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A Sollevi

Publications and source records attributed to A Sollevi.

At least 19 recordsLinked to original sources
PubMed1999

Intrathecal adenosine does not relieve allodynia-like behavior in spinally injured rats.

The intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) reduced pain-related behaviors after peripheral nerve or spinal cord injury in rats. The endogenous ligand adenosine is clinically available and has been tested i.t. as an analgesic. Thus, we set out to investigate whether i.t. adenosine could reduce allodynia in a model of central pain in spinally injured rats. I.t. adenosine did not reduce mechanical and cold allodynia-like behaviors at doses of 10, 100 and 187 nmol, whereas i.t. R-PIA at 10 nmol markedly alleviated allodynia in the same animals. The lack of effect by exogenous adenosine may be due to pharmacokinetic or pharmacodynamic reasons. Alternatively, adenosine may have reduced affinity and selectivity towards the A1-receptors which may be important for the antiallodynic effect.

Adenosine↗
PubMed1999

Effects of adenosine infusion on gastric emptying in healthy volunteers.

BACKGROUND: A low dose of systemic adenosine infusion has been shown to induce antinociception in clinical experimental studies as well as in patients. There is no clinical information about the effect of adenosine on the motility of the gastrointestinal tract. The aim of this study was therefore to evaluate the effect of exogenous adenosine administration on gastric emptying in man. METHOD: Ten healthy male volunteers (22-45 yrs) were included in a placebo-controlled, double-blind, randomised, cross-over study, where the experiments were separated by at least one week. During one session the volunteers received a continuous intravenous infusion of adenosine (50 micrograms.kg-1.min-1) initiated 15 min prior to the test of gastric emptying (a standard test meal, followed by oral acetaminophen, 2 g) and lasting throughout the experiment (2 h). During the other experimental session an infusion of saline was given. Acetaminophen absorption test was used as an indirect measure of the rate of gastric emptying. Venous acetaminophen concentration curves were produced and the maximum acetaminophen concentration (Cmax), the time to reach the maximum concentration (Tmax), and the area under the serum acetaminophen concentration time curve from 0 to 60 min (AUC60) were calculated. RESULTS: There was no difference between placebo and adenosine in Cmax (197 vs. 199 mumol.L-1, P = 0.80), Tmax (23 vs. 45 min, P = 0.14), AUC60 (9633 vs. 9111 min.mumol.L-1, P = 0.28). CONCLUSION: The results demonstrate that adenosine in a clinically antinociceptive dose of 50 micrograms.kg-1.min-1 does not affect the rate of gastric emptying in healthy volunteers.

Absorption↗
PubMed1999

Pneumoperitoneum in healthy humans does not affect central blood volume or cardiac output.

BACKGROUND: This study addresses the question of whether the elevation of the mean arterial pressure and central venous pressure in response to pneumoperitoneum for laparoscopic surgery is caused by increases in central blood volume and/or cardiac output. METHODS: Eleven patients in good cardiopulmonary health and scheduled for laparoscopic cholecystectomy, with a mean age of 42 years, were included. After induction of anaesthesia with fentanyl and propofol, radial arterial and central venous lines were introduced. The central blood volume and cardiac output were determined by the indicator-dilution technique, using inline densitometric measurements of indocyanine green (ICG). The measurements were made before and after the establishment of pneumoperitoneum by insufflation of carbon dioxide to an intra-abdominal pressure level of 11-13 mmHg. RESULTS: The mean arterial pressure (62+/-6 mmHg) increased after induction of pneumoperitoneum by 40+/-26% (P<0.05) and the central venous pressure increased from 6+/-4 mmHg to 8+/-6 mmHg (P<0.05). The cardiac output (4.3+/-0.9 L/min) and central blood volume (1.5+/-0.5 L) were not affected by the induction of pneumoperitoneum. CONCLUSIONS: In healthy anaesthetized subjects, the elevation of mean arterial pressure and central venous pressure in response to pneumoperitoneum was not caused by enhancement in cardiac output or central blood volume.

Adult↗
PubMed1999

Spinal cord morphology after chronic intrathecal administration of adenosine in the rat.

BACKGROUND: The endogenous compound adenosine is known to have various modulatory effects both in the peripheral and central nervous system. Adenosine and its analogues induce antinociception in animal models when administrated systemically and intrathecally (IT), both in acute and chronic models of pain. Before a new drug is introduced for spinal pain treatment in humans, experimental studies of neurotoxicity must be undertaken. METHODS: This study was performed in rats in order to reveal morphological or morphometric signs of spinal cord damage after chronic (two weeks) administration of adenosine. After insertion of IT catheters, the animals were injected twice a day during two weeks with adenosine (100 microg) or saline (controls). Potential spinal neurotoxicity was evaluated morphologically by light and electron microscopy supplemented by a morphometric analysis. RESULTS: There were no signs of histologic changes indicating neurotoxic effects by any of the methods of analysis. The morphological findings in the adenosine treated rats did not differ in any case from those of the saline treated animals. CONCLUSION: The results suggest that chronic IT administration of a high dose of adenosine is not associated with neurotoxicity in the rat spinal cord.

Adenosine↗
PubMed1999

Differentiated effects on splanchnic homeostasis by selective and non-selective endothelin receptor antagonism in porcine endotoxaemia.

1. The non-selective endothelin (ET) receptor antagonist bosentan has been shown to restore systemic and gut oxygen delivery and reverse intestinal mucosal acidosis in porcine endotoxin shock. 2. To further elucidate the specific role of the ETA as opposed to the ETB receptor and their effects in the splanchnic region a non-selective (ET(MIX)ra) A-182086 and selective ETA (ET(A)ra) PD155080 and ETB (ET(B)ra) A-192621 receptor antagonists were administered, separately or simultaneously (ET(A+B)ra) 2 h after onset of endotoxin shock. These four groups were compared to a control group receiving only endotoxin and vehicle. 3. Thirty-nine pigs were anaesthetized and catheterized for measurement of central and regional haemodynamics. A tonometer in the distal ileum was used for measurement of mucosal PCO2. Blood gases and plasma ET-1-LI levels as well as histological samples from the gut were assessed. Intervention was started 2 h after onset of endotoxemia and the experiments were terminated after 5 h. 4. Endotoxin-induced changes in systemic, gut oxygen delivery and portal hepatic vascular resistance and systemic acidosis were effectively counteracted by both ET(A+B)ra an ET(MIX)ra. ET(A)ra administration was not effective while ET(B)ra proved to be fatal as all animals in this group died prior to full time of the experiment. While both ET(A+B)ra and ET(MIX)ra improved gut oxygen delivery only the latter attenuated the profound endotoxin-induced ileal mucosal acidosis. 5. The lethal effect seen from selective ETB receptor antagonism in the current study may be due to increased ETA receptor activity as plasma levels of ET-1 is increased several fold by blocking the ETB receptor and thereby the plasma-ET-1-clearing function. Furthermore, a loss of endothelial ETB receptor vasodilating properties may also have contributed to the lethal course in the ET(B)ra group. 6. The findings in this study suggest that ET is involved in the profound endotoxin-induced disturbances in splanchnic homeostasis in porcine endotoxaemia. Furthermore, antagonism of both ETA and ETB receptors is necessary to effectively counteract these changes.

Animals↗
PubMed1999

Adenosine reduces secondary hyperalgesia in two human models of cutaneous inflammatory pain.

UNLABELLED: Secondary hyperalgesia is characterized by increased sensitivity to noxious mechanical stimuli in the area surrounding injured skin. The pathophysiological mechanisms involve increased excitability of second-order neurons located in the spinal cord, i.e., central sensitization. The mechanisms behind this phenomenon may be of importance in clinical pain, including neuropathic pain. To study the effects of systemic infusion of the endogenous compound adenosine (ADO) on sensory function, a superficial cutaneous burn injury was induced by the 4-min topical application of mustard oil or by heat (47 degrees C for 7 min) during i.v. ADO infusion (60 microg x kg(-1) x min(-1)). Healthy human subjects (n = 10 for each model) were tested, using a blinded, placebo-controlled procedure. The area of secondary hyperalgesia, as well as tactile and thermal sensory function, was tested using psychophysical methods during and after treatments. ADO significantly reduced the area of secondary hyperalgesia in both models. The maximal reduction compared with placebo was 58% +/- 20% (heat burn) and 39% +/- 13% (mustard oil burn). No other differences in sensory function were observed. The results are interpreted as an ADO-induced modulatory effect on the mechanisms of central sensitization. IMPLICATIONS: We tested the effects of adenosine on the development of increased sensitivity in the skin surrounding a superficial skin injury in humans. A superficial skin bum was induced with a chemical irritant or heat. The results show that adenosine reduces the skin area with increased sensitivity surrounding the injury.

Adenosine↗
PubMed1999

The safety and efficacy of intrathecal adenosine in patients with chronic neuropathic pain.

UNLABELLED: Adenosine and adenosine analogs decrease pain-like behavior in animal models of both acute nociceptive and neuropathic pain via adenosine receptor activation at spinal and/or supraspinal levels. This open study is the first in a series of intrathecal (IT) adenosine administration studied for the evaluation of efficacy and side effects in 14 patients. All had chronic neuropathic pain with tactile hyperalgesia and/or allodynia primarily of traumatic origin. The effects of IT adenosine (500 microg [n = 9] or 1000 microg [n = 5]) were evaluated. Approximate areas of tactile pain were mapped. Spontaneous and evoked pain (visual analog scale score 0-100) and tactile pain thresholds were assessed before and 60 min after injection. The injection caused transient pain (<60 min) in the lumbar region in five patients. There were no other side effects. Spontaneous and evoked pain was reduced (median score from 65 to 24 [P<0.01] and from 71 to 12 [P<0.01], respectively) in parallel with increased tactile pain thresholds in allodynic areas. Areas of tactile hyperalgesia/allodynia were reduced (median reduction 90%; P<0.001). Twelve patients experienced pain relief (median 24 h). We conclude that IT adenosine transiently causes lumbar pain in a subgroup of patients and may reduce various aspects of chronic neuropathic pain. IMPLICATIONS: This is the first series of patients with chronic neuropathic pain in which tolerability to spinal adenosine administration has been evaluated. A subset of patients reported transient low back pain as the only side effect. Spontaneous and evoked pain intensity decreased in most patients, an effect lasting for a median of 24 h.

Adenosine↗
PubMed1999

Ventilatory responses to acute and sustained hypoxia during sevoflurane anesthesia in women.

UNLABELLED: We investigated the isocapnic hypoxic (i.e., pulse oximetry monitored arterial saturations 70%-75%) ventilatory response (HVR) for 20 min in the awake state and during sevoflurane anesthesia at an end-tidal concentration of 1.6% in eight healthy (ASA physical status I) women. Our aims were to determine if a prolonged isocapnic hypoxic period during sevoflurane anesthesia showed a biphasic response pattern (i.e., an initial acute HVR followed by a decline to a lowered sustained HVR) and, if so, to quantify to what extent the acute and sustained HVRs were depressed by anesthesia. The study was conducted before laparoscopic gynecological surgery. Pneumotachography and in-line infrared capnography were used. The pattern of awake biphasic HVR was maintained during anesthesia but was depressed during both the acute and the sustained phases by 60% and 70%, respectively. Further, HVR during anesthesia was accomplished by an increase in respiratory rate, in contrast to an increase in tidal volume in the awake state. In conclusion, sevoflurane anesthesia at 1.6% depresses HVR in women, but the biphasic response is maintained. IMPLICATIONS: Acute and sustained hypoxic ventilatory responses were investigated in eight women before and during sevoflurane anesthesia. A biphasic ventilatory response was persistent but blunted during anesthesia.

Adult↗
PubMed1999

Tissue hypoxanthine reflects gut vulnerability in porcine endotoxin shock.

OBJECTIVE: To study differences in organ sensitivity during progressive endotoxin shock tissue levels of hypoxanthine, used as an indicator of adenosine triphosphate depletion and cellular energy failure, were monitored simultaneously in several organs by in vivo microdialysis. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Seventeen landrace pigs. MEASUREMENTS AND MAIN RESULTS: Tissue levels of hypoxanthine, assessed by in vivo microdialysis, were monitored (in the ileum, liver, lung, skeletal muscle, subcutaneous fat, and arterial blood) simultaneously in addition to central hemodynamics during endotoxin shock in ten pigs. Seven sham animals not receiving endotoxin served as controls. Marked changes were seen in central hemodynamic parameters in response to endotoxemia. Very prominent increases were seen in the ileum and liver, followed by the lung, whereas only limited changes were observed in subcutaneous fat. These results indicate a differentiated development of cellular energy failure in response to endotoxemia in different organs. By considering the high amounts of xanthine oxidase seen in the gut, the increases in hypoxanthine may provide an important substrate for reactive oxygen species formation in this organ. The limited changes seen in subcutaneous fat suggest that this tissue may provide limited sensitivity when monitoring the septic patient. CONCLUSIONS: These findings support the concept of specific vulnerability of the gut during endotoxemia.

Adipose Tissue↗
PubMed1999

Endothelin(A)-receptor antagonism attenuates pulmonary hypertension in porcine endotoxin shock.

Porcine endotoxin shock is characterized by pulmonary hypertension, decreased mean arterial pressure and deteriorated cardiac performance. These pathophysiological findings are accompanied by increased plasma endothelin-1 levels. Previous studies have shown that both the pulmonary and systemic circulation are improved by combined endothelinA- and endothelinB-receptor antagonism. This study was designed to evaluate further the specific involvement of the endothelinA-receptor in cardiopulmonary pathophysiology during endotoxin shock. In a porcine endotoxin shock model, the endothelinA-receptor antagonist PD 155080 was administered after the onset of endotoxaemia. Cardiopulmonary vascular changes, dynamic lung compliance, oxygen-related variables and plasma levels of endothelin-1-like immunoreactivity were compared with a control group receiving only endotoxin. PD 155080 counteracted the increase in pulmonary artery pressure seen in control animals. In contrast, cardiac performance was not improved. Dynamic lung compliance was not affected by PD 155080. Plasma levels of endothelin-1-like immunoreactivity increased to a similar degree in both groups. These findings indicate that the endothelin system is involved in the pathophysiology of endotoxin shock. Furthermore, the change in pulmonary circulation seen in the present shock model is to a large extent mediated by the endothelinA-receptor mechanism. In view of previous findings, the deterioration of cardiac performance may involve the endothelinB-receptor, either alone or in combination with the endothelinA-receptor.

Animals↗
PubMed1998

Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.

In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw induced by a photochemical sciatic lesion, an intrathecal catheter was inserted to the lumber enlargement and an epidural electrode was implanted at T11. I.t. administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent fashion. When the two agonists were given together, each in an ineffective dose, there was a normalization of the thresholds. Rats, in which spinal cord stimulation (SCS) could not suppress the allodynia (non-responders), were transformed into SCS-responders by injection of baclofen and R-PIA in low, ineffective doses, combined with SCS. In SCS responding rats, combination of a selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in low, ineffective doses abolished the SCS-induced threshold normalization. These results indicate that GABAergic and adenosine-dependent mechanisms are involved in the SCS effect and further suggest a strategy for enhancing the therapeutic efficacy of SCS.

Adenosine↗
PubMed1998

Intrathecal administration of the adenosine A1 receptor agonist R-phenylisopropyl adenosine reduces presumed pain behaviour in a rat model of central pain.

Effects of intrathecally (i.t.) administered R-phenylisopropyl adenosine (R-PIA), an adenosine A1 receptor agonist, on presumed pain behaviour were assessed in a rat model of chronic central pain. Spinal cord injury was induced photochemically via laser irradiation of the spinal cord after intravenous injection of erythrosin B in rats. The chronic allodynia-like behaviour that developed in some animals was studied. R-PIA (3 and 10 nmol), injected i.t. reduced the mechanical and cold allodynia-like symptoms as tested with von Frey filaments and ethyl-chloride spray, respectively. No side effects were observed. The effect of R-PIA was significant for up to 5 h and was reversed by theophylline, an adenosine receptor antagonist.

Adenosine↗
PubMed1998

Lack of neurohumoral response to pneumoperitoneum for laparoscopic cholecystectomy.

BACKGROUND: Pneumoperitoneum (PP) for laparoscopic surgery induces prompt changes in circulatory parameters. The rapid onset of these changes suggests a reflex origin, and the present study was undertaken to evaluate whether release of vasopressor substances could be responsible for these alterations. The influence of two different anesthesia techniques was also evaluated. METHODS: American Society of Anesthesiologists (ASA) class I patients, scheduled for laparoscopic cholecystectomy, were investigated. The first group (n = 10) was anesthetized intravenously. The second group (n = 6) had inhalation anesthesia. Plasma vasopressin, catecholamines, and plasma renin activity were investigated as neurohumoral vasopressor markers of circulatory stress. The general stress response to surgery was assessed by analysis of plasma cortisol. RESULTS: Induction of pneumoperitoneum caused no apparent activation of vasopressor substances, although several hemodynamic parameters responded promptly. CONCLUSION: The hemodynamic alterations, seen at the establishment of PP during stable anesthesia, cannot be explained by elevation of vasopressor substances in circulating blood.

Adolescent↗
PubMed1998

Pneumoperitoneum for laparoscopic cholecystectomy is not associated with compromised splanchnic circulation.

OBJECTIVE: To investigate the influence of increased intra-abdominal pressure during pneumoperitoneum on splanchnic circulation. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Five otherwise healthy patients (mean age of 34 years), undergoing laparoscopic cholecystectomy. INTERVENTIONS: Arterial and hepatic vein catheterization and simultaneous arterial and hepatic vein blood gas sampling in the awake state, during anaesthesia, after the establishment of pneumoperitoneum (intra-abdominal pressure level 11-13 mmHg) and after 30 and 60 minutes of pneumoperitoneum. MAIN OUTCOME MEASURES: Hepatic blood flow was estimated by the continuous infusion method and used as a measure of splanchnic blood flow. Splanchnic oxygen consumption was calculated according to the Fick principle. RESULTS AND CONCLUSION: Splanchnic blood flow and splanchnic oxygen consumption were not affected by pneumoperitoneum at this level of intra-abdominal pressure.

Abdomen↗
PubMed1998

Ventilatory responses to acute and sustained hypoxia during isoflurane anesthesia.

UNLABELLED: In the awake state, isocapnic hypoxic ventilatory responses (HVRs) are biphasic, with an acute response within 5 min of hypoxic stimulation followed by a less pronounced sustained response. In this study, we investigated the influence of isoflurane anesthesia (end-tidal concentration 1.1 kPa) on acute and sustained isocapnic HVRs in eight healthy women at pulse oximetry arterial saturations of 75%-80%. The aims were to determine whether HVR (20 min of hypoxia) during anesthesia was biphasic and to quantify ventilatory responses. Pneumotachography and in-line infrared capnometry were used. A biphasic HVR was found both in awake and anesthetized patients. Of the subjects, six had decreased and two had increased acute and sustained isocapnic HVRs in the anesthetized, compared with the awake state, which resulted in an approximately 50% reduction in both acute and sustained HVRs. In addition, the ventilatory response pattern was altered by anesthesia. Awake HVR was accomplished by increased tidal volumes while respiratory rates were unchanged. The opposite occurred during anesthesia. The underlying mechanisms for this biological action of inhaled anesthetics remains to be elucidated. In conclusion, this study clearly demonstrates the persistence of hypoxic ventilatory sensitivity during clinical anesthesia. IMPLICATIONS: We studied the ventilatory effects of 20 min of breathing air with low oxygen content (hypoxic) in eight women, before and during anesthesia with inhaled isoflurane. We demonstrated a persistent but blunted hypoxic ventilatory response during clinical anesthesia.

Adult↗
PubMed1998

Intrathecal adenosine administration: a phase 1 clinical safety study in healthy volunteers, with additional evaluation of its influence on sensory thresholds and experimental pain.

BACKGROUND: Several animal studies show antinociceptive effects of intrathecally administered adenosine and its analogs. However, there is no clinical experience regarding the effects of intrathecal adenosine in humans. METHODS: The side effects and analgesic effects of intrathecal adenosine (500-2,000 microg) on experimental pain were studied in 12 healthy volunteers. Before and after adenosine was given, the authors evaluated the cold pain rating of the foot (submersion in ice water for 1 min), the forearm ischemic pain rating during a 30-min tourniquet test, and the thermal and tactile pain thresholds on healthy and inflamed skin after application of mustard oil (4 min) to the calf. The areas of secondary allodynia surrounding the inflammation were also determined. The cerebrospinal fluid level of adenosine was determined before and after injection. RESULTS: Intrathecal adenosine caused a 1,000- to 2,000-fold elevation of the cerebrospinal fluid concentration. One volunteer experienced transient (30 min) lumbar pain after injection at a dose of 2,000 microg. There were no other complications in any other volunteers. Adenosine reduced, in a non-dose-dependent manner, the areas of secondary allodynia after skin inflammation (brush, P < 0.06; and von Frey hair, P < 0.03) and reduced the forearm tourniquet ischemic pain rating (P = 0.01). Tactile pain thresholds were significantly reduced by mustard oil inflammation during control, whereas adenosine treatment prevented this reduction. The ice water-induced cold pain rating was not influenced by adenosine. CONCLUSIONS: An intrathecal adenosine injection of 1,000 microg lacked side effects in healthy volunteers. The compound attenuated different types of experimental pain.

Adenosine↗
PubMed1998

The endothelin receptor antagonist bosentan restores gut oxygen delivery and reverses intestinal mucosal acidosis in porcine endotoxin shock.

BACKGROUND: Endothelin-1, the most potent vasoconstrictor known, is produced in septic states and may be involved in the pathophysiology of the deteriorated splanchnic circulation seen in septic shock. AIMS: To elucidate the capability of bosentan, a non-peptide mixed endothelin receptor antagonist, to attenuate splanchnic blood flow disturbances and counteract intestinal mucosal acidosis in endotoxic shock. METHODS: In 16 anaesthetised pigs, central and regional haemodynamics were monitored by thermodilution and ultrasonic flow probes, respectively. A tonometer in the ileum was used for measurement of mucosal pH. Onset of endotoxin challenge was followed by bosentan administration (to eight pigs) two hours later. RESULTS: Endotoxin infusion reduced cardiac index and systemic oxygen delivery; bosentan restored these parameters. The reduced mean arterial blood pressure and renal blood flow remained unaffected by bosentan. The profound reduction in gut oxygen delivery in response to endotoxin was completely abolished by bosentan. Bosentan significantly improved the notably deteriorated intestinal mucosal pH and mucosal-arterial PCO2 gap. The mucosal-portal vein PCO2 gap, used to monitor the mucosa in relation to the gut as a whole (including the spleen and pancreas), was also greatly increased by endotoxaemia and significantly reversed by bosentan. CONCLUSION: Bosentan completely restored the profound endotoxin induced reductions in systemic and gut oxygen delivery with a concomitant reversal of intestinal mucosal acidosis. Results suggest that endothelin is involved in the pronounced perfusion disturbances seen in the gut in endotoxic shock. Bosentan may prove useful in reducing gut ischaemia in septic shock.

Acidosis↗