Hemodynamic Perspectives in Anemia

Oxygen delivery in normal physiologic states is determined by cardiac output, hemoglobin, oxygen saturation, and to a lesser extent, dissolved oxygen in the blood. Compensatory mechanisms such as an increase in stroke volume, heart rate, and re-distribution of blood flow helps in scenarios with increased oxygen demand. In cases of acute hemodynamic decompensation, this pre-existing physiologic relation between oxygen delivery and oxygen consumption is altered, resulting in tissue hypoxia and resultant anaerobic metabolism. A persistent state of sub-critical O2 delivery correlates with increased mortality. Oxygen consumption itself is usually independent of delivery unless a critical threshold is unmet. We can use various parameters such as serum lactate, oxygen extraction, and central venous oxygen saturation to determine this pathology. A basic understanding of this physiology will help better tailor therapy to improve outcomes in critically ill patients.

New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin

Crocodilians are unique among vertebrates in that their hemoglobin (Hb) O2 binding is allosterically regulated by bicarbonate, which forms in the red blood cell upon hydration of CO2. Although known for decades, this remarkable mode of allosteric control has not yet been experimentally verified with direct evidence of bicarbonate binding to crocodilian Hb, probably because of confounding CO2-mediated effects. Here we provide the first quantitative analysis of the separate allosteric effects of CO2 and bicarbonate on purified Hb of the spectacled caiman (Caiman crocodilus). Using thin-layer gas diffusion chamber and Tucker chamber techniques, we demonstrate that both CO2 and bicarbonate bind to Hb with high affinity and strongly decrease Hb-O2 saturation. We propose that both effectors bind to an unidentified positively charged site containing a reactive amino group in the low-O2 affinity T conformation of the Hb. These results provide the first experimental evidence that bicarbonate binds directly to crocodilian Hb and promotes O2 delivery independently of CO2. Using the gas-diffusion chamber, we observed similar effects in Hbs of a phylogenetically diverse set of other caiman, alligator, and crocodile species, suggesting that the unique mode of allosteric regulation by CO2 and bicarbonate evolved >80-100 million years ago in the common ancestor of crocodilians.Our results show a tight and unusual linkage between O2 and CO2 transport in the blood of crocodilians, where build-up of erytrocytic CO2 and bicarbonate ions during breath-hold diving or digestion facilitates O2 delivery, while Hb desaturation facilitates CO2 transport as protein-bound CO2 and bicarbonate.

Acute Moderate Hypoxia Reduces One-Legged Cycling Performance Despite Compensatory Increase in Peak Cardiac Output: A Pilot Study

In severe hypoxia, single-leg peak oxygen uptake (VO2peak) is reduced mainly due to the inability to increase cardiac output (CO). Whether moderate altitude allows CO to increase during single-leg cycling, thereby restoring VO2peak, has not been extensively investigated. Five healthy subjects performed an incremental, maximal, two-legged cycle ergometer test, and on separate days a maximal incremental one-leg cycling test in normoxia and in moderate hypoxia (fraction of inspired oxygen (FiO2) = 15%). Oxygen uptake, heart rate, blood pressure responses, power output, and CO (PhysioFlow) were measured during all tests. Moderate hypoxia lowered single-leg peak power output (154 ± 31 vs. 128 ± 26 watts, p = 0.03) and oxygen uptake (VO2) (36.8 ± 6.6 vs. 33.9 ± 6.9 mL/min/kg, p = 0.04), despite higher peak CO (16.83 ± 3.10 vs. 18.96 ± 3.59 L/min, p = 0.04) and systemic oxygen (O2) delivery (3.37 ± 0.84 vs. 3.47 ± 0.89 L/min, p = 0.04) in hypoxia compared to normoxia. Arterial–venous O2 difference (a–vDO2) was lower in hypoxia (137 ± 21 vs. 112 ± 19 mL/l, p = 0.03). The increases in peak CO from normoxia to hypoxia were negatively correlated with changes in mean arterial pressure (MABP) (p < 0.05). These preliminary data indicate that the rise in CO was not sufficient to prevent single-leg performance loss at moderate altitude and that enhanced baroreceptor activity might limit CO increases in acute hypoxia, likely by reducing sympathetic activation. Since the systemic O2 delivery was enhanced and the calculated a–vDO2 reduced in moderate hypoxia, a potential diffusion limitation cannot be excluded.

New insights into the allosteric effects of CO2 and bicarbonate on crocodilian hemoglobin

Crocodilians are unique among vertebrates in that their hemoglobin (Hb) O2 binding is allosterically regulated by bicarbonate, which forms in the red blood cell upon hydration of CO2. Although known for decades, this remarkable mode of allosteric control has not yet been experimentally verified with direct evidence of bicarbonate binding to crocodilian Hb, probably because of confounding CO2-mediated effects. Here we provide the first quantitative analysis of the separate allosteric effects of CO2 and bicarbonate on Hb of the spectacled caiman (Caiman crocodilus). Using thin-layer gas diffusion chamber and Tucker chamber techniques, we demonstrate that both CO2 and bicarbonate bind to Hb with high affinity and strongly decrease Hb-O2 saturation, and propose that both effectors bind to an unidentified positively charged site containing a reactive amino group in the low-O2 affinity T conformation of the Hb. These results provide the first experimental evidence that bicarbonate binds directly to crocodilian Hb and promotes O2 delivery independently of CO2. Using the gas-diffusion chamber, we observed similar effects in the Hbs of a phylogenetically diverse set of other caiman, alligator, and crocodile species, suggesting that the unique mode of allosteric regulation by CO2 and bicarbonate evolved >80-100 million years ago in the common ancestor of crocodilians. Taken together, our results show a tight and unusual linkage between O2 and CO2 transport in the blood of crocodilians, where build-up of blood CO2 and bicarbonate ions during breath-hold diving or digestion facilitates O2 delivery, while Hb desaturation facilitates CO2 transport as protein-bound CO2 and bicarbonate.

Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for three consecutive days. They performed cycling incremental exercise starting at 20-watt work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (V˙E) and CO2 output (V˙CO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF). Blood gases’ pH, lactate, and bicarbonate (HCO3−) concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower V˙E, V˙CO2, and higher HCO3−, partial pressures of CO2 (PCO2) versus placebo. During exercise, a significant pH decrease and greater HCO3− continued until 240-watt workload in HCP. The V˙E was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of V˙CO2 or oxygen uptake (V˙O2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

OXYGEN-DEPENDENT ADAPTATION PROCESSES IN THE HUMAN ORGANISM IN USUAL LIVING CONDITIONS AND DURING SPACE FLIGHT

The review examines various parties of oxygen-dependent human adaptation to microgravity belonging to different levels of the integral system organization. Particular emphasis has been placed on the cellular sensing systems of immediate and chronic reactions to altered O2 delivery. The authors expound the key oxygen sensors and heterogeneity of the sensing mechanisms. They also concern themselves with the role of O2 active forms and O2-sensing elements developing in the spaceflight environment. The first post-flight evidence of an increase in frequency of oxidation post-translational modifications in proteins suggests a hypothesis about the direction and systemic mechanisms of oxygen-dependent adaptation of the human organism to in microgravity.

Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 &micro;g/day of H2) or H2-depleted placebo (1500 mg/day) for 3 consecutive days. They performed cycling incremental exercise starting at 20-watts work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (VE) and CO2 output (VCO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved-NIRS in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and HCO3&minus; concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower VE, VCO2, and higher HCO3&minus;, PCO2 versus placebo. During exercise, a significant pH decrease and greater HCO3&minus; continued until 240-watts work rate in HCP. The VE was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of VCO2 or oxygen uptake (VO2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Effects of hypercarbia on arterial oxygenation during one-lung ventilation: prospective randomized crossover study

BackgroundThis study aimed to evaluate the effects of hypercarbia on arterial oxygenation during one-lung ventilation (OLV).MethodsFifty adult patients undergoing elective video-assisted thoracoscopic lobectomy or pneumonectomy were enrolled. Group I patients (n = 25) were first maintained at normocarbia (PaCO2: 38‒42 mmHg) for 30 min and then at hypercarbia (45‒50 mmHg). In Group II patients (n = 25), PaCO2 was maintained in the reverse order. Arterial oxygen partial pressure (PaO2), respiratory variables, hemodynamic variables, and hemoglobin concentration were compared during normocarbia and hypercarbia. Arterial O2 content and O2 delivery were calculated.ResultsPaO2 values during normocarbia and hypercarbia were 66.5 ± 10.6 and 79.7 ± 17.3 mmHg, respectively (mean difference: 13.2 mmHg, 95% CI for difference of means: 17.0 to 9.3, P < 0.001). SaO2 values during normocarbia and hypercarbia were 92.5 ± 4.8% and 94.3 ± 3.1% (P = 0.009), respectively. Static compliance of the lung (33.0 ± 5.4 vs. 30.4 ± 5.3 ml/cmH2O, P < 0.001), arterial O2 content (15.4 ± 1.4 vs. 14.9 ± 1.5 ml/dl, P < 0.001) and O2 delivery (69.9 ± 18.4 vs. 65.1 ± 18.1 ml/min, P < 0.001) were significantly higher during hypercarbia than during normocarbia.ConclusionsHypercarbia increases PaO2 and O2 carrying capacity and improves pulmonary mechanics during OLV, suggesting that it may help manage oxygenation during OLV. Therefore, permissive hypercarbia may be a simple and valuable modality to manage arterial oxygenation during OLV.

Oxygen delivery during cardiopulmonary bypass and acute kidney injury: Preliminary Study

Objective: to assess the relationship between oxygen delivery during cardiopulmonary bypass and the incidende of acute kidney injury in the immediate postoperative period of patients undergoing cardiac surgery, as well as to identify possible risk factors. Methods: A retrospective observational study of patients undergoing cardiac surgery scheduled between May 2016 and February 2018 was carried out in which the M-M4 System was used for online blood gases. Patients with preoperative diagnosis of chronic renal failure were excluded. For the oxigen delivery, the average of all M4 records was made. Results: 133 patients (35.3% women) with a mean age of 64.9 ± 10.9 years were studied. The incidence of acute kidney injury was 18.8% (AKI I: 12%; AKI II: 3%; AKI III: 3.8%). There was no correlation between acute kidney injury and O2 delivery (251 ± 43 vs 247 ± 52, ns), if there was a difference when patients needed renal replacement therapy (251 ± 43 vs 198 ± 18, p = 0.04). There was a significant increase risk in diabetes; HTA; pulmonary arterial hypertension; chronic atrial fibrilation; red blood cell concentrate and blood products administration in the operating room; redo for bleeding; high lactic acid and glycemia post cardiopulmonary bypass; prolonged pump and ischemia times; and combined surgery. Conclusions: There was no direct relationship between O2 delivery and acute kidney injury, although there was a significantly lower O2 delivery in patients who needed postoperative renal replacement therapy.