Biomedical subjects

A Sollevi

Publications and source records attributed to A Sollevi.

At least 55 records · Page 3Linked to original sources

PubMed1997

Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography.

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 micrograms kg-1 min-1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2-3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus [15O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 +/- 0.2 kPa, mean +/- s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 +/- 66 mL min-1, equivalent to about 64 +/- 5 mL 100 g-1 min-1. The cerebral blood flow measured by positron emission tomography technique, was 59 +/- 4 mL 100 g-1 min-1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 +/- 7 micrograms kg-1 min-1.) the cerebral blood flow, measured by magnetic resonance imaging was 60 +/- 5 mL 100 g-1 min-1. The end tidal CO2 level was slightly lower (0.2 +/- 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.

Adenosine↗

PubMed1997

Cerebral blood flow of the exposed brain surface measured by laser Doppler perfusion imaging.

A novel application of laser Doppler flowmetry (LDF) laser Doppler perfusion imaging (LDPI), was used to study cerebral cortical blood flow (CBFcortex). In contrast to the conventional laser Doppler perfusion monitor, LDPI creates two dimensional maps of the tissue perfusion in a well defined area of up to 120 x 120 mm comprising 4096 measurements points. Measurements of CBFcortex were made through an optically transparent polyester film applied to a cranial window preparation in ventilated anaesthetized pigs. Temporal and spatial heterogeneity in CBFcortex were visualized by LDPI during provocations which are known to alter CBF (varying arterial PCO2 or MABP, or infusion of adenosine at constant MABP (concomitant angiotensin administration) or by hyperoxemia). During hypercapnia the recorded CBFcortex increased homogeneously. The adenosine-mediated increase in recorded CBFcortex was concentrated on the lower flow interval, as was the hyperoxemia-caused decline. At decreasing MABP the autoregulatory threshold was found to vary locally within the cortex. The results suggest that LDPI, apart from detecting localized changes in CBFcortex' also visualizes flow changes within different vascular segments. Together with the practical advantages of the system, i.e. not necessitating direct contact with the tissues, this feature makes the technique suitable for studies of CBFcortex distributions.

Animals↗

PubMed1997

Intrathecal adenosine analog administration reduces substance P in cerebrospinal fluid along with behavioral effects that suggest antinociception in rats.

UNLABELLED: Adenosine and adenosine analogs induce analgesia in humans and presumed antinociception in animal models when administered both systemically and intrathecally. In the present investigation in rats, we studied the effects of intrathecally administered adenosine analogs, with or without systemic coadministration of an adenosine antagonist (theophylline), on substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations in cerebrospinal fluid (CSF). In parallel, nociceptive reflex testing (tail immersion latency) and motor function were evaluated. The potent unselective adenosine receptor agonist N-ethylcarboxamide-adenosine (NECA) and the relatively adenosine A1 receptor selective agonist R-phenyl-isopropyl-adenosine (R-PIA) both reduced SP-like immunoreactivity (-LI) by 50%, whereas CGRP-LI remained unchanged. There was a dose-dependent increase in tail immersion latency. This effect was present without motor impairment when R-PIA was administered in doses up to 5 nmol. R-PIA (10-100 nmol), as well as 1-100 nmol of the unselective agonist NECA, produced dose-dependent motor impairment. The reduction of SP-LI as well as the behavioral effects were reversed by theophylline. We conclude that SP reduction in CSF, which possibly reflects reduced SP turnover after adenosine receptor stimulation, provides an additional possible mechanism of action for the analgesic effects of adenosine. IMPLICATIONS: We studied the interactions between the known pain mediator substance P and substances with effects similar to the endogenous pain modulator adenosine in rats. The results suggest that the pain-reducing effect of adenosine is, at least partly, due to a reduction of substance P in cerebrospinal fluid.

Adenosine↗

PubMed1997

Effects of propofol on cerebral blood flow, metabolism, and cerebral autoregulation in the anesthetized pig.

We studied the effects of propofol on the cerebral circulation and flow/pressure autoregulation in eight anesthetized pigs. Regional cerebral blood flow (rCBF) was measured with a cerebral venous outflow technique. Autoregulation was tested with angiotensin infusions and gradual blocks of the caval vein for hyper- and hypotensive challenges, respectively. Propofol was given in a bolus of 2.5 mg.kg-1 followed by an infusion starting at 12 mg.kg-1.h-1 and gradually reduced to 8 mg.kg-1.h-1. As expected, propofol caused a substantial reduction in cerebral metabolic rate of oxygen, which was accompanied by an increase in cerebrovascular resistance and a decrease in CBF. In the control situation, i.e., during background anesthesia (low-dose isoflurane+nitrous oxide) only, the autoregulation was well preserved, and its lower limit was found at a mean arterial blood pressure (MABP) of 48 mm Hg. Propofol did not affect autoregulation in the group as a whole: the slope of the regression line of regional cerebrovascular resistance (rCVR) versus MABP during blood pressure reduction (caval test) was not significantly changed during propofol when compared to the control, neither was the lower limit of autoregulation (MABP, 54 mm Hg). All pigs but one followed this response pattern. The nonautoregulating pig had a completely pressure-dependent rCBF during propofol anesthesia, despite a perfectly intact auto-regulation in the control situation. It is concluded that propofol in clinical dosage does not affect autoregulation in this pig model, although individual animals may display a different response pattern.

Anesthetics, Intravenous↗

PubMed1997

Cardiopulmonary dysfunction during porcine endotoxin shock is effectively counteracted by the endothelin receptor antagonist bosentan.

In a porcine endotoxin shock model, the mixed nonpeptide endothelin receptor antagonist bosentan was administered 2 h after onset of endotoxemia (n = 8). Cardiopulmonary vascular changes, oxygen-related variables, and plasma levels of endothelin-1-like immunoreactivity were compared with a control group that received only endotoxin (n = 8). Bosentan abolished the progressive increase in mean pulmonary artery pressure and pulmonary vascular resistance seen in controls. Possible mechanisms include blockade of vasoconstrictive endothelin receptors, and a lesser degree of edema and inflammation indicated by less alveolar protein and a lower inflammatory cell count observed in bronchoalveolar lavage. Further, bosentan restored cardiac index to the pre-endotoxin level by an increase in stroke volume index, improved systemic oxygen delivery, and acid base balance. Because mean arterial blood pressure was unaffected, bosentan reduced systemic vascular resistance. Endotoxemia resulted in an increase in tumor necrosis factor-alpha and endothelin-1-like immunoreactivity plasma levels, the latter being further increased by bosentan. In conclusion, in porcine endotoxemia, treatment with the endothelin receptor antagonist bosentan, administered during fulminate shock, abolished pulmonary hypertension and restored cardiac index. These findings suggest that bosentan could be an effective treatment for reversing a deteriorated cardiopulmonary state during septic shock.

Acid-Base Imbalance↗

PubMed1997

Antinociceptive effect of perioperative adenosine infusion in abdominal hysterectomy.

BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert antinociceptive action in cutaneous and deep somatic pain under experimental and clinical conditions in animals and in humans. The aims of this randomized double-blind placebo-controlled study were to evaluate if a low dose of intravenous (i.v.) ADO could reduce the requirements of volatile anesthetic and postoperative opioid in connection to hysterectomy, where visceral nociception significantly contributes to pain. METHODS: Forty-three women, age 32-65 years, ASA I and II, scheduled for abdominal hysterectomy, were assigned to receive an i.v. infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo during surgery. Anesthesia was maintained with isoflurane (ISO)/N2O/ O2 inhalation. Postoperatively, a reduced dose of 40 micrograms.kg-1.min-1 was continued for 3 h. RESULTS: The end-tidal (ET-) ISO was equal between groups before surgery. During surgery, the ISO requirement was increased, compared to the preoperative level, in the placebo group, while the requirement declined in the ADO group. The overall ISO requirement in the ADO group was reduced by 36% (P < 0.002). The first 24 h postoperative opioid requirement, with equal resting pain in both groups, was 18% (P < 0.05) lower in the ADO group. CONCLUSION: A low dose of perioperative adenosine infusion in abdominal hysterectomy reduces the requirements of volatile anesthetic and postoperative opioid analgesic.

Adenosine↗

PubMed1997

Vectorcardiographic changes during laparoscopic cholecystectomy may mimic signs of myocardial ischaemia.

BACKGROUND: Laparoscopic surgery involves the use of intra-abdominal carbon dioxide insufflation (pneumoperitoneum). The increased intra-abdominal pressure causes marked haemodynamic changes, which may influence electrocardiographic monitoring. The aim of the present study was to elucidate the influence of pneumoperitoneum on vectorcardiographic recordings. METHODS: Vectorcardiographic changes (QRS vector difference = QRS-VD, QRS loop area, QRS magnitude, ST vector magnitude, spatial ST vector change) were recorded continuously applying computerized vectorcardiography in 12 anaesthetised cardiovascularly healthy patients, scheduled for laparoscopic cholecystectomy. Measurements were made before and during pneumoperitoneum in three different body positions (supine, Trendelenburg and reversed Trendelenburg), also employing transesophageal echocardiography and invasive blood pressure monitoring. RESULTS: Pneumoperitoneum significantly increased QRS-VD, in parallel with an enlargement in loop area and magnitude. The magnitude was significantly increased in the transversal and frontal planes and there was a tendency to increase the magnitude in the sagittal plane. The increase in QRS-VD reached levels previously associated with the development of myocardial ischaemia in patients with coronary artery disease. The ST-variables were not changed by the pneumoperitoneum. The positional changes also influenced QRS-VD significantly. CONCLUSIONS: When computerized vectorcardiography is used for ischaemia monitoring during pneumoperitoneum, the ST-variables seem reliable. However, vectorcardiographic QRS-changes should be interpreted with caution, as the QRS alterations found during pneumoperitoneum mimic the changes seen during myocardial ischaemia.

Adult↗

PubMed1997

Adenosine for pain control.

The antinociceptive actions of adenosine and adenosine analogs in animal models has been known for more than 10 years. The recent development with regard to the pain modulatory effects of adenosine, primarily in clinical studies, has generated a renewed interest in this principle for pain control. This review summarizes the current knowledge in adenosine mediated pain modulation in acute and chronic conditions, with focus on studies in man. The endogenous compound adenosine has various modulatory effects in the peripheral and central nervous system, mediated through specific cell-surface associated receptors. The current view is that adenosine receptors of the A1-subtype are associated with a modulatory effect on pain transmission at spinal cord level. Animal studies have repeatedly demonstrated adenosine- and adenosine analog mediated inhibitory influences on presumed nociceptive reflex responses (1,2). These examinations in rodents have tested acute pain models involving tactile, pressure and heat stimulations. More recently, animal lesion models presumably reflecting chronic pain, has shown that adenosine analogs can suppress nociceptive behaviour both by systemic and intrathecal (i.t.) administration (3,4). Consequently, there is substantial evidence that adenosine can modulate nociceptive input. Further, it has been proposed that endogenous adenosine formation is involved in physiological pain control at the spinal cord level and that its release is involved in the action of opioid antinociception (1). Clinical studies have revealed that adenosine administration by bolus injection or by infusion at doses above 70 micrograms x kg-1 x min-1 is associated with pain symptoms from different parts of the body. This algogenic effect of higher doses of adenosine is probably related to sensitization/activation of peripheral nociceptive afferents (5).

Acute Disease↗

PubMed1997

Modulation of spinal pain mechanisms by spinal cord stimulation and the potential role of adjuvant pharmacotherapy.

Experimental studies indicate that the effects of spinal cord stimulation (SCS) on 'hypersymptoms' in neuropathic pain conditions may at least partly be mediated via GABAergic and adenosine-dependent mechanisms. Concomitant intrathecal administration of receptor-active drugs modulating the function of the GABA and adenosine systems may both depress and enhance the effects of SCS. The first few patients with simultaneous intrathecal administration of the GABAB agonist baclofen and/or adenosine together with SCS, when the stimulation alone proved insufficient, are reported.

Adenosine↗

PubMed1996

Intrathecal and systemic R-phenylisopropyl-adenosine reduces scratching behaviour in a rat mononeuropathy model.

The aim of the present study was to investigate the effect of intravenous or intrathecal (i.t.) administration of R-phenylisopropyladenosine (R-PIA), a selective A1 adenosine receptor agonist, on spontaneous scratching behaviour, a phenomenon presumably related to pain in a mononeuropathy model (sciatic nerve ligation) in rats. The acute effect of daily i.t. R-PIA injections was studied up to 21 days following nerve ligation. The results demonstrate that both i.v. (30 nmol) and i.t. (3 nmol) R-PIA, in doses not producing any motor impairment, significantly reduces scratching behaviour in this animal model. The mechanism of action for this presumed antinociceptive effect is suggested to occur at the spinal cord level.

Adenosine↗

PubMed1996

Effects of posture and pneumoperitoneum during anaesthesia on the indices of left ventricular filling.

BACKGROUND: Laparoscopic surgery requires the use of pneumoperitoneum (PP). When combined with positional changes, pneumoperitoneum may cause marked circulatory alterations. METHODS: Eight anaesthetized cardiovascularly healthy patients, scheduled for laparoscopic cholecystectomy, were studied before and during pneumoperitoneum in three different postures (supine, Trendelenburg and reversed Trendelenburg), employing transesophageal echocardiography and pulmonary artery pressure monitoring. RESULTS: PP significantly increased end-diastolic area (EDA) and pulmonary capillary wedge pressure (PCWP) irrespective of posture. PCWP was significantly influenced by postural changes, whereas EDA was not. Further, changes in EDA and PCWP covaried during the investigation, but showed no linear correlation. Systolic function, measured as end-systolic area (ESA) and fractional area shortening (FAS), was not altered. Diastolic function, as assessed by the velocity rate of the transmitral flow during the early filling phase (E) and the atrial contraction (A), showed no change of the E/A ratio, whereas after the induction of PP there was a significant reduction of the E component. CONCLUSIONS: In cardiovascularly healthy patients, the left ventricular volume is increased during pneumoperitoneum. Further, changes in invasive pressure determinations (PCWP) do not correlate linearly with changes in volume indices of left ventricular filling (EDA).

Adult↗

PubMed1996

Peroperative adenosine infusion reduces isoflurane concentrations during general anesthesia for shoulder surgery.

BACKGROUND: Adenosine (ADO), and stable analogs thereof, have been shown to exert antinociceptive action under experimental conditions in animals and in humans. The aim of this randomized double-blind placebo-controlled study was to evaluate if a low dose of intravenous (i.v.) ADO could reduce isoflurane requirements during joint-associated surgery, as an indication of antinociception in deep somatic pain. METHODS: Thirty-two patients, age 19-62 years, ASA I and II, scheduled for shoulder joint surgery, were assigned to receive an i.v. infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during the surgical procedure. Anesthesia was maintained with isoflurane/N2O/O2 inhalation. RESULTS: The peroperative isoflurane concentration was significantly reduced at 50 minutes of surgery in the group receiving adenosine infusion. Also, the systolic blood pressure level was peroperatively more stable during adenosine infusion than during placebo. Other clinical parameters, such as pain, postoperative analgesic requirements and nausea, were not different between groups. CONCLUSION: A peroperative infusion of a low dose of adenosine during shoulder joint surgery may reduce the peroperative isoflurane requirement.

Adenosine↗

PubMed1996

Effects on skeletal muscle oxygenation and capillary blood flow by adenosine-, sodium nitroprusside- and acetylcholine-induced hypotension.

BACKGROUND: Adenosine (ADO)-induced hypotension during diethyl ether anesthesia has been shown to increase skeletal muscle oxygenation. Whether this beneficial effect of ADO hypotension is present also during another anesthetic technique was tested in the present study using ketamine-xylazine anesthesia, and its actions were compared with sodium nitroprusside (SNP) and acetylcholine (ACh) induced hypotension in rabbits. METHODS: Local oxygen pressure and capillary blood flow were measured with a multiwire microelectrode which was placed on the surface of the left vastus medialis muscle. The experiments were performed in three groups, in which either ADO, SNP or ACh was infused into a central vein in a dose that produced a reduction of the mean arterial pressure by 20-25%, to approximately 60 mmHg. RESULTS: In the ADO group (60-170 micrograms kg-1 min-1) the tissue oxygen pressures increased by 23% while capillary blood flow decreased by 38%. During SNP administration (1-3 micrograms kg-1 min-1) the oxygen pressures decreased by 21% and an increase of 31% in capillary flows was seen. When ACh was infused (1-4 micrograms kg-1 min-1) the oxygen pressures decreased by 21% and, in parallel, capillary blood flow decreased by 50%. During hypotension no low tissue oxygen pressure values (< 1.5 kPa) were found in the ADO group, whereas they were present in both the SNP and ACh group. CONCLUSION: Compared to sodium nitroprusside and acetylcholine, adenosine appears to have an oxygen-sparing effect in the skeletal muscle during pharmacologically induced hypotension.

Acetylcholine↗

PubMed1996

Splanchnic homeostasis during endotoxin challenge in the pig as assessed by microdialysis and tonometry.

The splanchnic region is particularly susceptible to shock. The purpose of this study was to evaluate microdialysis of the liver and small intestine as a monitor of splanchnic metabolic deterioration (elevation of lactate and hypoxanthine) in porcine endotoxic shock. Tonometry of the small intestine was used as a reference. Microdialysis probes (liver, ileum, and artery), tonometer, and pulmonary artery catheter were inserted. Eight animals were given Escherichia coli lipopolysaccharide endotoxin (20 micrograms kg-1 h-1 for 2 h). Five animals served as controls. Measurements were made every half-hour. Three hours after onset of endotoxin challenge, there were significant differences between endotoxin and control groups in intestinal lactate and hypoxanthine, as well as liver lactate, in addition to mucosal pH obtained by tonometry. Lactate elevation in blood was first seen at 4 h, while there was no significant hypoxanthine elevation in arterial blood over 5 h. Hence, data obtained from the splanchnic region became significantly different early, when compared with data obtained from arterial blood. Microdialysis of liver and small intestine as well as intestinal tonometry are sensitive tools for detection of splanchnic metabolic deterioration during endotoxin shock.

Animals↗

PubMed1995

Systemic adenosine attenuates touch evoked allodynia induced by mustard oil in humans.

The effect of adenosine on tactile allodynia (secondary hyperalgesia) was studied in 6 healthy volunteers, using a double-blind, placebo controlled, cross-over design. Tactile allodynia was induced by topical application of mustard oil on the skin of the volar aspect of the forearm. Adenosine (50 micrograms kg-1 min-1) or saline was given intravenously for 20 min before the mustard oil application and continued for another 50 min. The tactile allodynic areas for brush and von Frey filament stimulation were both significantly reduced by approximately 50% during adenosine infusion, compared with placebo. The threshold for eliciting allodynia with von Frey filaments was not influenced by adenosine. The study shows that adenosine can reduce the area of mustard oil induced tactile allodynia.

Adenosine↗

PubMed1995

Peroperative adenosine infusion reduces the requirements for isoflurane and postoperative analgesics.

The aims of this study were to investigate the influence of adenosine infusion, firstly, on postoperative analgesic requirements, and secondly, on peroperative isoflurane requirements. Seventy-five women, aged 18-70 yrs, ASA grades I and II, scheduled for breast surgery, were randomly assigned to peroperatively receive a double-blind intravenous infusion of either adenosine, 80 micrograms.kg-1.min-1, or placebo, during surgery under isoflurane/N2O/O2 anesthesia. The peroperative isoflurane requirements were significantly reduced at 30 and 90 min of surgery during adenosine treatment. The number of patients reporting pain when regaining consciousness after surgery was reduced by 57% in the adenosine group, 8/31 vs 19/32 (P < 0.02). Further, the postoperative 24-h opioid requirements were reduced by 27% in the adenosine group (P < 0.03). In conclusion, we found that a peroperative infusion of a small dose of adenosine during breast surgery, reduces the peroperative anesthetic requirements, and the demand for post-operative analgesics.

Adenosine↗

PubMed1995

Systemic adenosine infusion alleviates spontaneous and stimulus evoked pain in patients with peripheral neuropathic pain.

In seven patients with peripheral neuropathic pain, the effect of systemic adenosine infusion on pain symptoms was evaluated in a double-blind, placebo controlled, cross-over study. The study infusions, adenosine (50 micrograms.kg-1.min-1) or placebo, were given intravenously (IV) during 45-60 min at two separate occasions. Before and during infusions, bedside examination of sensibility and quantitative sensory testing (QST), i.e., assessments of perception thresholds for touch, touch-evoked pain, cold, warmth, painful heat, and cold, were performed. In the neuropathic area, sensation magnitude was rated by a visual analog scale (100 mm VAS) using a pin and at perception threshold for touch-evoked pain using von Frey filaments. Adenosine infusion reduced spontaneous pain (P < 0.05), and caused an increase of the touch-evoked pain threshold from 10.8 +/- 5.3 to 22.2 +/- 6.9 g (P < 0.05), whereas placebo had no effect. Pain intensity at perception threshold for touch-evoked pain was, however, unaltered. Pinprick-evoked pain in the neuropathic areas was reduced from 53 +/- 11 to 29 +/- 10 mm (P < 0.05). No other sensory modality was consistently changed during adenosine infusion. In conclusion, the present study demonstrates that adenosine infusion alleviates spontaneous neuropathic pain, tactile allodynia, and pinprick hyperalgesia in patients with peripheral neuropathic disorders, probably by a central mechanism of action.

Adenosine↗

PubMed1995

Adenosine for per-operative blood pressure control in an infant with neuroblastoma.

We describe a child with a localised pelvic neuroblastoma and a hypertensive crisis during the first weeks of life due to elevated systemic norepinephrine of tumoural origin. In spite of treatment with high doses of alpha-blockers, blood pressure did not respond fully and the boy had a very unstable circulation. Surgery was performed at one month of age. Adenosine, a potent short-acting vasodilator, was used for peroperative blood pressure control to protect the patient from an uncontrolled hypertensive crisis. During tumour manipulation the child became hypertensive with systolic pressure exceeding 130 mm Hg and adenosine infusion (100 micrograms.kg-1.min-1) was started with a prompt normalisation of the blood pressure. Adenosine infusion could be discontinued after tumour removal. Norepinephrine, dopamine, homovanillic acid and vanillylmandelic acid in urine were elevated preoperatively and normalised at follow up. Plasma concentrations of norepinephrine and dopamine were elevated preoperatively. Norepinephrine increased during hypertension due to tumour manipulation. Plasma neuropeptide Y increased during tumour manipulation but still within the normal range for infants. It is concluded that adenosine can be used peroperatively in children with severe hypertension and in this case no adverse effects of adenosine were noted. Furthermore, tumour synthesis and systemic release of norepinephrine, but not neuropeptide Y, contributed to hypertension in this child with neuroblastoma.

Adenosine↗