Increase In Arterial O2 Content Research Articles

Oxygen is rocket fuel for the human brain; a radical perspective!

Oxygen is rocket fuel for the human brain; a radical perspective!

Effects of erythropoietin on systemic hematocrit and oxygen transport in the splenectomized horse

To test the hypotheses that erythropoietin (rhuEPO) treatment increases systemic hematocrit, maximal O2 uptake (V˙O2max, by elevated perfusive and diffusive O2 conductances) and performance five female horses (4–13 years) received 15IU/kg rhuEPO (erythropoietin) three times per week for three weeks. These horses had been splenectomized over 1 year previously to avoid confounding effects from the mobilization of splenic red blood cell reserves. Each horse performed three maximal exercise tests (one per month) on an inclined (4°) treadmill to the limit of tolerance; two control trials and one following EPO treatment. Measurements of hemoglobin concentration ([Hb] and hematocrit), plasma and blood volume, V˙O2, cardiac output as well as arterial and mixed venous blood gases were made at rest and during maximal exercise. EPO increased resting [Hb] by 18% from 13.3±0.6 to 15.7±0.8g/dL (mean±SD) corresponding to an increased hematocrit from 36±2 to 46±2% concurrent with 23 and 10% reductions in plasma and blood volume, respectively (all P<0.05). EPO elevated V˙O2max by 20% from 25.7±1.7 to 30.9±3.4L/min (P<0.05) via a 17% increase in arterial O2 content and 18% greater arteriovenous O2 difference in the face of an unchanged cardiac output. To achieve the greater V˙O2max after EPO, diffusive O2 conductance increased ∼30% (from 580±76 to 752±166mL O2/mmHg/min, P<0.05) which was substantially greater than the elevation of perfusive O2 conductance. These effects of EPO were associated with an increased exercise performance (total running time: control, 216±72; EPO, 264±48s, P<0.05). We conclude that EPO substantially increases V˙O2max and performance in the splenectomized horse via improved perfusive and diffusive O2 transport.

Brain tissue oxygen reactivity: clinical implications and pathophysiology.

It is generally accepted that PbO2 reflects the balance between O2 delivery and consumption (Diringer et al., 2007; Diringer, 2008). However, implementation in the perioperative period of various ventilatory modes using high FiO2 leads to a dramatic and non-physiologic increase in PbO2 with approximating levels of 147 ± 36 mmHg (McLeod et al., 2003). This phenomenon doesn't correlate with the extent of slight increase in arterial O2 content. At the same time, the jugular venous PO2 increases only slightly (37–40 mmHg) (Forkner et al., 2007). Moreover, hyperoxia does not affect significantly the regional CBF, and there is no improvement in cerebral metabolism with oxygen therapy (Magnoni et al., 2003; Diringer et al., 2007; Diringer, 2008; Xu et al., 2012). The PbO2 increase is more pronounced in edematous (but not necrotized) brain tissues compared to normal areas (Meixensberger et al., 1993). Although, this can be considered a positive phenomenon, it masks the real state of rCBF and local oxidative metabolism. Recording of high PbO2 absolute values may create a false impression of safety and negatively impact the clinical decision making. Apparently, better indicators of the status of energy exchange in the brain tissue are needed for practical use in the perioperative and critical care settings.

Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain

Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia. The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon-enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 x 100/change in PaO2. The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11-15, 16-20, 21-40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min. Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.

Acute effects of inhaled nitric oxide in adult respiratory distress syndrome.

This study evaluated the dose-response effect of inhaled nitric oxide (NO) on gas exchange, haemodynamics, and respiratory mechanics in patients with adult respiratory distress syndrome (ARDS). Of 19 consecutive ARDS patients on mechanical ventilation, eight (42%) responded to a test of 10 parts per million (ppm) NO inhalation with a 25% increase in arterial oxygen tension (Pa,O2,) over the baseline value. The eight NO-responders were extensively studied during administration of seven inhaled NO doses: 0.5, 1, 5, 10, 20, 50 and 100 ppm. Pulmonary pressure and pulmonary vascular resistance exhibited a dose-dependent decrease at NO doses of 0.5-5 ppm, with a plateau at higher doses. At all doses, inhaled NO improved O2 exchange via a reduction in venous admixture. On average, the increase in Pa,O2, was maximal at 5 ppm NO. Some patients, however, exhibited maximal improvement in Pa,O2 at 100 ppm NO. In all patients, the increase in arterial O2 content was maximal at 5 ppm NO. The lack of further increase in arterial O2 content above 5 ppm partly depended on an NO-induced increase in methaemoglobin. Respiratory mechanics were not affected by NO inhalation. In conclusion, NO doses < or =5 ppm are effective for optimal treatment both of hypoxaemia and of pulmonary hypertension in adult respiratory distress syndrome. Although NO doses as high as 100 ppm may further increase arterial oxygen tension, this effect may not lead to an improvement in arterial O2 content, due to the NO-induced increase in methaemoglobin. It is important to consider the effect of NO not only on arterial oxygen tension, but also on arterial O2 content for correct management of inhaled nitric oxide therapy.

Enhanced oxygen delivery induced by perfluorocarbon emulsions in capillary tube oxygenators.

Previous studies showed that a new generation of perfluorocarbon (PFC) emulsions increased tissue PO2 in the cat retina to a degree that could not be explained by the small increase in arterial O2 content seen after the infusion of low doses of 1 g PFC/kg body weight. It seems that increased O2 delivery at the tissue level after PFC infusion is caused by a local effect in the microcirculation. The authors studies this effect in vitro at steady state in a closed loop circuit, consisting of one of two types of capillary tube oxygenators, deoxygenator(s), a reservoir bag filled with anticoagulated bovine blood or saline (control), and a roller pump, to see if the addition of PFC would have an effect on the PO2 difference (delta PO2) across the capillary tube membrane oxygenator at a blood flow rate of 3 l/min. Perfluorocarbon was added in three incremental doses, each giving about 0.7 vol% of PFC. The delta PO2 across the oxygenator was measured before and after each dose. The mean percent increases in delta PO2 in blood for two types of oxygenators were 19.2 +/- 8% (mean +/- SD, n = 6, P = 0.002) and 9.9 +/- 4% (n = 3, P = 0.05), respectively, whereas the mean percent change in delta PO2 in saline was -4.9 +/- 2% (n = 2, P = 0.2). Inlet PO2s to the oxygenator were only minimally increased. The authors conclude that O2 delivery was significantly enhanced after injection of PFC in blood in this capillary tube model. A near wall excess of PFC particles may account for the augmentation of O2 diffusion in this model.

Increased Exercise Capacity in Hypoxemic Patients after Long-term Oxygen Therapy

Low-flow continuous oxygen can lead to significant improvement in exercise capacity in selected patients with stable hypoxemic pulmonary disease. Although the mechanisms of improvement are incompletely understood, two tenable hypotheses are (1) the relief of hypoxic pulmonary vasoconstriction and (2) improved peripheral oxygen delivery. This prospective study was performed to examine these two hypotheses. Stable patients with hypoxemic lung disease performed symptom-limited ergometry with hemodynamic monitoring before and after greater than one month of long-term home oxygen therapy. There were 22 patients who increased exercise capacity by greater than 100 KPM/min and greater than 4 min duration and 11 patients who did not increase their exercise capacity greater than 2 min or in KPM/min. Neither the responders nor the nonresponders had significant changes in pulmonary pressures or resistances or effective arterial volume elastances at exercise after long-term O2 therapy. The responders had significant increases in oxygen delivery during exercise (148 +/- 33 ml/min vs 184 +/- 51 ml/min, p = 0.004), cardiac output (7.7 +/- 1.6 L/min vs 8.7 +/- 2.1 L/min, p = 0.003), and arterial oxygen content (18.6 +/- 2.6 ml/dl vs 20.2 +/- 2.8 ml/dl, p = 0.02). The nonresponders had no significant changes in these parameters during exercise. Increased exercise capacity in response to long-term O2 therapy is associated with increased O2 delivery not relief of hypoxic vasoconstriction (in terms of pressure or resistance or arterial elastance). Increased O2 delivery can accrue from both increased cardiac output and increased arterial O2 content. Increase in arterial O2 content is unique to O2 relative to all vasodilator drugs.

Oxygen transport during steady-state submaximal exercise in chronic hypoxia

Arterial O2 delivery during short-term submaximal exercise falls on arrival at high altitude but thereafter remains constant. As arterial O2 content increases with acclimatization, blood flow falls. We evaluated several factors that could influence O2 delivery during more prolonged submaximal exercise after acclimatization at 4,300 m. Seven men (23 +/- 2 yr) performed 45 min of steady-state submaximal exercise at sea level (barometric pressure 751 Torr), on acute ascent to 4,300 m (barometric pressure 463 Torr), and after 21 days of residence at altitude. The O2 uptake (VO2) was constant during exercise, 51 +/- 1% of maximal VO2 at sea level, and 65 +/- 2% VO2 at 4,300 m. After acclimatization, exercise cardiac output decreased 25 +/- 3% compared with arrival and leg blood flow decreased 18 +/- 3% (P less than 0.05), with no change in the percentage of cardiac output to the leg. Hemoglobin concentration and arterial O2 saturation increased, but total body and leg O2 delivery remained unchanged. After acclimatization, a reduction in plasma volume was offset by an increase in erythrocyte volume, and total blood volume did not change. Mean systemic arterial pressure, systemic vascular resistance, and leg vascular resistance were all greater after acclimatization (P less than 0.05). Mean plasma norepinephrine levels also increased during exercise in a parallel fashion with increased vascular resistance. Thus we conclude that both total body and leg O2 delivery decrease after arrival at 4,300 m and remain unchanged with acclimatization as a result of a parallel fall in both cardiac output and leg blood flow and an increase in arterial O2 content.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of oxygen inhalation in ascitic cirrhotic patients: Therapeutic implications?

In patients with cirrhosis, O2 uptake, i.e., O2 consumption, is abnormally deceased. We administered 50% O2 for 30 min in eight patients with alcoholic cirrhosis to determine whether the subsequent increase in arterial O2 content may correct the low O2 consumption. In addition, we studied in these patients the reflex control of cardiac output and blood pressure by arterial baroreceptors, as O2 inhalation induces a systemic vasoconstriction. Arterial O2 tension, oxyhaemoglobin saturation and arterial O2 content significantly increased as well as systemic vascular resistance and arterial pressure. In contrast, O2 consumption (which was below normal values) under basal conditions, O2 transport, O2 extraction ratio, heart rate, right atrial and pulmonary wedged pressures, cardiac output, hepatic venous pressures, hepatic and azygos blood flows were unaffected by O2 administration. In three patients receiving air, no significant change was observed. Our results show that, in patients with cirrhosis, inhalation of 50% O2 does not correct O2 consumption. We may conclude that reflex control of cardiac output and arterial pressure by arterial baroreceptors is impaired in these patients.

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs.

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.

Effect of hematocrit on cerebral blood flow with induced polycythemia.

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.

Effects of breathing a normoxic He-O2 gas mixture on exercise tolerance and VO2 max.

The purpose of these experiments was to compare the effects of breathing air (79% N2-21% O2) and a normoxic helium oxygen gas mixture (He-O2) (79% He-21% O2) on maximal oxygen uptake (VO2 max) and work tolerance during both incremental and high-intensity constant load exercise. First, eight subjects underwent two separate short incremental cycle ergometer exercise tests until the subject could not maintain the desired power output. Second, four subjects exercised to exhaustion on two separate occasions at a constant exercise intensity (100% VO2 max). Each exercise protocol required the subject to breathe air on one test and a normoxic He-O2 mixture on an additional occasion. Data analysis revealed higher (P less than 0.05) minute ventilations, an increased time to exhaustion, and a greater VO2 max during He-O2 breathing in both exercise conditions. Small but significant (P less than 0.05) differences existed in the percent hemoglobin saturated with O2 (% SO2) at exercise demands greater than 120 W during the incremental experiment and during each minute of the constant load test with He-O2 giving the higher value. These data support the hypothesis that breathing a normoxic He-O2 gas mixture during exercise elevates VO2 max and increases exercise tolerance. Further, although it appears that breathing a He-O2 mixture results in higher %SO2 during intense exercise, the increase in arterial O2 content is small and probably does not fully account for the higher VO2 max observed under these conditions.