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Jarle Vaage

Publications and source records attributed to Jarle Vaage.

17 recordsLinked to original sources
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

Hemostasis in off-pump compared to on-pump coronary artery bypass grafting: a prospective, randomized study.

BACKGROUND: We hypothesized that off-pump coronary artery bypass grafting has less impact on the hemostatic systems than on-pump surgery. METHODS: Thirty-one patients were randomized to on-pump or off-pump coronary artery bypass grafting. Factors of hemostasis as well as markers of endothelial activation were measured up to 24 hours after the operation: Fibrin D dimer, prothrombin fragment 1+2, alpha2-macroglobulin, protein C1 esterase inhibitor, fibronectin, and von Willebrand factor. Overall hemostasis potential, overall coagulation potential, and overall fibrinolysis potential were determined with a previously developed assay. We also measured platelet count before and after surgery. RESULTS: Fibrin D dimer and prothrombin fragment 1+2 concentrations were lower during surgery in the off-pump group (p < 0.001). Four hours after admission to the intensive care unit, these differences were eliminated. alpha2-macroglobulin, protein C1 esterase inhibitor, fibronectin, and von Willebrand factor concentrations did not differ between groups (p = 0.59, p = 0.28, p = 0.22, and p = 0.69). Protein C1 esterase inhibitor and von Willebrand factor concentrations increased over time (p < 0.001) in both groups. Overall hemostasis potential and overall coagulation potential increased over time (p < 0.001), while overall fibrinolysis potential decreased (p < 0.001) with no difference between groups (p = 0.69, p = 0.91). Platelet count decreased on the first postoperative day (p < 0.001), but increased from the first to the third postoperative day (p = 0.004) in both groups without any inter group difference (p = 0.82). CONCLUSIONS: There was a tendency toward less activation of coagulation and fibrinolysis in low-risk patients during elective off-pump coronary artery bypass surgery when compared with on-pump surgery.

Aged↗
PubMed2005

Peripheral blood monocyte activation during coronary artery bypass grafting with or without cardiopulmonary bypass.

OBJECTIVE: The aim of this prospective, randomized study was to investigate the impact of coronary artery bypass grafting (CABG) on peripheral monocytes and to evaluate the additional effect of cardiopulmonary bypass (CPB). DESIGN: Twenty patients admitted for elective CABG were randomized to either on-pump (ONCAB, n = 9) or off-pump (OFFCAB, n = 11) surgery and blood samples were drawn before, during and 24 h after the operation. The total number of monocytes and the proportion of the more mature CD16+/CD14+ monocytes were measured. Expression of activation markers (CD11b, CD35 and CD62L) and oxidative burst were determined using flow cytometry on both resting and in vitro stimulated cells. Serum concentrations of soluble CD14 and monocytes/macrophage chemotactic protein 1 (MCP-1) were analysed. RESULTS: During surgery there was a selective decrease in the proportion of CD16+/CD14+ monocytes compared to total monocytes. These had returned to preoperative values 24 h after surgery while the total number of monocytes had increased more than 100%. Intracellular production of oxygen free radical H2O2 was increased in the ONCAB group during surgery compared to OFFCAB. Monocyte expression and in vitro mobilization of complement receptors, CD11b and CD35, were similar in both study groups during and after surgery as was the expression of CD62L. Serum levels of MCP-1 decreased during surgery as did soluble CD14, both with increased levels again the day after surgery. CONCLUSION: It is concluded that the circulating monocyte population is activated during and as a consequence of CABG. There were few apparent additional effects of CPB found in this study. In this setting the inflammation caused by the surgery procedure per se probably surpasses the impact of the CPB on circulating blood monocytes.

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↗
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

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

Activation of complement and leukocyte receptors during on- and off pump coronary artery bypass surgery.

OBJECTIVE: The aim of this prospective, randomised study was to investigate the influence of extracorporeal circulation on the inflammatory response, our hypothesis being that off pump coronary artery bypass grafting (OFFCAB) procedures would generate less activation than on pump procedures (ONCAB). METHODS: Patients admitted for elective CABG were randomised to either ONCAB or OFFCAB surgery and blood samples were taken during and up to 24 h after the operation. We measured complement factors C5a and the terminal complement complex (TCC, C59-b), and the interleukins IL-6 and IL-8. Leukocytes were studied for cellular counts and adhesion molecules (CD11b, CD35 and CD62L) by flow cytometry. We included a combination of activity markers with different aspects of neutrophil function and combined these with in vitro activation. RESULTS: The complement factors C5a and TCC showed a more rapid (P=0.02, P<0.001) and TCC a more profound (P<0.001) increase in the ONCAB group than in the OFFCAB group during the operation, after that there were no inter-group differences. Cellular markers, cell counts and interleukin levels were activated by surgery but with no difference between groups. CONCLUSION: This prospective, randomised study showed less complement activation in low risk OFFCAB, compared to ONCAB patients.

Aged↗
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

Preconditioning and cardiac surgery.

Preconditioning is in experimental studies the most powerful mode of cardioprotection known. The signal transduction pathways involve a variety of trigger substances, mediators, receptors, and effectors. The studies of preconditioning in cardiac surgery provide conflicting results but the majority of studies show that ischemic preconditiong is an effective adjunct to myocardial protection. However, ischemic preconditioning with repeated clamping of the aorta will never get widespread use. If the "preconditioning response" is to be exploited in cardiac surgery, targeting the underlying molecular mechanisms must provide easily applicable techniques or drugs, which are shown in large scale clinical studies to be beneficial.

Animals↗
PubMed2003

Protective effect of antioxidants on pulmonary endothelial function after cardiopulmonary bypass.

OBJECTIVES: Pulmonary endothelium-dependent vasodilation is impaired after cardiopulmonary bypass. One explanation might be the generation of reactive oxygen species during the period without flow in the pulmonary artery. The aim of the current study was to investigate if treatment with antioxidants could improve pulmonary endothelial function after cardiopulmonary bypass and influence the blood oxidative status. DESIGN: A prospective, randomized, double-blind study. SETTING: The operating room, intensive care unit, and the biochemistry laboratory in University Hospitals. PARTICIPANTS: Patients scheduled for cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Treatment with vitamin E, vitamin C, allopurinol, and acetylcysteine (n = 12) or placebo (n = 10). MEASUREMENTS AND MAIN RESULTS: The pulmonary reactivity to an infusion of acetylcholine and markers of oxidative stress in blood were measured before and after cardiopulmonary bypass. Sixteen control patients received saline instead of acetylcholine. Before surgery the pulmonary vascular resistance index decreased during infusion of acetylcholine by 24% and 21% in the treatment and placebo groups. After surgery the decrease was 20% and 8%, respectively, (p = 0.422 and p = 0.026) compared with preoperative response. Pulmonary vasodilation induced by acetylcholine was better maintained in the group treated with antioxidants (p = 0.048). In the treatment group, the blood concentrations of early intermediates of lipid peroxidation were higher, but not that of the end products. Glutathione and oxidized glutathione increased after cardiopulmonary bypass in the treatment group. CONCLUSION: The better maintained endothelium-dependent vasodilation after cardiopulmonary bypass in the treatment group indicated that antioxidant therapy reduced endothelial dysfunction.

Acetylcholine↗
PubMed2003

Biochemical markers of cerebrospinal ischemia after repair of aneurysms of the descending and thoracoabdominal aorta.

OBJECTIVE: To investigate the clinical potential of several markers of spinal cord ischemia in cerebrospinal fluid (CSF) and serum during aneurysm repair of the descending thoracic or thoracoabdominal aorta. DESIGN: Observational study of consecutive patients. Nonblinded, nonrandomized. SETTING: University hospital thoracic surgical unit. PARTICIPANTS: Eleven consecutive elective patients. INTERVENTIONS: Distal extracorporeal circulation and maintenance of CSF pressure <10 mmHg until intrathecal catheter removal. MEASUREMENTS AND MAIN RESULTS: CSF and serum levels of S100B (and its isoforms S100A1B and S100BB), neuronal-specific enolase (NSE), and the CSF levels of glial fibrillary acidic protein (GFAp) and lactate were determined. Two patients had postoperative neurologic deficit. One with a stroke showed a 540-fold increased GFAp, a 6-fold NSE, and S100B increase in CSF. One with paraplegia had a 270-fold increase in GFAp, a 2-fold increase in NSE, and 5-fold increased S100B in CSF. One patient without deficit increased GFAp 10-fold, NSE 4-fold, and S100B 23-fold in CSF. CSF lactate increased >50% in 6 of 9 patients without neurologic deficit. Serum S100B increased within 1 hour of surgery in all patients without any concomitant increase in CSF. S100A1B was about 70% of total S100B in both serum and CSF in patients with or without neurologic defects. S100B in CSF increased 3-fold in 3 of 9 asymptomatic patients. CONCLUSIONS: In patients with neurologic deficit, GFAp in CSF showed the most pronounced increase. Biochemical markers in CSF may increase without neurologic symptoms. There is a significant increase in serum S100B from surgical trauma alone without any increase in CSF.

Adult↗
PubMed2003

Hyperoxia elicits myocardial protection through a nuclear factor kappaB-dependent mechanism in the rat heart.

OBJECTIVE: Hyperoxia has been previously shown to protect the heart from ischemia-reperfusion injury. In the present study we investigated whether the cardioprotective effects of hyperoxia were dependent on the redox-sensitive transcription factor nuclear factor kappaB. METHODS: Rats were kept in a hyperoxic (> or =95% O(2)) environment for 60 minutes. Their hearts were isolated immediately afterward, buffer perfused in a Langendorff apparatus, and subjected to 25 minutes of global ischemia and 60 minutes of reperfusion. Cardiac pressures and coronary flow were measured, and infarct size was determined by means of triphenyl tetrazolium chloride staining. Activation of nuclear factor kappaB was assessed by means of the electrophoretic mobility shift assay, whereas the inhibitor IkappaBalpha was evaluated by means of immunoblotting. Pharmacologic inhibition of nuclear factor kappaB was achieved with 2 different agents, SN50 and pyrrolidine dithiocarbamate. RESULTS: Preischemic exposure to hyperoxia improved postischemic recovery of myocardial contractile function and coronary flow and reduced infarct size. Hyperoxia activated pulmonary and myocardial nuclear factor kappaB. Pretreatment with SN50 (400 microg/kg administered intraperitoneally) or pyrrolidine dithiocarbamate (100 mg/kg administered intraperitoneally) before hyperoxia abolished the functional and infarct-limiting protection. Hyperoxia reduced nuclear factor kappaB activation in the heart during sustained ischemia and reperfusion and increased the cytoplasmatic inhibitory factor IkappaBalpha. Administration of pyrrolidine dithiocarbamate or SN50 during ischemia and reperfusion to isolated hearts from normoxic control animals improved postischemic contractile function and coronary flow and reduced infarct size. CONCLUSIONS: Hyperoxia protects the rat heart against ischemia-reperfusion injury. The cardioprotection depends on myocardial activation of the transcription factor nuclear factor kappaB. Our results support evidence for a dual role of nuclear factor kappaB in the heart.

Analysis of Variance↗