Heart and brain circulation and CO2 in healthy men

Aim: To compare blood flow response to arterial carbon dioxide tension change in the heart and brain of normal elderly men. Methods: Thirteen healthy elderly male volunteers were studied. Hypercapnea was induced by carbon dioxide inhalation and hypocapnea was induced by hyperventilation. Myocardial blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] and cerebral blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] were measured simultaneously at rest, under carbon dioxide gas inhalation and hyperventilation using the combination of two positron emission tomography scanners. Results: Arterial carbon dioxide tension increased significantly during carbon dioxide inhalation (43.1 ± 2.7 mmHg, P < 0.05) and decreased significantly during hyperventilation (29.2 ± 3.4 mmHg, P < 0.01) from baseline (40.2 ± 2.4 mmHg). Myocardial blood flow increased significantly during hypercapnea (88.7 ± 22.4, P < 0.01) from baseline (78.2 ± 12.6), as did the cerebral blood flow (baseline: 39.8 ± 5.3 vs. hypercapnea: 48.4 ± 10.4, P < 0.05). During hypocapnea cerebral blood flow decreased significantly (27.0 ± 6.3, P < 0.01) from baseline as did the myocardial blood flow (55.1 ± 14.6, P < 0.01). However, normalized myocardial blood flow by cardiac workload [100 mL mmHg^?1 × (heart beat)^?1 × (gram of perfusable tissue)^?1] was not changed from baseline (93.4 ± 16.6) during hypercapnea (90.5 ± 14.3) but decreased significantly from baseline during hypocapnea (64.5 ± 18.3, P < 0.01). Conclusion: In normal elderly men, hypocapnea produces similar vasoconstriction both in the heart and brain. Mild hypercapnea increased cerebral blood flow but did not have an additional effect to dilate coronary arteries beyond the expected range in response to an increase in cardiac workload.     

Thermogenic response to adrenaline during restricted blood flow in the forearm

To elucidate the underlying mechanism behind the thermogenic effect of adrenaline in human skeletal muscle, nine healthy subjects were studied during intravenous infusion of adrenaline. Restriction of blood flow to one forearm was obtained by external compression of the brachial artery, to separate a direct metabolic effect of adrenaline from an effect dependent on increased blood flow. The other arm served as the control arm. In the control arm, the forearm blood flow increased 4.7-fold (from 2.0 ± 0.3 to 9.3 ± 1.5 mL 100 g^–1 min^–1, P < 0.001) during the adrenaline infusion. Adrenaline significantly increased forearm oxygen consumption (from 4.7 ± 2.1 to 7.0 ± 3.6 μmol 100 g^–1 min^–1, P < 0.025). In the arm with restricted blood flow, the forearm blood flow increased 2.9-fold (from 1.6 ± 0.3 to 4.6 ± 0.8 mL 100 g^–1 min^–1, P < 0.002) but the forearm oxygen consumption did not increase (baseline period: 5.6 ± 2.3 μmol 100 g^–1 min^–1, adrenaline period: 6.1 ± 2.1 μmol 100 g^–1 min^–1, P = 0.54). The experimental design and the difficulties in interpretation of the result are discussed. The results give evidence for the hypothesis that the vascular system plays a key role in the thermogenic effect of adrenaline in skeletal muscle in vivo.     

The Kety–Schmidt technique for repeated measurements of global cerebral blood flow and metabolism in the conscious rat

Cerebral activation will increase cerebral blood flow (CBF) and cerebral glucose uptake (CMR_glc) more than it increases cerebral uptake of oxygen (CMR_O2). To study this phenomenon, we present an application of the Kety–Schmidt technique that enables repetitive simultaneous determination of CBF, CMR_O2, CMR_glc and CMR_lac on awake, non-stressed animals. After constant intravenous infusion with ¹³³Xenon, tracer infusion is terminated, and systemic arterial blood and cerebral venous blood are continuously withdrawn for 9 min. In this paper, we evaluate if the assumptions applied with the Kety–Schmidt technique are fulfilled with our application of the method. When measured twice in the same animal, the intra-individual variation for CBF, CMR_O2, and CMR_glc were 10% (SD: 25%), 8% (SD: 25%), and 9% (SD: 28%), respectively. In the awake rat the values obtained for CBF, CMR_O2 and CMR_glc were 106 mL [100 g]^?1 min^?1, 374 μmole [100 g]^?1 min^?1 and 66 μmole [100 g]^?1 min^?1, respectively. The glucose taken up by the brain during wakefulness was fully accounted for by oxidation and cerebral lactate efflux. Anaesthesia with pentobarbital induced a uniform reduction of cerebral blood flow and metabolism by ≈40%. During halothane anaesthesia CBF and CMR_glc increased by ≈50%, while CMR_O2 was unchanged.     

Role of adenosine in exercise‐induced human skeletal muscle vasodilatation

The role of adenosine in exercise‐induced human skeletal muscle vasodilatation remains unknown. We therefore evaluated the effect of theophylline‐induced adenosine receptor blockade in six subjects and the vasodilator potency of adenosine infused in the femoral artery of seven subjects. During one‐legged, knee‐extensor exercise at ～48% of peak power output, intravenous (i.v.) theophylline decreased (P < 0.003) femoral artery blood flow (F_aBF) by ～20%, i.e. from 3.6 ± 0.5 to 2.9 ± 0.5 L min^?1, and leg vascular conductance (VC) from 33.4 ± 9.1 to 27.7 ± 8.5 mL min^?1 mmHg^?1, whereas heart rate (HR), mean arterial pressure (MAP), leg oxygen uptake and lactate release remained unaltered (P = n.s.). Bolus injections of adenosine (2.5 mg) at rest rapidly increased (P < 0.05) F_aBF from 0.3 ± 0.03 L min^?1 to a 15‐fold peak elevation (P < 0.05) at 4.1 ± 0.5 L min^?1. Continuous infusion of adenosine at rest and during one‐legged exercise at ～62% of peak power output increased (P < 0.05) F_aBF dose‐dependently to level off (P = ns) at 8.3 ± 1.0 and 8.2 ± 1.4 L min^?1, respectively. One‐legged exercise alone increased (P < 0.05) F_aBF to 4.7 ± 1.7 L min^?1. Leg oxygen uptake was unaltered (P = n.s.) with adenosine infusion during both rest and exercise. The present findings demonstrate that endogenous adenosine controls at least ～20% of the hyperaemic response to submaximal exercise in skeletal muscle of humans. The results also clearly show that arterial infusion of exogenous adenosine has the potential to evoke a vasodilator response that mimics the increase in blood flow observed in response to exercise.     

Nitric oxide regulates coronary blood flow at various coronary arterial pressures in intact porcine hearts

Nitric oxide (NO) is known to regulate basal coronary blood flow (CBF). The objective of the present study was to examine the importance of NO in CBF regulation at various coronary arterial pressures (CAPs) in vivo. Experiments were performed in 11 open-chest pentobarbitone sodium anaesthetized pigs. CAP was reduced in steps by a hydraulic occluder on the mid left anterior descending coronary artery (LAD) before and after a 5-min intracoronary infusion of the inhibitor of NO synthesis, A-nitro-L-arginine (NOARG, 30 /imo\ min“¹). CAP was recorded and NOARG infused through a catheter inserted into the LAD just distal to the occluder. CBF was measured by Doppler flowmetry on the LAD. NOARG significantly reduced CBF by 11±4, 20 ± 5, 10 ± 3, 15 ± 4, 19 ± 2, 25 ± 4 and 25 ± 5 mL min^-1 100 g^-1 (mean ± SE) at CAPs of 30 (n = 6), 40 (n = 9), 50 (n= 9), 60 (n = 9), 70 (n = 9), 80 (n = 8) and 90 (n = 6) mmHg, respectively. These decrements were not statistically different, but the percentage reductions in CBF after infusion of NOARG were significantly greatest at the lowest CAPs. The slight haemodynamic alterations induced by NOARG could not explain the reductions in CBF. Thus, the reductions in CBF after infusion of NOARG were caused by inhibition of a continuous NO release from the coronary endothelium. Coronary NO contributes significantly to CBF at all CAPs between 30 and 90 mmHg. The pronounced reduction in CBF during NO inhibition at the lower CAPs indicates an important vasodilating role of intact endothelium in a region supplied by a stenosed coronary artery.     

Effects of adenosine on ex vivo filtragometry platelet aggregation in relation to plasma levels

The aim of the present study was to investigate the concentration effect of adenosine on unstimulated platelet aggregation in humans. Adenosine infusion was given intravenously to 12 volunteers in the antecubital vein with infusion rates increasing from 20 to 100 μg kg^?1 min^?1. Filtragometry measurements were obtained from the contralateral antecubital vein before and during 100 μg kg^?1 min^?1 or during maximal tolerable infusion rate. In another set of experiments with 10 volunteers, basal filtragometry measurements were obtained before and after infusion of various concentrations of adenosine into the filtragometer test unit. With intravenous infusion aggregation time tended to increase from 333±42 to 418±8 s (mean±SEM) and increased the venous plasma adenosine concentration from 0.42±0.09 μM to 1.52±0.38 μM . Adenosine infusion into the filtragometer tubing system dose-dependently inhibited aggregation (P<0.05). Adenosine was rapidly eliminated with a half-life of adenosine in the filtragometry tubing system calculated to be about 6 s. These data extend our knowledge from an in vitroto an ex vivo situation that adenosine dose-dependently has a platelet antiaggregatory effect.     

No role of interstitial adenosine in insulin-mediated vasodilation

The mechanisms behind the vasodilatory effect of insulin are not fully understood, but nitric oxide plays an important role. We have investigated the possibility that insulin mediates vasodilatation in the human skeletal muscle via an increase in extracellular adenosine concentrations. In eight healthy subjects (H) and in four subjects with a complete, high (C5–C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min^–1 kg^–1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 ± 25 and 318 ± 18 mL min^–1 to 451 ± 41 and 530 ± 29 mL min^–1, SCI and H, respectively [mean ± SEM]). Concentrations of adenosine in the muscle ECF did not change with infusion of insulin and did not differ between groups (before: 147 ± 55 [SCI] and 207 ± 108 [H] nmol L^–1; during: 160 ± 36 [SCI] and 165 ± 74 [H] nmol L^–1). No significant correlation between concentrations of adenosine and corresponding LBF rates was achieved (LBF=[–0.0936 · Adenosine] + 475. R=–0.092, P=0.22, number of samples=181, number of subjects=12). Conclusion: the mechanism by which insulin mediates an increase in skeletal muscle blood flow is not associated with adenosine in the ECF.     

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans

The effect of intravenous administration of the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1 0.2, 1 and 8 pmol kg^?1 min^?1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95±5 mmHg to 110±6 mmHg (P<0.01) and reduced heart rate from 64±4 beats min^?1 to 58±4 beats min^?1 (P<0.05) at 8 pmol kg^?1 min^?1. Coronary sinus blood flow was reduced maximally by 23±4% (P<0.01) and coronary vascular resistance increased by 48±11% (P<0.01). Coronary sinus oxygen saturation decreased from 35±1% to 22±2% at 2 min after the infusion (P<0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction in coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24±3% over the myocardium (P<0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.     

Influence of adenosine on the vascular responses to sympathetic nerve stimulation in the canine subcutaneous adipose tissue

Adenosine appears to regulate resting blood flow in canine subcutaneous adipose tissue. Sympathetic nerve stimulation has been shown to enhance the adenosine production in this tissue. This study therefore tested the possibility that adenosine may influence the vascular responses to sympathetic nerve stimulation. Intraarterial infusion of adenosine (5–20 μM in arterial blood) increased the resting vascular conductance (from 0.048 ± 0.007 to 0.095 ± 0.013 ml ± min^-1100 g^-1± mmHg^-1) and the percental reduction in vascular conductance due to sympathetic nerve stimulation (4 Hz) by 34 per cent (p<0.05) and to i. a.noradrenaline by 27 per cent (p<0.05). The vasodilator response due to nerve stimulation after α-blockade was reduced by adenosine. Dipyridamole (0.5–1.5 μM) + EHNA (3–10 μM), which increases plasma adenosine levels, had similar effects to adenosine, while theophylline (30–80 μM) decreased the vasoconstrictor response. The vasoconstrictor escape was enhanced by EHNA alone and in combination with dipyridamole, but was reduced by theophylline. On the other hand, the poststimulatory hyperemia was unaffected by adenosine, dipyridamole and EHNA, and theophylline. The results show that adenosine does not reduce the magnitude of the initial vasoconstrictor response in proportion to the increase in resting blood flow. The autoregulatory escape in adipose tissue during nerve stimulation appears to be mediated both by adenosine and by noradrenaline acting on β-adrenoceptors. Poststimulatory hyperemia does not seem to be greatly influenced by exogenous or endogenous adenosine     

Blood flow in the rabbit tenuissimus muscle Influence of preparative procedures for intravital microscopic observation

LINDBOM, L., TUMA, R. F. & ARFORS, K.-E.: Blood flow in the rabbit tenuissimus muscle: Influence of preparative procedures for intravital microscopic observation. Acta Physiol Scand 1982, 114 :121–127. Received 21 April 1981. ISSN 0001–6772. Department of Experimental Medicine, Pharmacia AB, Uppsala, Sweden. The tenuissimus muscle in the rabbit and the cat is a suitable tissue for intravital microscopic investigation of skeletal muscle blood flow. In this study the influence of surgical procedures necessary for direct microscopic observation on the physiological state of the rabbit tenuissimus muscle was assessed by means of blood flow measurements. Mean resting blood flow was 2.8±0.8 (mean ± S.D.) ml. min^-1. 100 g^-1 in the left tenuissimus muscle when prepared for microscopic observation as determined by the radioactive microsphere method. This value was not significantly different from that in the intact unexposed muscle in the contralateral leg, 3.3 ±1.1 ml. min^-1. 100 g^-1. Exposure of the muscle to atmospheric oxygen tension resulted in a reduction of blood flow to 0.7±0.4 ml. min^-l. 100g^-l, suggesting that local metabolic control mechanisms were active. The normal range of vascular control seemed to be maintained, as demonstrated by an increase in blood flow to 64.2± 18.8 ml. min-¹. 100 g^-l during “maximal” vasodilation induced by topical application of PGE₁. The tenuissimus muscle showed a marked sensitivity to mechanical stimulation. Slight stretching of the muscle, similar to what may occur during surgical preparation, resulted in an increase in blood flow to 17.5±5.7 ml. min^-1. 100 g^-1. Flow values calculated from data obtained by direct microscopic measurements in the tenuissimus muscle agreed well with those obtained by the microsphere method.     

High afterload during 10 min of regional ischaemia affects diastolic creep but not systolic function in reperfused (stunned) myocardium

The effect of afterload during regional ischaemia on myocardial stunning was studied in 15 pentobarbital anaesthetized cats. 10 min occlusion of the left anterior descending artery (LAD) was followed by 60 min of reperfusion. Afterload was decreased by intravenous infusion of nitroglycerine 3–8 μg kg^-1 min^-1 in group I (n=8); left ventricular peak systolic pressure (LVSP) 84±4 mmHg (mean±SEM) during coronary artery occlusion. In group II (n=7) LVSP was increased to 188±10 mmHg by inflating an intraaortic balloon during coronary artery occlusion. Regional function in the LAD perfused region was evaluated by cross-oriented sonomicrometry. Myocardial tissue blood flow was evaluated by radio-labelled microspheres. Afterload alterations did not affect regional systolic shortening (10.8±2.0% vs. 11.0±1.5% in group I and II, respectively, after 60 min of reperfusion). However, increased end-diastolic dimensions (diastolic creep) in both the circumferential and longitudinal segments were markedly more pronounced in the high afterload group (group II). Also important, the markedly increased myocardial tissue blood flow during reperfusion in group II as compared with group I (2.30±0.18 vs.  1.34±0.08 mL min^-1 g^-1 and 2.58±0.23 vs. 1.49±0.07 mL min^-1 g^-1 in subepicardial and subendocardial layers in the LAD perfused region) suggests that increased diastolic creep increased metabolic demands. This study indicates that passive stretching of the ischaemic area during coronary artery occlusion is an important mechanism behind diastolic creep.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

Spatial heterogeneity of blood flow in the dog heart. II. Temporal stability in response to adrenergic stimulation

 The effects of adrenergic stimulation on local myocardial blood flow in the left ventricle were studied in 13 anaesthetized Beagle dogs using the tracer microsphere technique. Adrenergic stimulation was induced by intravenous infusion of orciprenaline (1–2 μg kg⁻¹ min⁻¹) over 15 min or by electrical stimulation of the left ansa subclavia (10 Hz, 1 ms, 4–8 V) over 5 min. Local myocardial blood flow was analysed in 256 samples with an average (±SD) mass of 318±49 mg from the left ventricular myocardium using a standardized dissection procedure. Orciprenaline increased the average myocardial blood flow from 0.85±0.18 to 1.73±0.27 ml min⁻¹ g⁻¹, while oxygen consumption and the pressure-rate product increased by 129 and 119% respectively. The coefficients of variation of local myocardial blood flow, a measure of spatial blood flow heterogeneity, were 0.21 and 0.18 under control and orciprenaline respectively. Except for a slight transmural gradient (endomyocardium/epimyocardium flow ratio 1.19) myocardial blood flow did not exhibit significant spatial gradients. Stimulation with orciprenaline increased the average blood flow in all regions of the left ventricle by comparable extents. However, local blood flow during orciprenaline was significantly lower in samples from regions which had a lower blood flow under resting control conditions. A significant positive relationship was obtained between local myocardial blood flow under resting conditions and orciprenaline (r=0.45±0.18). Moreover, after recovery from orciprenaline stimulation (i.e. 40–112 min after the end of orciprenaline infusion) local myocardial blood flow exhibited a high degree of correlation with local flow before orciprenaline (r=0.71±0.08). Comparable results were obtained with electrical stimulation of the left ansa subclavia. For the comparison stimulation vs. control, the correlation coefficient of local blood flow was 0.52±0.04 and for recovery vs. control 0.77±0.06. From these results it is concluded firstly that local myocardial blood flow under resting conditions is an important determinant of local flow during adrenergic stimulation. Secondly, the anatomical region does not have any predictive value for the blood flow change during adrenergic stimulation and finally, the close relationship between local blood flow before and after cardiac stimulation indicates that the spatial blood flow heterogeneity is temporally stable over hours. Received: 19 January 1996 / Received after revision and accepted: 15 March 1996     

K+ as a vasodilator in resting human muscle: implications for exercise hyperaemia

Aim: Potassium (K⁺) released from contracting skeletal muscle is considered a vasodilatory agent. This concept is mainly based on experiments infusing non‐physiological doses of K⁺. The aim of the present study was to investigate the role of K⁺ in blood flow regulation. Methods: We measured leg blood flow (LBF) and arterio‐venous (A‐V) O₂ difference in 13 subjects while infusing K⁺ into the femoral artery at a rate of 0.2, 0.4, 0.6 and 0.8 mmol min^?1. Results: The lowest dose increased the calculated femoral artery plasma K⁺ concentration by approx.1 mmol L^?1. Graded K⁺ infusions increased LBF from 0.39 ± 0.06 to 0.56 ± 0.13, 0.58 ± 0.17, 0.61 ± 0.11 and 0.71 ± 0.17 L min^?1, respectively, whereas the leg A‐V O₂ difference decreased from 74 ± 9 to 60 ± 12, 52 ± 11, 53 ± 9 and 45 ± 7 mL L^?1, respectively (P < 0.05). Mean arterial pressure was unchanged, indicating that the increase in LBF was associated with vasodilatation. The effect of K⁺ was totally inhibited by infusion (27 μmol min^?1) of Ba²⁺, an inhibitor of Kir2.1 channels. Simultaneous infusion of ATP and K⁺ evoked an increase in LBF equalled to the sum of their effects. Conclusions: Physiological infusions of K⁺ induce significant increases in resting LBF, which are completely blunted by inhibition of the Kir2.1 channels. The present findings in resting skeletal muscle suggest that K⁺ released from contracting muscle might be involved in exercise hyperaemia. However, the magnitude of increase in LBF observed with K⁺ infusion suggests that K⁺ only accounts for a limited fraction of the hyperaemic response to exercise.     

Assessment of renal function by 51Cr-EDTA and endogenous creatinine clearances in the pig

In anaesthetized pigs, clearances of ⁵¹Cr-EDTA (EDTA) and endogenous creatinine were compared with renal clearance of inulin measured during constant infusion after bolus injection. Creatinine was determined by enzymatic (Kodak Ektachem) as well as conventional (Jaffé) methods. In saline-loaded pigs, renal clearance of constantly infused EDTA was 97.0 ± 6.7 mL min^?1 and identical to the clearance of inulin (94.1 ± 9.1 mL min^?1). There was good agreement between individual clearances. The extraction fractions of the two markers were indistinguishable (0.26 ± 0.02 and 0.28 ± 0.03, respectively). In other experiments the clearance of EDTA calculated from the first 4 h of the time course of the plasma concentration after single injection was 64.4 ± 3.7 mL min^?1, correlating well with inulin clearance (63.0 ± 1.2 mL min^?1). When calculated only from the monoexponential phase of the disappearance curve (`slope clearance'), significantly higher results were obtained (+33%, P < 0.001). Renal clearance of EDTA after single injection was 7.5 ± 1.5 mL min^?1 (～12%) lower than inulin clearance (P < 0.001). Values of creatinine clearances determined by the two analytical methods showed a poor agreement with inulin clearance. It is concluded that, in pigs, glomerular filtration rate may be estimated by the clearance of EDTA using constant infusion or single injection of EDTA and that the renal clearance of endogenous creatinine is a less useful a measure of GFR.     

A Method for Determining Blood Flow and Oxygen Consumption in the Rat Brain

Cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo₂) were measured in rats under nitrous oxide anaesthesia, using a ¹³³Xenon modification of the Kety and Schmidt inert gas technique with sampling of cerebral venous blood from the retroglenoid vein. Extracerebral contamination of the venous blood sampled was studied by comparing the rates at which the activity of ¹³³Xenon decreased in blood and tissues. Contamination was avoided by gentle compression of the contralateral retroglenoid vein during sampling. CBF and CMRo₂ of the rat brain were 80±2 and 7.6 ± 0.2 ml·(100 g)^-1, min^-1, respectively. These values are about 25% lower than those previously obtained for cerebral cortical tissue under similar conditions. Induced hypercapnia (Paco₂ about 70 mm Hg) or hypocapnia (Paco² 15–20 mm Hg) gave rise to expected changes in CBF but did not alter CMRo² The CMRo² of the rat brain is at least twice that of the human brain. This species difference, which is similar to that previously reported for the oxygen uptake of cerebral tissue in vitro, probably reflects on inverse relationship between brain weight and neuronal packing density.     

Reduced coronary reserve in response to short-term ischaemia and vasoactive drugs in ex vivo hearts from diabetic mice

Aim: The aim of the present study was to compare the coronary flow (CF) reserve of ex vivo perfused hearts from type 2 diabetic (db/db) and non‐diabetic (db/+) mice. Methods: The hearts were perfused in the Langendorff mode with Krebs–Henseleit bicarbonate buffer (37 °C, pH 7.4) containing 11 mmol L^?1 glucose as energy substrate. The coronary reserve was measured in response to three different interventions: (1) administration of nitroprusside (a nitric oxide donor), (2) administration of adenosine and (3) production of reactive hyperaemia by short‐term ischaemia. Results: Basal CF was approximately 15% lower in diabetic when compared with non‐diabetic hearts (2.1 ± 0.1 vs. 2.6 ± 0.2 mL min^?1). The maximum increase in CF rate in response to sodium nitroprusside and adenosine was significantly lower in diabetic (0.6 ± 0.1 and 0.9 ± 0.1 mL min^?1 respectively) than in non‐diabetic hearts (1.2 ± 0.1 and 1.4 ± 0.1 mL min^?1 respectively). Also, there was a clear difference in the rate of return to basal CF following short‐term ischaemia between diabetic and non‐diabetic hearts. Thus, basal tone was restored 1–2 min after the peak hyperaemic response in non‐diabetic hearts, whereas it took approximately 5 min in diabetic hearts. Conclusion: These results show that basal CF, as well as the CF reserve, is impaired in hearts from type 2 diabetic mice. As diabetic and non‐diabetic hearts were exposed to the same (maximum) concentrations of NO or adenosine, it is suggested that the lower coronary reserve in type 2 diabetic hearts is, in part, because of a defect in the intracellular pathways mediating smooth muscle relaxation.     

Increase in local cerebral blood flow induced by circulating adrenaline: involvement of blood-brain barrier dysfunction

The influence of intravenous infusion of adrenaline (8 μg · kg^-1· min^-1) upon local cerebral blood flow (CBF) in paralyzed and artificially ventilated rats was measured autoradio-graphically with ¹⁴C-iodoantipyrine as the diffusible tracer. At this dose, adrenaline invariably increased local CBF even though blood pressure was close to normal at the time of the CBF measurement. In average, local CBF increased to 400% of control. In 6 of 9 animals the increase in flow was inhomogenous with randomingly distributed areas of very high flow rates. Experiments with i.v. administration of Evans blue prior to infusion of adrenaline showed that areas of Evans blue extravasation appeared in 3 of 4 animals. Although areas of extravasation often corresponded to areas of high flow rates the former were much more circumscribed. Furthermore, very high flow rates were found in areas showing no sign of blood-brain barrier dysfunction. It is concluded that the increase in CBF was at least partly due to a pressure-mediated passage of adrenaline across the blood-brain barrier but that such a passage can occur in the absence of macroscopically visible extravasation of protein.     

Cerebral oxygenation decreases during exercise in humans with beta‐adrenergic blockade

Aim: Beta‐blockers reduce exercise capacity by attenuated increase in cardiac output, but it remains unknown whether performance also relates to attenuated cerebral oxygenation. Methods: Acting as their own controls, eight healthy subjects performed a continuous incremental cycle test to exhaustion with or without administration of the non‐selective beta‐blocker propranolol. Changes in cerebral blood flow velocity were measured with transcranial Doppler ultrasound and those in cerebral oxygenation were evaluated using near‐infrared spectroscopy and the calculated cerebral mitochondrial oxygen tension derived from arterial to internal jugular venous concentration differences. Results: Arterial lactate and cardiac output increased to 15.3 ± 4.2 mm and 20.8 ± 1.5 L min^?1 respectively (mean ± SD). Frontal lobe oxygenation remained unaffected but the calculated cerebral mitochondrial oxygen tension decreased by 29 ± 7 mmHg (P < 0.05). Propranolol reduced resting heart rate (58 ± 6 vs. 69 ± 8 beats min^?1) and at exercise exhaustion, cardiac output (16.6 ± 3.6 L min^?1) and arterial lactate (9.4 ± 3.7 mm ) were attenuated with a reduction in exercise capacity from 239 ± 42 to 209 ± 31 W (all P < 0.05). Propranolol also attenuated the increase in cerebral blood flow velocity and frontal lobe oxygenation (P < 0.05) whereas the cerebral mitochondrial oxygen tension decreased to a similar degree as during control exercise (delta 28 ± 10 mmHg; P < 0.05). Conclusion: Propranolol attenuated the increase in cardiac output of consequence for cerebral perfusion and oxygenation. We suggest that a decrease in cerebral oxygenation limits exercise capacity.     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.