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.     

Functional significance of collateral blood flow in working skeletal muscle of the dog

Summary The semitendinosus muscle of the dog is supplied by two separate arteries and drained by two corresponding veins. In the muscles used in this study no blood entering via the distal artery was found to leave via the proximal vein during perfusion through both arteries (orthograde perfusion). Therefore, collateral flow (CF) could be determined as proximal venous outflow during occlusion of the proximal artery. During orthograde perfusion total blood flow averaged 12 ml × min⁻¹ × 100 g⁻¹ at rest and 58.4 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was found to average 6.2 ml × min⁻¹ × 100 g⁻¹ at rest and increased to 9.2 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was sufficient to cover the metabolic demand of resting muscle. During exercise the O₂-uptake ( ) of the distal muscle portion was increased 13.4 fold in comparison to a 3.1 fold increase in the proximal muscle portion. The average contractile power decreased by 46%. Additional infusion of adenosine into the distal artery resulted in an increase of CF to 11.4 ml × min⁻¹ × 100 g⁻¹ and of orthograde flow to 71 ml × min⁻¹ × 100 g⁻¹. The average contractile power of the muscle increased by 13%. Both orthograde flow and CF were found to decrease with increasing muscle load. But this decrease was significantly more pronounced in the case of CF especially at a. lower range of loads. It is concluded that after acute occlusion of orthograde flow, CF is limited by the number, the size and the dilatory capacity of precapillary network vessels. Furthermore, CF is influenced considerably by changes of extravascular support. Presented in part at the 43rd Meeting of the Deutsche Physiologische Gesellschaft [9] and at the XXVI International Congress of Physiological Sciences, New Delhi [6] Supported by the Deutsche Forschungsgemeinschaft (Hi 137/6)     

Non‐invasive and quantitative evaluation of peripheral vascular resistances in rats by combined NMR measurements of perfusion and blood pressure using ASL and dynamic angiography

The in vivo determination of peripheral vascular resistances (VR) is crucial for the assessment of arteriolar function. It requires simultaneous determination of organ perfusion (F) and arterial blood pressure (BP). A fully non‐invasive method was developed to measure systolic and diastolic BP in the caudal artery of rats based on dynamic NMR angiography. A good agreement was found between the NMR approach and the gold standard techniques (linear regression slope = 0.98, R² = 0.96). This method and the ASL‐MRI measurement of skeletal muscle perfusion were combined into one single NMR experiment to quantitatively evaluate the local vascular resistances in the calf muscle of anaesthetized rats, in vivo and non‐invasively 1) at rest: VR = 7.0 ± 1.0 mmHg·min 100 g·ml^?1, F = 13 ± 3 ml min^?1.100 g^?1 and mean BP (MBP) = 88 ± 10 mmHg; 2) under vasodilator challenge (milrinone): VR = 3.7 ± 1.1 mmHg min.100 g ml^?1, F = 21 ± 4 ml min^?1.100 g^?1 and MBP = 75 ± 14 mmHg; 3) under vasopressor challenge (norepinephrine): VR = 9.8 ± 1.2 mmHg min 100 g ml^?1, F = 14 ± 3 ml min^?1.100 g^?1 and MBP = 137 ± 2 mmHg. Copyright © 2009 John Wiley & Sons, Ltd.     

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.     

Effect of regional hypoxia and blood flow on capillary permeability in canine myocardium

The effect of hypoxia and blood flow on the capillary permeability-surface area product (PS) of ⁵¹Cr-EDTA was investigated in canine myocardium of open chest anesthetized dogs at constant aortic pressure, heart rate, and cardiac output. PS was determined by bolus injection of ⁵¹Cr-EDTA into the left anterior descending coronary artery (LAD) and external registration of the response curve. Vascular conductance (G) and PS were measured: (1) during pump perfusion of LAD with arterial blood (control state), and (2) during vasodilation obtained by LAD perfusion with deoxygenated blood at same blood flow as in control state, and (3) during increased blood flow with deoxygenated blood. Mean value of G in control state was 1.31 ml. min^-l. (100 g)^-1 (mmHg)^-1. The ratio G-hypoxialG-control used to assess the extent of vasodilation was 2.42 (range 1.67–3.56) during hypoxia and unchanged flow and 2.82 (range 1.81447) during hypoxia and increased flow. Mean value of PS in control state was 36 ml. (100 g)^-1. min^-1. With maximum vasodilation and constant blood flow PS increased to 47.3 ml.(100 g)-¹.min-¹ (37%) and during increased blood flow to 69.0 ml.(100 g)^-1. min^-1 (96%). The increase in PS most likely reflects an increase in capillary surface area available for exchange of ⁵¹Cr-EDTA indicating a 1.4– to 2-fold recruitment of capillaries.     

The cortical and medullary blood flow at different levels of renal nerve activity

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64±0.09 ml·min^-1·g^-1 tissue increasing significantly (p<0.02) to 4.39±0.28 ml·min^-1·g^-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99±0.24 ml·min^-1·g^-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88±0.09 to 1.30±0.16 ml·min^-1·g^-1, i.e. a 50% increase (p<0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml·min^-1·g^-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms. It is concluded that the renal nerve activity influences the blood flow of all regions of the kidney within the entire range 0–10 Hz. The renal medullary blood flow is affected presumably to a greater extent in the low level range around the basal tone. The sympathetic nerves might then also be important with respect to the urine concentration mechanism.     

Cardiovascular responses during one- and two-legged exercise in middle-aged men

Eight healthy and regularly physically active men, 44–69 years old, performed one- and two-legged dynamic knee extension exercise at increasing work intensities, including one leading to exhaustion. Leg blood flow increased linearly in relation to work rate, reaching a peak value of 5.1 ±0.4 1 min^-1. With a mean weight of quadriceps femoris of 2.2 ±0.1 kg, a peak perfusion of 2.3 ±0.11 kg^-1 min^-1 was attained. The maximal leg oxygen uptake was 0.72 ±0.071 min^-1 (0.33 ±0.03 1 kg^-1 min^-1). At submaximal work the elevation in limb oxygen uptake accounted for between 70 and 100% of the rise in pulmonary oxygen uptake. Comparing two- with one-legged knee extension the cardiac output was 1.5 1 min^-1 higher at each work level, reaching 13.7±0.7 and 12.3 ± 1.0, respectively at exhaustion, leaving 3.5 and 7.2 1 min^-1 of blood flow to the remaining body (cardiac output –leg blood flow). The mean arterial pressure was 119 ±5 mmHg at rest and increased to 155 mmHg for both test modes at the maximal work rate. The femoral arterial and venous plasma concentrations of lactate, ammonia and noradrenaline were significantly higher for two-legged as compared with one-legged exercise at the maximal load performed. However, the rate of release per leg, for both lactate and ammonia, did not differ between the two test conditions. It is concluded that physically active middle-aged men, with a well-retained muscle mass, can maintain a high skeletal muscle perfusion, similar to that of young males. However, the blood flow is achieved with a higher mean arterial pressure and an elevated sympathetic activity, as reflected by noradrenaline in plasma and spillover from the exercising limb.     

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

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg 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 μg 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.     

The effects of hypothermia on renal function and haemodynamics in the rat

The effects of 1–2 h of hypothermia a t 28d?C and rewarming on renal function were investigated in anaesthetized rats, using conventional clearance methods and the micropuncture technique. Renal blood flow (RBF) decreased from 7.3 ± 0.51 mL min^-1 at 37.5d?C (control) to 4.0 ± 0.47 at 28d?C, with almost complete restoration to 6.9 ± 0.59 mL min^-1 after rewarming. Systemic blood pressure remained essentially unaltered. The RBF reduction seen during hypothermia was due to a 75% increase in vascular resistance, mainly attributable to constriction of the afferent arteriole and increased blood viscosity. This was accompanied by a decline in glomerular capillary pressure from 56.7 ± 0.6 to 46.4 ± 1.3 mmHg, overshooting to 59.0 ± 0.7 mmHg. The glomerular filtration rate (GFR) decreased from 1.1 ± 0.08 to 0.6 ± 0.04 mL min^-l, returning to 1.0 ± 0.07 after rewarming, a pattern also observed for single nephron GFR. This resulted from a decrease in net driving force for glomerular filtration, whereas the filtration coefficient was not affected. Both proximal and distal tubular fluid flow decreased, but fractional reabsorption remained unchanged. In contrast, urine flow increased from 1.8 ± 0.16 to 5.7 ± 1.08 μL min^-1, returning to 2.1 ± 0.18, the increase during hypothermia mainly resulting from a disproportionately reduced fluid reabsorption beyond the mid-distal tubule.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of α-adrenoceptor antagonists

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an a-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H₂ technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n= 10); yohimbine-treated (200/μg^-kg^-1 h^-1, n= 7); and prazosin-treated (50μg-kg^-1 h^-1, n= 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102±1 mmHg (mean ± SE) to approximately 50.1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109±12 ml-100 g^-1 min^-1) compared to the control group (69 ±6 ml-100 g^-1 min^-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 ± 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by α₂-adrenoceptors in the feline cerebrovascular bed.     

Capillary diffusion capacity for Cr-EDTA and cyanocobalamine in spontaneously beating rat hearts

In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr-EDTA (mol. wt = 341) and cyanocobalamine (vitamin B₁₂, mol. wt = 135) was determined in spontaneously beating Langendorff-perfused rat hearts over a wide range of coronary flow rates (700–3000 ml min-¹ 100 g-^l). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 ± 33 and 220 ± 22 ml min^-1 100 g^-1 for Cr-EDTA and vitamin B₁₂ respectively at the highest flow (2917 ±74 ml min^-1 100 g^-1). The vasculature of the heart was found to be highly hererogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of ‘equivalent pore radius’ was obtained from the ratio PS_Cr.EDTA/PS_B12, which was 2.61 ± 0.15 demonstratiag a marked restriction to diffusion corresponding to a pore radius of 51 (41–75) Å. This value is similar to that from skeletal muscle determined by the same method while PS-values are 40–45 times higher in the heart (Haraldsson & Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3-fold increase in the density of pores available for diffusion in the myocardium, compared to skeletal muscle.     

Effects of alpha2-adrenoceptor blockade and thyrotropin-releasing hormone (TRH) on the cardiovascular system in the rabbit

The effects of two different doses of thyrotropin-releasing hormone on regional blood flows were studied in urethane-anaesthetized rabbits pretreated with the α₂ adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin-releasing hormone was injected i. v. at a dose of either 0.1 mg kg^-1 or 2.0 mg kg^-1. Yohimbine and idazoxan did not modify the effect of thyrotropin-releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the α₂ adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin-releasing hormone administration. Pretreatment with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin-releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53± 1 to 75±4 g min^-1 100 g^-1 (P < 0.01) after the administration of the lower dose of thyrotropin-releasing hormone and from 64±5 to 112±17 g min^-1 100 g^-1 (P < 0.01) after the higher dose. In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P <0.05) and the caudate nucleus (P < 0.05). The results indicate that there is a yohimbine-sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin-releasing hormone in anaesthetized rabbits. There is also an activation of the sympathetic nervous system by thyrotropin-releasing hormone which results in increased vascular resistance and mean arterial blood pressure. Its effect on the vascular resistance may be enhanced by α₂ adrenoceptor blockade. In conscious animals, there seems to be a yohimbine-sensitive mechanism involved in the control of cerebral blood flow.     

In vivo evaluation of signal processors for laser Doppler tissue flowmeters

The performance of different signal processors for laser Doppler tissue flowmeters was evaluated by the use of a well defined flow model comprising a segment of the feline intestinal wall. The processor that, apart from being based on the calculation of the first moment of the power spectral density, also takes into account the effect of multiple scattering in a number of blood cells gave an output signal that was linearly related to the intestinal wall perfusion as recorded independently by a drop-counting technique. At a recording bandwidth of 12 kHz, this linear relationship was valid for the entire flow range 0–300 ml min⁻¹ 100 g⁻¹ (r=0·98). The processor based on the first moment of the power spectral density alone under-estimated the highest flow rates by about 35 per cent, while within the flow range 0–100 ml min⁻¹ 100 g⁻¹ this processor also gave an output signal linearly related to flow at a recording bandwidth of 12 kHz (r=0·96). When the bandwidth was limited to 4 kHz, the output signals from both processors were linearly related to flow only within the range 0–100 ml min⁻¹ 100 g⁻¹ (r=0·90). The output signals recorded with the 4 kHz systems were, however, generally only about 65 per cent of those recorded with the 12 kHz systems.     

Leg muscle blood flow during reactive hyperemia

Summary In normal man at rest transition from the supine to the upright body position is accompanied by autoregulation of the blood flow to tissues in the dependent extremities.In 11 young healthy males the influence of postural changes and external pressure changes on the blood flow in the anterior tibial muscle during reactive hyperemia was studied. The muscle blood flow was evaluated by means of the Xenon-133 wash-out technique. Transmural pressure changes in the resistance vessels were estimated by measuring the systolic blood pressure at ankle level, using the strain-gauge plethysmograph technique. The mean leg muscle blood flow increased from 48 ml·100 g^–1·min^–1 in a body position with the legs elevated 65 cm above heart level, to 101 ml·100 g^–1·min^–1 in the supine position, and to 151 ml·100 g^–1·min^–1 in a sitting position with dependent legs 70 cm below heart level. The muscle blood flows increased from 92 ml·100 g^–1·min^–1 at ambient pressure to 139 ml·100 g^–1·min^–1 at a subatmospheric pressure of –50 mm Hg. The differences were highly significant (P<0.001). Systemic blood pressure measured at heart level did not change during postural changes and external pressure changes. The post-ischemic muscle blood flow was found to increase with the increasing vascular transmural pressure.It is concluded that during reactive hyperemia the normal compensatory vaso-reactions can be inactivated, so that the vessels react passively to changes in transmural pressure.     

Skeletal muscle perfusion in electrically induced dynamic exercise in humans

Leg blood flow, blood pressure and metabolic responses were evaluated in six men during incremental one-legged dynamic knee extension exercise tests (no load exercise - 40 W); one performed with voluntary contractions (VOL) and one with electrically induced contractions (EMS). Pulmonary oxygen uptake was the same in both exercise modes, but the ventilatory coefficient was 2–5 L per L O₂ higher in EMS than VOL (P < 0.05). Heart rate and mean arterial pressure were slightly higher with EMS than VOL at all exercise intensities reaching 138 (EMS) and 126 bpm (VOL), as well as 148 (EMS) and 137 mmHg (VOL) at 40 W, respectively (P < 0.05). Leg blood flow, oxygen uptake and conductance were similar in the two exercise modes. At 40 W, mean muscle blood flow was close to 200 (range: 165–220) mL 100 g^-1 min^-1, mean peak muscle oxygen uptake reached 230 mL kg^-1 min^-1, and mean conductance became as high as around 45 mL min^-1 mmHg^-1, and normalized for muscle size and arterial pressure it approached 100 mL min^-1 100 g^-1 100 mmHg^-1. Lactate and ammonia efflux from the leg were higher with EMS than with VOL and the difference became larger with increasing exercise intensity (P < 0.05). Muscle glucose uptake was the same in each exercise mode. Femoral venous K⁺ concentration increased with exercise intensity and was higher with EMS than with VOL, reaching 5.1 (EMS) and 4.7 mmol L^-1 (VOL) at 40 W (P < 0.05). The study demonstrates that electrically induced dynamic exercise is associated with a marked cardiovascular response similar to voluntarily performed exercise and a more pronounced activation of the anaerobic metabolism of the muscle. Furthermore, as the electrically activated muscle group is well defined, the present results confirm that peak muscle blood flow can reach 200–250 mL 100 g^-1 min^-1.     

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.     

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart

 Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere technique (mean sample mass 319 ± 131 mg). Nitric oxide production was effectively inhibited by intravenous infusion of 20 mg/kg nitro-L-arginine methylester (L-NAME) as evidenced by a shift of the dose/response curve for the effect of intracoronary administration of bradykinin (0.004–4.0 nmol/min) on coronary blood flow. L-NAME enhanced left and right ventricular systolic pressures from 132 ± 18 to 155 ± 15 mm Hg and from 26 ± 3 to 29 ± 3 mm Hg respectively (both P = 0.043). Mean left ventricular blood flow was 1.14 ± 0.38 before and 0.99 ± 0.28 ml min^–1 g^–1 after L-NAME (P = 0.068), while right ventricular blood flow fell from 0.72 ± 0.28 to 0.53 ± 0.20 ml min^–1 g^–1 (P = 0.043). Coronary conductance of left and right ventricular myocardium fell by 31 and 43% respectively (both P = 0.043). The coefficient of variation of left ventricular blood flow was 0.26 ± 0.07 before and 0.29 ± 0.07 after L-NAME (P = 0.068), that of right ventricular blood flow was 0.27 before and after L-NAME. Skewness (0.51) and kurtosis (4.23) of left ventricular blood flow distribution were unchanged after L-NAME, while in the right ventricle skewness decreased from 0.54 to 0.09 (P = 0.043) and kurtosis (3.68) tended to decrease after L-NAME (P = 0.080). The fractal dimension (D = 1.20–1.27) and the corresponding nearest-neighbor correlation coefficient (r _n = 0.37–0.53) of left and right ventricular myocardium remained unchanged after infusion of L-NAME. From these results it is concluded that firstly, local nitric oxide release does not explain the higher perfusion of physiological high flow samples and secondly, that spatial myocardial blood flow coordination is not dependent on nitric oxide. Received: 11 July 1996 / Received after revision: 29 October 1996 / Accepted: 17 December 1996     

Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man

Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 5540%VO_2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean ± SE) 82 ± 4% of Vo_2max. During leg exercise, leg blood flow average 6.15 4.511 minutes^-1, mean arterial blood pressure 137 ± 4 mmHg and leg conductance 42.3 ± 2.2 ml minutes^-1 mmHg^-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 ± 5 mmHg and leg vascular conductance decreased transiently to 33.5 ± 3.1 ml minutes^-1 mmHg^-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure. The decrease in leg vascular conductance observed when arm cranking increased mean arterial blood pressure could be regarded more as a measure to prevent overperfusion than a measure to maintain arterial blood pressure.     

Angiotensin II infusion during β-adrenergic stimulation by isoproterenol. Effects on hepatic,splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1–0.2 μg kg^-1 min^-1 i.v.) during high β-adrenergic activity by a continuous isoproterenol infusion (0.2–0.3 μg kg^-1 min^-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic-technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 ± 3 mmHg and the stroke volume by 17 ± 6 %. Concomitantly, the hepatic and splenic blood volumes declined by 29 ± 4 and 14 ± 6 ml, respectively, and the LV end-diastolic segment length increased by 3 ± 1 %. The flow through the inferior caval vein increased by 39 ± 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.,     

Decrease of Oxygen Consumption in the Dog Liver during Temporary Arterial Occlusion

The effects of occlusion of the hepatic artery on total and regional splanchnic oxygen consumption were studied in lightly anaesthetized dogs. Mean whole body oxygen uptake (± S.D.) was 4.72 ± 0.55 ml/kg b.w. min-¹, mean liver oxygen uptake (± S.D.) 1.18 ± 0.42 ml/kg b.w. min^-1 and mean oxygen uptake of the portally-drained tissues (±S.D.) was 0.80±0.54 ml/kg b.w. min^-l during the control period. The hepatic artery contributed 45 ± 24% of the total liver oxygen uptake. The duration of occlusion was 45 min. Mean liver oxygen uptake was found to decrease to 64 % of control values. The extraction of oxygen from the portal blood increased slightly. Mean whole body oxygen uptake and mean oxygen uptake of the portally-drained tissues were unchanged. 45 min after release of the hepatic artery occlusion, liver oxygen consumption had returned to control values. It is concluded that oxygen uptake in the liver is correlated to oxygen tension.