Biomedical subjects

Guro Valen

Publications and source records attributed to Guro Valen.

At least 19 recordsLinked to original sources

PubMed2006

Caught in the act: in vivo molecular imaging of the transcription factor NF-kappaB after myocardial infarction.

Nuclear factor kappaB (NF-kappaB) is a ubiquitous transcription factor activated by various stimuli implicated in heart failure progression. However, its activation in heart failure has not been well defined yet. Therefore, we investigated activation of NF-kappaB after myocardial infarction. For the first time, we performed serial, non-invasive in vivo molecular imaging of transcription factor activation in the heart. We used mice expressing a luciferase reporter whose transcription is dependent upon NF-kappaB activation for up to 8 weeks after myocardial infarction. There was a significant increase of NF-kappaB activity with a maximum at day 3 after myocardial infarction when compared to sham controls. Thus, in vivo measurement of the activation of NF-kappaB is feasible. NF-kappaB activity might play an important role for the remodeling process.

Animals↗

PubMed2006

Gene deletion of NF-kappaB p105 enhances neointima formation in a mouse model of carotid artery injury.

The role of nuclear factor kappa-B (NF-kappaB) p105 for vascular inflammatory gene expression and neointima formation after arterial injury was studied. Mice carotid arteries were injured by ligation. Vascular NF-kappaB activation was monitored using a NF-kappaB luciferase reporter mouse. Mice with gene deletion of the NF-kappaB p105 subunit (p50 precursor) and the corresponding wild types were assessed for vascular gene expression and neointimal hyperplasia. NF-kappaB was activated in the injured vessel wall in wild type mice, and this was accompanied by increased expression of the proinflammatory genes tumor necrosis factor alpha, interleukin 1 beta, and inducible nitric oxide synthase. In contrast, NF-kappaB p105 knockout mice had reduced expression of the inflammatory genes and enhanced neointima formation four weeks after ligation. Basic fibroblast growth factor (bFGF) gene expression increased after arterial ligation. A higher percentage of bFGF positive cells were found in lesions from NF-kappaB p105 knock out mice. These data indicate that the p105 subunit of NF-kappaB plays an essential role in vascular healing, and defects in NF-kappaB p105 promote neointima hyperplasia.

Animals↗

PubMed2006

Vein graft harvesting induces inflammation and impairs vessel reactivity.

BACKGROUND: Saphenous veins are often used for coronary artery bypass grafting (CABG), but loss of patency is a problem. The surgical procedure may contribute to graft injury. Our aim was to study the impact of surgical handling of saphenous veins on graft inflammation and vascular function. METHODS: Biopsy samples of saphenous veins were taken from 9 patients undergoing elective CABG at the start of vein harvesting (open technique) and after the last proximal anastomosis was sutured. Messenger RNA was extracted and amplified with semiquantitative reverse transcription polymerase chain reaction. Gene expression of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta), leukocyte adhesion molecules (E-selectin, intercellular adhesion molecule-1), and vasoactive substances (endothelin-1, inducible and endothelial nitric oxide synthase) was investigated. Translocation of nuclear factor-kappaB (NFkappaB) was evaluated with electrophoretic mobility shift assay. Immunostaining for von Willebrand factor was performed to evaluate loss of endothelium, and in vitro vein reactivity to phenylephrine and endothelin-1 was studied. RESULTS: Gene expression of cytokines and leukocyte adhesion molecules increased after graft harvesting and storage, whereas vasoactive substances did not change. Nuclear translocation of NFkappaB occurred after surgical handling, concurrent with partial loss of endothelium and impaired contractile function. CONCLUSIONS: Standard surgical handling of vein grafts induces NFkappaB-driven inflammation in the vessel wall and impairs vascular function. This may potentially contribute to both early and late graft occlusion.

Biopsy↗

PubMed2006

Postconditioning in rats and mice.

OBJECTIVE: For subsequent studies on the molecular mechanisms of postconditioning, we aimed to identify a robust postconditioning protocol in rat and mouse heart. DESIGN: Isolated rat hearts were subjected to different postconditioning protocols (study 1 and 2). The protection was compared to preconditioning. Rats (study 3) in vivo in two different laboratories were postconditioned. Isolated mouse hearts (study 4) and mice in vivo (study 5) were postconditioned. RESULTS: Postconditioning did not protect isolated, perfused rat hearts, however, preconditioning improved function and reduced infarct size. Postconditioning tended to protect rat hearts in vivo in one laboratory (p = 0.10), whereas protection was seen in the other laboratory (infarct size 51+/-11% vs controls 62+/-3%, p = 0.01). Postconditioned mouse hearts were protected, both ex vivo (16+/-9% vs controls 33+/-18%, p = 0.02) and in vivo (21+/-5% vs 42+/-7%, p < 0.001). CONCLUSIONS: Rat hearts are less suitable for studies of mechanisms of postconditioning. The results suggest that the signaling pathways differ between pre- and postconditioning. Mouse hearts were strongly protected by postconditioning, and genetically engineered mice may be useful for postconditioning research.

Animals↗

PubMed2006

Isoflurane and other commonly used anaesthetics do not protect the isolated buffer perfused mouse heart from ischemia-reperfusion injury.

1. Some anaesthetic agents such as barbiturates and opioids possess cardioprotective properties in rats, rabbits, dogs and pigs. The purpose of this study was to evaluate the effects of some commonly used anaesthetic agents (pentobarbital, isoflurane and a mixture of midazolam, fentanyl and fluanisone) on the tolerance of the isolated mouse heart to ischaemia-reperfusion injury. 2. The isolated, Langendorff-perfused hearts were subjected to 45 min of global ischaemia followed by 60 min of reperfusion. Left ventricular pressures, heart rate and coronary flow were measured and infarct size was determined using triphenyltetrazolium staining. 3. There were no differences in haemodynamic variables during reperfusion between groups. Infarct size was not influenced by the choice of anaesthesia. 4. None of the anaesthesia protocols exerted significant protective effects on the ischaemic-reperfused isolated mouse heart performance. In mice, isoflurane as well as pentobarbital, opioids and benzodiazepines may be safely used for anaesthesia without a risk of protective side-effects in isolated mouse heart studies.

Anesthetics, Inhalation↗

PubMed2005

Lazaroid U-83836E improves tolerance to hemorrhagic shock and limb ischemia and reperfusion in rats and increases cardiac heat shock protein 72.

OBJECTIVES: Aminosteroids of the lazaroid type protect organs from ischemia-reperfusion damage. The authors hypothesized that lazaroid U-83836E may be beneficial in a shock model with hemorrhage combined with limb ischemia. Furthermore, the authors hypothesized that lazaroids induce expression of heat shock proteins (HSPs) of the 72-kDa family. METHODS: Rats were divided into two groups (lazaroid and control groups, n = 8 each) and pretreated with the lazaroid U-83836E (5 mg/kg) or with vehicle intraperitoneally at 12 and 24 hours before experiments. At the time of the experiment, rats were anesthetized, and the femoral artery of each rat was cannulated. After 20 minutes of stabilization, blood was shed from each rat to bring its mean arterial pressure to 24-28 mmHg for 2 hours. Bilateral tourniquets were tightened proximally on the rat thighs during those 2 hours and then released. Shed blood plus equal amounts of Ringer acetate then were infused to restore normal blood pressure, followed by a continuous infusion of Ringer acetate, the rate of which was regulated to maintain blood pressure, until 30 minutes after start of resuscitation. Fluid resuscitation was stopped, and rats were observed for another 3.5 hours. At the end of the observation period, the rats' hearts were collected for immunoblot analysis of HSP72. Additional hearts were collected from similarly pretreated rats not undergoing the episode of hemorrhagic shock and fluid resuscitation. RESULTS: Pretreatment with U-83836E improved mean arterial blood pressure after hemorrhagic shock and fluid resuscitation (p = 0.02), combined with improvements in acid-base balance (improved base excess and standard bicarbonate; p = 0.02 and p = 0.01, respectively). Western blot of cardiac protein extracts demonstrated that lazaroid pretreatment increased expression of HSP72. CONCLUSIONS: Pretreatment with the lazaroid U-83836E improved outcome markers in this hemorrhagic shock model. The observed protection may be caused by increased expression of HSP72.

Acid-Base Equilibrium↗

PubMed2005

Pre- and postconditioning during cardiac surgery.

In spite of improved myocardial protection, postoperative arrhythmias and cardiac failure are still important problems causing morbidity and mortality in cardiac surgery. Ischemic preconditioning has been widely investigated experimentally with the purpose of identifying new therapeutic agents, but we have not unraveled the underlying mechanisms and we are not able yet to exploit them pharmacologically in clinical practice. Studies of preconditioning in cardiac surgery provide conflicting results, but the majority of studies show that ischemic preconditioning is an effective adjunct to myocardial protection in cardiac surgery. Interventions aimed at modifying reperfusion, or postconditioning, have the advantage that they also can be used after the ischemic insult has occurred, i.e. also in situations with "non-scheduled" ischemia. Postconditioning, as preconditioning, needs pharmacological mimics to be used routinely in settings of cardiac surgery or other human interventions. Possible common signaling pathways of the two phenomena are discussed, and suggested directions for clinical studies are outlined.

Animals↗

PubMed2005

Apoptosis and angiogenesis are induced in the unstable coronary atherosclerotic plaque.

OBJECTIVE: Apoptosis and angiogenesis may be involved in the pathogenesis of atherosclerosis and plaque destabilization. In this study, we investigated if apoptosis and angiogenesis were induced in the unstable human coronary atherosclerotic plaque compared to stable atherosclerotic plaque. METHODS: Atherosclerotic plaques from patients with stable (n = 9) and unstable angina (n = 13) were obtained by directional coronary atherectomy performed during percutaneous transluminal coronary angioplasty. Apoptosis was detected by terminal deoxynucleotidyl transferase end labelling (TUNEL), as well as by immunostaining for caspase 3, Bax and Bcl-2. Neovascularization was determined by immunostaining for the endothelial cell-specific CD31, vascular endothelial growth factor (VEGF-A), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), hypoxia inducible factor-1alpha (HIF-alpha), and the sections were quantified blindly. RESULTS: The apoptotic nuclei were more frequently found in the unstable coronary atherosclerotic plaques. When the number of apoptotic cells was quantified, an increased apoptotic index was found in the unstable plaques (P = 0.04). The positive staining for caspase-3 was increased in the unstable plaques (P = 0.0008), while no difference in either Bax or Bcl-2 was found between groups. Neovascularization, as evidenced by lumens surrounded by a CD31 positive endothelial layer, was more frequently present in the plaques from patients with unstable angina (P = 0.04). The number of cells with positive staining for VEGF-A was increased in unstable plaques (P = 0.005). No difference of Ang I, Ang II, HIF1-alpha was found between groups. CONCLUSIONS: In unstable human coronary plaques, apoptosis probably involving caspase 3 was found. The plaques had an increased neovascularization, probably induced by VEGF-A. These factors may contribute to explaining plaque destabilization and intraplaque haemorrhage.

Aged↗

PubMed2005

Intraperitoneal injection induces a delayed preconditioning-like effect in mice.

We hypothesized that intraperitoneal injections of anaesthetics or fluid per se might evoke a delayed preconditioning-like response in mice hearts isolated and Langendorff perfused 24 h later. To test this, mice were given opioid anaesthesia by intraperitoneal injections or sham treated and the hearts were harvested and subjected to global ischaemia and reperfusion 24 h later in series 1. In series 2, mice were subjected to intraperitoneal injection of Ringer, sham needle prick procedure, or no intervention 24 h before heart isolation. In series 3, intraperitoneal Ringer injection 24 h earlier was compared with the effects of classic preconditioning or no pretreatment of the isolated heart or no treatment. Heart function was measured in all series. At the end of reperfusion, hearts in series 1 and 2 were frozen and infarct size was estimated by triphenyltetrazolium chloride solution. In series 3, separate hearts were frozen for immunoblotting to detect phosphorylation of mitogen-activated protein (MAP) kinases. Cardiac activation of nuclear factor kappa B (NFkappaB) was measured using a NFkappaB luciferase firefly reporter mouse. The ischaemia-induced impairment of left ventricular function was attenuated by opioid anaesthesia injected 24 h earlier, which also reduced infarct size. Injection of fluid, but not the sham needle prick procedure, reduced infarct size. The functional protection afforded by classic preconditioning and Ringer pretreatment was comparable. Neither cardiac MAP kinases nor NFkappaB were influenced by the interventions. In conclusion, this study demonstrates a delayed preconditioning-like effect of the heart caused by intraperitoneal administration of opioid anaesthetics and of fluid only in the mouse. The mechanism of protection remains to be determined.

Analysis of Variance↗

PubMed2005

Expression of matrix metalloproteinase 9 and its regulators in the unstable coronary atherosclerotic plaque.

Unstable coronary syndromes, initiated by rupture of an atherosclerotic plaque, may involve the activation of matrix metalloproteinases (MMPs). The regulation of MMP activity is complex and involves three steps. First, an inactive pro-MMP is transcriptionally regulated, a process that is likely to involve the transcription factor activator protein-1 (AP-1) and nuclear factor kappa B (NF-kappaB). Secondly, the pro-MMP is proteolytically cleaved into an active MMP. Plasmin has been suggested to be the major activator of MMPs in vivo. Thirdly, the activated MMP can be inhibited by tissue inhibitors of metalloproteinase (TIMPs). We investigated if expression of MMP9 and its potential regulators are induced in unstable coronary plaques. Atherosclerotic plaques from patients with stable (n=22) and unstable (n=39) angina were obtained by directional coronary atherectomy and analysed by semiquantitative RT-PCR and immunohisto-chemistry. Plasma was collected for ELISA analysis. mRNA for MMP9 as well as plasminogen activator inhibitor-1 (PAI-1) was increased in unstable plaques, while tissue type plasminogen activator (tPA) expression was similar in stable and unstable plaques. Plaques from unstable patients had an increased infiltration of macrophages and T-lymphocytes, nuclear localisation of AP-1 and the NF-kappaB subunit p65, as well as increased positive immunostaining for MMP9 and tPA. Plasma MMP9 antigen was elevated in unstable patients. MMP9 is expressed in the unstable coronary atherosclerotic plaque, as are its transcriptional and posttranscriptional regulators.

Adult↗

PubMed2004

Role of tumor necrosis factor alpha and its receptor I in preconditioning by hyperoxia.

Hyperoxic pretreatment (>95% O(2)) can evoke myocardial adaptation to ischemia, a method which is potentially clinically usable. We wanted to investigate the role of tumor necrosis factor alpha (TNFalpha) and its p55 receptor (receptor I) in signaling of hyperoxic adaptation to ischemia. Mice deficient for TNFalpha (TNFalpha -/-) or the TNF receptor I (TNFRI -/-) gene and their wild types were subjected to 60 minutes of hyperoxia or sham treatment. Their lungs were then collected for immunoblotting, their hearts isolated and subjected to global ischemia and reperfusion in a Langendorff system, and aortic rings mounted in organ baths for reactivity studies. Hyperoxia increased expression of TNFalpha and TNFalpha converting enzyme in pulmonary proteins from wild type mice, in which hyperoxia increased myocardial tolerance to ischemia. Post-ischemic heart function was improved and infarct size reduced in wild type mice, but not in TNFalpha -/- or TNFRI -/-. The contractile response to TNFalpha on aortic rings was attenuated by hyperoxic pretreatment and by TNFRI -/-. Thus we conclude that TNFalpha, acting through TNFRI, appears important for the protective effects of hyperoxia.

ADAM Proteins↗

PubMed2004

Cardiac troponin T content in heart and skeletal muscle and in blood samples from ApoE/LDL receptor double knockout mice.

BACKGROUND: The isolated perfused mouse heart is a useful experimental model, and cardiac troponin T (cTnT) in coronary effluent may be a sensitive marker of myocardial damage. In recent years, the apolipoprotein E/low-density lipoprotein receptor double knockout (apoE/LDLr KO) mice have become valuable tools in atherosclerosis research. The aim of the study was to validate measurements of cTnT in heart, skeletal muscle, and serum of apoE/LDLr KO mice. METHODS: Wild-type C57BL/6J mice were fed with standard diet, and apoE/LDLr KO mice were fed an atherogenic diet. Blood was sampled from the jugular vein or the thoracic cavity. Heart and femoral skeletal muscle were sampled and homogenized. cTnT was measured with the third-generation cTnT assay (Troponin T STAT) on Elecsys 2010 immunoassay analyser (Roche Diagnostics). RESULTS: Median serum cTnT in samples from the thoracic cavity of C57BL/6J mice was about 20-90 times higher, and from ApoE/LDLr KO mice about 30 times higher than serum cTnT in samples from the external jugular vein. There was no difference in cTnT content (microg cTnT/g heart muscle) in hearts from C57BL/6J and apoE/LDLr KO mice. The median cTnT content in skeletal muscle was less than 0.1% of the cTnT content in heart muscle. CONCLUSION: There is no difference in cTnT content of heart muscle comparing C57BL/6J and ApoE/LDLr KO mice, which have larger hearts. Sampling from the thoracic cavity causes unacceptably high cTnT levels. Serum cTnT in samples from the jugular vein is only slightly elevated. Elevated baseline levels of cTnT in mice are not caused by troponin T from skeletal muscle.

Animals↗

PubMed2004

Ischemic postconditioning: brief ischemia during reperfusion converts persistent ventricular fibrillation into regular rhythm.

OBJECTIVES: Brief episodes of myocardial ischemia-reperfusion employed during reperfusion after a prolonged ischemic insult may attenuate the total ischemia-reperfusion injury. This phenomenon has been termed ischemic postconditioning. In the present study, we studied the possible effect of postconditioning on persistent reperfusion-induced ventricular fibrillation (VF) in the isolated rat heart model. METHODS: Isolated Langendorff-perfused rat hearts (n = 46) were subjected to 30 min of regional ischemia and reperfusion. The hearts with persistent VF (n = 11) present after 15 min of reperfusion were then randomly assigned into one of the two groups: (1) control hearts (n = 6) in which perfusion was continued without intervention; (2) postconditioned hearts (n = 5) subjected to 2 min of global ischemia followed by reperfusion. Left ventricular pressures, heart rate, coronary flow, and electrogram were monitored throughout the experiment. RESULTS: Conversion of VF into regular rhythm was observed in all hearts subjected to postconditioning. Regular beating was maintained by all postconditioned hearts during the subsequent reperfusion. None of the hearts in the control group had normal rhythm at the end of the experiment. At the end of reperfusion, the left ventricular developed pressure was lower in beating postconditioned hearts compared to the hearts that did not develop persistent VF. CONCLUSIONS: Ischemic postconditioning possesses strong antiarrhythmic effect against persistent reperfusion-induced tachyarrhythmias. Postconditioning may be an interesting, novel adjunct strategy to protect the heart.

Animals↗

PubMed2004

Myocardial protection by remote preconditioning: the role of nuclear factor kappa-B p105 and inducible nitric oxide synthase.

OBJECTIVE: Adaptation to ischemia by brief episodes of ischemia and reperfusion (preconditioning) of the heart protects the heart against sustained ischemia, where the transcription factor nuclear factor kappa-B (NFkappaB) appears crucial for the protection. Preconditioning of the heart may even be evoked by brief episodes of ischemia and reperfusion in other organs. The present study investigates a possible role for NFkappaB and inducible nitric oxide synthase (iNOS) in adaption to ischemia by remote, delayed protection. METHODS: Mice (wild-types, or with targeted deletions of the NFkappaB p105 or the iNOS gene) were subjected to cycles of occlusion and reperfusion of both hind limbs, and 24 h later their hearts were isolated and Langendorff-perfused with induced global ischemia and reperfusion. Infarct size was measured. Skeletal muscles from ischemized limbs as well as hearts were also collected for polymerase chain reaction (PCR) and electromobility shift assay (EMSA). RESULTS: Hind limb preconditioning protected left ventricular function and reduced infarct size during reperfusion in wild-type mice. Nuclear translocation of NFkappaB was detected in both heart and preconditioned skeletal muscle 1-2 h after the preconditioning episodes (EMSA); while cardiac mRNA for iNOS gradually increased in a 24-h time course after hind limb preconditioning (real-time PCR). When hind limbs of mice with targeted deletions for the p105 subunit of NFkappaB or the iNOS gene were preconditioned, no beneficial effect was observed in the heart. CONCLUSIONS: Delayed cardioprotection induced by hind limb preconditioning involves signaling through NFkappaB and iNOS.

Animals↗

PubMed2004

Metabolic changes induced by ischemia and cardioplegia: a study employing cardiac microdialysis in pigs.

OBJECTIVE: The present study investigates dynamic changes of myocardial metabolism in response to ischemia, cardioplegia, and extracorporeal circulation (ECC) in order to differentiate between the contributing effects of each of these interventions. Furthermore, warm blood cardioplegia versus empty beating of the heart were compared as methods to resuscitate the ischemic myocardial metabolism. METHODS: Swedish Landrace pigs on ECC (ECC) were compared with pigs on ECC with warm ischemic cardiac arrest (ischemia) or on ECC with warm ischemic arrest followed by warm blood cardioplegia (ischemia-cardioplegia), using sham-operated pigs as controls (n=7 in each group). Microdialysis probes were placed on the surface of the left ventricle and in the femoral artery for serial evaluation of metabolites in the intracardiac extracellular fluid and arterial blood. When hearts started in ventricular fibrillation (VF), it was electroconverted after 10 min of normal blood reperfusion. If VF started after 10 min of reperfusion electroconversion was immediately performed. RESULTS: There were no differences between groups in arterial contents of serine, citrulline, arginine, inosine, hypoxanthine, guanosine, aspartate, glutamate, pyruvate, or asparagine throughout the observation period. Systemic lactate increased in pigs subjected to ischemia (P<0.001) or ischemia and cardioplegia (P=0.002), highest in the ischemia only group (P=0.002). In left ventricular microdialysates, lactate increased in pigs subjected to ischemia alone (P<0.001 vs. ECC) and ischemia and cardioplegia (P=0.004 vs. ECC). Guanosine increased in ischemia versus ECC (P=0.002), while hypoxanthine was increased in microdialysates of both ischemic (P=0.002) and ischemic-cardioplegic (P=0.001) pig hearts. Inosine was increased in pigs subjected to ischemia and cardioplegia (P<0.001 vs. ECC). All ischemic hearts started with VF, but while in the warm ischemia group VF started within 10 min of reperfusion, the ischemia-cardioplegia group had a longer asystolia with VF starting 11-22 min of blood reperfusion. CONCLUSION: The heart should be allowed to start empty beating rather than by the use of warm continuous blood cardioplegia. Microdialysis and sampling of interstitial metabolites may be advantageous when an increased sensitivity is needed or when repeated blood sampling is difficult or contraindicated in monitoring of the myocardium.

Analysis of Variance↗

PubMed2003

Nitric oxide mediates protective effect of endothelin receptor antagonism during myocardial ischemia and reperfusion.

Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. We hypothesized that the cardioprotective effect is related to nitric oxide (NO) bioavailability. Buffer-perfused rat and mouse hearts were subjected to ischemia and reperfusion. At the onset of ischemia, the rat hearts received vehicle, the dual endothelin type A/type B (ETA/ETB) receptor antagonist bosentan (10 microM), the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 microM), the combination of bosentan and L-NMMA or the combination of bosentan, L-NMMA, and the NO substrate L-arginine (1 mM). Hearts from wild-type and endothelial NO synthase (eNOS)-deficient mice received either vehicle or bosentan. Myocardial performance, endothelial function, NO outflow, and eNOS expression were monitored. Bosentan significantly improved myocardial function during reperfusion in rats and in wild-type mice, but not in eNOS-deficient mice. The functional protection afforded by bosentan was inhibited by L-NMMA, whereas it was restored by L-arginine. Myocardial expression of eNOS (immunoblotting) increased significantly in bosentan-treated rat hearts compared with vehicle hearts. Recovery of NO outflow during reperfusion was enhanced in the bosentan-treated rat heart. The endothelium-dependent vasodilator adenosine diphosphate increased coronary flow by 18 +/- 9% at the end of reperfusion in the bosentan group, whereas it reduced coronary flow by 7 +/- 5% in the vehicle group (P < 0.001). The response to the endothelium-independent dilator sodium nitroprusside was not different between the two groups. In conclusion, the dual ETA/ETB receptor antagonist bosentan preserved endothelial and cardiac contractile function during ischemia and reperfusion via a mechanism dependent on endothelial NO production.

Adenosine Diphosphate↗

PubMed2003

Signal transduction through nuclear factor kappa B in ischemia-reperfusion and heart failure.

Ischemic heart disease is the major cause of morbity and mortality in the Western world, with chronic heart failure as one complication. Ischemia-reperfusion injury may induce cardiomyocyte cell death by necrosis or apoptosis. The heart can be adapted to tolerate an ischemic event by preceeding brief episodes of ischemia and reperfusion, called preconditioning. Innate immunity has the latest years surfaced as important for the development of cardiovascular pathology as well as for myocardial protection. Nuclear factor kappa B (NFkappaB) is a redox sensitive transcription factor which contributes to the regulation of innate and adaptive immunity. NFkappaB regulates a battery of inflammatory genes, and has been indicated to play a role in the development of numerous pathological states. Activation of NFkappaB induces gene programs leading to transcription of factors which promote inflammation, among them leukocyte adhesion molecules, cytokines such as tumor necrosis factor alpha, and chemokines, but may in some situations also promote tissue remodelling, the resolution of inflammation, and transcription of some few substances with possible antiinflammatory effects. The present paper reviews the basic regulation of NFkappaB, and the possible role of NFkappaB activation in ischemia-reperfusion injury, in adaptation to ischemia-reperfusion injury, and in chronic heart failure.

Heart Diseases↗

PubMed2003

The basic biology of apoptosis and its implications for cardiac function and viability.

Apoptosis or programed cell death is a continuous process of destruction of nonfunctional cells. It is a physiologic process whereby the body disposes of unwanted cells by self-destruction and is our utmost defense against damaged cells. There are several pathways leading to programed cell death. Apoptosis is seen in failing, infarcted, and hibernating human hearts, and during open heart surgery. Apoptosis appears to be induced by myocardial ischemia-reperfusion injury and this is reduced by ischemic preconditioning. Antiapoptotic interventions may be a future target for myocardial protection.

Animals↗