Intravenous Interferon-β1a for the Treatment of Ischemia-Reperfusion Injury in Acute Myocardial Infarct in Pigs.

Background: To investigate the potential of intravenously administered porcine recombinant interferon-β1a (IFN-β1a) for myocardial protection during acute ischemia-reperfusion (IR) injury in an experimental animal model.

Methods: Twenty-two piglets (mean ± standard deviation, 26.7 ± 1.

Assessment of myocardial viability with [O]water PET: A validation study in experimental myocardial infarction.

Background: Assessment of myocardial viability is often needed in patients with chest pain and reduced ejection fraction. We evaluated the performance of reduced resting MBF, perfusable tissue fraction (PTF), and perfusable tissue index (PTI) in the assessment of myocardial viability in a pig model of myocardial infarction (MI).

Methods And Results: Pigs underwent resting [O]water PET perfusion study 12 weeks after surgical (n = 16) or 2 weeks after catheter-based (n = 4) occlusion of the proximal left anterior descending coronary artery.

Determinants of Myocardial Strain in Experimental Chronic Myocardial Infarction.

We evaluated the relationships between regional myocardial strain measured by speckle tracking echocardiography and viability, fibrosis, hypertrophy and oxygen consumption in the infarcted or remote myocardium in a pig model of chronic myocardial infarction (MI). Thirteen farm pigs with surgical occlusion of the left anterior descending coronary artery and five sham-operated pigs were studied 3 mo post-MI. Computed tomography revealed significant left ventricle remodeling.

Receptor tyrosine kinase profiling of ischemic heart identifies ROR1 as a potential therapeutic target.

Background: Receptor tyrosine kinases (RTK) are potential targets for the treatment of ischemic heart disease. The human RTK family consists of 55 members, most of which have not yet been characterized for expression or activity in the ischemic heart.

Methods: RTK gene expression was analyzed from human heart samples representing healthy tissue, acute myocardial infarction or ischemic cardiomyopathy.

Pegylated and liposomal doxorubicin is associated with high mortality and causes limited cardiotoxicity in mice.

Objective: We wanted to determine the impact of different doses of a pegylated and liposomal formulation of the cardiotoxic drug doxorubicin on cardiac function, fibrosis and survival in mice. The drug causes myocardial damage by producing reactive oxygen species, mitochondrial damage and lipid peroxidation. Thymosin beta 4 is a peptide with cardioprotective, anti-oxidant and anti-fibrotic properties and we further investigated whether the peptide could attenuate this drug-induced injury by measuring cardiac function and fibrosis.

Early and late outcomes after open ascending aortic surgery: 47-year experience in a single centre.

The aims of the study are to describe the long-term survival of patients undergoing primary open ascending aortic surgery and to portray the evolution of aortic surgery during six decades in a single centre. Included were all 614 patients who underwent primary ascending aortic surgery in 1968-2014 at one Nordic university hospital. Patients were identified and data were collected from patient records and surgical logs.

Imaging of αβ integrin expression in experimental myocardial ischemia with [Ga]NODAGA-RGD positron emission tomography.

Background: Radiolabeled RGD peptides detect αβ integrin expression associated with angiogenesis and extracellular matrix remodeling after myocardial infarction. We studied whether cardiac positron emission tomography (PET) with [Ga]NODAGA-RGD detects increased αβ integrin expression after induction of flow-limiting coronary stenosis in pigs, and whether αβ integrin is expressed in viable ischemic or injured myocardium.

Methods: We studied 8 Finnish landrace pigs 13 ± 4 days after percutaneous implantation of a bottleneck stent in the proximal left anterior descending coronary artery.

Accuracy of echocardiographic area-length method in chronic myocardial infarction: comparison with cardiac CT in pigs.

Background: We evaluated echocardiographic area-length methods to measure left ventricle (LV) volumes and ejection fraction (EF) in parasternal short axis views in comparison with cardiac computed tomography (CT) in pigs with chronic myocardial infarction (MI).

Methods: Male farm pigs with surgical occlusion of the left anterior descending coronary artery (n = 9) or sham operation (n = 5) had transthoracic echocardiography and cardiac-CT 3 months after surgery. We measured length of the LV in parasternal long axis view, and both systolic and diastolic LV areas in parasternal short axis views at the level of mitral valve, papillary muscles and apex.

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h.

Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion.

Background: Levosimendan is an inotropic agent with cardioprotective and vasodilating properties used for the management of acutely decompensated heart failure. We studied the effects of levosimendan treatment on the size of myocardial infarction (MI) and left ventricular (LV) function in experimental pig model of post MI heart failure.

Methods: After occlusion of the left anterior descending (LAD) coronary artery, animals received levosimendan 5 mg/kg/day orally for 8 weeks (n=7) or no treatment (n=18).

[18F]FDG Accumulation in Early Coronary Atherosclerotic Lesions in Pigs.

Objective: Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis.

Cardiac remodeling in a new pig model of chronic heart failure: Assessment of left ventricular functional, metabolic, and structural changes using PET, CT, and echocardiography.

Aims: Large animal models are needed to study disease mechanisms in heart failure (HF). In the present study we characterized the functional, metabolic, and structural changes of myocardium in a novel pig model of chronic myocardial infarction (MI) by using multimodality imaging and histology.

Methods And Results: Male farm pigs underwent a two-step occlusion of the left anterior descending coronary artery with concurrent distal ligation and implantation of a proximal ameroid constrictor (HF group), or sham operation (control group).

Therapeutic potential of thymosin β4 in myocardial infarct and heart failure.

Thymosin β4 (Tβ4) is a peptide known for its abilities to protect and facilitate regeneration in a number of tissues following injury. Its cardioprotective effects have been evaluated in different animal models and, currently, a clinical trial is being planned in patients suffering from acute myocardial infarction. This paper focuses on the effects of Tβ4 on cardiac function in animal studies utilizing different imaging modalities for outcome measurements.

Intracoronary Levosimendan during Ischemia Prevents Myocardial Apoptosis.

Background: Levosimendan is a calcium sensitizer that has been shown to prevent myocardial contractile depression in patients post cardiac surgery. This drug exhibits an anti-apoptotic property; however, the underlying mechanism remains elusive. In this report, we characterized the myocardial protective of levosimendan in preventing cardiomyocyte apoptosis and post-operative stunning in an experimental ischemia-reperfusion model.

Evaluation of 68Ga-labeled tracers for PET imaging of myocardial perfusion in pigs.

Purpose: We evaluated four potential gallium-68 (68Ga)-labeled tracers for positron emission tomography (PET) imaging of myocardial perfusion in comparison with oxygen-15-labeled water ([15O]water) in healthy pigs. Four hexadentate salicylaldimine ligands derived from bis(3-aminopropyl)ethylenediamine (BAPEN) that showed promise in previous rat experiments were selected for this study.

Methods: Following an evaluation of myocardial blood flow with [15O]water PET, the pigs (total n=14) underwent a dynamic 90-min PET study with one of four 68Ga-labeled BAPEN derivatives (n=3-5 per tracer) either at rest or under adenosine stress.

Initial healing of sternotomy wounds: correlation between preoperative data and wound inflammatory cell response.

Local inflammation after a surgical incision is an essential prerequisite for wound healing and later scar formation both in children and adults. However, the underlying regulatory mechanisms are still poorly known and need further investigations. In this study, one hundred sternotomy patients, operated on routinely for cardiac disease, were studied with the Cellstick device to harvest wound inflammatory cells for differential count and subsequent computerized analysis using an artificial neural network.

Novel electrophilic synthesis of 6-[¹⁸F]fluorodopamine and comprehensive biological evaluation.

Purpose: 6-[(18)F]Fluorodopamine (4-(2-aminoethyl)-5-[(18)F]fluorobenzene-1,2-diol, 6-[(18)F]FDA) is a tracer for imaging sympathetically innervated tissues. Previous electrophilic labelling methods produced 6-[(18)F]FDA with low specific radioactivity (SA) which has limited its wider use. Our aim was to employ electrophilic labelling and increase the SA to around 15 GBq/μmol.

Cardiomyocyte apoptosis after antegrade and retrograde cardioplegia during aortic valve surgery.

Background: Retrograde delivery is associated with inadequate perfusion of cardioplegia to all regions of the heart, but the effects on cardiomyocyte death and functional outcome remain unknown. We compared antegrade and retrograde cardioplegia in a randomized clinical trial to see whether it has effect on cardiomyocyte apoptosis and left ventricular function.

Methods: Patients underwent elective aortic valve replacement surgery due to aortic valve stenosis.

Fatty acid metabolism in the liver, measured by positron emission tomography, is increased in obese individuals.

Background & Aims: Hepatic lipotoxicity results from and contributes to obesity-related disorders. It is a challenge to study human metabolism of fatty acids (FAs) in the liver. We combined (11)C-palmitate imaging by positron emission tomography (PET) with compartmental modeling to determine rates of hepatic FA uptake, oxidation, and storage, as well as triglyceride release in pigs and human beings.

Non-invasive diagnosis of acute mesenteric ischaemia using PET.

Purpose: Acute mesenteric ischaemia (AMI) is a lethal disease with an increasing incidence. Despite the availability of effective treatment, AMI remains a vascular emergency with over 60% mortality rate mainly due to late diagnosis. The difficulty in diagnosing this fatal condition stems from non-specific clinical and laboratory findings and lack of appropriate imaging study.

Ischemia-reperfusion injury is attenuated in VAP-1-deficient mice and by VAP-1 inhibitors.

Neutrophils mediate the damage caused by ischemia-reperfusion both at the site of primary injury and in remote organs. Vascular adhesion protein-1 (VAP-1) is an ectoenzyme expressed on endothelial cells and it has been shown to regulate leukocyte extravasation. Here we show for the first time using VAP-1-deficient mice that VAP-1 plays a significant role in the intestinal damage and acute lung injury after ischemia-reperfusion.

Long-term outcome of infective endocarditis: a study on patients surviving over one year after the initial episode treated in a Finnish teaching hospital during 25 years.

Background: Only a few previous studies have focused on the long-term prognosis of the patients with infective endocarditis (IE). Our purpose was to delineate factors potentially associated with the long-term outcome of IE, recurrences of IE and requirement for late valve surgery.

Methods: A total of 326 episodes of IE in 303 patients were treated during 1980-2004 in the Turku University Hospital.

Quantification of liver perfusion with [(15)O]H(2)O-PET and its relationship with glucose metabolism and substrate levels.

Background/aims: Hepatic perfusion plays an important role in liver physiology and disease. This study was undertaken to (a) validate the use of Positron Emission Tomography (PET) and oxygen-15-labeled water ([(15)O]H(2)O) to quantify hepatic and portal perfusion, and (b) examine relationships between portal perfusion and liver glucose and lipid metabolism.

Methods: Liver [(15)O]H(2)O-PET images were obtained in 14 pigs during fasting or hyperinsulinemia.

IFN-beta protects from vascular leakage via up-regulation of CD73.

Changes in endothelial permeability are crucial in the pathogenesis of many diseases. Adenosine is one of the endogenous mediators controlling endothelial permeability under normal conditions, and an endothelial cell surface enzyme CD73 is a key regulator of adenosine production. Here we report that IFN-beta is a novel inducer of CD73.

Short-term and one-year outcome of infective endocarditis in adult patients treated in a Finnish teaching hospital during 1980-2004.

Background: Previous studies on factors predicting the prognosis of infective endocarditis have given somewhat conflicting results. Our aim was to define the factors predicting the outcome of patients treated in a Finnish teaching hospital.

Methods: A total of 326 episodes of infective endocarditis in 303 patients treated during 1980-2004 were evaluated for short-term and 1-year outcome and complications.