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Biomedical subjects

F Nilsson

Publications and source records attributed to F Nilsson.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased levels of circulating nitrates and impaired endothelium-mediated vasodilation suggest multiple roles of nitric oxide during acute rejection of pulmonary allografts.

Experiments were designed to determine whether changes in pulmonary artery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. Single lung transplantation was performed in three groups of dogs: group 1 was maintained on immunosuppression for 8 days after operation (immunosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative day 8 (rejecting, n = 6); in group 3, immunosuppression was discontinued after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/kg) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasma nitric oxide (NO(x)) was measured by use of chemoluminescence. On postoperative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine diphosphate were reduced in pulmonary arteries from rejecting lungs. Responses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenous nitric oxide. However, plasma levels of NO(x) increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The result extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NO(x). Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with allograft rejection.

Acute Disease↗
PubMed1997

Saliva cotinine levels as a function of collection method.

Saliva cotinine is commonly used to estimate nicotine intake but laboratories use different methods of collection. In three small trials, comparisons were made between (1) sugar vs. unstimulated saliva production (n = 29), (2) wax chewing vs. unstimulated production (n = 15) and (3) between two consecutive unstimulated saliva samples (n = 10). Sugar-stimulated saliva cotinine scores were 26% below unstimulated levels (p < 0.001); correlation between measures was high (r = 0.90; p < 0.001). Wax stimulated saliva yielded levels 6% below unstimulated (p < 0.05; correlation: r = 0.98; p < 0.001). No differences were observed between two unstimulated samples taken within a approximately 20-minute period (correlation: r = 0.99; p < 0.001). It is postulated that changes in salivary flow can account for the findings.

Biomarkers↗
PubMed1996

Sumatriptan-induced cerebral vasoconstriction as treatment of experimental intracranial hypertension.

BACKGROUND: Increased intracranial pressure (ICP) is a major cause of mortality in severe head injuries and pharmacologically induced cerebral vasoconstriction has been suggested as a possible treatment. In the present study a porcine model of increased ICP was utilized to study the changes in cerebral haemodynamics and energy metabolism induced by a selective 5-hydroxytryptamine1 agonist (sumatriptan). METHODS: ICP was raised by inflation of two balloons covering both parieto-occipital regions extradurally. The animals were randomized into four groups receiving sumatriptan. 0.01 mg.kg-1 (A), 0.03 mg.kg-1 (B), 0.1 mg.kg-1 (C), and 0.5 mg.kg-1 (D) intravenously over 10 min. Measurements of cerebral blood flow (CBF), arterio-venous oxygen content difference (CavO2), and jugular venous pH (vpH) were performed 5, 20, 40, 60, and 75 min after start of the infusion. ICP, mean arterial pressure, and EEG were recorded continuously. Direct effects of sumatriptan were also compared in cortical arteries and veins in vitro. RESULTS: Significant decreases in ICP were obtained in groups A, B, and C while group D exhibited a progressive increase in ICP. Significant reductions in CBF, increase in CavO2, and slowing of EEG were observed in groups B, C, and D. Sumatriptan caused moderate constriction of the arteries and a more pronounced dilatation of veins in vitro. CONCLUSION: The results indicate that a low dose of sumatriptan has the potential to reduce a raised ICP. High doses of sumatriptan cause a further increase of ICP possibly by dilatation of intracerebral veins.

Animals↗
PubMed1996

Activation of eosinophils and fibroblasts assessed by eosinophil cationic protein and hyaluronan in BAL. Association with acute rejection in lung transplant recipients.

Lung transplantation has become an accepted therapy for end-stage lung disease. Acute rejection of the transplanted hung still remains a major clinical problem since it decreases graft survival. Eosinophil cationic protein (ECP) from activated eosinophils, hyaluronan (HYA) from fibroblasts, and circulating intercellular adhesion molecule 1 (1CAM-1) have been associated with acute rejection in kidney and liver grafts. We investigated whether these, as well as other molecules, were increased in acute rejection of lung allografts. Serum and BAL fluid from 38 bronchoscopies performed in 9 single lung, 2 bilateral lung, and 4 heart-lung transplant patients were studied. Differential cell counts were made from the BAL fluid. Levels of ECP, myeloperoxidase (MPO), and HYA were used as indirect markers for activation of eosinophils, neutrophils, and fibroblasts, respectively. In addition, levels of circulating ICAM-1, cVCAM-1, and cE-selectin were analyzed. Twenty-two episodes with acute rejection were diagnosed. Of these, 7 were minimal, 13 were mild, and 2 were of moderate character. We found increased levels of ECP and HYA in BAL fluid during mild acute rejection of the allograft. Numbers of eosinophils were also increased. Activation of neutrophils or neutrophil numbers were not significantly increased. Levels of circulating ICAM-1, cVCAM-1, and cE-selectin did not differ between the groups. This retrospective study shows that measurements of ECP and HYA can give information about the inflammatory process present during acute rejection in patients who have undergone lung transplants. Analysis of cCAMS, however, appears to be of limited value as markers for acute rejection.

Acute Disease↗
PubMed1996

Impaired endothelium-mediated vasodilatation in the peripheral vasculature of patients with acute pulmonary allograft rejection.

BACKGROUND: Experimental studies have provided evidence that, during acute pulmonary allograft rejection, endothelial dysfunction occurs not only in the transplanted lung but also in arteries of organs native to the transplant recipient. We therefore tested the hypothesis that allograft rejection leads to the release of factors into the circulation that could affect the endothelial function in lung transplant recipients. METHODS: Acetylcholine (10, 30, and 60 micrograms/min) and sodium nitroprusside (1, 3, and 6 micrograms/min) were infused into the brachial artery in nine transplant recipients (five single lung, one double lung, three heart-lung) 2 to 37 weeks after transplantation, during both acute rejection and rejection-free episodes. Changes in forearm blood flow were assessed with venous occlusion plethysmography. Plasma levels of interleukin-2, -6, and -8, endothelin-1, L-arginine, and asymmetric dimethylarginine were measured and correlated to rejection episodes. RESULTS: The vasodilatory response to acetylcholine was significantly reduced during acute rejection compared with rejection-free episodes (percentage increase from basal flow: 156% +/- 21%, 395% +/- 65%, and 585% +/- 87% during rejection versus 272% +/- 75%, 633% +/- 113%, and 933% +/- 158% during absence of rejection, p < 0.05). No statistically significant difference was found between vasodilatory responses to nitroprusside during acute rejection and rejection-free episodes. Plasma levels of L-arginine, asymmetric dimethylarginine, interleukin-6, and endothelin-1 were not significantly altered during lung rejection. CONCLUSIONS: These data indicate that a reversible peripheral decrease in endothelium-dependent vasodilatation occurs during acute rejection in lung transplant recipients. This result may be due to interactions among circulating cytokines and leukocytes activated by the rejection process and the endothelium.

Acetylcholine↗
PubMed1996

Efficacy of a nicotine inhaler in smoking cessation: a double-blind, placebo-controlled trial.

A non-combustible nicotine inhaler, administered orally, has been developed for treatment of smokers. The inhaler allows weaning from nicotine while maintaining partial reinforcement of the ritual/sensory phenomena of smoking. Subjects were randomly assigned to active (n = 112) and placebo (n = 111) groups. Some behavioral intervention occurred as a function of participation. Strict abstinence (primary outcome criterion) was defined by CO < or = 8 ppm with no slips allowed at any time and cotinine values < or = 14 at 1 year. Survival analysis showed active inhaler was superior to placebo (p < 0.01). Active vs. placebo success rates were: 63% vs. 47% (day 3), 46% vs. 28% (week 1), 36% vs. 19% (week 2), 33% vs. 16% (week 3), 29% vs. 14% (week 6), 24% vs. 10% (3 months), 17% vs. 9% (6 months) and 13% vs. 8% (1 year). chi 2 analyses were significant through 3 months but not at 6 months (p < 0.08) or 1 year. Craving was relieved with active inhalers at day 3 and week 1. Subjects averaged six inhalers/day. Cotinine levels were 57-61% of smoking levels. Common side effects included throat/mouth irritation and coughing. Failure was predicted by early slips. The inhaler is clearly useful for short-term smoking cessation with potential for long-term efficacy. Extended access to the inhaler and relapse prevention training could improve success rates. Another promising approach would be to combine the inhaler with a nicotine patch.

Adult↗
PubMed1995

Protective effects of an indenoindole antioxidant on coronary endothelial function after long-term storage.

Experiments were designed to evaluate function of the endothelium and smooth muscle of coronary arteries following storage of hearts in cardioplegia containing an inhibitor of lipid peroxidation (H 290/51, cis-7-methyl-9-methoxy-5,5a, 6,10b tetrahydroindeno [2,1-b] indole). Canine hearts were perfused with crystalloid cardioplegia (Plegisol, 15 ml/kg, 4 degrees C) and left circumflex arteries were isolated and studied either immediately (group I, n = 6), or after storage of the hearts at 4 degrees C for 10 (group II, n = 6) or 24 hr with (group III, n = 6) or without (group IV, n = 6) addition of H 290/51. The final concentration of H 290/51 was 1 mumol/L. Arteries were removed, cut into rings, and suspended in organ chambers for measurements of isometric force. In selected rings, the endothelium was removed in order to study the function of the smooth muscle. In order to discriminate effects of ischemia/reperfusion and protective properties on coronary endothelium or smooth muscle, drugs with different mechanisms were used. The function of the endothelium were studied with the alpha 2-adrenergic agonist UK 14,304, bradykinin and A 23187. The smooth muscle function were studied with isoproterenol and nitric oxide. Endothelium-dependent relaxations to the alpha 2-adrenergic agonist UK 14,304 and bradykinin, but not to A 23187, were reduced significantly in arteries from hearts stored for 24 hr in cardioplegic solution alone. Relaxations of arteries from hearts stored for 24 hr with H 290/51 were comparable to those arteries from hearts that were not stored. Endothelium-independent relaxations to isoproterenol and nitric oxide among the different groups were comparable. These results suggest that storage of canine hearts with crystalloid cardioplegia selectively inhibits endothelium-dependent relaxations mediated by receptor activation. Inhibition of lipid peroxidation with H 290/51 preserves these relaxations and may therefore represent a therapeutic alternative to preserve hearts used for transplantation.

Adrenergic alpha-Agonists↗
PubMed1995

Alpha-ketoglutarate for myocardial protection in heart surgery.

A low myocardial content of alpha-ketoglutarate during heart surgery might aggravate ischaemic injury. 24 men undergoing coronary surgery participated in a randomised controlled study. 28 g alpha-ketoglutarate was added to blood cardioplegia for intermittent antegrade intracoronary perfusion in 13 cases. alpha-ketoglutarate reduced the appearance in blood of the ischaemic markers creatine kinase MB and troponin T (at 4 h after release of aortic cross-clamp; median [95% CI] 49 [37-60] micrograms/L in controls vs 32 [27-37] micrograms/L for creatine kinase MB, 2.0 [1.2-2.8] vs 1.1 [0.8-1.4] micrograms/L for troponin T). These findings signify attenuated ischaemic injury, possibly secondary to enhanced myocardial oxidative capacity.

Aged↗
PubMed1995

Cerebral vasoconstriction by indomethacin in intracranial hypertension. An experimental investigation in pigs.

BACKGROUND: Uncontrolled increase in intracranial pressure is the most significant cause of mortality in patients with severe traumatic brain lesions, and the efficacy of common non-surgical treatments has been questioned. Pharmacologically induced cerebral vasoconstriction aiming at a decrease of cerebral blood volume and brain edema has recently been suggested as an alternative. Limited clinical experience with indomethacin as a cerebral vasoconstrictor has been reported but dose- or concentration-effect relationships were not investigated. In particular, there is a lack of data showing whether a therapeutic window exists in which risk of cerebral ischemia is minimized. METHODS: In a porcine model of intracranial hypertension induced with two epidural balloons to a level of 26-28 mmHg, 18 animals were randomized into three groups receiving 0.1, 0.3, and 3.0 mg.kg-1.h-1 indomethacin, respectively, as an infusion during 80 min. Intracranial pressure, mean arterial blood pressure, and electrocortical activity were recorded continuously and measurements of cerebral blood flow, arteriovenous difference in oxygen content and cerebral venous pH were performed at 5, 20, 40, 60, and 75 min during and 10 min after the indomethacin infusion. Baseline measurements, performed before the indomethacin infusion, were used as an internal control. The infusions were pharmacokinetically designed to mimic the reported clinical conditions. RESULTS: An 11% mean decrease in intracranial pressure during the infusion, but no effects on cerebral blood flow, arteriovenous difference in oxygen content, venous pH, and electrocortical activity were observed in the group of animals receiving 0.1 mg.kg-1.h-1. When the rate of infusion was 0.3 and 3.0 mg.kg-1.h-1, the decrease in intracranial pressure was 20 and 25%, respectively, but this was accompanied by a decrease in cerebral blood flow and venous pH, an increase in arteriovenous difference in oxygen content, and a slowing of the electrocortical activity. All changes were statistically significant. CONCLUSIONS: Indomethacin, which is known to constrict precapillary resistance vessels, caused a decrease in intracranial pressure during experimental intracranial hypertension. This was accompanied by signs of cerebral ischemia when indomethacin was used in a dose that has previously been suggested for the treatment of increased intracranial pressure in patients.

Animals↗
PubMed1995

A porcine model for evaluation of cerebral haemodynamics and metabolism during increased intracranial pressure.

In patients with severe head injuries raised intracranial pressure (ICP) constitutes the most important cause of mortality. Several new therapies for increased ICP have recently been suggested and it is of importance to study the physiological effects of these treatments in animal experiments during steady state conditions. A porcine model for evaluation of cerebral haemodynamics and metabolism during increased ICP is presented. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering a major part of the parietooccipital region bilaterally. The distribution of the blood flow supplied by the carotid artery used for the cerebral blood flow (CBF) measurements was studied by intraarterial (i.a.) injection of 99mTc-HMPAO. The measurements showed that following ligation of the external carotid and the occipital artery no accumulation of tracer substance occurred in extracranial tissues during normal or increased ICP. Cerebral physiological variables (CBF, Cavo2, and ICP) were measured 5, 20 and 60 min after induction of intracranial hypertension. The results confirm that the experimental situation gives a reproducible increase in ICP (25-28 mm Hg) and that the physiological variables remain stable during the period of intracranial hypertension. We conclude that the model simulates the effects of an acute intracranial focal mass and is well suited for the evaluation of different pharmacological therapies of increased ICP.

Animals↗
PubMed1995

Effects of dihydroergotamine on cerebral circulation during experimental intracranial hypertension.

Different cerebral vasoconstrictors have recently been suggested for the treatment of raised intracranial pressure (ICP), in patients with severe traumatic brain lesions. Such treatment may be associated with severe side effects. A porcine model simulating an intracranial mass lesion was utilized to examine the haemodynamic cerebral effects of dihydroergotamine (DHE), a recently introduced pharmacological treatment for raised intracranial pressure. Intracranial hypertension was induced by inflation of two tonometric gastric balloons placed extradurally covering the parieto-occipital region bilaterally. The animals were randomized into one group with six animals receiving 1.0 mg of DHE i.v. followed by a continuous infusion of 0.2 mg/h (high dose) and another group of six animals receiving 0.15 mg i.v. followed by 0.03 mg/h (low dose). Measurements of cerebral blood flow (CBF) and arterio-venous difference in oxygen content (CaVO2) were performed by 5, 20 and 60 min after the DHE infusion. Intracranial pressure (ICP), mean arterial blood pressure (MAP) and cerebral electrical activity (EEG) were recorded continuously. In both groups infusion of DHE caused a lasting decrease in ICP probably achieved mainly by a decrease in cerebral blood volume due to constriction of both arterial and venous capacitance vessels. In the group treated with high-dose DHE, but not in that given low-dose DHE, a progressive increase in CaVO2, a fall in jugular venous pH and an increase in EEG delta activity were observed indicating cerebral hypoxia. The study supports the view that DHE may be a valuable tool in the pharmacological treatment of increased ICP in traumatic brain lesions but underscores the importance of a proper dosage.

Animals↗
PubMed1995

Improved long-term preservation of the coronary vasculature with University of Wisconsin solution.

Experiments were designed to investigate coronary vascular function after prolonged cold storage of isolated rat hearts, using University of Wisconsin (UW) solution. Hearts perfused with crystalloid cardioplegic solution (Plegisol) were used as controls. After perfusion with 10 ml at 4 degrees C, hearts were stored for 1 or 10 hours in the respective solutions at 4 degrees C. To evaluate coronary vascular function after perfusion and storage, endothelium-dependent vasodilation was induced with 5-hydroxytryptamine (5-HT) and smooth muscle-dependent dilation with nitroglycerin (GTN). After perfusion only, or perfusion plus 1-hour storage, there was no intergroup difference in response to 5-HT and GTN. After 10-hour storage the vasodilatory response to 5-HT was abolished in the Plegisol group and slight vaso-constriction was observed, whereas in the UW group the vasodilatory effect of 5-HT persisted. The findings suggest that UW solution may be more favorable for prolonged cardiac preservation, as the coronary vascular reactivity was less affected.

Adenosine↗
PubMed1994

Subfractional analysis of cyanobacterial membranes and isolation of plasma membranes by aqueous polymer two-phase partitioning.

The present work demonstrates that partition in aqueous polymer two-phase systems offers a rapid method for separation and isolation of thylakoid, plasma, and outer membranes from cyanobacteria. Pure plasma membranes from Phormidium laminosum can be isolated by this method within 3 h, starting with total membranes obtained by French press treatment of the cyanobacterial cells. The isolated plasma membranes have a broad density profile, giving rise to three subpopulations. The main fraction has the same density as the abundant thylakoid membranes. This fraction has not been resolved in previous separations based on sucrose gradient centrifugation, which is the only method previously used for isolation of cyanobacterial plasma membranes. Another advantage of the aqueous polymer two-phase system is that it can handle large quantities of starting material, which is essential to obtain a satisfactory yield since plasma membranes constitute only a very small fraction of the total membrane content in a cyanobacterial cell. The isolation procedure results in a pure plasma membrane preparation with retained cytochrome c oxidase activity. The results also point to the possibility of a lateral heterogeneity in the organization of the cyanobacterial plasma membrane.

Cell Membrane↗
PubMed1994

Glucose-insulin-potassium (GIK) prevents derangement of myocardial metabolism in brain-dead pigs.

Brain death is associated with neuroendocrine changes resulting in reduced myocardial glycogen content. The purpose of this study was to investigate the effects of glucose-insulin-potassium (GIK), on myocardial metabolism in brain-dead pigs. Sixteen brain-dead pigs were given GIK infusion (n = 8), or Ringer solution (n = 8). At end-point (7 h post brain death) arterial concentrations and myocardial arteriovenous (a-v) concentration differences of glucose, lactate and free fatty acids (FFA) were assessed, and myocardial biopsy specimens were taken from the right atrium and left ventricle. Biopsies were also taken from five normal pigs. Myocardial glycogen content in the GIK group was significantly higher compared to the control group, but comparable to the non-brain-dead animals. There was a higher and significant myocardial uptake of glucose and lactate in the GIK group compared to the controls. Plasma levels of FFA were significantly lower in the GIK group, and the myocardial uptake of FFA was 5 times higher in the control group compared to the GIK group. There were no significant differences in hemodynamic variables among the groups. In conclusion, intravenous supply of GIK to brain-dead pigs results in increased myocardial glycogen content and seems to prevent abnormal myocardial metabolism, which may have clinical implications for the myocardial protection of donor hearts.

Animals↗
PubMed1994

A novel anti-oxidative agent improves recovery of the heart after cardiac arrest.

Experiments were designed to determine whether adding a synthetic anti-oxidative agent H 290/51 (cis-7methyl-9-methoxy-5,5 a,6,10 b-tetrahydroindeno [2,1-b] indole), to a crystalloid cardioplegic solution was beneficial for myocardial recovery and coronary reactivity in isolated rat hearts after six hours cold arrest. Two groups of hearts were single-flush perfused using the Langendorff technique (10 ml at 4 degrees C) with either Plegisol (St. Thomas' Hospital Solution) (n = 6) or Plegisol with H 290/51 (n = 6) added to a final concentration of 1 mummol/L. The heart were then stored for six hours in the respective solution at 4 degrees C. A third group of hearts (n = 6) were single-flush with Plegisol and reperfusion was immediately started (the 'non-stored' group). Before and after the arrest phase the hearts were perfused at constant pressure with Krebs-Henseleit bicarbonate buffer. To evaluate coronary vascular function, endothelium-dependent vasodilatation was induced with 5-hydroxy-tryptamine (5-HT) and smooth-muscle relaxation with nitroglycerin (GTN). Myocardial contractility after 30 min reperfusion, measured as left-ventricular developed pressure (LVDP), was significantly improved in hearts in the Plegisol+H 290/51 group compared to hearts in the Plegisol group (LVDP 89 +/- 8.5% vs 57.2 +/- 10.7% of prearrest values; p < 0.05). LVDP in hearts receiving Plegisol+H 290/51 was comparable to non-stored hearts (88.2 +/- 1.3%). The vasodilatory response to GTN was significantly reduced in hearts perfused with plain Plegisol (p < 0.05) but not in hearts receiving Plegisol+H 290/51 or in the non-stored hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

The effect of thiopental on cerebral blood flow, and its relation to plasma concentration, during simulated induction of anaesthesia in a porcine model.

The reversible effect of an induction dose of thiopental on the cerebral blood flow (CBF) was characterized by repeated 133Xe washout measurements during stable physiological conditions in anaesthetized pigs. A thiopental effect corresponding to induction of light and transient anaesthesia was confirmed by electroencephalography (EEG). The concentration (arterial plasma) -effect (-% CBF) relationship of thiopental was estimated using a sigmoidal Emax model. The injection caused a rapid 36 +/- 4.5% (mean +/- s.d.) drop in CBF, with return to baseline by 80 min. According to the pharmacodynamic model, the maximal effect of thiopental (Emax) in this experimental set-up was a 58% lowering of the CBF and the concentration at half-maximal effect (EC50) was 25 micrograms.ml-1. This study provides a complete characterization of the effect of thiopental on the CBF, including the time-course and concentration-effect relationship. A comparison to limited data in the literature suggests that the findings in the pigs constitute a fair approximation of the action of thiopental during the clinical induction of anaesthesia.

Anesthesia, Intravenous↗