptide Y2 blockade on malignant ventricular arrhythmias in rats with acute myocardial infarction. Vagotonic dose-finding study for neuropeptide Y2 receptor antagonist, (S)-N2-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H-1,2,4-triazol-4-yl]ethyl]-argininamid (AR-H05359) was conducted in guinea pigs (n=50) and rats (n=3).

In vivo effects of myocardial creatine depletion on left ventricular function, morphology, and energy metabolism--consequences in acute myocardial infarction.

Background: The failing heart is characterized by disturbed myocardial energy metabolism and creatine (Cr) depletion. The aims of this study were to in vivo evaluate the effects of Cr depletion on: a) left ventricular (LV) function and morphology during rest and stress, b) LV energy metabolism, c) catecholamine in LV and plasma content, and d) incidence of malignant ventricular arrhythmias (MVA) during acute myocardial infarction (MI).

Methods And Results: Male rats weighing approximately 200 g were used.

Cardiac remodeling rather than disturbed myocardial energy metabolism is associated with cardiac dysfunction in diabetic rats.

Background: Diabetes mellitus (DM) alters the energy substrate metabolism in the heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction. Although it is known that the extracellular matrix must be altered in the presence of diabetes, its local regulation has not been fully elucidated. Our aim was to evaluate in vivo left ventricular (LV) structure; function and bioenergetics in streptozotocin (STZ) induced diabetes mellitus.

In vivo MR imaging of magnetically labeled human embryonic stem cells.

Introduction: Human embryonic stem cells (hES) have emerged as a potentially new therapeutic approach for treatment of heart and other diseases applying the concept of regenerative medicine. A method for in vivo visualization and tracking of transplanted hES would increase our understanding of in vivo hES behavior in both experimental and clinical settings. The aim of this study was to evaluate the feasibility of magnetic labeling and visualization of hES with magnetic resonance imaging (MRI).

Hyperinsulinemia: effect on cardiac mass/function, angiotensin II receptor expression, and insulin signaling pathways.

To investigate the association between hyperinsulinemia and cardiac hypertrophy, we treated rats with insulin for 7 wk and assessed effects on myocardial growth, vascularization, and fibrosis in relation to the expression of angiotensin II receptors (AT-R). We also characterized insulin signaling pathways believed to promote myocyte growth and interact with proliferative responses mediated by G protein-coupled receptors, and we assessed myocardial insulin receptor substrate-1 (IRS-1) and p110 alpha catalytic and p85 regulatory subunits of phospatidylinositol 3 kinase (PI3K), Akt, MEK, ERK1/2, and S6 kinase-1 (S6K1). Left ventricular (LV) geometry and performance were evaluated echocardiographically.

Decreased mortality in a rat model of acute postinfarction heart failure.

Introduction: The rat model of postinfarction heart failure (HF) has been very valuable in experimental cardiology. One disadvantage of this model is the very high acute mortality (70-80%). The aim of this study was to evaluate whether measures of intensive cardiac care applied to rats with acute myocardial infarction (MI) would reduce mortality.

Selective cerebral overexpression of growth hormone alters cardiac function, morphology, energy metabolism and catecholamines in transgenic mice.

Background: Growth hormone (GH) has important regulatory effects on cardiac morphology and function both during normal development as well as in pathophysiological settings such as myocardial infarction (MI) and congestive heart failure (CHF). In order to investigate in more detail the interaction between GH and sympathetic nervous system (SNS) system we studied the effects of selective cerebral GH overexpression on myocardial content of catecholamines, myocardial and brain energy metabolism as well as on cardiac function during resting and stress conditions in a transgenic mouse model.

Methods: Transgenic mice with selective bovine GH overexpression under control of glial fibrillary acidic protein promoter in the brain (GFAP-bGH, n=15) were created and compared to genetically matched non-transgenic mates (Control, n=15).

Selective beta1-blockade attenuates post-infarct remodelling without improvement in myocardial energy metabolism and function in rats with heart failure.

Objective: To investigate in vivo effects of long-term selective beta1-blockade on cardiac energy metabolism, remodelling, function and plasma cytokines in a rat model of post-infarct congestive heart failure (CHF).

Methods: Myocardial infarction (MI) was induced in male rats by ligation of the left coronary artery. Three different groups of rats were studied, MI rats treated with metoprolol (n=17), MI rats treated with saline (n=14) and sham-operated rats (n=12).