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Lars Wiklund

Publications and source records attributed to Lars Wiklund.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory response and platelet activation after off-pump coronary artery bypass surgery.

BACKGROUND: Cardiac surgery induces a systemic inflammatory activation and alterations in the hemostatic cascade. The responses contribute to postoperative complications but may also have protective effects. We investigated the relationship between inflammation, hemostasis and bleeding after off-pump coronary artery bypass surgery (OPCAB). METHODS: Ten OPCAB patients were included in a prospective descriptive study. Selected markers of inflammation (IL-6, IL-8, PMN-elastase, C3a, and SC5b-9), and hemostasis (platelet count, ss-thromboglobulin, anti-thrombin, D-dimer and fibrinogen) were measured before and immediately after surgery. Postoperative bleeding was registered. RESULTS: Inflammatory variables did not alter significantly during surgery while ss-thromboglobulin concentrations increased and anti-thrombin and fibrinogen decreased. There were significant postoperative correlations between PMN-elastase and ss-thromboglobulin (r=0.82, p=0.004), between PMN-elastase and fibrinogen (r=0.69, p=0.03) and between C3a and ss-thromboglobulin (r=0.71, p=0.02). In addition, there were significant inverse correlations between postoperative bleeding and pre- and postoperative fibrinogen levels (r=-0.76, p=0.011 and r=-0.84, p=0.002 respectively), between bleeding and postoperative ss-thromboglobulin levels (r=-0.66, p=0.04) and between bleeding and postoperative PMN-elastase (r=-0.75, p=0.01). CONCLUSIONS: The results give further evidence for an association between the inflammatory response and hemostasis after cardiac surgery.

Aged↗
PubMed2006

Methylene blue added to a hypertonic-hyperoncotic solution increases short-term survival in experimental cardiac arrest.

OBJECTIVE: Methylene blue (MB), a free-radical scavenger inhibiting the production and actions of nitric oxide, may counteract excessive vasodilatation induced by nitric oxide during cardiac arrest. Effects of MB in cardiac arrest and cardiopulmonary resuscitation were investigated. DESIGN: Randomized, prospective, laboratory animal study. SETTING: University animal research laboratory. SUBJECTS: A total of 63 piglets of both sexes. INTERVENTIONS: A pig model of extended cardiac arrest (12 mins of untreated cardiac arrest and 8 mins of cardiopulmonary resuscitation) was employed to assess the addition or no addition of MB to a hypertonic saline-dextran solution. These two groups (MB and hypertonic saline-dextran group [MB group] and hypertonic saline-dextran-only group) of 21 animals were each compared with a group receiving isotonic saline (n = 21). MEASUREMENTS AND MAIN RESULTS: Although the groups were similar in baseline values, 4-hr survival in the MB group was increased (p = .02) in comparison with the isotonic saline group. Hemodynamic variables were somewhat improved at 15 mins after restoration of spontaneous circulation in the MB group compared with the other two groups. The jugular bulb levels of 8-isoprostane-prostaglandin F2alpha and 15-keto-dihydro-prostaglandin F2alpha (indicators of peroxidation and inflammation) were significantly decreased in the MB group compared with the isotonic saline group. Significant differences were recorded between the three groups in levels of protein S-100beta (indicator of neurologic injury), with lower levels in the MB group compared with the isotonic saline and hypertonic saline-dextran-only groups. Troponin I and myocardial muscle creatine kinase isoenzyme arterial concentrations (indicators of myocardial damage) were also significantly lower in the MB group. CONCLUSIONS: MB co-administered with a hypertonic-hyperoncotic solution increased 4-hr survival vs. saline in an experimental porcine model of cardiac arrest and reduced oxidative, inflammatory, myocardial, and neurologic injury.

Animals↗
PubMed2006

A potent serotonin-modulating compound AP-267 attenuates morphine withdrawal-induced blood-brain barrier dysfunction in rats.

The possibility that a serotonin 5-HT2c receptor-modulating compound, AP-267, will influence spontaneous morphine withdrawal symptoms and the alterations in the brain fluid microenvironment was examined in a rat model. Daily administration of morphine (10 mg/kg, i.p.) for 10 days resulted in dependence of rats as seen by loss of analgesic response. On the 11th day, no morphine administration was given. This resulted in profound withdrawal symptoms 24 h after morphine withdrawal. The magnitude and severity of these symptoms were increased further 48 h after withdrawal. Measurement of the blood-brain barrier (BBB) permeability, a measure of perturbed brain fluid microenvironment showed leakage of Evans blue and radioiodine tracers in several parts of the brain in rats showing withdrawal symptoms. Whereas, rats treated with AP-267 either on the 1st day or 2nd day morphine withdrawal showed much less symptoms and leakage of the BBB. Taken together, these observations suggest that (a) stress associated with the withdrawal symptoms are sufficient enough to induce breakdown of the BBB function, and (b) modulation of serotonin 5-HT2c receptors may have some protective influence on the stress symptoms and the BBB disruption.

Animals↗
PubMed2005

Beta-cyclodextrin reduces bioavailability of orally administered [3H]benzo[a]pyrene in the rat.

The excretion and plasma kinetics of total radioactivity were studied following single oral administration of [(3)H]benzo[a]pyrene after multiple oral administration of beta-cyclodextrin at 0, 5, 50, or 500 mg/kg/day. The AUC and C(max) values in male and female rats following administration of [(3)H]benzo[a]pyrene in combination with 5 to 500 mg/kg beta-cyclodextrin were considerably lower than that in rats administered [(3)H]benzo[a]pyrene alone. At all dose levels of beta-cyclodextrin, the excretion of total radioactivity was almost entirely via feces, with <2% recovered in urine, demonstrating either that absorption of the orally administered dose was low or that, for any absorbed material, biliary excretion was the main route of excretion. However, following administration of vehicle, up to 5% of the administered radioactivity was recovered in the urine, suggesting that absorption may have been reduced by the presence of beta-cyclodextrin in the intestine. At all dose levels of beta-cyclodextrin, there was minimal retention of radioactivity in the carcase at the end of the collection period. Beta-cyclodextrin did not affect the apparent terminal half-life of radioactivity. Therefore, the reduced systemic exposure of rats to radioactivity in the presence of beta-cyclodextrin is likely related to a reduced oral bioavailability.

Animals↗
PubMed2005

Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury-induced pathophysiology and motor functions: an experimental study in the rat.

The role of nitric oxide (NO) in spinal cord injury (SCI)-induced motor dysfunction, breakdown of the blood-spinal cord barrier (BSCB), edema formation, and cell injury was examined using a pharmacological approach. We used three types of nitric oxide synthase (NOS) inhibitors: a nonselective blocker, L-NAME; an irreversible inhibitor of all isoforms of NOS, L-NMMA; and a long-term competitive inhibitor of neuronal NOS with equal potency to inhibit endothelial NOS, L-NNA. The compounds were administered once daily in separate groups of rats for 7 days. On the 8th day, SCI was performed by making a longitudinal incision into the right dorsal horn of the T10-11 segments, and the rats were allowed to survive 5 h after injury. Long-term treatment with L-NNA attenuated SCI-induced NOS upregulation, BSCB breakdown, edema formation, and cell injury, whereas comparatively less neuroprotection is offered by L-NMMA. The magnitude of neuroprotection is much less evident in injured animals that received L-NAME. Interestingly, SCI-induced motor dysfunction measured according to the Tarlov scale showed close correlation with the magnitude of neuroprotection. Thus, an improvement in motor function was seen in animals pretreated with L-NNA, whereas rats treated with L-NAME or L-NMMA did not show any influence on motor dysfunction after SCI. This observation suggests that inhibition of neuronal NOS is important for neuroprotection, and the disturbances in motor function following SCI are associated with the state of spinal cord pathology.

Animals↗
PubMed2005

Circulatory arrest as a model for studies of global ischemic injury and neuroprotection.

Despite many programs aimed at better immediate care of cardiac arrest victims, the subsequent mortality rate is high, with myocardial and central nervous system (CNS) injuries as the most common causes of death. Preclinical research is badly needed to produce a sound base for future clinical trials and possible improvements in clinical outcome. In our laboratory, we use piglets weighing approximately 25 kg. Ventricular fibrillation is produced by an AC current and left without treatment for 8-12 min, after which cardiopulmonary resuscitation according to current human guidelines is undertaken. The heart is then defibrillated and restoration of spontaneous circulation induced. During the procedure, blood pressure and flow measurements are obtained in the systemic, pulmonary, and cerebral circulation. Peroxidation and inflammation are monitored by systemic and cerebral venous plasma concentrations of isoprostane (8-iso-PGF(2alpha)), an indicator of oxidative damage, and prostaglandin F(2alpha) metabolite (15-keto-dihydro-PGF(2alpha)), an indicator of cyclooxygenase-2 activity, respectively. Neurocellular damage is monitored by the jugular plasma concentration of protein S-100beta. Neurological outcome is assessed at >24 h after the incident. Our results show that plasma concentrations of 8-iso-PGF(2alpha) are greater after more extended periods of ischemia. PBN (alpha-phenyl-N-tert-butyl nitrone), a so-called spin-trap scavenger, has a neuroprotective effect since neurological outcome is enhanced, and the 8-iso-PGF(2alpha) concentration is decreased during reperfusion. Use of water-soluble sulfonated PBN (S-PBN) results in better autoregulation of cerebral cortical blood flow and less peroxidation of CNS lipids during reperfusion. These observations suggest that our model can be used to explore neuroprotective effects of potential therapeutic agents.

Animals↗
PubMed2004

Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study.

OBJECTIVE: Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN: Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS: C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION: OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.

Acetylcholine↗
PubMed2003

Risk factor analysis of Swedish Left Ventricular Assist Device (LVAD) patients.

BACKGROUND: The use of left ventricular assist devices (LVADs) is established as a bridge to heart transplantation. METHODS: All Swedish patients on the waiting list for heart transplantation, treated with LVAD since 1993 were retrospectively collected into a database and analyzed in regards to risk factors for mortality and morbidity. RESULTS: Fifty-nine patients (46 men) with a median age of 49 years (range, 14 to 69 years), Higgins score median of 9 (range, 3 to 15), EuroScore median of 10 (range, 5 to 17) were investigated. Dominating diagnoses were dilated cardiomyopathy in 61% (n = 36) and ischemic cardiomyopathy in 18.6% (n = 11). The patients were supported with LVAD for a median time of 99.5 days (range, 1 to 873 days). Forty-five (76%) patients received transplants, and 3 (5.1%) patients were weaned from the device. Eleven patients (18.6%) died during LVAD treatment. Risk factor analysis for mortality before heart transplantation showed significance for a high total amount of autologous blood transfusions (p < 0.001), days on mechanical ventilation postoperatively (p < 0.001), prolonged postoperative intensive care unit stay (p = 0.007), and high central venous pressure 24 hours postoperatively and at the final measurement (p = 0.03 and 0.01, respectively). Mortality with LVAD treatment was 18.6% (n = 11). High C-reactive protein (p = 0.001), low mean arterial pressure (p = 0.03), and high cardiac index (p = 0.03) preoperatively were risk factors for development of right ventricular failure during LVAD treatment. CONCLUSIONS: The Swedish experience with LVAD as a bridge to heart transplantation was retrospectively collected into a database. This included data from transplant and nontransplant centers. Figures of mortality and morbidity in the database were comparable to international experience. Specific risk factors were difficult to define retrospectively as a result of different protocols for follow-up among participating centers.

Adolescent↗
PubMed2003

Cerebral blood flow and metabolism after cardiopulmonary resuscitation. A pathophysiologic and prognostic positron emission tomography pilot study.

BACKGROUND: Prolonged coma is not an uncommon clinical problem following resuscitation from cardiac arrest. Early and precise prediction of outcome is highly desirable for ethical and economical reasons. The aims of this study were to use positron emission tomography (PET) to investigate the regional dynamic changes of cerebral blood flow and metabolism during the early period after cardiopulmonary resuscitation (CPR) in unconscious patients and to evaluate if PET may be a potential prognostic evaluator. METHODS AND RESULTS: PET and Glasgow Coma Scale examinations were sequentially performed on days 1, 3 and 7 in seven patients remaining comatose post CPR. Each PET included regional determinations of cerebral blood flow (rCBF), oxygen metabolism (rCMRO(2)), oxygen extraction ratio (rOER), and cerebral blood volume (rCBV). One patient was excluded due to complex trauma problems. Three patients remained unconscious until death and three woke up. All patients initially exhibited low CMRO(2) and CBF. Increased OER was only found exceptionally and when present was predominantly in focal areas. The comatose patients showed progressive depression of CMRO(2) and after 1 week had lower CMRO(2) than those patients who woke up. This difference was most pronounced in the putamen and occipital cortex. Two of the seven patients developed large focal infarcts. CONCLUSIONS: An initially low CMRO(2) was common to all patients. Early development of subclinical focal ischemic lesions was also common. The progressive depression of CMRO(2) over the first week in those patients remaining unconscious may be an indication of prolonged but not necessarily permanent coma. Further studies are required to identify pathophysiological features that can predict the long-term clinical outcome in patients who remain unconscious after 1 week.

Aged↗
PubMed2003

Evidence for time-dependent maximum increase of free radical damage and eicosanoid formation in the brain as related to duration of cardiac arrest and cardio-pulmonary resuscitation.

Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

Animals↗
PubMed2002

Angiographic results after the use of a sutureless aortic connector for proximal vein graft anastomoses.

The sutureless aortic connector system was recently developed to create anastomoses between the aorta and saphenous vein grafts for coronary artery bypass grafting. Ten consecutive patients scheduled for coronary artery bypass grafting were studied; in each patient one proximal anastomosis was performed using the aortic connector and another was sutured in the conventional manner to serve as the patient's own control. One graft in the sutured group had a significant stenosis and one of the grafts in which the aortic connector was used, was occluded. In this limited study the use of the sutureless connector system for proximal anastomosis shows satisfactory early graft patency (90%).

Aged↗
PubMed2002

Buffer administration during CPR promotes cerebral reperfusion after return of spontaneous circulation and mitigates post-resuscitation cerebral acidosis.

To explore the effects of alkaline buffers on cerebral perfusion and cerebral acidosis during and after cardiopulmonary resuscitation (CPR), 45 anaesthetized piglets were studied. The animals were subjected to 5 min non-interventional circulatory arrest followed by 7 min closed chest CPR and received either 1 mmol/kg of sodium bicarbonate, 1 mmol/kg of tris buffer mixture, or the same volume of saline (n=15 in all groups), adrenaline (epinephrine) boluses and finally external defibrillatory shocks. Systemic haemodynamic variables, cerebral cortical blood flow, arterial, mixed venous, and internal jugular bulb blood acid-base status and blood gases as well as cerebral tissue pH and PCO(2) were monitored. Cerebral tissue acidosis was recorded much earlier than arterial acidaemia. After restoration of spontaneous circulation, during and after temporary arterial hypotension, pH in internal jugular bulb blood and in cerebral tissue as well as cerebral cortical blood flow was lower after saline than in animals receiving alkaline buffer. Buffer administration during CPR promoted cerebral cortical reperfusion and mitigated subsequent post-resuscitation cerebral acidosis during lower blood pressure and flow in the reperfusion phase. The arterial alkalosis often noticed during CPR after the administration of alkaline buffers was caused by low systemic blood flow, which also results in poor outcome.

Acidosis↗
PubMed2002

Glutamine concentration and tissue exchange with intravenously administered alpha-ketoglutaric acid and ammonium: a dose-response study in the pig.

OBJECTIVE: We investigated the effects of an intravenous load of alpha-ketoglutaric acid, ammonium (NH(4)(+)), and metabolic acidosis on plasma concentration and splanchnic and hindleg tissue exchange of glutamine, glutamate, alanine, and arginine in postabsorptive, anesthetized pigs. METHODS: Sixteen anesthetized piglets received a constant infusion of NH(4)Cl for 4 h and alpha-ketoglutaric acid in incremental dosages for 3 h (group 1, n = 8) or a constant infusion of alpha-ketoglutaric acid for 4 h and NH(4)Cl in incremental dosages for 3 h (group 2, n = 8). Plasma amino acids were analyzed and splanchnic blood flow was calculated according to the indocyanine green dye infusion technique. Femoral artery blood flow was measured with ultrasound flowmetry. Statistical evaluation of within-group differences was made with the Wilcoxon signed rank test. RESULTS: Plasma glutamine levels increased dose-dependently in group 2 (P < 0.05) but not in group 1. Glutamate concentration increased, mainly in group 2 (P < 0.05), whereas the plasma concentration of alanine decreased in both groups (P < 0.05). Plasma concentration of arginine increased in both groups (P < 0.05). Splanchnic uptake and skeletal muscle release of glutamine did not change in either group compared with baseline values. Splanchnic glutamate release decreased (P < 0.05) in group 1 at 240 min; muscular uptake was unaffected in both groups. Splanchnic uptake and muscular release of alanine were unaffected in both groups. The significance level was set at 0.05. CONCLUSION: Our findings indicate that the splanchnic bed or hindleg skeletal muscle was not the source of the increased plasma concentration of glutamine in this study.

Acidosis↗
PubMed2002

Predictors of allograft ischemic injury in clinical heart transplantation.

OBJECTIVES: 1. Identify clinical, biochemical and inflammatory predictors of allograft ischemic injury in clinical heart transplantation. 2. Evaluate the impact of high dose insulin (GIK) on allograft metabolism during blood cardioplegia and post-ischemic injury. DESIGN: A clinical, prospective, randomized open trial comprising 25 consecutive heart transplantations at a university hospital. Ischemic injury was evaluated from plasma levels of creatine kinase isoenzyme MB (CK-MB). Blood cardioplegic arterial and coronary sinus concentrations of C3a, IL-6, substrates, amino acids and blood gases were measured at the end of the implantation period, prior to reperfusion. Twelve patients received high dose insulin with glucose, potassium and amino acids. RESULTS: CK-MB increased from 1.9 +/- 0.2 to 161 +/- 13 microg/l (range 47-293 microg/l). The peak level of CK-MB correlated with donor age (r = 0.48, p = 0.02) and implantation time (r = 0.53, p = 0.02); and with recipient plasma IL-6 (r = 0.56, p = 0.02), allograft oxygen extraction (r = 0.56, p = 0.02), lactate release (r = 0.47, p = 0.02) and allograft arterial-coronary sinus (cs) pH (r = 0.47, p = 0.02) all during final cardioplegia before reperfusion. Seventy-two percent of the variance of CK-MB was explained by a model which included donor age, art-cs pH difference and arterial IL-6. In contrast, CK-MB was unrelated to total ischemic time (r = -0.17, p = 0.38). Insulin infusion had no effect on myocardial substrates during cardioplegia, or on post-ischemic CK-MB. CONCLUSION: Donor age, duration and quality of the implantation period are significant predictors of allograft ischemic injury in heart transplantation. High dose insulin had no detectable effects on allograft metabolism during cardioplegia, or on subsequent ischemic injury.

Adolescent↗