Physiological carbon dioxide, bicarbonate, and pH sensing

In biological systems, carbon dioxide exists in equilibrium with bicarbonate and protons. The individual components of this equilibrium (i.e., CO₂, HCO ₃ ^? , and H⁺), which must be sensed to be able to maintain cellular and organismal pH, also function as signals to modulate multiple physiological functions. Yet, the molecular sensors for CO₂/HCO ₃ ^? /pH remained unknown until recently. Here, we review recent progress in delineating molecular and cellular mechanisms for sensing CO₂, HCO ₃ ^? , and pH.     

The placental transfer of lactate and bicarbonate in the guinea-pig

Summary In order to study the lactic acid transfer in a hemochorial placenta, the placenta of the guinea-pig was perfusedin situ through the umbilical circulation with a colloidal solution containingl(+)-lactate and bicarbonate in various concentrations. It was found that the transfer rates of lactate and bicarbonate were proportional to the respective materno-fetal arterial concentration differences. When the concentration gradients for lactate and bicarbonate were opposite to each other, an exchange of lactate for bicarbonate occurred which is equivalent to a lactic acid transfer. The placental permeability for lactate was found to be 25 mol/(h·mol/ml) per g of placental weight (S.E.=2). A similar value was obtained for bicarbonate (23 mol/(h·mol/ml) per g; S.E.=1.3). It is calculated that fetal concentrations of lactate and bicarbonate follow maternal concentration changes with a half time of 23 min.     

Effect ofP CO2, bicarbonate and lactate on the isometric contractions of isolated soleus muscle of the rat

Summary Isometric contractions of isolated soleus muscles of 3 weeks old rats show a potentiation of the maximal twitch tension when theP _CO2 is increased, or when the [HCO ₃ ^– ] is increased with a reciprocal decrease in [Cl^–]. The reverse response is observed on decrease of theP _CO2 and on decrease of the [HCO ₃ ^– ] with a reciprocal increase in [Cl^–].The addition of lactate ions results in a potentiation of the maximal twitch, whether accompanied by a reciprocal decrease in [HCO ₃ ^– ] or in [Cl^–].The maximal tetanic tension is augmented by rising theP _CO2, by increasing the [HCO ₃ ^– ] with simultaneous lowering of [Cl^–], or by the addition of lactate ions.     

Blood lactate and pyruvate concentrations,and their ratio during exercise in healthy children: developmental perspective

Blood concentrations of lactate normally increase during and after intense exercise as does the ratio of concentrations of lactate to pyruvate (L:P). Since there appear to be differences in blood lactate concentrations on exercise, in muscle metabolic enzyme activities, and in anaerobic capacity between children and adults, we speculated that there would be age related differences in lactate and pyruvate concentrations, and their ratio among children. Whole blood concentrations of lactate and pyruvate were measured in 28 healthy children aged 7–17 years, split into three age groups: less than 11, 11–14, and 15–17 years. Blood was drawn at rest, immediately after 6 min of exercise at one-third and two-thirds of maximum work capacity (W _max), and 20 min after completion of work. Lactate and pyruvate concentrations increased significantly from rest to exercise at two-thirds W _max [72% of peak oxygen consumption ( O_2peak)]. Whereas greater increments in lactate concentration were seen with groups of increasing age, exercise-related increments in pyruvate concentrations were no different among age groups. There was a significant rise in L:P ratio on exercise, with greater increments found from the youngest to the oldest group. There were no sex differences. We concluded that in healthy children exercising at 70% Of O_2peak there is a rise in blood lactate concentration in excess of that of pyruvate, such that the L:P ratio rises to a degree determined by age. This suggests age dependent changes, perhaps coincident with puberty, in pathways involved in lactate production and/or elimination.     

Effect of hypercapnia on changes in blood pH, plasma lactate and ammonia due to exercise

The present study examined the effects of hypercapnia on changes in blood pH, plasma lactate and ammonia due to exhaustive exercise. Six male subjects underwent exercise of increasing intensity until exhaustion: (1) breathing air = MAX (maximal exercise), or (2) under hypercapnia (HC: 21% O₂, 6% CO₂) that had been maintained from 60 min before to 30 min after exercise = HC; and (3) exercise of the same intensity as HC in air = SUB (submaximal exercise). Arterialized blood was drawn from a superficial vein. Blood pH in HC was significantly lower than in MAX or SUB at rest, at the end of exercise and throughout recovery (P<0.05). Plasma lactate and ammonia concentration in HC was significantly lower than in MAX (P<0.05), and similar to that in SUB at the end of exercise and throughout recovery. Respiratory acidosis resulting from hypercapnia shifted the linear lactate to blood pH relationship during exhaustive exercise below that at normocapnia (P<0.001). The reduced slope of linear blood pH to ammonia relationship under hypercapnia (P<0.001) is attributed to lactic acidosis that is less, due to the lesser work intensity at the end of exhaustion, than that of normocapnia. From these results we conclude that (1) hypercapnia-induced respiratory acidosis promoted the decrease in blood pH due to lactate production throughout recovery; (2) plasma lactate concentration at maximal exercise was lowered under hypercapnia; (3) plasma ammonia concentration at maximal exercise was reduced, probably due to a less intense lactic acidosis.     

Effect of low oxygen inhalation on changes in blood pH, lactate, and ammonia due to exercise

The present study examined the effect of hypoxia-induced respiratory alkalosis on exercise-induced metabolic acidosis and increases in plasma lactate and ammonia levels. Six male subjects underwent exercise of increasing intensity until exhaustion: (1) in normoxia (20.9% O₂) (=MAX), (2) in hypoxia (12% O₂) (=HP) in which hypoxic condition had been maintained from 60 min before to 30 min after exercise, and (3) the same intensity of exercise as HP in normoxia (=SUB). Arterialized blood was drawn from a superficial vein. Post-exercise blood pH was significantly higher in HP than in MAX (P<0.05), although plasma lactate was at the same level. For hypoxia as compared to normoxia, regression analysis confirmed a parallel shift of plasma lactate to higher pH levels indicating the effect of respiratory alkalosis (P<0.01). After exercise plasma levels of ammonia were lower in HP than in MAX (P<0.05). Regression analysis between ammonia and pH revealed nearly identical changes in hypoxia and normoxia at low pH. From these results, we conclude that: (1) hypoxia-induced respiratory alkalosis attenuated exhaustive exercise-induced metabolic acidosis, (2) plasma lactate concentration was determined by the relative exercise intensity, (3) the maximum plasma ammonia concentration under exhaustive exercise was reduced at hypoxia because of respiratory alkalosis.     

甲基强的松龙对大鼠颅脑损伤后内皮素的影响

目的观察甲基强的松龙对大鼠颅脑损伤后脑组织中内皮素含量的影响,并探讨其作用机制。方法将45只SD大鼠随机分为3组,采用骨窗形成后硬膜外打击法造成鼠脑挫裂伤模型,正常组5只,麻醉后,只行开颅手术,不作头颅打击;治疗组大鼠致伤后即刻腹腔内注射30mg/kg甲基强的松龙,对照组则即刻腹腔内注射30mg/kg生理盐水。对照组和治疗组大鼠分别在伤后1h、6h、12h、24h时间点断头取脑,对大鼠脑外伤后脑组织中内皮素含量进行检测。结果大鼠脑皮质中的内皮素在伤后1h后较对照组升高显著(P<0.01),24h达到高峰。甲基强的松龙治疗组在伤后各时间点,内皮素较损伤组明显降低(P<0.05)。结论颅脑损伤后,受损脑组织中内皮素升高,甲基强的松龙可通过抑制损伤后内皮素活性,起到保护创伤神经元的作用。     

Effect of lactate, pyruvate, and pH on secretion of angiogenesis and mitogenesis factors by macrophages

Macrophages secrete substances that stimulate angiogenesis and mitogenesis at wound sites. To test whether metabolic characteristics of the wound such as high lactate concentration and low pH may regulate the expression of these substances, macrophages were cultured in lactalbumin hydrolysate and then in increasing concentrations of lactate, pyruvate, and hydrogen ions, and cell-free supernatants were collected. Cultures incubated in concentrations of lactate approximating those observed in wounds secreted an angiogenesis factor or factors, but cultures incubated in equivalent concentrations of pyruvate or at pH 6.2 did not. These observations seem to be specific to macrophages because capillary endothelial cells and fibroblasts failed to secrete an angiogenesis factor when cultured under hypoxic conditions or in high concentrations of lactate. None of these conditions changed the expression of macrophage mitogens.     

pCO2,pH对兔离体肺动脉缺氧性收缩的影响

观察了二氧化碳（ＣＯ＿２）和ｐＨ对兔离体肺动脉缺氧性收缩（ｈｙｐｏｘｉｃｐｕｌｍｏｎａｒｙｖａｓｏ－ｃｏｎｓｔｒｉｃｔｉｏｎ，ＨＰＶ）反应的影响。浴槽内ＣＯ＿２浓度降低（ｐＣＯ＿２＝１．３３ｋＰａ）使ＨＰＶ加强，Ｋ％为４２．６３±３．１１；而ＣＯ＿２浓度增高则抑制ＨＰＶ（ｐＣＯ＿２＝９．３３ｋＰａ），Ｋ％为１８．４７±２．３１，均与对照值（ｐＣＯ＿２＝５．３３ｋＰａ，Ｋ％为３１．５４±２．６６）有显著差异。相关分析表明ｐＣＯ２与ＨＰＶ的改变呈负相关（ｒ＝一０．４８１，Ｐ＜０．０１，ｎ＝８２）。浴槽内ｐＨ的增高或降低均有使ＨＰＶ增高的趋势，但ｐＨ低至７．１０时ＨＰＶ被抑制。一氧化氮（ＮＯ）合成酶抑制剂ＮＧ一硝基左旋精氨酸抑制了ＨＰＶ，也抑制了低ＣＯ＿２加强ＨＰＶ的作用。结果提示ＣＯ＿２可经对ＮＯ的影响而改变肺血管对缺氧的反应。     

The influence of carbon dioxide,bicarbonate and other buffers on the potential of antimony microelectrodes

Summary Antimony microelectrodes were calibrated at 37° C in phosphate buffers, in different bicarbonate solutions at various CO₂-partial pressures and in buffers like TRIS, TES, MES and malonic acid. By use of the latter buffers (with exception of malonic acid) the most reliable calibration curves were obtained (normal values). The usual calibration in 67 mmol/l standard phosphate buffers turned out to be unacceptable bacause the obtained mV-values were too high (negative) in comparison to all other buffers. Different calibration curves resulted from the use of pure bicarbonate solutions whether the pH-values were changed by variation ofpCO₂ or of the bicarbonate concentration. Low bicarbonate concentrations in combination with lowpCO₂ gave mV-values which were too low relative to the other buffers. Both the increase ofpCO₂ as well as of the bicarbonate concentration caused a shift of the potential of the antimony electrodes toward normal values. In solutions containing other buffers the influence of bicarbonate andpCO₂ became negligible with increasing buffer concentration.Decreasing oxygen partial pressure was found to cause an increase of the potential of the antimony electrodes.The influence of liquid junction potentials at the reference electrode is discussed.     

Viewpoint on the role of tissue maintenance in ageing: focus on biomarkers of bone,cartilage, muscle,and brain tissue maintenance

Specific hallmarks are thought to underlie the ageing process and age-related functional decline. In this viewpoint, we put forward the hypothesis that disturbances in the process of tissue maintenance are an important common denominator that may lie in between specific hallmarks of ageing (i.e. damage and responses to damage) and their ultimate (patho)physiological consequences (i.e. functional decline and age-related disease). As a first step towards verifying or falsifying this hypothesis, it will be important to measure biomarkers of tissue maintenance in future studies in different study populations. The main aim of the current paper is to discuss potential biomarkers of tissue maintenance that could be used in such future studies. Among the many tissues that could have been chosen to explore our hypothesis, to keep the paper manageable, we chose to focus on a selected number of tissues, namely bone, cartilage, muscle, and the brain, which are important for mobility and cognition and affected in several common age-related diseases, including osteoporosis, osteoarthritis, sarcopenia, and neurodegenerative diseases. Furthermore, we discuss the advantages and limitations of potential biomarkers for use in (pre)clinical studies. The proposed biomarkers should be validated in future research, for example by measuring these in humans with different rates of ageing.     

Effects of carbon dioxide inhalation on hematology, coagulation, and serum clinical chemistry values in rats

Blood samples from adult male and female Charles River Crl:CD (SD) BR rats were collected at weekly intervals for 4 wk to evaluate the effects of inhalation of an anesthetic dose of carbon dioxide (CO2) or of a carbon dioxide-oxygen mixture (CO2/O2) on hematology, coagulation, and serum biochemistry values. During the first 3 wk of the study, rats were assigned to 1 of 3 groups and were bled from the orbital sinus once weekly. Prior to the blood collection, rats in group 1 were exposed to room air only, rats in group 2 received CO2/O2 (approximately 66%:34% CO2:O2) by inhalation, and rats in group 3 received 100% CO2 by inhalation. In the rats exposed to CO2/O2 or CO2, leukocyte counts, lymphocyte counts, and glucose values were higher, and aspartate aminotransferase, creatine kinase, and calcium values were lower compared with those of rats exposed to room air only. Rats exposed to 100% CO2 had slightly (but statistically significant) lower mean corpuscular hemoglobin concentration when compared with rats exposed only to room air. During week 4, all rats were reassigned to 1 of 2 groups and were bled terminally via closed cardiac puncture following exposure to either CO2/O2 or CO2. Increased lymphocyte counts (males only) and glucose and chloride concentrations were noted for rats exposed to CO2/O2 compared with those exposed to CO2. These alterations reiterate the importance of comparing clinical pathology values to those of concurrent control groups that have experienced blood collection under identical conditions in order to avoid potential errors in the interpretation of data.