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Anti-inflammatory effects of adenosine were evaluated in two randomized, double-blind, placebo-controlled studies. In one study healthy male volunteers received no endotoxin (adenosine study, n 10), in the other intravenous endotoxin (4 ng/kg, endotoxin study n 11) was given. All subjects were treated with adenosine infusion (40 g/kg/min) and placebo (saline) infusion in a crossover design. Heart rate, body temperature, blood pressure and plasma cytokines (tumor necrosis factor TNF-, interleukin IL-6, IL-10, and soluble TNF receptors I and II), nitric oxide oxidation products, nitrite and nitrate, as well as superoxide anions were determined. There were no significant changes of any measured parameter after adenosine treatment alone. Endotoxin elicited clinical signs of an inflammatory reaction, prominent release of all cytokines and O2−synthesis by neutrophils (N-formyl-methionin-leucyl-phenylalanin-stimulated cells measured by cytochrome C reduction). The plasma IL-6 response to endotoxin was attenuated by adenosine, as IL-6 increased from 0.9 (0.8–1.6) to 1345 (743–1906) pg/mL (median; 25–75th percentiles) with adenosine infusion, and from 0.8 (0.5–1) to 1,959 (1,344–2,505) pg/mL with placebo (P0.0065). There was no significant influence of adenosine infusion on the other variables examined. In conclusion, systemic adenosine infusion counteracts the release of IL-6 in healthy volunteers, indicating an anti-inflammatory effect of adenosine which should be further explored.

Deep tissue pain can be related to reduced muscle blood flow, which comprises the metabolic demand under muscle work. The tissues and receptors involved in nociception after ischaemic muscle contractions are not known. The concentration of adenosine is increased after ischaemic contractions and might act as an algesic substance. In 15 subjects, adenosine, hypertonic saline (algesic), and isotonic mannitol (placebo) were infused into the tibialis anterior muscle and compared with the pain caused by ischaemic contractions. The muscle pain intensity (visual analogue scale; VAS), distribution, and quality were assessed. Pressure pain thresholds were recorded to assess the deep tissue sensitivity. Adenosine did not induce more pain than the placebo. The maximal VAS score after hypertonic saline and ischaemic contractions was higher compared with adenosine/placebo infusions. The duration and area of pain were significantly increased after hypertonic saline infusions compared with ischaemic contractions. Higher scores on the McGill pain questionnaire were given to the “stabbing”, “burning”, “heavy”, and “exhausting” word categories after ischaemic contractions, and “cramping” was rated higher during hypertonic saline-induced muscle pain compared with ischaemic contractions. During hypertonic saline infusions, the pressure pain threshold was decreased compared with before and immediately after the pain had vanished. The present study shows that pharmacological levels of adenosine in skeletal muscle did not induce pain. Excitation of muscle nociceptors by hypertonic saline evoked hyperalgesia, larger areas of pain, and a different quality of pain compared with ischaemic contractions, suggesting that the pain after ischaemic contractions is mediated by other populations of nociceptors in muscle and/or other tissues than excited by hypertonic saline.

The present study assessed the efficacy and potency of intrathecal (i.t.) administration of the opiate morphine, the γ-aminobutyric acid-B (GABAB) receptor agonist baclofen, the α2-adrenoceptor agonist clonidine and the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) on the acute allodynia-like behaviour after photochemically induced spinal cord injury (SCI) in rats. Rats displaying allodynia-like behaviours to brushing, von Frey hairs and cold stimulation 1–2 days after photochemically induced SCI were studied. In a cumulative dose regime, morphine (0.1–10 μg), baclofen (0.1–1 μg), clonidine (0.1–10 μg) and R-PIA (0.01–10 nmol) were administered i.t. through an implanted catheter at the lumbar spinal cord. All tested drugs dose-dependently reduced the brushing, von Frey hairs and cold stimulation-induced allodynia-like behaviour. No increase in adverse effects such as motor deficits was found for morphine, clonidine and R-PIA. There was a slight increase in motor impairments at the highest dose of baclofen. For the mechanical allodynia, morphine appeared to be most effective, whereas baclofen, clonidine and R-PIA only provided a partial alleviation. For the cold allodynia, morphine and baclofen were more effective than clonidine and R-PIA. In relieving acute mechanical and cold allodynia-like behaviours in rats 1–2 days after SCI, i.t. morphine and baclofen were superior to clonidine and R-PIA.

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.To further elucidate the specific role of the ETAas opposed to the ETBreceptor and their effects in the splanchnic region a non‐selective (ETMIXra) A‐182086 and selective ETA(ETAra) PD155080 and ETB(ETBra) A‐192621 receptor antagonists were administered, separately or simultaneously (ETA+Bra) 2 h after onset of endotoxin shock. These four groups were compared to a control group receiving only endotoxin and vehicle.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.Endotoxin‐induced changes in systemic, gut oxygen delivery and portal hepatic vascular resistance and systemic acidosis were effectively counteracted by both ETA+Bra and ETMIXra. ETAra administration was not effective while ETBra proved to be fatal as all animals in this group died prior to full time of the experiment. While both ETA+Bra and ETMIXra improved gut oxygen delivery only the latter attenuated the profound endotoxin‐induced ileal mucosal acidosis.The lethal effect seen from selective ETBreceptor antagonism in the current study may be due to increased ETAreceptor activity as plasma levels of ET‐1 is increased several fold by blocking the ETBreceptor and thereby the plasma‐ET‐1‐clearing function. Furthermore, a loss of endothelial ETBreceptor vasodilating properties may also have contributed to the lethal course in the ETBra groupThe 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 ETAand ETBreceptors is necessary to effectively counteract these changes.

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.

This overview summarizes the current clinical state of knowledge in the field of adenosine-mediated pain reduction, also including a condensed experimental background of relevance for clinical implementation. Clinical investigations have been systematically performed and include experimental pain models in volunteers, as well as studies in acute perioperative pain and in chronic neuropathic pain. Adenosine has been administered as a low-dose intravenous infusion and as an intrathecal injection. Effects on pain and on signs of hyperexcitability in the nervous system have been investigated, both after administration of adenosine alone and in combination with well-known analgesic agents. The different modes of adenosine administration demonstrate reduced pain, primarily in modalities that involve mechanisms of hyperexcitability of the central nervous system, i.e., central sensitization. Because this phenomenon is an important factor in chronic pain conditions, the promising results of pain relief in patients with neuropathic pain suggest that this is especially relevant for future development and research. In addition, the potential use of adenosine in combination with other pain-modulating agents deserves further evaluation. Drug Dev. Res. 45:151–158, 1998. © 1998 Wiley-Liss, Inc.

This overview summarizes the current clinical state of knowledge in the field of adenosine‐mediated pain reduction, also including a condensed experimental background of relevance for clinical implementation. Clinical investigations have been systematically performed and include experimental pain models in volunteers, as well as studies in acute perioperative pain and in chronic neuropathic pain. Adenosine has been administered as a low‐dose intravenous infusion and as an intrathecal injection. Effects on pain and on signs of hyperexcitability in the nervous system have been investigated, both after administration of adenosine alone and in combination with well‐known analgesic agents. The different modes of adenosine administration demonstrate reduced pain, primarily in modalities that involve mechanisms of hyperexcitability of the central nervous system, i.e., central sensitization. Because this phenomenon is an important factor in chronic pain conditions, the promising results of pain relief in patients with neuropathic pain suggest that this is especially relevant for future development and research. In addition, the potential use of adenosine in combination with other pain‐modulating agents deserves further evaluation. Drug Dev. Res. 45:151–158, 1998. © 1998 Wiley‐Liss, Inc.

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-α 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.

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 μg 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.

The influence of isoflurane-induced hypotension on regional cerebral blood flow (rCBF) and cerebrovascular autoregulation was evaluated in 11 normocapnic pigs during anesthesia comprising fentanyl and nitrous oxide in oxygen. rCBF was determined as sagittal sinus outflow and recorded continuously by an electromagnetic technique. Regional cerebral metabolic rate for oxygen (rCMRO2) was calculated as rCBF multiplied by the arteriosagittal sinus oxygen content difference. Cerebral autoregulation was evaluated by two formal tests; blood pressure increase by infusion of angiotensin and blood pressure decrease by caval block. Light hypotension [mean arterial blood pressure (MABP) 94 ± 3 mm Hg] and moderate hypotension (MABP 56 ± 1 mm Hg) were achieved with the inspired concentrations of 1.7 ± 0.2 and 2.7 ± 0.2 isoflurane, respectively. rCBF was measured and the tests were performed before, during, and after isoflurane administration. Isoflurane produced no significant change in rCBF at either level of hypotension. At moderate hypotension the rCMRO2was decreased by 40 ± 6. At both levels of hypotension, isoflurane produced a dose-dependent impairment of the auto-regulatory response to the angiotensin test as well as to the caval block. After hypotension, the autoregulatory response to increased blood pressure was restored within 15–25 min and to decreased blood pressures within 25–50 min.

1. Forearm blood flow was measured bilaterally in healthy young male and female volunteers, in the basal state and after upper‐arm occlusion of arterial or venous blood flow for 1‐20 min. The investigations were repeated after pre‐treatment with drugs affecting vascular prostaglandins and/or adenosine. 2. Simultaneous arterial occlusion in one arm and venous occlusion in the contralateral arm for up to 20 min elicited a considerable reactive hyperaemia in the arm subjected to arterial occlusion, but completely failed to elevate the post‐occlusive flow in the arm subjected to venous occlusion above the pre‐occlusive level. 3. When the arterial occlusion was increased from 1 to 20 min there was a progressive increase in the subsequent reactive hyperaemia, up to 30 ml 100 ml tissue‐1. The time dependence following 1‐3 min of arterial occlusion was based on a facilitation of the peak post‐occlusive flow, while prolongation of the arterial occlusion from 3 to 20 min augmented the reactive hyperaemia mainly by increasing its duration. 4. Inhibition of prostaglandin synthesis with ibuprofen reduced the total reactive hyperaemia following 3‐5 min of arterial occlusion by up to 70%. This attenuation was due both to a reduction of peak post‐occlusive flow and to a shortening of the duration of the post‐occlusive hyperaemia. 5. The adenosine receptor antagonist theophylline reduced the reactive hyperaemia following 5 min of arterial occlusion by about 35%. Combined treatment with ibuprofen and theophylline did not reduce the reactive hyperaemia more than either drug alone. 6. Infusion of dipyridamole, a drug which inhibits the elimination of adenosine, reinforced the reactive hyperaemia by about 45%. This effect of dipyridamole was completely inhibited by administration of theophylline, and also by ibuprofen. 7. Plasma levels of adenosine, hypoxanthine and uric acid were maintained during the reactive hyperaemia, indicating increased production of purines during or immediately after the ischaemia. 8. It is concluded that the adequate stimulus for vascular relaxation in response to interruption of blood flow is omission of vessel wall distension. Local metabolic factors like endogenously formed prostaglandins and adenosine may act synergistically to this myogenic response but seem to be inactive alone. The lack of additive effects of ibuprofen and theophylline suggests a link between vascular relaxation induced by prostaglandins and by adenosine.

During exhausting exercise adenylate kinase in the muscle cells is activated and a degradation of adenosine 5'-diphosphate occurs. Consequently, degradation products of adenosine 5'-monophosphate including hypoxanthine and uric acid, accumulate in plasma. The aim of this study was to compare the concentration changes of hypoxanthine and uric acid in plasma following running of varying duration and intensity. In addition, plasma creatine kinase activity was measured to assess the possible relationship between metabolic stress and protein release. Four groups of competitive male runners ran 100 m (n = 7), 800 m (n = 11), 5000 m (n = 7) and 42 000 m (n = 7), respectively, at an exhausting pace. Subsequent to the 100 m event (mean running time 11 s) plasma concentrations of hypoxanthine and uric acid increased by 364% and 36% respectively (P<0.05), indicating a very high rate of adenine nucleotide degradation during the event. Following the 800-m event (mean running time 125 s), hypoxanthine and uric acid concentrations had increased by 1598% and 66%, respectively (P<0.05). Both the events of longer duration, 5000 m and 42 000 m, also caused a significant increase in plasma concentration of hypoxanthine (742% and 237% respectively,P< 0.05) and plasma uric acid (54% and 34% respectively,P<0.05). Plasma activities of creatine kinase were significantly increased at 24 h only following the 5000 m and 42 000 m events (64% and 1186% respectively,P<0.05). Changes in plasma creatine kinase activity showed no correlation with changes in plasma concentration of either hypoxanthine or uric acid for the 5000 m and 42000 m events (r=0.00–0.45,P>0.05). These findings suggest that metabolic stress induced by exhausting exercise cannot be considered an important factor for the release of intracellular proteins. It was, furthermore, concluded that the rate of elimination of adenine nucleotides from cells was markedly elevated with the increasing intensity of exercise and only moderately affected by the duration of running.

1. The effects of local intra-arterial infusion of adenosine on renal blood flow, glomerular filtration and renin release in eight healthy awake subjects have been examined. 2. Renal blood flow and glomerular filtration rate were measured as the clearances of p-aminohippurate and inulin, respectively. After basal samplings, adenosine was infused intra-arterially at successive rates of 2 and 10 μg min−1 kg−1 for 40 min at each rate. 3. Apart from a small increase in heart rate (65 ± 4 to 71 ± 4 beats/min), there were no signs of sympathetic activation (unchanged blood pressure and catecholamine levels) during the infusion. Clearance of p-aminohippurate tended to increase, but not significantly, during adenosine infusion (518 ± 48 ml/min basal, 563 ± 52 ml/min during the highest dose of adenosine). The arterial plasma concentration of p-aminohippurate decreased by 9 ± 3% (P < 0.05), consistent with a small increase in renal blood flow in the infused kidney. Inulin clearance was reduced from 115 ± 3 to 97 ± 2 ml/min (P <0.001). The extraction of inulin, reflecting the filtration fraction, was 18% in both kidneys in the basal state. During infusion of adenosine the extraction in the infused kidney decreased to 12 ± 3% (P < 0.01 compared with the control kidney, 23 ± 3%). 4. The total excretion of Na+ was unchanged, but there was a minor decrease in K+ clearance. Thus, the K+/Na+ excretion ratio decreased from a basal value of 13 ± 2 to 10 ± 2 (P <0.01) at the highest dose of adenosine. The calculated renal uptake of oxygen was unchanged in the control kidney, but decreased in the adenosine-infused kidney from a basal value of 5.4 ± 0.5 ml/min to 3.8 ± 0.4 ml/min at the highest dose of adenosine (P < 0.01). 5. During continued intra-arterial adenosine infusion, nitroprusside was infused (0.3-2.5 μg min−1 kg−1) for 15 min to decrease blood pressure and stimulate renin production. Mean blood pressure decreased from 90 ± 2 to 63 ± 2 mmHg, whereas heart rate remained unaffected. There were increases in the arterial concentrations of adrenaline (0.3 ± 0.1 to 1.3 ± 0.3 nmol/l; P<0.01), aldosterone (136 ± 24 to 491 ± 144 pmol/l; P<0.001) and renin activity (0.8 ± 0.2 to 1.8 ± 0.5 pmol) of angiotensin I h−1 min−1; P < 0.05; values correspond to the basal state and 15 min of nitroprusside infusion, respectively). In the control kidney the arteriovenous concentration difference for renin activity increased from the basal state by 2.3 ± 0.8 pmol of angiotensin I h−1 ml−1, but remained unchanged in the adenosine-infused kidney (0.0 ± 0.3 pmol of angiotensin I h−1 ml−1, P < 0.02). 6. In conclusion, the direct renal effects of adenosine in healthy awake subjects include a local dilatation of postglomerular vessels, thereby decreasing glomerular filtration, and a reduction in renal oxygen consumption. Furthermore, adenosine prevents an increase in renin release during nitroprusside-induced hypotension.

1. The circulatory and metabolic effects of temperature reduction were studied in autoperfused canine subcutaneous adipose tissue in situ. 2. Cooling the adipose tissue sufficiently to reduce venous effluent temperature by 5‐‐6 degrees C decreased blood flow from an average of 6.4‐‐4.1 ml. min‐1 . 100g‐1. 3. Vasoconstrictor responses to sympathetic nerve stimulation (4 HZ) and injected noradrenaline (5 n‐mole) were potentiated by cooling while vasodilator components of the vascular responses, such as autoregulatory escape and post‐stimulatory hyperaemia, were virtually abolished by this treatment. 4. Oxygen uptake was reduced by cooling without signs of tissue hypoxia. This reduced oxygen demand may partly cause the decrease in adipose tissue blood flow. 5. Cooling inhibited glycerol mobilization from the adipose tissue during sympathetic nerve stimulation. Post‐stimulatory lipolysis was, however, not inhibited. In vitro studies with 'perifused' rat fat cells suggest that this may be due to impaired inactivation of the lipolytic process, rather than to changes in transmitter removal, following stimulation at low temperature. 6. Cooling inhibited the mobilization of fatty acids more than that of glycerol, suggesting increased re‐esterification of fatty acids within the tissue at low temperature. 7. It is concluded that cooling increases the sensitivity to vasoconstrictor stimuli and that inhibition of metabolic vasodilator mechanisms play a role for this effect. The stimultaneous inhibition of activating and inactivating mechanisms could explain the unchanged vascular and lipolytic responses to brief stimuli. Some possible implications of the present findings for the physiology of adipose tissue during cooling are discussed.

1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high‐performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n‐mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/‐ 0.03 and 0.16 +/‐ 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/‐ 0.04 and 0.28 +/‐ 0.06 microM under basal conditions. The arterio‐venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/‐ 0.22 to a peak value of 1.2 +/‐ 0.26 n‐mole/min. This corresponds to a net release of 8.7 +/‐ 3.0 n‐mole/100 g tissue. Inosine outflow rose from 0.64 +/‐ 0.37 to 5.3 +/‐ 1.4 n‐mole/min, corresponding to a net release of 24.6 4/‐ 8.7 n‐mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre‐labelled adipose tissue. The fractional release increased 15‐fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve‐stimulation‐induced release of [3H]purines was mainly in the form of adenosine. 4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small. 5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.

An unusual case is reported with severe erythromelalgia secondary to a sensorimotor polyneuropathy of immunological aetiology. The dominating symptoms were ongoing burning dysesthesia and pain in the legs, sustained thermal hyperalgesia and allodynia to pressure which produced intolerable pain on standing and walking. The primary pain-producing pathophysiology was apparently peripheral neurogenic inflammation with sensitization and excitation of nociceptors. The variable and progressive course prompted reassessments and successively amended multitargeted analgesic regimens. The most intensive bout of widespread pain and allodynia indicating secondary central sensitization was only controlled by adenosine treatment.

The effect of the calcium blocker nimodipine on the cerebral blood flow CBF and cerebral autoregulatory responses was examined in seven fentanylN2Oanesthetized pigs. CBF was measured continuously from the sagittal sinus by a venous outlet flow technique. Cerebral autoregulation tests were performed before, after 30 min of nimodipine infusion 0.5 g · kg1· min1, and at 30 min after the infusion. The autoregulatory response to a gradual blood pressure increase was tested by infusion of angiotensin, and to a gradual blood pressure decrease was tested by caval block. The slope of the relationship between the regional cerebral vascular resistance rCVR and mean arterial blood pressure MABP was used as a measure of the autoregulatory capacity. The lower limit of autoregulation was determined as the MABP at which rCVR did not further decrease. An i.v. bolus dose 10 g · kg1of nimodipine resulted in a transient increase in rCBF during 3 min, together with an MABP reduction. After 1 h of nimodipine infusion, MABP was reduced 19, while rCBF, rCVR, and cerebral metabolism were unaffected. In the control condition, a preserved cerebral autoregulatory response to the increase of MABP 30 mm Hg was indicated by an unaffected rCBF and determined by the slope of the rCVRMABP regression line 0.053, not different from the slope during blood pressure decrease 0.063. The cerebral autoregulatory responses to increase or decrease in MABP were not attenuated by nimodipine infusion. The lower limit of autoregulation 48 ± 6 mm Hg was not altered by nimodipine.

After 1 hour of arterial or venous occlusion, the circulatory and metabolic events in island skin flaps of the pig were studied. Both occlusion types showed significant but transient increases in glucose uptake and a parallel release of lactate, hypoxanthine, and potassium. Oxygen uptake and noradrenaline release were not significantly affected. No significant difference between the arterial and venous occlusions was seen in the metabolic parameters. The flap blood flow, measured by total venous outflow and laser Doppler flowmetry, was significantly lower after venous than after arterial occlusion. This long-lasting difference in flow response may help to explain the observation that venous occlusion is more deleterious to skin flaps than arterial occlusion. A mechanism underlying these results may be more pronounced microthrombotization and/or edema formation after venous occlusion than after arterial occlusion.

Severe hypertension and cardiac arrhythmias are well known problems during surgical removal of pheochromocytoma. This is due to extremely high circulating catecholamines during tumor manipulation. In this study, peroperative blood pressure control was obtained by the infusion of adenosine, which antagonized cardiovascular effects of catecholamines. During operation of 10 patients, none had systolic blood pressure exceeding 200 mm Hg or any cardiac arrhythmias despite extremely high plasma catecholamine levels. A mean blood pressure of 120–150 mm Hg was maintained in all patients. Peroperative use of adenosine seems to be a most effective compound for hemodynamic control during pheochromocytoma surgery.

1. The anti-aggregatory effect of adenosine (0.3–10 μmol/l), alone or in combination with the adenosine-uptake inhibitor dipyridamole (2 μmol/l), was studied in vitro in whole blood from 11 healthy subjects by filtragometry. 2. ADP (0.05–0.1 μmol/l) was used to reduce the filter occlusion time (tA, a measure of platelet aggregate formation in blood) from approximately 600 s to 71–101 s in the absence of other agents. 3. Adenosine was infused into the tubing system of the filtragometer, yielding a contact time of >25 s with the blood before the filter. Adenosine did not influence the aggregatory response to ADP significantly at 0.3 μmol/l in plasma, whereas tA was prolonged by 19 ± 6% (P <0.02) at 1 μmol/l adenosine and by 259 ± 78% (P <0.02) at 3 μmol/l adenosine. 4. When the rapid elimination of adenosine from plasma was prevented by 2 μmol/l dipyridamole, adenosine caused marked prolongation of ADP-induced tA, with significant effects at 0.3 μmol/l (± 143 ± 72%, P <0.05). Dipyridamole per se did not affect tA values. 5. The present results suggest that adenosine has a transient anti-aggregatory effect in whole blood at about 0.3 μmol/l, as this is the highest possible calculated concentration of adenosine at the filter of the apparatus when 1 μmol/l adenosine is infused in the absence of dipyridamole or when 0.3 μmol/l adenosine is infused in its presence. 6. It is concluded that adenosine has anti-aggregatory effects at submicromolar (physiological) concentrations in human whole blood. The effect of adenosine seems to be transient, indicating a role for adenosine as a localized platelet-stabilizing factor in the vicinity of, for example, the endothelium.

1. Haemodynamic and metabolic effects of intravenous infusion of adenosine, an endogenous vasodilator, were studied in healthy humans. 2. Catheters were inserted into pulmonary and brachial arteries and into the hepatic and subclavian veins. Cardiac output was determined according to the Fick principle, and splanchnic blood flow was measured by using extraction of Indocyanine Green. Skin blood flow was estimated by a laser Doppler technique, calf blood flow by venous occlusion plethysmography and skeletal muscle and adipose tissue blood flow by a local isotope clearance technique. 3. Adenosine (infused in steps from 40 to 80 μg min−-1 kg−-1 into a central vein) elicited a gradual reduction in the peripheral vascular resistance to less than 50% of the basal level. There was a slight increase in the systemic blood pressure, but the pulmonary arterial and the ventricular filling pressures were unchanged. Cardiac output was doubled, accomplished by a combination of a positive chronotropic effect and an increase in stroke volume, which may be secondary to diminished peripheral resistance. 4. Skin blood flow increased by 100% at 50 μg of adenosine min−-1 kg−-1, whereas splanchnic blood flow rose significantly at 60 μg of adenosine min−-1 kg−-1. Blood flow in the calf, gastrocnemius muscle and adipose tissue did not change significantly. 5. Arterial concentrations of noradrenaline and adrenaline increased by 62 and 43%, respectively, during infusion of adenosine. Arterial levels of glycerol were depressed by more than 50%, but those of glucose and pyruvate were unchanged. 6. In conclusion, exogenous adenosine caused a marked systemic vasodilatation, with different responsiveness in the investigated vascular beds. The vasodilatation occurred in the presence of an increase in generalized sympathetic activity. Adipose tissue blood flow was unaltered despite a considerable reduction in fat mobilization.

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 μg kg−1min−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.

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 A1adenosine 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.

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 α‐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 peroperalive 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 μg‐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.

The effect of intravenous infusion of adenosine on CBF was studied in seven patients with cerebral arteriovenous malformation. The patients were examined with positron emission tomography with controlled ventilation using [15O] water and [11C] fluoromethane as tracers. Total and regional CBF were determined before and during infusion of adenosine at rates producing a reduction of the MABP by ∼10–40%. Six patients were normoventilated, and one was hyperventilated. Mean CBF in areas with normal brain tissue was 54 ml/100 g/min before adenosine infusion under normoventilation. Adenosine infusion increased mean CBF with 23–85%. Mean CVR was decreased with 43–65% and exceeded the percentage reduction of MABP in all normoventilated subjects. In the hyperventilated patient, the reduction of CVR was similar to the reduction of MABP, and CBF was unaffected, except for a 30% increase in the thalamus. It is concluded that intravenous administration of adenosine produces marked cerebral vasodilation in normoventilated subjects and that this response can be counteracted by hyperventilation.

The effect of infusing adenosine during cardio-pulmonary bypass (CPB) on platelet count and mean arterial blood pressure (MABP) was studied in 13 patients (age 42-74), with 12 patients (age 47-66) as controls. Adenosine infusion (0.1 mg/kg/min in a central vein) caused a ten- to twentyfold increase of the adenosine concentration in the venous blood to the oxygenator, while the arterial levels were close to basal values (0.3±0.1 μM). The platelet count was significantly higher in the treated than in the placebo group during and 30 min after CPB, but not on the postoperative day. The groups did not differ with regard to the postoperative blood loss from tube drainage. Adenosine did not cause major systemic vasodilation (MABP <30 mmHg) in any case, and the blood pressure levels showed no intergroup difference during CPB. However, seven control patients but none in the adenosine group required vasodilator treatment (sodium nitroprusside) during CPB to prevent MABP from exceeding 70 mmHg. We conclude that adenosine infusion during CPB in man spares platelets, with minor changes in blood pressure.

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.

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (&lt; 100 mug 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 emmission tomography technique, was 59 ± 4 mL 100 g-1 min-1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 ± 7 mug 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, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg kg−1min−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−1min−1. The cerebral blood flow measured by positron emmission tomography technique, was 59 ± 4 mL 100 g−1min−1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 ± 7 μg kg−1min−1) the cerebral blood flow, measured by magnetic resonance imaging was 60 ± 5 mL 100 g−1min−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.

Severe hypertension and cardiac arrhythmias are well known problems during surgical removal of pheochromocytoma. This is due to extremely high circulating catecholamines during tumor manipulation. In this study, peroperative blood pressure control was obtained by the infusion of adenosine, which antagonized cardiovascular effects of catecholamines. During operation of 10 patients, none had systolic blood pressure exceeding 200 mm Hg or any cardiac arrhythmias despite extremely high plasma catecholamine levels. A mean blood pressure of 120–150 mm Hg was maintained in all patients. Peroperative use of adenosine seems to be a most effective compound for hemodynamic control during pheochromocytoma surgery. Hypertension sévère at arythmie cardiaque surviennent fréquemment pendant la chirurgie d'exérèse des phéochromocytomes. Ce phénomène est en rapport avec le taux élevé de catécholamines libérées dans la circulation pendant la manipulation tumorale. Dans cette étude, on a contrôlé la tension artérielle peropératoire par une perfusion d'adénosine, antagoniste des effets cardiovasculaires des catécholamines. Pendant l'intervention sur 10 patients, la tension artérielle n'a pas dépassé 200 mm Hg, et il n'y avait aucun cas d'arythmie malgré les taux plasmatiques de catécholamines extrêmement élevés. La tension artérielle moyenne de 120–150 mm Hg était maintenue chez tous les patients. L'utilisation peropératoire d'adénosine semble être efficace dans le contrôle hémodynamique pendant la chirurgie du phéochromocytome. La hipertensión severa y las arritmias cardiacas son dos bien conocidos problemas que pueden presentarse durante la resección quirúrgica de un feocromocitoma. Esto se debe a los muy altos niveles de catecolaminas circulantes que ocurren durante la manipulación del tumor. En el presente estudio se logró un control peroperatorio de la presión arterial mediante la infusión de adenosina, la cual antagoniza los efectos cardiovasculares de las catecolaminas. En el curso de la operación efectuada en 10 pacientes, no se observó, en ninguno de ellos, una presión arterial en exceso de 200 mm Hg o algún tipo de arritmia, a pesar de niveles extremadamente elevados de catecolaminas; se mantuvo una presión media de 120–150 mm Hg en todos los pacientes. El uso peroperatorio de la adenosina parece ser un muy efectivo agente para el control hemodinámico en el curso de la cirugía para feocromocitoma.

Summary The adenine nucleotide metabolites hypoxanthine, xanthine and uric acid were determined by high performance liquid chromatography in cerebrospinal fluid (CSF) from 25 patients with subarachnoid haemorrhage (SAH) and from 26 control subjects. In addition, the haemoglobin and protein levels in the CSF of the patients were determined.

The effects of diclofenac sodium on the kidneys were studied during 4 1/2 hours in eight patients with normal renal function. Urinary output decreased within 10 min after the injection, and maximally by 80%. The renal plasma flow and the glomerular filtration rate initially diminished significantly, by 35%, but began to increase after only 2 hours. The dominant and persistent effect was reduction of free water clearance, with maximum fall from 5.9 to 0.08 ml/min after 2 1/2 hours. The long-lasting increased tubular reabsorption of water probably is important for the lowered intrapelvic pressure that is associated with good analgetic effect of diclofenac in ureteral colic.

The influence of adenosine on blood flow, lipolysis and adrenergic neurotransmission was studied in canine subcutaneous adipose tissue in situ. Tissue concentrations of endogenous adenosine were elevated in 2 ways: (1) by inhibition of adenosine elimination by i. a. infusion of the uptake blocker dipyridamole (0.5–1.5 µM in arterial plasma) + the deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA; 3–5µM) or (2) by prolonged nerve stimulation (4 Hz for 30 min). Furthermore, effects of exogenous adenosine and the adenosine antagonist theophylline were studied. Dipyridamole+EHNA increased resting vascular conductance from 0.055 to 0.096 ml×min-1×100 g-1×mm Hg-1, whereas lipolysis induced by sympathetic nerve stimulation (2,4 and 8 Hz during 2 min) was inhibited (by 91, 71 and 34%, respectively). “Therapeutic” concentrations of theophylline (5–15 µg/ml plasma) completely reversed the effects of dipyridamole + EHNA on blood flow and significantly reversed the antilipolytic effect of these drugs. In untreated adipose tissue theophylline reduced resting vascular conductance by 40% and enhanced the lipolytic response to prolonged nerve stimulation but not that to brief nerve stimulation. Transmitter release, evaluated by the outflow of endogenous noradrenaline and/or by the outflow of radioactivity after 3H-noradrenaline labelling, was linearly related to the stimulation frequency (2,4 and 8 Hz). Dipyridamole + EHNA increased plasma noradrenaline by inhibiting uptake or binding of noradrenaline to blood cells. However, noradrenaline release induced by nerve stimulation was not significantly affected by dipyridamole + EHNA or by theophylline. It is concluded that a rise in endogenous adenosine concentration caused by drugs or by prolonged sympathetic nerve stimulation inhibits the lipolytic response to nerve stimulation without any effect on noradrenaline release. The results also show that theophylline in a therapeutic dose range is capable of enhancing lipolysis only if endogenous adenosine concentrations are raised.

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 colilipopolysaccharide endotoxin (20 μg kg−1h−1for 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.

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-1followed by an infusion starting at 12 mg·kg-1.h-1and 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 autoregulation 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.

Adenosine has been found to contract human bronchial smooth muscle in vitroand to induce bronchoconstriction in asthmatic patients when administered by inhalation. The aim of the present study was to investigate if elevation of circulating levels of adenosine influence bronchial tone or bronchial reactivity. Seven patients with bronchial asthma in whom bronchial hyperreactivity had been confirmed in a pretrial bronchial histamine challenge (PC20FEV1, 0.064 to 2.45 mg/ml) received intravenous infusions of adenosine in increasing doses (10, 30 and 50 μg/kg/min, 6 min on each dose step) or placebo (saline solution) on two different days in a randomized, single-blind manner. Heart rate, blood pressure and lung function (lung volumes, flow-volume loops and airway conductance) wre measured on each dose step. Infusion rate was held constant (at 50 μg/kg/min) throughout the trial and a bronchial methacholine challenge was performed during the infusion of adenosine or placebo. Infusions of adenosine and placebo did not influence heart rate, blood pressure or bronchial tone on either day and bronchial reactivity was similar on both days. We conclude that bronchial tone and bronchial reactivity in asthmatic patients are not increased by intravenously administered adenosine at a dose level which, in other studies, has been shown to induce regional effects in the systemic arterial circulation.

The influence of systemic adenosine infusion (30-50 μg/kg/min) on peroperative coronary graft flow was investigated in 16 patients undergoing bypass surgery. The central hemodynamic and graft flow (electromagnetic flow determination) responses were studied after 5-min, and in nine patients also after 30-min infusion. The low-dose adenosine infusion had little effect on the central hemodynamic parameters, while the graft flow increased in all patients (mean 84±12%. total 22 grafts). The adenosine-induced increase in graft flow was maintained when the infusion was prolonged. It is concluded that adenosine can produce marked coronary vasodilation in man at infusion rates that exert only minor systemic hemodynamic effects.

Myocardial energy metabolism during deep general hypothermia (20°C) and multidose crystalloid cardioplegia, and also during subsequent reperfusion, was studied in eight pat ients undergoing isolated aortic valve replacement. Six serial transmural biopsy samples from the left ventricular apex were analyzed for high-energy phosphates and their degradation products. Reductions in ATP, total adenine nucleotide content and energy charge were insignificant during cardioplegia, as were changes in adenosine and uric acid concentrations. During reperfusion, however, there was slight but significant reduction in total adenine nucleotide content, despite adequate oxygenation as indicated by reversal of lactate accumulation. These observations suggest that the reperfusion phase is accompanied by metabolic aberrations which are not overcome by good oxygenation in relation to the metabolic rate.

No abstract available.

Umbilical blood was collected immediately at birth (<30 s) in full-term infants after vaginal deliveries (n33) and elective cesarean sections (n11). Blood gases, plasma adenosine, hypoxanthine, and catecholamine concentrations were determined. In vaginally born infants the median arterial adenosine concentration was found to be 0.46 µM (range 0.13-2.06) and the venous 0.48 µM (0.09-1.62). These levels were significantly higher (p<0.01) than in infants delivered by elective cesarean section; 0.16 µM (0.04-0.42) in the artery and 0.17 µM (0.02-0.56) in the vein. Vaginally born infants showed about a 4-fold higher level of umbilical arterial catecholamines than infants born by elective cesarean section. There was a strong inverse correlation between arterial hypoxanthine concentration and pH (r =-0.81, p<0.01). It is suggested that increased adenosine release at vaginal delivery modulates the stress response elicited by the strong catecholamine surge and may furthermore exert protective effects in perinatal asphyxia

ABSTRACT: Umbilical blood was collected immediately at birth (<30 s) in full-term infants after vaginal deliveries (n = 33) and elective cesarean sections (n = 11). Blood gases, plasma adenosine, hypoxanthine, and catecholamine concentrations were determined. In vaginally born infants the median arterial adenosine concentration was found to be 0.46 µM (range 0.13-2.06) and the venous 0.48 µM (0.09-1.62). These levels were significantly higher (p < 0.01) than in infants delivered by elective cesarean section; 0.16 µM (0.04-0.42) in the artery and 0.17 µM (0.02-0.56) in the vein. Vaginally born infants showed about a 4-fold higher level of umbilical arterial catecholamines than infants born by elective cesarean section. There was a strong inverse correlation between arterial hypoxanthine concentration and pH (r =-0.81, p < 0.01). It is suggested that increased adenosine release at vaginal delivery modulates the stress response elicited by the strong catecholamine surge and may furthermore exert protective effects in perinatal asphyxia.

No abstract available.