133Xe Clearance Research Articles

Advanced Imaging Modalities in the Detection of Cerebral Vasospasm

The pathophysiology of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is complex and is not entirely understood. Mechanistic insights have been gained through advances in the capabilities of diagnostic imaging. Core techniques have focused on the assessment of vessel caliber, tissue metabolism, and/or regional perfusion parameters. Advances in imaging have provided clinicians with a multifaceted approach to assist in the detection of cerebral vasospasm and the diagnosis of delayed ischemic neurologic deficits (DIND). However, a single test or algorithm with broad efficacy remains elusive. This paper examines both anatomical and physiological imaging modalities applicable to post-SAH vasospasm and offers a historical background. We consider cerebral blood flow velocities measured by Transcranial Doppler Ultrasonography (TCD). Structural imaging techniques, including catheter-based Digital Subtraction Angiography (DSA), CT Angiography (CTA), and MR Angiography (MRA), are reviewed. We examine physiologic assessment by PET, HMPAO SPECT, 133Xe Clearance, Xenon-Enhanced CT (Xe/CT), Perfusion CT (PCT), and Diffusion-Weighted/MR Perfusion Imaging. Comparative advantages and limitations are discussed.

Impaired Delivery of Insulin to Adipose Tissue and Skeletal Muscle in Obese Women with Postprandial Hyperglycemia

An impaired transfer of insulin from the circulation to the interstitial fluid has been suggested to contribute to insulin resistance. The objective of the study was to address whether the delivery of insulin from the circulation to adipose tissue and skeletal muscle is impaired in obese women with postprandial hyperglycemia compared with lean healthy controls. Seven obese nondiabetic women with postprandial hyperglycemia and nine lean healthy women were recruited. The interstitial insulin concentration in adipose tissue and muscle tissue was measured by the microdialysis technique during an oral glucose tolerance test (75 g). In parallel, arterial insulin levels were measured. We used ¹³³Xe clearance and plethysmography to monitor blood flow. Subcutaneous needle biopsies were taken to obtain fat cell size. After oral glucose ingestion, mean arterial insulin levels were higher in obese women than in the lean group. However, interstitial insulin levels in sc adipose tissue and forearm muscle were similar in both groups. Accordingly, the proportion of circulating insulin being transported across the vascular endothelium to the interstitial fluid in adipose tissue and in muscle tissue was significantly lower in the obese compared with the lean group. Obese subjects with postprandial hyperglycemia need higher circulating insulin levels than lean controls to attain similar interstitial insulin levels in adipose tissue and skeletal muscle, indicating an impaired transfer of insulin across the endothelium.

Prolonged Exercise-Induced Stimulation of Skeletal Muscle Glucose Uptake Is due to Sustained Increases in Tissue Perfusion and Fractional Glucose Extraction

The mechanisms behind the positive effects of physical activity on glucose metabolism in skeletal muscle and the time course of the effects need to be more elucidated. The aim was to examine the prolonged effects of an acute bout of one-legged exercise on local skeletal muscle glucose utilization and tissue perfusion. Interstitial glucose concentration, local tissue perfusion, glucose uptake, and effects of insulin infusion were studied 12 h after an acute bout of exercise and without prior exercise. Ten healthy subjects, five women and five men, participated in the study. Microdialysis measurements, (133)Xe clearance, and a 2-h hyperinsulinemic euglycemic clamp were performed on two occasions. We measured interstitial glucose concentration and tissue perfusion in the quadriceps femoris muscle of both legs. Tissue perfusion (3.3 ± 0.6 ml × 100 g(-1) × min(-1) vs. 1.4 ± 0.2 ml × 100 g(-1) × min(-1); P = 0.007) and basal glucose uptake (2.3 ± 0.5 μmol × 100 g(-1) × min(-1) vs. 0.9 ± 0.2 μmol × 100 g(-1) × min(-1); P = 0.006) were increased in the leg that had exercised compared to the resting leg; the findings in the resting leg were comparable to those in the control experiment without prior exercise. The relative effect of insulin on fractional skeletal muscle glucose uptake was the same in all experimental settings, and insulin did not affect tissue perfusion. The prolonged stimulatory effect of physical exercise on skeletal muscle glucose uptake was mediated via vascular effects combined with an increase in basal glucose transport independent of enhancement of insulin responses.

Human Cerebral Blood Flow Increases After Acute Exercise: Arterial Spin Labeling MRI

There is interest in functional magnetic resonance imaging (fMRI) to measure brain activation after exercise. The blood oxygen level dependent (BOLD) fMRI signal varies with cerebral blood flow (CBF), however, it is not known if CBF changes after acute exercise. Previous methods used during exercise (Xe clearance, transcranial doppler) do not provide good spatial localization of CBF. We report the first use of arterial spin labeling (ASL) to detect changes in CBF after exercise. PURPOSE: The aims of this study were to examine: 1) the optimal inversion time to detect changes in CBF in the motor cortex from before to after acute exercise; and 2) if acute exercise alters CBF in the motor cortex at rest or during a finger tapping task. METHODS: Subjects (n = 6) performed 30 minutes of moderate intensity exercise on an electronically braked cycle ergometer (RPE 'somewhat hard'). Before and 10 minutes after exercise relative CBF was measured over four superior contiguous, 6-mm slices (1mm gap) on a 3T GE Signa scanner (8-channel coil) using multiple inversion time (TI) pulsed arterial spin labeling (PASL): FOV=24 cm2, 3.75 mm2 in-plane resolution, FA=90deg, TE=3.2 ms, TR=2000 ms, tag width=600 ms, tag thickness=10 cm, with a 1 cm gap between the tagging band and proximal slice. Two multiple TI runs were obtained at rest and during 4Hz finger-tapping. Four inversion times (675, 975, 1275, 1575 ms) were acquired per run, with 20 interleaved pairs of tag and control images per inversion time (run time 320 s). Heart rate, blood pressure and O2 content, pCO2, and respiration were recorded throughout. RESULTS: Resting CBF increased up to 20% following exercise, with significant differences obtained at an inversion time of 1575 ms (p <.05). Finger tapping-induced CBF in the motor cortex significantly increased from before to after exercise at TI = 1575 ms (p <.01). CONCLUSION: These findings suggest changes in human cerebral blood flow can be detected up to 30 minutes after moderate intensity cycling exercise using pulsed arterial spin labeling at 3T with an inversion time of 1575 ms. This study has important implications for using fMRI after exercise. Prior exercise may introduce variance into the fMRI BOLD signal that reflects increased CBF, not neural activation. Future fMRI studies should take into consideration exercise-induced changes in CBF.

The effects of vitamin E and selenium on blood flow to experimental skin burns in rats using the 133Xe clearance technique

Abstract The aim of the present experimental study was to determine and to compare the effects of vitamin E and of selenium on the blood flow to a wound region in rats, using the xenon-133 (133Xe) clearance technique. Burn wounds were made on the right thighs of rats followed by oral administration of vitamin E or selenium for a period of 10 days. The effect of vitamin E and of selenium individually on blood flow in the wound region was assessed before and after oral administration using the 133Xe clearance technique. Both vitamin E and selenium significantly increased the blood flow in the wound region (P&lt;0.05). Our results in rats suggest that both vitamin E and selenium have beneficial effects on the skin wound healing process by increasing the skin blood flow.

Muscle blood flow response to mental stress and adrenaline infusion in man: microdialysis ethanol technique compared to 133Xe clearance and venous occlusion plethysmography

Adrenaline, administered locally by microdialysis in skeletal muscle, causes vasoconstriction around the microdialysis catheter. This is contrary to the vasodilation that normally occurs when adrenaline is infused intravenously or intra-arterially. The hypothesis was tested that vasoconstriction, measured by microdialysis, would not occur with two interventions causing increased plasma levels of adrenaline, mental stress and intravenous adrenaline infusion (0.1 nmol kg(-1) min(-1)). Twenty-four men (27 +/- 1.6 years) underwent these interventions. Blood flow was determined by the microdialysis ethanol technique and (133)Xe clearance (gastrocnemius muscle, medial head) and by venous occlusion plethysmography (calf). The ethanol outflow/inflow ratio, which is inversely related to blood flow, decreased to 92.0 +/- 3.4% of basal, P = 0.014 (mean +/- SEM, n = 16) during the mental stress test, but increased to 108.3 +/- 2.2% of basal, P = 0.001 (n = 16) during the adrenaline infusion. The latter increase was abolished when adrenaline was infused during alpha-receptor blockade by phentolamine. On the contrary, by (133)Xe clearance and venous occlusion plethysmography, blood flow increased during both interventions; 2.0-1.7-fold (mental stress) and 1.3-1.4-fold (adrenaline infusion), respectively, P<0.05. Adrenaline causes vasoconstriction in skeletal muscle when blood flow is measured with the microdialysis ethanol technique, irrespective of the mode of administration. The discrepant blood flow result obtained with the microdialysis ethanol technique might, at least partly, be explained by differential diffusion properties of ethanol and (133)Xe. An additional or alternative explanation might be that an inserted microdialysis catheter shifts the balance of vasoconstrictor and vasodilator effects of adrenaline in skeletal muscle.

The Hemodynamic Response of the Cerebral Bridging Veins to Changes in ICP

To investigate the hemodynamic response of the cerebral bridging veins to increased intracranial pressure (ICP) during normo- and hyperventilation. Flow velocity (FV(m)), diameter (D), and pulsatility index (PI) were measured and calculated in the cerebral bridging veins using Color Doppler Ultrasound in seven pigs, and cerebral blood flow (CBF) was measured using (133)Xe clearance in nine pigs, both during normo- and hyperventilation. ICP was increased stepwise from baseline (about 10 mmHg) to 20 and 30 mmHg by infusion of mock CSF into the cisterna magna. Moderate elevations of ICP caused venous relative stasis as evidenced by a decrease in FV(m) and increase in diameter and PI, but no change of volume flow in the veins. CBF was stable indicating autoregulation at ICP of 20 and 30 mmHg. Parallel observations were made during normo- and hyperventilation, but at two different levels of CBF. The cerebral bridging veins dilation and blood flow velocity decrease indicate the venous relative stasis in response to the elevated ICP. This response is proposed to be caused by an ICP-dependent increase in resistance to the outflow from the cerebral bridging veins.

Effect of Insulin Catheter Wear-Time on Subcutaneous Adipose Tissue Blood Flow and Insulin Absorption in Humans

Insertion of an insulin catheter for continuous subcutaneous insulin infusion into the subcutaneous adipose tissue (SAT) causes a tissue trauma that may have consequences for insulin absorption. We evaluated the importance of insulin catheter wear-time on subcutaneous adipose tissue blood flow (ATBF) and absorption of the rapid-acting insulin analog insulin aspart over a period of 4 days. Teflon insulin catheters (Medtronic, Minneapolis, MN) were inserted into the abdominal SAT of 10 healthy men without diabetes (mean +/- SEM age, 23.0 +/- 1.1 years; body mass index, 22.1 +/- 0.7 kg/m(2)) and connected to an insulin pump delivering a constant rate of isotonic saline for 4 days. Subjects participated in four study days (days 0, 1, 2, and 4) during which ATBF around the catheter tip was measured by (133)Xe clearance and absorption of an insulin aspart bolus (0.1 U/kg) was measured for 4 h. ATBF increased from day 0 to day 2 after catheter insertion (2.6 +/- 0.6 to 4.5 +/- 0.8 mL/100 g/min; P = 0.030). By day 4, ATBF had returned to day 0 level. Time to peak plasma insulin aspart concentration after bolus administration decreased with catheter wear-time from 55 +/- 3 min on day 0 to 45 +/- 4 min on day 4 (P = 0.019). Neither peak plasma concentration nor area under the curve of insulin aspart changed significantly. Insertion of a Teflon insulin catheter into the SAT results in increased ATBF and faster absorption of insulin aspart in a period of 4 days without any change in the total amount of insulin aspart absorbed.

Decreased 133Xe clearance in the proximal femur in acromegaly.

Using the 133Xe tissue clearance method, the blood flow in the greater trochanter of the femur was studied in 30 patients with acromegaly. Both the washout rate constant (k2) and blood flow (P2) values are significantly decreased in acromegaly (p less than 0.01). There is a significant negative correlation (r = -0.42, p less than 0.05) between the flow values and mean daily concentrations of growth hormone in serum of acromegalic patients. The observations is presented as a preliminary evidence of a possible influence of growth hormone on the blood flow in bone.

A large slice of cardiac output or humble pie for the respiratory muscles?

A large slice of cardiac output or humble pie for the respiratory muscles?

Relation between angiographic cerebral vasospasm and regional CBF in patients with SAH

The relation between angiographically determined cerebral vasospasm following a subarachnoid hemorrhage and regional cerebral blood flow (CBF) was studied in 63 investigations of 45 patients. The CBF was measured using the intra-arterial 133-Xe clearance technique within one hour of angiography. A positive correlation between regional CBF and diameter of major supplying vessel was observed. However, in the 13 cases with focal vasospasm the reduction in CBF was global and not restricted to the area of the spastic vessel. The cerebral oxygen extraction was reduced but independent of the degree of vasospasm, speaking against vasospasm as the cause for the reduction in CBF. The observed association between reduction in CBF and vasospasms could be caused by a common factor responsible for development of both. Thus, it is proposed that the amount of blood escaping at time of aneurysm rupture determines 1) the amount of reduction in cerebral oxygen uptake and thereby the reduction in CBF and 2) the degree of vasospasm. If so a correlation, yet not causal, between reduction in CBF and degree of vasospasm, will be observed.

Low cerebral blood flow in hypotensive perinatal distress.

Hypoxic brain injury is the most important neurological problem in the neonatal period and accounts for more neurological deficits in children than any other lesion. The neurological deficits are notably mental retardation, epilepsy and cerebral palsy. The pathogenesis has hitherto been poorly understood. Arterial hypoxia has been taken as the obvious mechanism but this does not fully explain the patho-anatomical findings. In the present investigation we have examined the arterial blood pressure and the cerebral blood flow in eight infants a few hours after birth. The 133Xe clearance technique was used for the cerebral blood flow measurements. The study confirmed that perinatal distress may be associated with low arterial blood pressure, and it was shown that cerebral blood flow is very low, 20 ml/100 g/min or less, in hypotensive perinatal distress. It is concluded that cerebral ischaemia plays a crucial role in the development of perinatal hypoxic brain injury.

Acute Effects of Nicotine and Smoking on Blood Flow, Tissue Oxygen, and Aerobe Metabolism of the Skin and Subcutis

Nicotine released from tobacco smoke causing reduction in blood flow has been suggested as causative for postoperative wound complications in smokers, but the mechanism remains unknown. In eight healthy male smokers and eight ex-smokers, the cutaneous and subcutaneous blood flow (QBF, SqBF) was assessed by Laser Doppler and 133Xe clearance. Tissue oxygen tension (TO(2)) was measured by a LICOX O(2)-electrode. Tissue glucose and lactate (Tgluc, Tlact) were assessed by microdialysis. The parameters were studied after intravenous infusion of 1.0 mg nicotine, smoking of one cigarette, arterial occlusion, and reperfusion. Nicotine infusion decreased SqBF from 4.2 +/- 2.0 to 3.1 +/- 1.2 mL/100 g tissue/min (P < 0.01), whereas QBF was 21.7 +/- 8.6 and 22.7 +/- 9.6 Arbitrary Units (AU), respectively (P = 0.21). TO(2) increased from 49.3 +/- 12.0 to 53.9 +/- 12.0 mm Hg (P = 0.01). Tgluc and Tlact remained unaffected. Smoking decreased SqBF from 4.2 +/- 2.0 to 2.7 +/- 1.2 mL/100 g tissue/min (P < 0.01). QBF decreased from 23.4 +/- 9.2 to 20.3 +/- 7.4 AU (P < 0.01), and TO(2) decreased from 53.9 +/- 12.0 to 48.4 +/- 11.1 mm Hg (P < 0.01). Following smoking, Tgluc decreased from 0.7 +/- 0.1 to 0.6 +/- 0.1 ng/mL (P < 0.01), and Tlact increased from 0.2 +/- 0.1 to 0.3 +/- 0.2 ng/mL (P < 0.01). The observed alterations were similar in smokers and ex-smokers. Nicotine has a limited vasoactive effect in the skin and subcutis unlikely to be explained by smoking, which distinctly decreases tissue blood flow, oxygen tension, and aerobe metabolism independent of smoking status.

Effects of local α2‐adrenergic receptor blockade on adipose tissue lipolysis during prolonged systemic adrenaline infusion in normal man

During prolonged adrenaline infusion, lipolysis peaks within 30 min and thereafter tends to decline, and we hypothesized that the stimulation of local adipose tissue alpha2-adrenergic receptors accounts for this decline. The lipolytic effect of a prolonged intravenous adrenaline infusion combined with local infusion of the alpha2-blocker phentolamine in superficial and deep abdominal subcutaneous adipose tissue and in preperitoneal adipose tissue was studied in seven healthy subjects. The interstitial glycerol concentration in the three adipose tissue depots was measured by the microdialysis method. Regional adipose tissue blood flow was measured by the (133)Xe clearance technique. Regional glycerol output (lipolytic rate) was calculated from these measurements and simultaneous measurements of arterial glycerol concentrations. Adrenaline infusion increased lipolysis in all three depots (data previously published). Phentolamine infusion did not augment lipolysis in the subcutaneous depots while it increased the lipolytic rate in the preperitoneal depot. It is concluded that alpha2-adrenergic receptors do not have a significant effect on subcutaneous adipose tissue lipolysis during high circulating adrenaline concentrations, and the decrease in lipolysis in subcutaneous adipose tissue under prolonged adrenaline stimulation is thus not attributed to alpha2-adrenergic receptor inhibition of lipolysis. However, in the preperitoneal adipose tissue depot, alpha2-adrenergic receptor tone plays a role for the lipolytic rate obtained during prolonged adrenaline stimulation.

Cerebral blood flow and metabolism during exercise: implications for fatigue

During exercise: the Kety-Schmidt-determined cerebral blood flow (CBF) does not change because the jugular vein is collapsed in the upright position. In contrast, when CBF is evaluated by (133)Xe clearance, by flow in the internal carotid artery, or by flow velocity in basal cerebral arteries, a approximately 25% increase is detected with a parallel increase in metabolism. During activation, an increase in cerebral O(2) supply is required because there is no capillary recruitment within the brain and increased metabolism becomes dependent on an enhanced gradient for oxygen diffusion. During maximal whole body exercise, however, cerebral oxygenation decreases because of eventual arterial desaturation and marked hyperventilation-related hypocapnia of consequence for CBF. Reduced cerebral oxygenation affects recruitment of motor units, and supplemental O(2) enhances cerebral oxygenation and work capacity without effects on muscle oxygenation. Also, the work of breathing and the increasing temperature of the brain during exercise are of importance for the development of so-called central fatigue. During prolonged exercise, the perceived exertion is related to accumulation of ammonia in the brain, and data support the theory that glycogen depletion in astrocytes limits the ability of the brain to accelerate its metabolism during activation. The release of interleukin-6 from the brain when exercise is prolonged may represent a signaling pathway in matching the metabolic response of the brain. Preliminary data suggest a coupling between the circulatory and metabolic perturbations in the brain during strenuous exercise and the ability of the brain to access slow-twitch muscle fiber populations.

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

To study the local tissue lactate production in the normal state and its possible disturbances in insulin resistance, rates of lactate release from adipose tissue (AT) and skeletal muscle (SM) were compared postabsorptively and during a hyperinsulinemic euglycemic clamp in 11 healthy nonobese and 11 insulin-resistant obese women. A combination of microdialysis, to measure interstitial lactate, and the 133Xe clearance technique, to determine local blood flow, were used. In the controls, local blood flow increased by 40% in SM (P<0.05) and remained unchanged in AT, whereas the interstitial-plasma difference in lactate doubled in AT (P<0.005) and was unaffected in SM during hyperinsulinemia. In the obese, blood flow and interstitial-plasma difference in lactate remained unchanged in both tissues during hyperinsulinemia. The lactate release (micromol100 g-1min-1) was 1.17+/-0.22 in SM and 0.43+/-0.11 in AT among the controls (P<0.01) and 0.86+/-0.23 in SM and 0.83+/-0.25 in AT among the obese women in the postabsorptive state. During insulin infusion, lactate release in the controls increased to 1.92+/-0.26 in SM (P<0.005) and to 1.14+/-0.22 in AT (P<0.005) but remained unchanged in the obese women. It is concluded that AT and SM are both significant sources of lactate release postabsorptively, and AT is at least as responsive to insulin as SM. The ability to increase lactate release in response to insulin is impaired in AT and SM in insulin-resistant obese women, involving defective insulin regulation of both tissue lactate metabolism and local blood flow.

Comparative Analysis of Different Scintigraphic Approaches to Assess Pulmonary Ventilation

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

Muscle blood-flow following insertion of a by-pass vein-graft in femoropopliteal occlusive disease.

Abstract Muscle blood-flow has been measured by the local clearance of 133Xe in 32 patients (34 limbs) following arterial replacement with a by-pass vein-graft for atherosclerotic occlusive disease affecting the femoropopliteal segment. In 27 cases (29 limbs) in which the graft was functioning satisfactorily there was a marked improvement in muscle blood-flow with a return to within normal range in most instances. In 5 patients the graft occluded within 3 months of operation and in these cases there was no significant alteration in the muscle blood-flow following operation. The measurement of muscle blood-flow therefore provided objective corroborative evidence of the success or failure of the procedure. Seventeen of the group had muscle blood-flow measurements carried out at 3-monthly intervals for a year or more after operation. The postoperative flow tended to remain stable throughout this period, and did not show any tendency to return to the preoperative levels as has previously been reported for thrombo-endarterectomy. This lends further support for the view that in reconstructive surgery for femoropopliteal occlusive disease the long-term results are better with by-pass vein-grafts than with thrombo-endarterectomy.

Colonic anastomotic healing and oxygen tension.

Using a Clark oxygen electrode and a 133Xe clearance technique, tissue oxygen tension (T02) and blood flow have been determined in the small and large bowel of a rabbit experimental model. The predictive value of perianastomotic T02 in colonic anastomoses was determined, healing being assessed by leakage rate, tensile strength and hydroxyproline content. The effect of suture technique on colonic perianastomotic T02 has also been studied. Colonic and small intestinal T02 correlated with blood flow (r = 0.93). Basal colonic blood flow and oxygen tension were significantly lower than in the small intestine (P less than 0.01). Interrupted and continuous suture techniques decreased colonic perianastomotic T02, although mean T02 in the continuous group was significantly lower than in the interrupted group (P less than 0.01). The leakage rate was 10 per cent (1/10) for anastomoses constructed with a perianastomotic T02 above 55 mmHg compared with 100 per cent (10/10) if less than 25 mmHg (P less than 0.001). Perianastomotic T02 correlated with breaking energy (P less than 0.001), breaking strength (P less than 0.01) and hydroxyproline content (P less than 0.05).

Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo

The regulation of skeletal muscle lipolysis is not fully understood. In the present study, the effects of systemic and local noradrenaline administration on lipolysis and blood flow rates in skeletal muscle and adipose tissue were studied in vivo. First, circulating noradrenaline levels were raised tenfold by a continuous i.v. infusion (n=12). Glycerol levels (an index of lipolysis) were measured in m. gastrocnemius and in abdominal adipose tissue using microdialysis. Local blood flow was determined with the (133)Xe clearance technique and whole-body lipolysis rates assessed with a stable glycerol isotope technique ([(2)H(5)] glycerol). Second, interstitial glycerol levels in m. gastrocnemius, m. vastus and adipose tissue were measured by microdialysis during local perfusion with noradrenaline (10(-8)-10(-6) mol/l) (n=10). Local blood flow was monitored with the ethanol perfusion technique. With regard to systemic noradrenergic stimulation, no change in fractional release of glycerol (difference between tissue and arterial glycerol) was seen in skeletal muscle. In adipose tissue it transiently increased twofold (p<0.0001), and the rate of appearance of glycerol in plasma showed the same kinetic pattern. Blood flow was reduced by 40% in skeletal muscle (p<0.005) and increased by 50% in adipose tissue (p<0.05). After noradrenaline stimulation in situ, a discrete elevation of skeletal muscle glycerol was registered only at the highest concentration of noradrenaline (10(-6) mol/l) (p<0.05). Adipose tissue glycerol doubled already at the lowest concentration (10(-8) mol/l) (p<0.05). In skeletal muscle a decrease in blood flow was seen at the highest noradrenaline concentrations (p<0.05). Lipolysis and blood flow rates are regulated differently in adipose tissue and skeletal muscle. Adipose tissue displays a high, but transient (tachyphylaxia) sensitivity to noradrenaline, leading to stimulation of both lipolysis and blood flow rates. In skeletal muscle, physiological concentrations of noradrenaline decrease blood flow but have no stimulatory effect on lipolysis rates.