Villus tip microcirculation in the rat duodenum

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rev) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rev increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by ～ 10% of the blood volume) reduced rev in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rev in the villus capillaries exposed to abdominal Po₂ (～ 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.     

Effect of indomethacin on cerebral blood flow and development of oxygen convulsions

Hyperbaric oxygenation modulates cerebral blood flow affecting the development of oxygen convulsions. Before hyperbaric oxygenation-induced convulsions in rats the initial decrease in blood flow gave place to hyperemia, Po₂ increased. In rats receiving cyclooxygenase inhibitor indomethacin no convulsions were observed, blood flow and Po₂ were lower than in controls. Our results indicate that indomethacin prevents hyperemia and alleviates oxygen convulsions under conditions of hyperbaric oxygenation. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 142, No. 7, pp. 31–33, July, 2006     

A non-invasive measure of changes in blood flow in the human anterior tibial muscle

We used photoplethysmography (PPG) to monitor blood flow changes in the human anterior tibial muscle during arterial occlusion and during isometric and concentric contractions. Single-fibre laser-Doppler flowmetry (LDF) was used as a reference in 12 healthy subjects (5 men, 7 women; mean age 24 years). Post-exercise hyperaemic muscle blood flow (MBF) was measured immediately after isometric dorsiflexion of the ankle joint at maximal contraction for 1 min and full range-of-motion dorsiflexion and plantar flexion of the ankle joint for 1 min. A thigh tourniquet was applied for the evaluation of post-occlusive reactive hyperaemia. The MBF (baseline=100%) was [mean (SD)] 150 (31)% (P=0.003) by PPG (880 nm) and 182 (66)% (P=0.012) by LDF. After 1 min of maximal isometric contraction, MBF increased to 150 (51)% (P=0.003) by PPG (880 nm) and to 169 (43)% (P=0.005) by LDF. After 1 min of maximal concentric contractions, MBF increased to 158 (59)% (P=0.003) by PPG (880 nm) and to 170 (99)% (P=0.008) by LDF. Skin blood flow, PPG (560 nm), did not change significantly after isometric or concentric contractions. The results indicate that reactive hyperaemia after exercise and arterial occlusion can be assessed in the human anterior tibial muscle using PPG. Electronic Publication     

Laser-Doppler measurements of concentration and velocity of moving blood cells in rat cerebral circulation

In brain cortex all capillaries are perfused with plasma at anyone time while the flow of blood cells is heterogenous. Increased blood flow is associated with increased number of moving erythrocytes in the microcirculation, while capillary recruitment in its classical anatomical sense appears not to exist in the brain. Modulation of the concentration of flowing erythrocytes may influence the oxygen supply to the tissue. Therefore, we examined the possibility that laser-Doppler flowmetry (LDF) could be used to quantify changes in the microvascular concentration of moving blood cells (CMBC) and blood cell velocity (< v >) by comparing LDF measurements with electromagnetic flow measurements in vitro, and confocal laser-scanning microscopy in vivo in the brain of anaesthetized male Wistar rats. In vitro measurements showed that CMBC was affected by changes in haematocrit, while < v > correlated almost linearly with blood cell velocity measured electromagnetically within a relevant physiological range. In vivo studies during hypercapnia (Paco ₂ from 39 ± 4 to 66 ± 5 mmHg) with confocal laser scanning microscopy disclosed a 39 ± 10% increase of cortical capillary erythrocytes, while CMBC measured with LDF increased by 37 ± 5%. Erythrocyte flow velocity in brain cortex capillaries increased by 65 ± 17% with confocal microscopy as compared to 72 ± 8% with LDF. Local electrical stimulation of cerebellar cortex, and application of adenosine or sodium-nitroprusside, increased CMBC and < v > simultaneously, while during hypercapnia the < v > increase preceded the CMBC increase by 30 s. The CMBC rise rapidly reached a steady state in response to all types of stimulation, while < v > continued to increase during the major part, or the entire stimulation period. In conclusion, our data support the hypothesis that LDF may be useful for haemodynamic studies of brain microcirculation.     

Systemic hypoxia and hyperoxia,and liver blood flow and oxygen consumption in the greyhound

The effects of systemic hypoxia upon liver blood flow and oxygen consumption were studied in a group of six pentobarbitone anaesthetised greyhounds. The effect of systemic hyperoxia upon the same factors were also studied in a further group of six greyhounds.Hypoxia studied atPaO₂ tensions of 9.3, 7.3, 5.3 and 3.3 kPa was found to increase mean arterial pressure significantly at eachPaO₂ tension studied immediately the hypoxic gas mixture was introduced but this pressure had returned to control by the time 20 min had passed. At the same time a significant decrease in hepatic arterial blood flow was seen, returning to control by 20 min. No significant changes were seen in portal venous blood flow. Hepatic arterial and mesenteric vascular resistance increased significantly immediately hypoxia was instituted at allPaO₂ tensions.Hepatic oxygen consumption, measured after 20 min, decreased at allPaO₂ tensions, significantly at 3.3 kPa (25 mm Hg). Hepatic venous oxygen content decreased significantly at eachPaO₂, decreasing to 20% of control at 3.3 kPa (25 mm Hg).Hyperoxia studied atPaO₂ tensions of 26.6, 39.9 and 53.2 kPa produced no significant effects upon liver blood flow. However, there was a small increase in hepatic oxygen consumption.     

Energy turnover and lactate dehydrogenase activity in detrusor smooth muscle from rats with streptozotocin-induced diabetes

Force generation and tissue glucose metabolism were measured in the urinary bladder smooth muscle from rats with streptozotocin-induced diabetes (7–8 wk duration). Bladder wet wt was almost 4–fold higher in the diabetic animals compared with the untreated controls. Morphological analysis showed that the growth was associated with hypertrophy of the smooth muscle component in the bladder wall. Force generation of isolated bladder strip preparations was measured in vitro at different ambient oxygen tensions. Activation of intramural nerves, with electrical field stimulation, induced contractions that were unaffected by reduction of oxygen tension down to Po₂ 100 mmHg for both control and diabetic muscle strips. At zero Po₂ force was reduced by approximately 10–20% in both groups. High-K⁺ solution induced ‘tonic’ contractions that were slightly more inhibited by lowering Po₂. At intermediate Po₂ (between 100 and 20 mmHg) the diabetic muscle gave slightly higher force. At zero Po₂ no significant difference could be detected between strips from control and diabetic animals. Oxygen consumption and lactate production in the preparations were determined at a Po₂ of 290 mmHg and related to the volume of smooth muscle. At zero Po₂ lactate formation increased 3- to 4-fold. The metabolic tension cost was lower at zero Po₂ No differences in basal and contraction related metabolic rates could be detected between the two groups under normoxic and anoxic conditions. The maximal activity of lactate dehydrogenase (LDH) determined in tissue sampIes was about 2-fold higher in the diabetic bladder muscle. This increased enzymatic activity could thus not be correlated with any altered metabolic properties of the smooth muscle in the urinary bladder from diabetic rats.     

Beta2-adrenergic attenuation of capillary pressure autoregulation during hemorrhagic hypo tension,a mechanism promoting transcapillary fluid absorption in skeletal muscle

The aim of this study was to evaluate a possible humoral β₂-adrenergic effect on the capillary pressure autoregulation capacity in cat skeletal muscle during bleeding. For this purpose capillary pressure autoregulation in response to graded decrease in arterial pressure was studied in sympathectomized muscle in the control state, and during haemorrhagic hypovolaemia in the presence and absence of selective β₂-adrenoceptor blockade (ICI 118,551). The study was performed with a technique that permits continuous recordings of average capillary pressure in absolute terms and of the regional pre- and postcapillary vascular resistance, from which the pre- to post capillary resistance ratio could be determined. In the pre-haemorrhagic control state, an experimental decrease in arterial pressure from 100 to 50 mmHg caused a fall of capillary pressure from 17.6 by only 1.7 mmHg (ΔP_A/ΔP_c= 29), demonstrating an efficient capillary pressure autoregulation. This autoregulation was accomplished by a decrease in pre- to post capillary resistance ratio in turn being a result of active precapillary dilatation and a passive increase in post capillary vascular resistance. Haemorrhage per se, via a humoral α-adrenergic preferentially precapillary vaso-constriction, caused a decrease in capillary pressure to 16.8 mmHg at arterial pressure 100 mmHg. A superimposed decrease in arterial pressure to 50 mmHg resulted in a capillary pressure fall by 3.7 mmHg (ΔP_A/ΔP_e= 14), indicating impaired autoregulation capacity. This attenuation to a great extent could be ascribed to adrenaline-induced B₂-adrenoceptor stimulation, since β₂-blockade restored the Δ arterial pressure/capillary pressure ratio to 20. Low-dose isoprenaline infusion in the control state similarly caused marked impairment of capillary pressure autoregulation. The β₂-adrenergic attenuation of capillary pressure autoregulation appears to be a beneficial effect in haemorrhagic hypotension, since it lowers capillary pressure passively in relation to the arterial pressure fall, thereby reinforcing the a-adrenergic active capillary pressure decrease, leading to more effective transcapillary fluid absorption and, hence, improved replenishment of plasma volume.     

Laser-Doppler and plethysmographic skin blood flow during exercise and during acute heat stress in the sauna

Summary Forearm skin blood flow was measured in six male subjects by laser-Doppler flowmetry (LDF) and venous occlusion plethysmography (VOP) during constant-load (125–200 W) upright bicycle exercise in a warm environment ( + SD,t _a 34.6±0.2‡ C) and during a 15 min sauna bath (t _a 69.0±2.8‡ C). During the sauna test the LDF values correlated well with the VOP measurements in the initial phase of active cutaneous va-sodilation, after which the LDF values almost leveled off in spite of a steady increase in VOP measurements. During the exercise the mean VOP and LDF values rose in parallel with each other to steady state levels. The relationship between the results of the two methods proved to be nonlinear. It was concluded that different parameters were measured by VOP and LDF. The latter measured mainly the integrated velocity of blood flow in the outermost cutaneous tissue, and this velocity seemed to be partly dependent on the level of the arterial inflow (VOP), but also on the prevailing pressure-flow and pressure-volume relations in the cutaneous vascular bed.     

Tissue oxygenation measured with near-infrared spectroscopy during normobaric and hyperbaric oxygen breathing in healthy subjects

To evaluate the possibility of using near-infrared spectroscopy (NIRS) to measure tissue oxygenation (StO₂) during hyperbaric oxygen (HBO) therapy. Nine healthy volunteers (1 female) age 25−37 years, breathed air or oxygen. Tissue oxygenation was measured using NIRS on the thumb. Subjects were blinded to breathing gas. A range of partial pressures of oxygen were administered in 10-min intervals: 21, 101, 21 kPa (compression to 280 kPa), 59, 280, 59 (decompression), 21 kPa. Data were averaged over last 5 min at each pressure. When switching from air to normobaric oxygen (NBO 101 kPa) StO₂ increased from 83% (82−85%, median and interquartile range) to 85% (84−87%) (P < 0.01), while when switching from air at pressure (59 kPa O₂) to HBO (280 kPa), StO₂ increased from 85% (85−86%) to 88% (87−89%) (P < 0.001). There was no difference between baseline StO₂ while air breathing before NBO or after decompression. Values did not reach the maximal value of 100% at any point. The changes in hemoglobin oxygen saturation in tissue registered by the NIRS monitor when switching from air to oxygen followed inspired PO₂ under normobaric and hyperbaric conditions.     

Acute neurohormonal responses to hypoxaemia in man

We have studied the integrated neuroendocrine and haemodynamic effects of acute hypoxaemia in ten healthy volunteers studied on two separate occasions. After reaching a resting haemodynamic state, subjects breathed either room air or a nitrogen/oxygen mixture which rendered arterial oxygen saturation between 75% and 80%. Measurements of pulmonary and systemic haemodynamics were made and blood samples taken at baseline and after 30 min breathing air or the hypoxic gas. Blood was assayed for plasma sodium and potassium, renin-angiotensin-aldosterone system activity, natriuretic peptides, cortisol and catecholamines. Hypoxaemia significantly increased heart rate, cardiac output and mean pulmonary artery pressure (P _pa), but not mean arterial pressure compared with normoxaemia. Although plasma renin activity, angiotensin II and cortisol were unaffected by hypoxaemia, plasma aldosterone fell significantly in comparison with normoxaemia. This was associated with an increase in plasma atrial natriuretic peptide (ANP) but not b-type natriuretic peptide (BNP) during hypoxaemia whilst no changes were observed during normoxaemia. The increase in plasma ANP correlated positively with the increase inP _pa. During hypoxaemia there is therefore dissociation of the renin-angiotensin-aldosterone system where plasma aldosterone decreased, despite there being no effects on plasma renin activity and angiotensin II or on plasma cortisol. This dissociation may be due to increased levels of ANP but not BNP having specific inhibitory effects on aldosterone biosynthesis. ANP increased in proportion to the degree of pulmonary vasoconstriction induced by hypoxaemia which may indicate a counter-regulatory role.     

Regional cerebral blood volume response to hypocapnia using susceptibility contrast MRI

We used steady-state susceptibility contrast MRI to evaluate the regional cerebral blood volume (rCBV) response to hypocapnia in anesthetised rats. The rCBV was determined in the dorsoparietal neocortex, the corpus striatum, the cerebellum, as well as blood volume in extracerebral tissue (group 1). In addition, we used laser-Doppler flow (LDF) measurements in the left dorsoparietal neocortex (group 2), to correlate changes in CBV and in cerebral blood flow. Baseline values, expressed as a percentage of blood volume in each voxel, were higher in the brain regions than in extracerebral tissue. Hypocapnia (P(a)CO(2) approximately 25 mmHg) resulted in a significant decrease in CBV in the cerebellum (-17 +/- 9%), in the corpus striatum (-15 +/- 6%) and in the neocortex (-12 +/- 7%), compared to the normocapnic CBV values (group 1). These changes were in good agreement with the values obtained using alternative techniques. No significant changes in blood volume were found in extracerebral tissue. The CBV changes were reversed during the recovery period. In the left dorsoparietal neocortex, the reduction in LDF (group 2) induced by hypocapnia (-21 +/- 8%) was in accordance with the values predicted by the Poiseuille's law. We conclude that rCBV changes during CO(2) manipulation can be accurately measured by susceptibility contrast MRI. Copyright -Copyright 2000 John Wiley & Sons, Ltd. Abbreviations used: ANOVA analysis of variance CBF cerebral blood flow CBV cerebral blood volume CPMG Carr-Purcell-Meiboom-Gill FiO(2) fractional inspired oxygen ICP intracranial pressure LDF laser-Doppler flow MABP mean arterial blood pressure MRI magnetic resonance imaging MTT mean transit time PaCO(2) arterial partial pressure of carbon dioxide PaO(2) arterial partial pressure of oxygen PET positron emission tomography rCBV regional cerebral blood volume SPECT single-photon emission computed tomography     

Skeletal muscle StO<Subscript>2</Subscript> kinetics are slowed during low work rate calf exercise in peripheral arterial disease

The time course of muscle oxygen desaturation (StO₂ kinetics) following exercise onset reflects the dynamic interaction between muscle blood flow and muscle oxygen consumption. In patients with peripheral arterial disease (PAD), muscle StO₂ kinetics are slowed during walking exercise; potentially reflecting altered muscle oxygen consumption relative to blood flow. This study evaluated whether StO₂ kinetics measured using near infrared spectroscopy (NIRS) would be slowed in PAD during low work rate calf exercise compared with healthy subjects under conditions in which blood flow did not differ. Eight subjects with PAD and eight controls performed 3 min of calf exercise at 5, 10, 30, and 50% of maximal voluntary contraction (MVC). Calf blood flow responses were measured by plethysmography. Power outputs were similar between groups for all work rates. In PAD, the time constants of StO₂ kinetics were significantly slower than controls during 5% MVC (13.5 ± 1.7 vs. 6.9 ± 1.2 s, P < 0.05) and 10% MVC work rates (14.5 ± 2.7 vs. 6.8 ± 1.1 s, P < 0.05). Blood flow assessed when exercise was interrupted after 30 s did not differ between PAD and control subjects at these work rates. In contrast, the StO₂ time constants were not different between groups during 30 and 50% MVC work rates, where blood flow responses in PAD subjects were lower as compared with controls. Thus in PAD, the slowed StO₂ kinetic responses under conditions of unimpaired calf blood flow reflect slowed muscle oxygen consumption in PAD skeletal muscle during low work rate plantar flexion exercise as compared with healthy skeletal muscle.     

Exercise stimulus increases ventilation from maximal to supramaximal intensity

This study investigated the influence of an exercise stimulus on pulmonary ventilation (V _E) during severe levels of exercise in a group of ten athletes. The altered ventilation was assessed in relation to its effect on blood gas status, in particular to the incidence and severity of exercise induced hypoxaemia. Direct measurements of arterial blood were made at rest and during the last 15 s of two intense periods of cycling; once at an intensity found to elicit maximal oxygen uptake (VO_2max; MAX) and once at an intensity established to require 115% ofVO_2max (SMAX). Oxygen uptake (VO₂) and ventilatory markers were continually recorded during the exercise and respiratory flow-volume loops were measured at rest and during the final 30 s of each minute for both exercise intensities. When compared to MAX exercise, the subjects had higher ventilation and partial pressure of arterial oxygen (P _aO₂) during the SMAX intensity. Regression analysis for both conditions indicated the levels ofP _aO₂ and oxygen saturation of arterial blood (S _aO₂) were positively correlated with relative levels of ventilation during exercise. It was apparent that mechanical constraints to ventilate further were not present during the MAX test since the subjects were able to elevateV _E during SMAX and attenuate the level of hypoxaemia. This was also confirmed by analysis of the flow volume recordings. These data support the conclusions firstly, that overwhelming mechanical constraints onV _E were not present during the MAX exercise, secondly, the subjects exhibiting the most severe hypoxaemia had no consistent relationship with any measure of expiratory flow limitation, and thirdly, ventilatory patterns during intense exercise are strong predictors of blood gas status.     

Effects of noradrenaline and flow on lactate uptake in the perfused rat hindlimb

Skeletal muscle can release or take up lactate depending on the lactate concentration gradient across the cell membrane. In the perfused rat hindlimb without arterial lactate, both noradrenaline (NA) infusion and increased flow promote lactate release and oxygen consumption (VO ₂). However, it is unclear whether NA or increased flow rate have similar effects on lactate uptake. The present study compares these effects in the rat hindlimb perfused at a basal flow rate of 0.33 mL min^?1 g^?1 and 25 °C in the presence of added arterial lactate. When 10 mmol L^?1 L-(+)-lactate was added to the arterial perfusate, lactate was taken up (16 ± 1.0 μmol g^?1 h^?1, n = 13) by the hindlimb with a 35% higher VO ₂ than that without added lactate. Doubling perfusion flow rate enhanced lactate uptake and VO ₂ by 120% and 40%, respectively. Glucose uptake was also increased (by 253%) with increased flow. Infusion of NA increased perfusion pressure, VO ₂ and glucose uptake similarly to those induced by increased flow rate. However, lactate uptake was inhibited by NA. This inhibition was not altered by the β-adrenergic antagonist propranolol. Vasopressin also showed similar effects to NA to decrease lactate uptake associated with increased VO ₂ and vasoconstriction. These data indicate that in the presence of a high arterial lactate concentration, NA has opposite effects from increased flow rate on skeletal muscle lactate uptake although both have similar effects on lactate release in the absence of arterial lactate. Inhibition of lactate uptake may relate to the vasoconstrictive action of NA.     

Red blood cell flow cessation and diameter reductions in skeletal muscle capillaries in vivo — the role of oxygen

When perfusion pressure is reduced, red blood cell flow in the capillaries of skeletal muscle ceases at a positive pressure difference across the vascular bed, while arterioles dilate and venules are not constricted. This flow cessation (i.e., cessation of red blood cell flow) and luminal diameter changes in capillaries following femoral arterial pressure reduction were investigated in the rabbit tenuissimus muscle in situ (n=42) using intravital video microscopy. Arterial pressure was reduced by occlusion of the aorta distal to the renal arteries. During the experiments, leg and muscle were placed in a sealed box. The muscle was exposed to low PO₂ by leading a gas mixture deprived of O₂ through the box. Locally at the muscle surface, i.e., under the microscope objective, PO₂ was varied by varying the PO₂ in the superfusion solution. In all experiments, the remainder of the muscle was kept at low (< 20 mm Hg) PO₂. The incidence of flow cessation was virtually zero at low local (< 20 mm Hg) PO₂ and became almost 100% at local values above 70 mm Hg. Initial equivalent capillary diameters were 3.1–5.8 m (median 4.0 m) and did not correlate with local O₂ tension. During aorta occlusion, capillary diameters significantly (P < 0.0001) decreased by a median value of 8% at all local PO₂ values; in 14 out of 54 capillaries local diameter became less than 2.8 m. The extent of diameter reduction did not correlate with PO₂. In the 14 capillaries in which the diameter became less than 2.8 m flow cessation occurred in only four cases. The minimal diameter reached was always at the site of an endothelial nucleus. The capillary diameter reductions are probably due to passive recoil. In the 48 capillaries in which flow ceased, only in four cases did a red blood cell stop at the site of the nucleus. We conclude that capillary diameter reductions (local and generalized) lead to a considerable increase in capillary resistance which contributes to the occurrence of flow cessation but cannot solely explain it.     

Myogenic vascular regulation in skeletal muscle in vivo is not dependent of endothelium-derived nitric oxide

The hypothesis, based on in vitro experiments on large conduit arteries, that endothelium-derived nitric oxide is a mediator of vascular myogenic reactivity was tested in cat gastrocnemius muscle in vivo. This was done by comparing, in the absence and presence of effective endothelium-derived nitric oxide blockade by the specific inhibitors N_G-monomethyl-l -arginine or N^G-nitro-l -arginine methyl ester, myogenic responses in defined consecutive vascular sections to dynamic vascular transmural pressure stimuli, to arterial occlusion (reactive hyperaemia), and to arterial pressure changes (autoregulation of blood flow and capillary pressure). The results demonstrated that the myogenic vascular reactivity to quick ramp transmural pressure stimuli was not attenuated by endothelium-derived nitric oxide blockade, but rather reinforced. The amplitude of the reactive hyperaemia response was unaffected by endothelium-derived nitric oxide blockade, but its duration was shortened because of faster myogenic constriction, especially of large-bore arterial resistance vessels > 25 μm, in the recovery phase. Both the improved myogenic responsiveness to transmural pressure stimuli and the shortening of the reactive hyperaemia by endothelium-derived nitric oxide blockade suggested that endothelium-derived nitric oxide released in vivo acts as a ‘metabolic’ factor which certainly does not improve, but rather depresses myogenic vascular reactivity. Autoregulation of blood flow and capillary pressure were well preserved in the presence of endothelium-derived nitric oxide blockade. It was concluded from the results of these multifaceted tests that myogenic vascular regulation in skeletal muscle in vivo seems independent of endothelium-derived nitric oxide. Nor did, endothelium-derived nitric oxide seem to play a role as a ‘metabolic’ mediator of the functional hyperaemia response to muscle exercise, since the magnitude of this response was the same in the absence and presence of endothelium-derived nitric oxide blockade.     

Arterioles’ contribution to oxygen supply to the skeletal muscles at rest

We tested the hypothesis that oxygen is supplied to the resting skeletal muscle by arterioles rather than by capillaries. This hypothesis was evaluated in rats and rabbits by combining different approaches (1) determination of the intravascular oxygen tension (PO₂) in arterioles of different diameters, (2) measurement of the perfused capillary number in response to changes in tissue PO₂, and (3) estimation of the optimum capillary number to provide oxygen efficiently to the surrounding tissue. The intravascular PO₂ values of arterioles along the vessels decreased downstream, suggesting that a significant amount of oxygen diffuses from the arterioles to the surrounding tissue. The perfused capillary number decreased as the tissue PO₂ level was elevated, and this mutual relationship displayed a nonlinear correlation. The results suggest that a boundary PO₂ level affecting the capillary recruitment exists for tissue PO₂ of less than 40 mmHg with the capillary blood-flow stops above that PO₂ level. At a high PO₂ level, therefore, the oxygen is supplied from the arterioles. Furthermore, an estimation of optimum capillary number reveals that the capillary arrangement is constructed to achieve sufficient oxygen supply to the muscle during exercise, rather than at rest. These results suggest that oxygen is supplied from arterioles to the resting skeletal muscle, whereas the oxygen is supplied from the capillaries during exercise.     

Specific blood flow reducing effects of hyperoxaemia on high flow capillaries in the pig brain

The mechanisms behind oxygen mediated changes in tissue blood flow remain unsettled. Today these are thought to (from experiments on separate vessels and other tissues than the brain) operate through the vessels themselves, probably by involvement of the endothelium in the distal parts of the vascular tree. The aim of this study was to investigate how hyperoxaemia affects the cerebrocortical capillary blood flow distribution in order to gain further knowledge of oxygen mediated blood flow regulating mechanisms. The experiments were performed on seven ventilated anaesthetized pigs. A multiwire Clark-type microelectrode, placed on the brain surface (motor cortex), was used for capillary blood flow (hydrogen clearance) and oxygen pressure measurements, both of which were made at normoxaemia (arterial PO2 14.4 kPa) and hyperoxaemia (arterial PO2 50.4 kPa)(the animals serving as their own control). Blood pressure, arterial PCO2 and pH remained unchanged throughout the experiments. During hyperoxaemia a 11% reduction in the cerebrocortical capillary blood flow was found (P < 0.001). This flow reduction was seen mainly in two capillary blood flow classes (6/7 animals). In parallel a heterogeneous increase in the cerebrocortical oxygen pressures from 4.5 to 10.1 kPa (mean) (P < 0.001) was found. These results show that hyperoxaemia causes a selective reduction in capillary blood flow affecting capillaries at specific flow levels. A finding that suggests, for the brain, that both the oxygen sensor and effect mechanism is situated distally, in the vascular tree.     

Human cardiovascular adjustments to acute hypoxaemia

Traditionally, cardiovascular adjustments to hypoxaemia are viewed as resultants of competing local vasodilation and vasoconstriction via arterial chemoreflexes with net effects of increased cerebral and coronary blood flows (local) and reduced flow to visceral organs and muscle (reflex). Although true in asphyxia, breathing activates lung mechanoreceptors which reduce vagal outflow and apparently, in humans, abolishes sympathetic vasomotor activity (SNA). During rest, moderate to severe hypoxaemia (PaO2 = 35 to 27 mmHg) caused no splanchnic, cutaneous or muscle vasoconstriction. Local vasodilator effects of hypoxaemia were not sufficient to overwhelm vasoconstriction; splanchnic arterioles responded normally to infused noradrenalin (NA) during hypoxaemia. Possibly, central effects of hypoxaemia blunt SNA or peripheral, prejunctional effects impair neuronal release of NA. Persistent orthostatic tolerance with normal skeletal muscle vasoconstriction and retained spinal venomotor reflexes during hypoxaemia argue against prejunctional inhibition of NA release. Results so far suggest that beyond a certain threshold, hypoxaemia centrally inhibits SNA. In contrast to rest, even moderate hypoxaemia during exercise markedly increases plasma NA concentration (and SNA), but the usual relationship among splanchnic blood flow, plasma NA and heart rate was not observed--NA and heart rate rose together, whereas the predicted splanchnic vasoconstriction was not observed. In moderate hypoxaemia, muscle blood flow and cardiac output are greater than in normoxia at a given submaximal oxygen uptake; but at maximal oxygen uptake, blood pressure, total vascular conductance and maximal cardiac output are unaffected. Given the fixed upper limit to cardiac output and the greater capacity of active muscle to vasodilate and exceed cardiac pumping capacity during hypoxaemia, we conclude that blood pressure is maintained by baroreflex- (not chemoreflex-) mediated vasoconstriction in the active muscle which must be the primary target of increased SNA and the source of NA.     

In vivo effects of endothelin-2, endothelin-3 and ETA receptor blockade on arterial,venous and capillary functions in cat skeletal muscle

Ekelund , U. 1994. In vivo effects of endothelin-2, endothelin-3 and ET_A receptor blockade on arterial, venous and capillary functions in cat skeletal muscle. Acta Physiol Scand 150, 47–56. Received 31 March 1993, accepted 25 May 1993. ISSN 0001–6772. Department of Physiology & Biophysics, University of Lund, Sweden. This study describes, in quantitative terms, the effects of endothelin-2 and endothelin-3 on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 /μm), small arterioles (< 25 μm) and the veins, as well as on capillary pressure and fluid exchange in cat gastrocnemius muscle in vivo. Infusion of endothelin-2 or endothelin-3 (200–1600 ng kg^-1 min^-1, i.a.) elicited an initial transient dilation, followed by a dose-dependent, slowly developing constrictor response, being maintained after cessation of the infusion. At the dose of 400 ng kg^-1 min^-1 (n= 9), infused i.a. during 20 min, endothelin-2 caused an average increase in total regional vascular resistance of 80%, and endothelin-3 of 35%, and the site of constrictor action of both peptides was preferentially located to the small arterioles. Endothelin-2 also constricted the veins and, hence, evoked a pronounced capacitance response, whereas endothelin-3 was devoid of any venoconstrictor effect. This difference, via effects on the pre-/post-capillary resistance ratio, led to a more pronounced fall of capillary pressure in response to endothelin-3 than to endothelin-2. The new specific competitive ET_A receptor antagonist, FR 139317, abolished the vasoconstrictor response to both endothelin-2 and endothelin-3 in vivo, whereas the preceding vasodilator responses were unaffected. These results, taken together with those of our previous analogous study of the effects of endothelin-1, indicated that all three endothelins were approximately equally as effective in eliciting the transient dilator response in skeletal muscle in vivo, whereas the order of vasoconstrictor activity was endothelin-1 > endothelin-2 > endothelin-3. Due to an especially pronounced venoconstrictor activity of endothelin-1, this peptide, in contrast to endothelin-2 and -3, evoked a rise in capillary pressure, with a consequent net transcapillary fluid filtration and muscle tissue oedema formation. The results further indicated that the vasoconstrictor responses to all endothelins in skeletal muscle were mediated by the ET_A receptor, whereas the initial transient vasodilator responses seemed to be mediated by the ET_B receptor.