Accuracy of pulse oximetry at various haematocrits and during haemolysis in anin vitro model

In situations in which it may be impossible and/or unethical to evaluate pulse oximetry in humans, an in vitro model with circulating blood may be a necessity. The main objective was to develop such an in vitro model and, in this model, validate the pulse oximetry technique at various haematocrit levels. The pulsating character of arterial blood flow in a tubing system was simulated by using a specially constructed pressure-regulated roller pump. The tubing system was designed to minimise damage to red blood cells. The pulse oximeter readings (SpO₂) were compared with oxygen saturation analyses by a haemoximeter (SaO₂). The pulse oximetry readings were recorded at various haematocrit levels and during haemolysis in the SaO₂ range 60–100 per cent. At a haematocrit level of 41–44 per cent, there was no correlation between SaO₂ and SpO₂ readings. After diluting the blood with normal saline to a haematocrit of 10–11 per cent, a good correlation between SaO₂ and SpO₂ was found. Following haemolysis, the agreement between SaO₂ and SpO₂ was further improved. Using the developed in vitro model, the results indicate that the accuracy of a pulse oximeter may be dependent on the haematocrit level.     

A compartmental model for oxygen transport in brain microcirculation

A compartmental model is formulated for oxygen transport in the cerebrovascular bed of the brain. The model considers the arteriolar, capillary and venular vessels. The vascular bed is represented as a series of compartments on the basis of blood vessel diameter. The formulation takes into account such parameters as hematocrit, vascular diameter, blood viscosity, blood flow, metabolic rate, the nonlinear oxygen dissociation curve, arterial PO₂, P₅₀ (oxygen tension at 50% hemoglobin saturation with O₂) and carbon monoxide concentration. The countercurrent diffusional exchange between paired arterioles and venules is incorporated into the model. The model predicts significant longitudinal PO₂ gradients in the precapillary vessels. However, gradients of hemoglobin saturation with oxygen remain fairly small. The longitudinal PO₂ gradients in the postcapillary vessels are found to be very small. The effect of the following variables on tissue PO₂ is studied: blood flow, PO₂ in the arterial blood, hematocrit, P₅₀, concentration of carbon monoxide, metabolic rate, arterial diameter, and the number of perfused capillaries. The qualitative features of PO₂ distrbution in the vascular network are not altered with moderate variation of these parameters. Finally, the various types of hypoxia, namely hypoxic, anemic and carbon monoxide hypoxia, are discussed in light of the above sensitivity analysis.     

Computer control of respiration and anaesthesia

Control of a number of interactive physiological variables by an online computer, operating in real time, is demonstrated. It is shown that a computer-controlled system, by monitoring values of arterial blood pressure, end-tidal CO₂ percentage and inspired O₂ percentage, can maintain the respiration and anaesthesia of a ventialted animal within close tolerances. Under computer control, it is possible to compensate for random disturbances of the system parameters, and changes in the desired levels of the variables can be dealt with automatically.     

Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO₂) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O₂ extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO₂ of approximately 45 mmHg.     

Altered glucose metabolism and preserved energy charge and neuronal structures in the brain of mouse intermittently exposed to hypoxia

The key for an animal to survive prolonged hypoxia is to avoid rapid decline in ATP levels in vital organs such as the brain. This can be well achieved by a very few of hypoxia-tolerant animals such as freshwater turtles and newborn animals, since these animals can substantially suppress their metabolic levels by coordinated regulation of ATP-producing and ATP-demanding pathways. However, most animals, especially adult mammals, can only tolerate a short period of hypoxia since they are unable to maintain constant ATP levels and energy charge in vital organs during prolonged hypoxic exposure. Here, we described a special mouse model, in which a hypoxia intolerant adult mouse gradually built up an ability to survive prolonged hypoxia after intermittent hypoxic exposures. This increased ability was accompanied by reductions in body temperature and O₂ consumption as well as transient variations in blood pCO₂, pO₂ and pH. The glucose and energy metabolism in the brain of the mouse altered similarly to those reported in the brain of hypoxic turtles. Activities of phosphofructokinase and pyruvate kinase, the two rate-limiting enzymes controlling the rate of glycolysis decreased to baseline levels after a short period of increase. In contrast, the activity of complex I, the major enzyme complex controlling oxidative phosphorylation, was kept inhibited. These alterations in the ATP-producing pathway suggest the occurrence of reverse Pasteur effect, indicating that the animal had entered a hypometabolic state favoring maintenance of ATP level and energy charge in hypoxic conditions. In supporting this idea, the ATP levels and energy charge as well as neuronal structures in the brain were well preserved. This study provides evidence for a possibility that a hypoxic intolerant animal can build up an ability to survive prolonged hypoxia through regulation of its glucose and energy metabolism after an appropriate hypoxic training, which deserves further investigation.     

Near-infrared transmittance pulse oximetry with laser diodes

Pulse oximeters are widely used for noninvasive monitoring of oxygen saturation in arterial blood hemoglobin. We present a transmittance pulse oximetry system based on near-infrared (NIR) laser diodes (750 and 850 nm) for monitoring oxygen saturation of arterial blood hemoglobin. The pulse oximetry system is made up of the optical sensor, sensor electronics, and processing block. Also, we show experimental results obtained during the development of the whole NIR transmittance pulse oximetry system along with modifications in the sensor configuration, signal processing algorithm, and calibration procedure. Issues concerning wavelength selection and its implications for the improvement of the transmittance pulse oximetry technique are discussed. The results obtained demonstrate the proposed system's usefulness in monitoring a wide range of oxygen saturation levels.     

Cardiac output,arterial and mixed-venous O2 saturation,and blood O2 dissociation curve in growing rats adapted to a simulated altitude of 3500 m

Summary In rats adapted to a simulated altitude of 3500 m cardiac output measured at hypoxia by the direct Fick principle was significantly lower than in the control animals (mean values 54.3 ml/min and 69.8 ml/min, resp.). The decrease of cardiac output was accompanied by an increase of arterio-venous O₂ difference and a decrease of stroke volume in the adapted rats. It is suggested that the decrease of cardiac output might be related to the increase of hematocrit. The adapted rats also showed higher arterial and mixed-venous O₂ content (both at hypoxia) and increased O₂ capacity. Arterial O₂ saturation of the animals previously exposed to simulated high altitude hypoxia was significantly higher (67.3% as against 61.2% in the controls). The standard O₂ dissociation curve showed lower oxygen affinity in the blood of the adapted animals but no physiological advantage concerning the transport of O₂ to the tissues was found. In another group of animals the Bohr factor was estimated and no difference was found between rat and human blood.     

Accuracy of pulse oximetry during intense exercise under severe hypoxic conditions

There is a growing need to measure arterial oxygen saturation with a non-invasive method during heavy exercise under severe hypoxic conditions. Although the accuracy of pulse oximetry has been challenged by several authors, it has not been done under extreme conditions. The purpose of this study was to evaluate the accuracy of a pulse oximeter (Satlite, Datex, Finland) during exercise under hypoxic conditions where arterial oxygen saturation was below 75%, simulating exercise at extreme altitude. Ten healthy non-smoking men performed two exercise studies of 30?min under normoxia and under hypoxia on two consecutive days. The exercise intensity was 80% of maximal O₂ consumption of O_2max. Arterial oxygen saturation measured by pulse oximetry was corrected (S _pO_2[corr]) according to previously published equations and was compared to arterial oxygen saturation (S _aO₂) in blood samples taken simultaneously from the radial artery. Reference arterial saturation values ranged from 57.2 to 97.6% for the whole data set. This data set was split according to low (S _aO₂?≤?75%) and high (S _aO₂?>?75%) S _aO₂ values. The error of pulse oximetry (S _pO_2[corr]? S _aO₂) was 2.05 (0.87)% [mean (SD)] and 1.80 (1.81)% for high and low S _aO₂ values, respectively. S _pO_2[corr] and S _aO₂ were highly correlated (r?=?0.93, SEE?=?1.8) for low values. During high-intensity constant workload under severe hypoxic conditions, once corrected, pulse oximetry provides an estimate of S _aO₂ with a mean error of 2%. Thus, the correction previously described for S _pO₂ values above 75% saturation applies also to S _pO₂ values in the range of 57–75% during exercise under hypoxic conditions.     

Schlafbezogene Hypoventilationen bei COPD

Sleep-related hypoventilation in COPD patients is caused by a variety of biochemical as well as mechanical factors that take effect during the transition from waking to sleeping, especially in REM sleep. Here especially sleep-related hypoventilation is considered, which occurs primarily in REM sleep and can result in pathological oxygen saturation levels and an increase in p_aCO₂ levels. The effects of the nocturnal changes in blood gases have not been sufficiently analyzed (e.g., pathological increases in CO₂ levels while sleeping) and in relation to the development of high blood pressure in the pulmonary circulation or even mortality in nocturnal hypoxemia are contradictory, which probably is caused by the lack of definitions of the degree of severity (e.g., nocturnal p_aCO₂) or differing definitions of the degree of severity (e.g., for nocturnal oxygen saturation). In addition there are very short observation periods with regard to the problem of the emergence of PAP respectively mortality. The therapy of choice after all conservative methods have been tried is long-term oxygen therapy for predominantly pathological oxygen saturation. If there is evidence of fatigue of the respiratory pump, non-invasive ventilation therapy should be carried out.     

Cerebral Blood Flow and Oxygen Consumption in the Rat in Hypoxic Hypoxia

In order to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo₂) at pronounced degrees of hypoxic hypoxia the Pao₂ of artificially ventilated and normocapnic rats was reduced to between 47 and 22 mm Hg for 15–25 min with subsequent measurements of CBF, using a ¹³³Xenon modification of the Kety and Schmidt technique, and of the arteriovenous difference in oxygen content, the venous blood being obtained from the superior sagittal sinus. When the Pao₂ was reduced to minimal values of 22 mm Hg CBF increased 4- to 6-fold, the increase in CBF being unrelated to changes in blood pressure or Paco₂. The CMRo₂ remained unchanged at all levels of hypoxia. It is concluded that the maintenance of a normal, or near-normal, cerebral energy state even at extreme degrees of hypoxic hypoxia depends solely on a homeostatic increase in CBF.     

A system for investigating oesophageal photoplethysmographic signals in anaesthetised patients

The monitoring of arterial blood oxygen saturation in patients with compromised peripheral perfusion is often difficult, because conventional noninvasive techniques such as pulse oximetry (SpO₂) can fail. Poor peripheral circulation commonly occurs after major surgery including cardiopulmonary bypass. The difficulties in these clinical situations might be overcome if the sensor were to monitor a better perfused central part of the body such as the oesophagus. A new oesophageal photoplethysmographic (PPG) probe and an isolated processing system have been developed to investigate the pulsatile signals of anaesthetised adult patients undergoing routine surgery. Measurements were made in the middle third of the oesophagus, 25 cm to 30 cm from the upper incisors. The AC PPG signals are sampled by a data acquisition system connected to a laptop computer. The signals recorded correspond to infrared and red AC PPGs from the middle third oesophagus and the finger. Preliminary results from 20 patients show that good quality AC PPG signals can be measured in the human oesophagus. The ratio of the oesophageal to finger AC PPG amplitudes was calculated for the infrared and red wavelengths for each patient. The mean (±standard deviation) of this ratio was 2.9±2.1 (n=19) for the infrared wavelength and 3.1±2.4 (n=16) for the red wavelength. The red and infrared wavelengths used are appropriate for pulse oximetry and this investigation indicates that the mid-oesophagus may be a suitable site for the reliable monitoring of SpO₂ in patients with poor peripheral perfusion.     

Non-invasive system for applying airway obstructions to model obstructive sleep apnea in mice

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway obstructions during sleep. The most common animal model of OSA is based on subjecting rodents to intermittent hypoxic exposures and does not mimic important OSA features, such as recurrent hypercapnia and increased inspiratory efforts. To circumvent some of these issues, a novel murine model involving non-invasive application of recurrent airway obstructions was developed. An electronically controlled airbag system is placed in front of the mouse's snout, whereby inflating the airbag leads to obstructed breathing and spontaneous breathing occurs with the airbag deflated. The device was tested on 29 anesthetized mice by measuring inspiratory effort and arterial oxygen saturation (SaO₂). Application of recurrent obstructive apneas (6 s each, 120/h) for 6 h resulted in SaO₂ oscillations to values reaching 84.4 ± 2.5% nadir, with swings mimicking OSA patients. This novel system, capable of applying controlled recurrent airway obstructions in mice, is an easy-to-use tool for investigating pertinent aspects of OSA.     

Effect of hypoxia on arterial and venous blood levels of oxygen,carbon dioxide,hydrogen ions and lactate during incremental forearm exercise

Summary The purpose of the present study was to investigate whether, in humans, hypoxia results in an elevated lactate production from exercising skeletal muscle. Under conditions of both hypoxia [inspired oxygen fraction (F_IO₂): 11.10%] and normoxia (F_IO₂: 20.94%), incremental exercise of a forearm was performed. The exercise intensity was increased every minute by 1.6 kg·m·min^–1 until exhaustion. During the incremental exercise the partial pressure of oxygen (PO₂) and carbon dioxide (PCO₂), oxygen saturation (SO₂), pH and lactate concentration [HLa] of five subjects, were measured repeatedly in blood from the brachial artery and deep veins from muscles in the forearm of both the active and inactive sides. The hypoxia (arterial SO₂ approximately 70%) resulted in (1) the difference in [HLa] in venous blood from active muscle (values during exercise — resting value) often being more than twice that for normoxia, (2) a significantly greater difference in venous-arterial (v-a) [HLa] for the exercising muscle compared to normoxia, and (3) a difference in v-a [HLa] for non-exercising muscle that was slightly negative during normoxia and more so with hypoxia. These studies suggest that lower O₂ availability to the exercising muscle results in increased lactate production.     

Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen transport to tissues

The red blood cell (RBC) membrane may be reversibly opened using a lysis-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inostiol-Hexaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC). From ODC parameters in human volunteers, the potential effect of P₅₀ (oxygen pressure at 50% haemoglobin saturation) on oxygen exchangeable fraction (OEF%), for various oxygen partial pressures (oxemia) was evaluated. For hyperoxic or normoxic arterial oxygen pressure (paO₂), rightward shift greatly improved OEF%. In optimised conditions, engineered erythrocytes were potentially able to deliver two to three times more oxygen than normal cells. For patients with decreased paO₂, as observed in chronic obstructive pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO₂%) reduces the benefit of the treatment for paO₂ values between 60 and 80 mmHg. Below 60 mmHg, the saO₂% reduction cannot be compensated by a corresponding reduction in svO₂%, particularly for organs with physiologically low svO₂%. In these organs, deleterious effects could be observed for a very large rightward shift of the ODC. Such engineered cells have unique properties for oxygen transport improvement and may be used for the treatment of patients suffering from diseases associated with hypoxia and ischemia.     

Cheyne-Stokes respiration: hypoxia plus a deep breath that interrupts hypoxic drive, initiating cyclic breathing

In the 19th Century, Cheyne and Stokes independently reported cycles of respiration in patients with heart failure, beginning with apnea, followed by a few breaths. However Cheyne–Stokes respiration (C–SR) can also occur in healthy individuals with sleep, and was demonstrated in 1908 with voluntary hyperventilation, followed by apnea that Haldane blamed on hypoxia, subsequently called post-hyperventilation apnea. Additional theories explaining C–SR did not appear until 1954, based on control theory, specifically a feed-back regulator controlling CO₂. This certainly describes control of normal respiration, but to produce an unstable state such as C–SR requires either a very long transit time (3½ min) or an increase of the controller gain (13 times), physiologically improbable. There is general agreement that apnea initiates C–SR but that has not been well explained except for post-hyperventilation apnea, and that explanation is not compatible with a study by Nielsen and Smith in 1951. They plotted the effects of diminished oxygen on ventilation (V) in relation to CO₂ (Fig. 1). They found that the slope of V/CO₂ (gain) increased with hypoxia, but it flattened at a moderate CO₂ level and had nointercept with zero (apnea). It is also incompatible with our published findings in 1975 that showed that apnea did not occur until an extreme level of hypoxia occurred (the PO₂ fell below 10 mmHg), followed shortly by gasping. Much milder hypoxia underlies most cases of C–SR, when hypoxic drive replaces the normal CO₂-based respiratory drive, in a failsafe role. I hypothesize that the cause of apnea is a brief interruption of hypoxic drive caused by a pulse of oxygen from a stronger than average breath, such as a sigh. The rapidity of onset of apnea in response to a pulse of oxygen, reflects the large pressure gradient for oxygen from air to lung with each breath, in contrast to CO₂. With apnea, there is a gradual fall in oxygen, resulting in a resumption of hypoxic drive, and the cycle of C–SR continues until the next large breath. This novel theory, that a pulse of oxygen interrupts hypoxic drive to cause the initiating apnea of C–SR, is compatible with the known causes of C–SR: onset of sleep, mild hypoxia with congestive heart failure, and neurologic disorders. It is also compatible with factors known to abolish C–SR: waking, oxygen supplementation, and drugs that increase alertness such as caffeine.Testing of the hypothesis would require beat by beat recording of respiration, and arterial oxygen with a response time fast enough to demonstrate the rapid suppression of hypoxic drive. Alternatively, using a different theoretical approach such as limit-cycle oscillators instead of control theory.     

Circulatory effects of apnoea in elite breath‐hold divers

Aim: Voluntary apnoea induces several physiological adaptations, including bradycardia, arterial hypertension and redistribution of regional blood flows. Elite breath‐hold divers (BHDs) are able to maintain very long apnoea, inducing severe hypoxaemia without brain injury or black‐out. It has thus been hypothesized that they develop protection mechanisms against hypoxia, as well as a decrease in overall oxygen uptake. Methods: To test this hypothesis, the apnoea response was studied in BHDs and non‐divers (NDs) during static and dynamic apnoeas (SA, DA). Heart rate, arterial oxygen saturation (SaO₂), and popliteal artery blood flow were recorded to investigate the oxygen‐conserving effect of apnoea response, and the internal carotid artery blood flow was used to examine the mechanisms of cerebral protection. Results: The bradycardia and peripheral vasoconstriction were accentuated in BHDs compared with NDs (P < 0.01), in association with a smaller SaO₂ decrease (?2.7% vs. ?4.9% during SA, P < 0.01 and ?6% vs. ?11.3% during DA, P < 0.01). Greater increase in carotid artery blood flow was also measured during apnoea in BHDs than in controls. Conclusion: These results confirm that elite divers present a potentiation of the well‐known apnoea response in both SA and DA conditions. This response is associated with higher brain perfusion which may partly explain the high levels of world apnoea records.     

Lokale Durchblutung und capilläre Sauerstoffsättigung des Myokards unter Hypoxie und Hyperkapnie sowie nach Einwirkung von Adrenalin,Noradrenalin und Vasopressin

Zusammenfassung Gleichzeitige Messungen von lokaler Durchblutung und lokaler Sauerstoffsättigung im Versorgungsbereich eines Coronararterienastes sind durch Kombination von Wärmeleitmessung und Rapidspektroskopie möglich. Bei unseren Untersuchungen wurden O₂-Sättigung und Durchblutung in oberflächennahen, umschriebenen Bezirken des linken Ventrikelmyokards von Katzen gemessen. Arterielle Hypoxie führt zu Verminderung der O₂-Sättigung und Erhöhung der Durchblutung; 5% CO₂ in der Atemluft bewirkt geringe Durchblutungsanstiege und mäßige O₂-Sättigungsverminderung.Nach intravenöser Injektion von Vasopressin kommt es zugleich mit dem Blutdruckanstieg zu Durchblutungserniedrigung und erheblicher Verminderung der lokalen O₂-Sättigung.Intravenöse Injektion von 1 g/kg Noradrenalin führt stets zu Durchblutungssteigerungen, die mit Verminderungen der O₂-Sättigung einheregehen; nach i.v. Adrenalininjektionen (1 g/kg) kommt es ebenfalls zu Verminderungen der lokalen O₂-Sättigung und zu Durchblutungsanstiegen.Die Reaktionen der lokalen O₂-Sättigung weichen bei Catecholamininjektionen von denjenigen ab, die bei Sättigungsmessung im Coronarvenensinus gefunden wurden.

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Summary In anaesthetized cats regional myocardial blood flow and regiona oxygen saturation were simultaneously recorded within the supplementary area of a branch of the left coronary artery. For the blood flow measurements we used heat clearance probes, and for the measurements of the oxygen saturation a rapid spectroscope. In hypoxia, decreases of the oxygen saturation were combined with increases of myocardial blood flow. 5% CO₂ in the inspired air caused slight increases of myocardial blood flow and moderate decreases of the oxygen saturation. Intravenous injection of Vasopressin increases the systemic blood pressure and decreases myocardial blood flow moderately and oxygen saturation of the tissue considerably. Intravenous injection of 1 g/kg nor-epinephrine causes simultaneous increases of blood pressure and regional myocardial blood flow, but reductions of the oxygen saturation within the measuring area. Intravenous injection of 1 g/kg epinephrine also reduces the regional oxygen saturation and increases regional blood flow. The reactions of the regional oxygen saturation after injection of catecholamines are different from reactions which were seen in the coronary sinus by other investigators.

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Mit 5 Textabbildungen     

The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude

Animals native to hypoxic environments have adapted by increasing their haemoglobin oxygen affinity, but in-vitro studies of the oxyhaemoglobin dissociation curve (ODC) in humans show no changes in affinity under physiological conditions at altitudes up to 4000 m. We conducted the first in-vivo measurement of the ODC; inducing progressive isocapnic hypoxia in lowlanders at sea level, acutely acclimatized lowlanders at 3600 m, and native Andeans at that altitude. ODC curves were determined by administering isocapnic steps of increasing hypoxia, and measuring blood oxygen partial pressure and saturation. The ODC data were fitted using the Hill equation and extrapolated to predict the oxygen partial pressure at which haemoglobin was 50% saturated (P₅₀). In contrast to findings from in-vitro studies, we found a pH-related reduction in P₅₀ in subjects at altitude, compared to sea-level subjects. We conclude that a pH-mediated increase in haemoglobin oxygen affinity in-vivo may be part of the acclimatization process in humans at altitude.     

Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in rabbit skeletal muscle

Gustafsson , U., Sjöberg , F., Lewis , D. H. & Thorborg , P. 1994. Effect of hypoxic hypoxia and ritanserin on capillary flow and oxygenation in rabbit skeletal muscle. Acta Physiol Stand 150, 39–45. Received 2 April 1993, accepted 21 July 1993. ISSN 0001–6772. Clinical Research Centre and the Burns Unit, Department of Hand and Plastic Surgery, and Department of Anaesthesiology, University Hospital, Linkoping, Sweden, and Dept of Anesthesiology, University of Rochester Medical Center, NY, USA. This study examined capillary flow and oxygenation in rabbit skeletal muscle during hypoxic hypoxia (inspired oxygen fraction = 0.10) and after administration of ritanserin (highly selective 5-Hydroxytryptamine-2-receptor antagonist). Capillary flow (hydrogen clearance) or oxygen pressure was measured with a multiwire micro-electrode which was placed on the surface of the left vastus medialis muscle. For measurement of regional microcirculatory blood flow a laser-Doppler flowmeter probe was placed on the contralateral muscle. An experimental sequence with normoxaemia (arterial Po₂ 12.5 kPa), followed by hypoxaemia (arterial Po₂ 3.9 kPa) and thereafter sustained hypoxaemia (arterial Po₂ 4.0 kPa) during which ritanserin (0.035 mg kg^-1 i.v.) was administered, was used. During hypoxaemia a decrease was seen in mean arterial pressure (MAP) by 27%, capillary flow by 25%, muscle oxygen pressure by 32% and laser-Doppler flowmetry (LDF) flow by 24%. After the administration of ritanserin the mean arterial pressure was further reduced by 7%, whereas the capillary flow increased by 59% and the muscle oxygen pressure by 31 %. The LDF flow remained unchanged. These results demonstrate that, in this animal model, a decrease in skeletal muscle capillary flow and oxygenation during hypoxaemia can be reversed by the administration of ritanserin, despite a further reduction in blood pressure.     

Effects of acute hypoxia and CO2 inhalation on systemic and peripheral oxygen uptake and circulatory responses during moderate exercise

Summary The effect of acute hypoxia and CO₂ inhalation on leg blood flow (LBF), on leg vascular resistance (LVR) and on oxygen supply to and oxygen consumption in the exercising leg was studied in nine healthy male subjects during moderate one-leg exercise. Each subject exercised for 20 min on a cycle ergometer in four different conditions: normoxia, normoxia +2% CO₂, hypoxia corresponding to an altitude of 4000 m above sea level, and hypoxia +1.2% CO₂. Gas exchange, heart rate (HR), arterial blood pressure, and LBF were measured, and arterial and venous blood samples were analysed for , , oxygen saturation, haematocrit and haemoglobin concentration. Systemic oxygen consumption was 1.83 l · min^–1 (1.48–2.59) and was not affected by hypoxia or CO₂ inhalation in hypoxia. HR was unaffected by CO₂, but increased from 136 beat · min^–1 (111–141) in normoxia to 155 (139–169) in hypoxia. LBF was 6.5 l · min^–1 (5.4–7.6) in normoxia and increased significantly in hypoxia to 8.4 (5.9–10.1). LVR decreased significantly from 2.23 kPa · l^–1 · min (1.89–2.99) in normoxia to 1.89 (1.53–2.52) in hypoxia. The increase in LBF from normoxia to hypoxia correlated significantly with the decrease in LVR. When CO₂ was added in hypoxia a significant correlation was also found between the decrease in LBF and the increase in LVR. In normoxia, the addition of CO₂ caused a significant increase in mean blood pressure. Oxygen consumption in the exercising leg (leg ) in normoxia was 0.97 l · min^–1 (0.72–1.10), and was unaffected by hypoxia and CO₂. It is concluded that the O₂ supply to the exercising leg and its are unaffected by hypoxia and CO₂. The increase in LBF in hypoxia is caused by a decrease in LVR. These changes can be counteracted by CO₂ inhalation. It is proposed that the regulatory mechanism behind these changes is that change in brain causes change in the central regulation of vascular tonus in the muscles.