Measurement of myometrial blood flow in rabbits by washout of Xenon-133 after atraumatic local labelling

In vivo experiments were performed on the uterine tissue of non-pregnant estradiol treated rabbit anesthetized with sodium pentobarbitone. The average blood flow calculated from the washout of Xenon-133 after atraumatic labelling from the uterine surface was 25.4 ml-min^-1-(100 g)^-1 (range 7.4–66.6), and after local injection of the tracer in isotonic saline directly into the myometrium 24.4 ml-min^-1-(100 g)^-1(range 8.7–45.3). During the experiments a monoexponential washout curve was found for the whole washout process both after atraumatic labelling and when the injected volume was 5μl. No trauma of injection was observed using this injection volume. The results support the applicability of a monocompartmental model for the washout of inert gas from the myometrium. Thus myometrial blood flow can be calculated from the Xenon-133 washout rate at any time interval during the washout process.     

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.     

Regional blood flow in canine myocardium as determined by local washout of a freely diffusible radioactive indicator

The aim of this study has been to examine the utility of the washout of a freely diffusible radioactive indicator as a measure of regional myocardial blood flow in open-chest anesthetized dogs. The method employed was direct intramyocardial injection of Xenon-133 followed by measurement of its gamma-radiation. The experimental washout curves show, after a short acceleration period, monoexponential washout of the indicator over two decades. We found indications of insignificant veno-arterial shunting by diffusion of the blood flow level measured, insignificant arterial recirculation of the indicator, and minimal radioactive contribution to precordial residue versus time curves arising from right heart or non-myocardial tissue. We suggest that diffusion equilibrium between the tissue in the counting field and the blood leaving it is maintained during the linear down slope of two decades of the clearance curve, and that local blood flow can be calculated from washout rate constant obtained from this part of the curve. The method employing intramyocardial injection of Xenon-133 was found to give the same results as atraumatic epicardial labelling indicating negligible effect of the injection trauma and supporting the validity of the local injection method using small volumes (2–10 μl).     

Regional blood flow in canine myocardium as determined by local washout of a freely diffusable radioactive indicator.

The aim of this study has been to examine the utility of the washout of a freely diffusable radioactive indicator as a measure of regional myocardial blood flow in open-chest anesthetized dogs. The method employed was direct intramyocardial injection of Xenon-133 followed by measurement of its gamma-radiation. The experimental washout curves show, after a short acceleration period, monoexponential washout of the indicator over two decades. We found indications of insignificant veno-arterial shunting by diffusion of the blood flow level measured, insignificant arterial recirculation of the indicator, and minimal radioactive contribution to precordial residue versus time curves arising from right heart or non-myocardial tissue. We suggest that diffusion equilibrium between the tissue in the counting field and the blood leaving it is maintained during the linear down slope of two decades of the clearance curve, and that local blood flow can be calculated from washout rate constant obtained from this part of the curve. The method employing intramyocardial injection of Xenon-133 was found to give the same results as atraumatic epicardial labelling indicating negligible effect of the injection trauma and supporting the validity of the local injection method using small volumes (2-10 microliter).     

Right ventricular coronary blood flow patterns during aortic pressure reduction in renal hypertensive dogs

We measured right ventricular coronary blood flow with radioactive microspheres during graded aortic pressure reduction in 13 normal dogs and in 13 renal hypertensive dogs with left ventricular hypertrophy. Under anaesthesia and controlled loading conditions, mean aortic pressure was lowered from control (128 mmHg in normal and 146 mmHg in hypertensive dogs) to approximately 100, 90 and 80 mmHg. In normal dogs, right ventricular blood flow was not affected by this pressure reduction, consistent with effective right ventricular autoregulation. In hypertensive dogs, however, right ventricular blood flow was maintained between a mean aortic pressure of 146 and 90 mmHg (range 75–79 ml min^-1 100 g^-1) but fell by 18% to 63 ml min 100 g^-1 at a mean aortic pressure of 80 mmHg (P < 0.005). We conclude that autoregulation of right ventricular blood flow was preserved in chronic hypertension but that, compared to normal dogs, the lower limit of autoregulation was reset to a higher pressure level. Moreover, the similarity of right ventricular-to-body weight ratios in the two groups implied that this change was a consequence of hypertension-induced structural changes in the coronary vasculature.     

An evaluation of the metabolic interaction with myogenic vascular reactivity during blood flow autoregulation

An attempt was made to evaluate the possible metabolic interaction with myogenic vascular reactivity during autoregulation of blood flow in sympathectomized cat skeletal muscle. This was done by studying the extent to which a purely myogenic response, elicited by a standardized 2 s vascular transmural pressure impulse stimulus was altered when mean arterial inflow pressure was varied in the range from 160 down to 40 mmHg. The observations were made during the steady state blood flows encountered at the different pressure levels. The data were corrected for the effects of physical factors inherent in altered basal vascular tone and intravascular pressure with the aid of a mathematical model for purely myogenic responses. The results demonstrated a flow dependent decline in myogenic vascular reactivity during reduction of arterial pressure, even in the range where blood flow was autoregulated quite effectively. This suggested a significant metabolic interaction with myogenic reactivity, an interpretation corroborated by a similar decline in myogenic reactivity found during more defined activation of the vascular metabolic control system by graded light muscle exercise. The fact that a significant metabolic interaction was revealed even at such minute flow changes that occur in the autoregulatory range indicates a high ‘gain’ in the metabolic feedback interacting, directly or indirectly, with myogenic mechanisms in local vascular regulation.     

Effect of lower body negative pressure upon local regulation of blood flow in human subcutaneous tissue

Local regulation of subcutaneous blood flow in the forearm was studied during lower body negative pressure (LBNP) in 7 young healthy male subjects in supine position. Blood flow was measured on the forearm by the local ¹³³Xe washout technique. LBNP of -40 and -60 mmHg induced a decrease in the ¹³³Xe washout rate of 34 and 50% respectively. This response to LBNP could be blocked by proximal nervous blockade indicating that the vasoconstriction observed was due to a central sympathetic reflex mechanism. The vasoconstrictor response to increase in venous transmural pressure induced by lowering the arm (veno-arteriolar reflex mechanism) could not be demonstrated during 40 mmHg LBNP. The abolishment of this reflex is most likely due to centrally elicited increase in sympathetic activity as a normal veno-arteriolar reflex was elicited following proximal nervous blockade.     

Changes of collateral perfusion pressure and segmental coronary resistances during reactive hyperemia in anesthetized dogs

Changes of collateral perfusion pressure (CPP) and segmental coronary resistances during reactive hyperemia were studied in nine chloralose-urethan-morphine anesthetized open-chest dogs. Coronary perfusion pressure was controlled by a cannula in the left main coronary artery and inflow measured by an electromagnetic flowmeter. The first or second diagonal branch of the left anterior descending coronary artery was cannulated and perfused from a carotid artery; inflow was abolished by embolization with latex microspheres (diameter: 25±5 ) and peripheral coronary pressure was assumed to represent CPP. Segmental coronary resistances were defined as follows: Proximal coronary resistance (R₁) was calculated from the difference between coronary perfusion pressure and CPP devided by coronary inflow. Distal coronary resistance (R₂) was calculated from CPP divided by coronary inflow. Reactive hyperemia was produced by interruption of coronary inflow for 15 s and analysed at 30 s and 60 s of reperfusion when cardiac function had recovered. At baseline, R₁ was 0.52±0.04 mm Hg x min ×100 g/ml (RU) and R₂ 0.63±0.07 RU. At 30 s, R₁ was reduced by 19±3% (P<0.01) this was less (P<0.05) than R₂ which was reduced by 32±3% (P<0.01). At 60 s R₁ and R₂ were reduced by 11±2% and 13±2%, respectively; this was not significantly different. Accordingly, CPP (baseline: 59±4 mm Hg) at 30 s was reduced by 7±2% (P<0.03), at 60 s the reduction was not significant. The data suggest that reactive hyperemia, as a model of metabolic coronary dilatation, may reduce CPP equivalent to a coronary steal phenomenon.     

Mucosal/submucosal blood flow in the small intestine in pigs determined by local washout of 133Xe and microsphere techniques

In 11 anaesthetized pigs a laparotomy was performed and the mucosal and submucosal blood flow rate in the small intestine of the pig was determined by a local application of 133Xe and by 6.5-microns radioactive microspheres. The 133Xe washout plotted in a semilogarithmic diagram showed a multiexponential configuration. As localization studies of 133Xe in the intestinal mucosa showed a constant high concentration of 133Xe in the luminal part of the mucosa due to shunting by diffusion, the initial slope of the 133Xe washout was used for blood flow determination in the mucosa/submucosa. There was a good relationship between blood flow determined by the two techniques. The correlation coefficient, R, between the two techniques was 0.89.     

Transmural gradient of tissue gas tensions in the canine left ventricular myocardium during coronary clamping and reactive hyperemia

Mass spectrometry was used for the continuous, simultaneous and quantitative measurement of oxygen (PO₂) and carbon dioxide (PCO₂) partial pressures in the subendocardial and subepicardial layers of the left ventricle in 11 anaesthetized ventilated dogs. Under control conditions,PO₂ was significantly lower in the subendocardium (13.5±4.5 mm Hg) than in the subepicardium (20.7±2.3 mm Hg), whereasPCO₂ did not differ significantly (43±8.8 and 51±9.2 mm Hg respectively). These variables were not correlated with blood pressure or coronary blood flow. Subendocardial and subepicardialPO₂ decreased less than 5 s after coronary occlusion. These changes were more rapid and severe in the subendocardium. After occlusion for 90 s: subendocardialPO₂ was 4.1±6.3 mm Hg while subepicardialPO₂ was 6.7±15.0 mm Hg (P<0.05).PCO₂ reached peak values of 56±25 mm Hg subendocardial and 82±22 mm Hg subepicardial at 2.67±0.71 min and 3.43±0.93 min after coronary clamping. A reactive hyperemia occurred after coronary unclamping with different time courses and amplitudes for systolic and diastolic stroke flows whilePO₂ recovered with different kinetics. SubendocardialPO₂ increased with a lower initial slope, probably in relation with the delay in the diastolic hyperemia. The observed delayed subendocardial hyperoxia, unrelated to the hyperemia, may indicate a delay in the recovery of normal work and metabolism in the inner layers of the myocardium.     

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.     

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.     

Regional differences in skin blood flow as measured by radioactive microspheres

Regional skin blood flows in the trunk were measured by means of radioactive labeled microspheres in anesthetized rats and monkeys. Mean arterial pressure, heart rate, cardiac output and arterial pH, pO₂ and pCO₂ were registrated and body and ambient air temperature were kept constant for the duration of the experiments. The blood flows were determined on a total of 6 skin samples, 2 samples each from the thoracic, lumbar and sacral regions. The reproducibility of the microsphere technique for measurements of skin blood flow was evaluated in the rats by two separate microsphere injections which were given with a 10 min interval. The coefficient of variation varied with the region from 10.3 to 22.7%. In both species the skin blood flows in the thoracic regions were significantly higher than in the lumbar and sacral regions (P<0.05). The skin blood flows in the thoracic region of the rat ranged from 39–45 ml min^-1· 100 g^-1 in the lumbar region from 32–33 and in the sacral region from 29–30. In the monkeys the corresponding values for the different regions were: thoracic: 7–9, lumbar: 5–7 and sacral: 4–7 ml· min^-1· 100 g^-1, respectively. Our results support the use of radioactive microspheres for skin blood flow measurements, and demonstrate the existence of regional differences in the skin blood flow of the trunk. We suggest that this may be an important consideration during the development, and interpretation of data from experimental models in which skin blood flow is important.     

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of ‘“Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changinr the position from supine to head-up tilt, SBF decreased by 43 % (P < 0.01) at the arm level, 40% at the thigh (P < 0.01), 47% at the calf (P < 0.01) and decreased by 51 % at the ankle level (P < 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P < 0.01), 25% at the calf (P > 0.1) and increased by 18% at the ankle level (P > 0.1). At 40 heel-raisings per min SBF increased by 99% at the thigh (P < 0.0 1), 121 % at the calf (P < 0.0 1), but only 44% at the ankle level (P > 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.     

Effects of dynamic leg exercise on subcutaneous blood flow rate in the lower limb of man

Subcutaneous blood flow (SBF) was studied simultaneously in the upper arm at heart level and in the lower limb during positional changes and during leg exercise in seven healthy males. SBF was estimated by local clearance of ¹³³Xenon registered by portable cadmium telluride detectors. Venous pressure was recorded directly on dorsum on the foot. Changing the position from supine to head-up tilt, SBF decreased by 43% (P < 0.01) at the arm level, 40% at the thigh (P < 0.01), 47% at the calf (P < 0.01) and decreased by 51 % at the ankle level (P < 0.01). Performing 20 heel-raisings per min in nearly erect posture, SBF increased by 96% at the thigh (P < 0.01), 25% at the calf (P > 0.1) and increased by 18% at the ankle level (P > 0.1). At 40 heel-raisings per min SBF increased by 99% at the thigh (P < 0.01), 121% at the calf (P < 0.01), but only 44% at the ankle level (P > 0.1). During leg exercise subcutaneous vascular resistance was significantly increased at arm and ankle levels. In contrast, a vasodilatory response was noticed at the thigh and calf levels and seemed associated with a decrease in local venous pressure to below the trigger level of the sympathetic veno-arteriolar reflex mechanism. In conclusion, SBF in the lower limb of man was increased during exercise. The increase in SBF could only partly be ascribed to the concomitant increase in perfusion pressure. The local blood flow response seemed modified by changes in sympathetic nervous activity and metabolic rate.     

Variable effects of β-adrenoceptor blockade on muscle blood flow during exercise

The role of β-adrenoceptors in exercise-induced muscle hyperaemia was investigated. Exercise was performed with a small and a large muscle mass: knee extension (KE) and bicycle exercise (BE). Seven healthy subjects performed light and maximal KE and eight subjects performed stepwise dynamic BE to exhaustion before and after acute i.v. administration of propranolol (0.15 mg kg^-1). Leg blood flow was measured by a bolus dye dilution technique. During KE at low and high power leg blood flow was reduced by 8.7 and 10.5% after propranolol was administered, mean arterial blood pressure (MAP) was reduced at low, but not at high power resulting in increased leg vascular resistance (LVR) during high intensity. During BE propranolol reduced leg blood flow and increased LVR at low power, but not at high power. At high BE intensity LVR did not change with increasing power and was slightly decreased after propranolol was administered. In this situation oxygen uptake was close to maximum and the concentration of catecholamines was 3–5 times higher compared with KE. There was no significant effect of propranolol on lactate release or arterial-femoral venous (a-fv) differences for adrenaline or noradrenaline. We conclude that β-adrenoceptors modulate local vasodilation in skeletal muscles during exercise independently of local muscle energy demand, but that the effect is highly dependent on active muscle mass since a-adrenergic activity during maximal BE seemed to disguise any effect of propranolol on LVR.     

Contribution of local blood flow regulation mechanisms during head-up tilt in human subcutaneous tissue

Local and remote regulation of subcutaneous blood flow in the forearm and leg was studied during head-up tilt (30°, 457deg; and 70°) in 7 young healthy subjects. Relative blood flow was estimated by the local ¹³³Xe washout technique. Incremental levels of head-up tilt elicited increasing vascular resistance on arm and leg, respectively. Positive pressure similar to a blood column of the same height was able to prevent a significant part of the vasoconstrictor response on the leg to head-up tilt. Thus if venous distension is prevented the local veno-arteriolar reflex is abolished, whereas arteriolar constriction due to centrally elicited reflexes remains unaffected. Subcutaneous blood flow in the extremities are regulated by remote (baroreceptor) as well as local sympathetic reflex mechanisms (veno-arteriolar reflex); but the relative influence of the local veno-arteriolar reflex on the increase in total peripheral resistance seems to decrease with increasing tilt angles.