Effect of bicarbonate administration on skeletal muscle intracellular pH in the rat: implications for acute administration of bicarbonate in man.

1. The effect of bicarbonate administration on the intracellular pH of rat skeletal muscle was examined by using 31P n.m.r. 2. Bicarbonate administered intraperitoneally caused a significant intracellular acidosis in rat skeletal muscle in vivo. When the bicarbonate was administered intravenously there was no such change in the pH of the skeletal muscle. 3. Bicarbonate administration by either route resulted in an elevated mixed venous partial pressure of carbon dioxide and an elevated arterial pH, but no significant change in the arterial partial pressure of carbon dioxide. The increase in arterial bicarbonate concentration after intraperitoneal injection of bicarbonate was delayed when compared with that after intravenous injection. 4. The administration of hypertonic solutions intravenously caused a transient 40-50% fall in blood pressure, which had resolved within 1 min. 5. The data suggest that the effect of bicarbonate administration on intracellular pH in vivo is related not only to carbon dioxide loading of the cell but also to the rate of change in the extracellular bicarbonate concentration.     

Effects of different dosages and modes of sodium bicarbonate administration during cardiopulmonary resuscitation.

Systemic acidosis occurs during cardiac arrest and cardiopulmonary resuscitation (CPR). The present study investigated the effect of different modes of sodium bicarbonate administration on blood gas parameters during CPR. Arterial and venous blood gases were obtained during 10 minutes of CPR which was preceded by 3 minutes of unassisted ventricular fibrillation in 36 dogs. Following 1 minute of CPR, the animals received one of four treatments in a randomized and blinded manner: normal saline (NS), sodium bicarbonate bolus dose 1 mEq/kg (B), sodium bicarbonate continuous infusion 0.1 mEq/kg/min (I), and sodium bicarbonate bolus dose (0.5 mEq/kg) plus continuous infusion 0.1 mEq/kg/min (L+I). Eleven dogs completed NS, 8 B, 8 I, and 9 L+I protocol. Following NS infusion, both arterial and venous pH declined consistently over time. Significant differences compared with NS treatment in venous pH were observed at 12 minutes of ventricular fibrillation (L+I, 7.27 +/- 0.05; NS, 7.15 +/- 0.05; B, 7.20 +/- 0.05; I, 7.24 +/- 0.04, each bicarbonate treatment versus NS, and L+I versus B, (P < .05). The B group had an elevated venous PCO2 (mm Hg) concentration following 6 minutes of ventricular fibrillation compared with NS, L+I, and I groups (81 +/- 14 versus 69 +/- 10 versus 68 +/- 10 versus 71 +/- 8, respectively, (P = .07). Arterial pH and PCO2 values showed a similar trend as the venous data with the L+I group demonstrating arterial alkalosis (pH > 7.45) at 12 minutes of ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of glutamine metabolism in vitro by bicarbonate ion and pH

The effect of variations of medium pH and bicarbonate concentration on glutamine oxidation was studied in slices and mitochondria from dog renal cortex. Decreasing pH and bicarbonate concentration increased the rate of oxidation of glutamine-U-(14)C to (14)CO(2) in both slices and mitochondria, an effect comparable to the acute stimulation of glutamine utilization produced by metabolic acidosis. Decreases in the concentration of glutamate and alpha-ketoglutarate, which accompany metabolic acidosis in the intact animal, also occurred in tissue slices when pH and [HCO(3) (-)] were lowered; decrease in alpha-ketoglutarate but not in glutamate content occurred in mitochondria under these conditions. Study of independent variations of medium pH and [HCO(3) (-)] showed that simultaneous changes in both pH and [HCO(3) (-)] produced a greater effect on glutamine metabolism than did change in either of these parameters alone.The rate of glutamine oxidation was also compared in tissue preparations from pairs of litter-mate dogs with chronic metabolic acidosis and alkalosis. No significant difference in the rate of glutamine oxidation was present in mitochondria from the two sets of animals. Slices from animals with chronic metabolic acidosis consistently oxidized glutamine at a more rapid rate than slices from alkalotic dogs both at high and at low concentrations of bicarbonate in the medium. We believe this difference is a result of the same mechanism which leads to the delayed increase in ammonium excretion during induction of metabolic acidosis.The close parallel between the effects demonstrated here and the changes in ammonium production and glutamine utilization in the intact animal with metabolic acidosis suggest that the observed in vitro changes accurately represent the operation of the physiologic mechanism by which acid-base changes regulate ammonium excretion. The similarity between the changes in glutamine oxidation observed in this study and those described previously for citrate suggests that one control mechanism affects the metabolism of both citrate and glutamine. Thus, we believe that the increase in citrate clearance in metabolic alkalosis and the increase in glutamine utilization and ammonium production in metabolic acidosis reflect the operation of the same underlying biochemical mechanism. This mechanism permits changes in pH and [HCO(3) (-)] in the cellular environment to regulate the rate of mitochondrial uptake and oxidation of several physiologically important substrates.     

Significance of post-exercise increment of urinary bicarbonate and pH in subjects loaded with submaximal cycling exercise

We studied the changes in urinary bicarbonate, urinary pH and some physical parameters such as minute ventilation (VE), oxygen consumption (VO2), respiratory carbon dioxide (VCO2), heart rate, blood pressure, and blood lactate, before and after the submaximal exercise. Six male subjects aged 28-33 years were involved in the study. They performed the incremental exercise test using a bicycle ergometer until exhaustion. Levels of VE, VO2, VCO2, heart rate, and blood pressure increased continuously with an increase in cycling intensity. These parameters markedly decreased and reached the baseline levels within 5-10 minutes after the termination of exercise. According to an increase in cycling intensity, blood lactate increased continuously during exercise, but after termination of exercise the return of lactate to the baseline level was markedly retarded. Urinary bicarbonate and pH were within the range of those at 0 time (baseline levels) from the beginning until 30 minutes after the exercise. However, they began to increase abruptly about 30 minutes after the exercise, and continued to increase extensively for 2 hours thereafter. Such marked increase in urinary bicarbonate and pH seemed to be correlated with the aerobic metabolism of lactate in the muscles, liver, and kidney, finally producing CO2. It was also suggested that the measurement of urinary bicarbonate and pH may be useful for the estimation of physiological changes in the body after submaximal incremental cycling exercise loading.     

Marked increase in urinary bicarbonate and pH caused by heavy muscular exercise with dynamic knee extension

In order to estimate the physiological responses to heavy muscular exercise with dynamic knee extension, the levels of urinary variables such as bicarbonate, urinary pH and blood lactate were studied before and after the exercise. Nine male volleyball players aged 19 or 20 years were involved in the present study. They performed 10%, 30% and 80% 1 repetition maximum (RM) knee extension. The levels of urinary bicarbonate and urinary pH did not change for 2.5 hours after cessation of the exercise with 10% 1 RM load, compared with the baseline levels. When 30% 1 RM loading was given, urinary bicarbonate and pH moderately increased for 2.5 hours. When 80% 1 RM loading was given, both urinary bicarbonate and pH increased immediately after cessation of the exercise, for 2.5 hours. Levels of blood lactate increased extensively within 1 minute after cessation of the exercise in the subjects with 80% 1 RM load, but no significant increase was seen in subjects with 10% 1 RM load. The changes in urinary bicarbonate and pH could be explained by the continuous production of CO2 in the muscular tissues involved in the exercise with a submaximal load where excess postexercise oxygen consumption is accelerated. It is also possible that the liver and muscle where blood lactate is aerobically metabolized could be the cause of these changes. It was also suggested that the measurement of urinary bicarbonate and pH may be useful for the estimation of events in the body after submaximal exercise loading.     

Effects of erythrocytes, bicarbonate, temperature and albumin on in vitro ionized calcium variations with pH

Using a heart lung machine as an in vitro model, the relation between ionized calcium (cCa2+) and pH has been shown to depend on several variables such as erythrocytes, temperature and albumin as well as the total calcium and bicarbonate concentrations. The respiratory acid-base disturbances were simulated by changing the gas flow between 1.0 and 2.41 min-1 by adding CO2, to the machine at a concentration of 0 to 17%. When pCO2 was used to alter pH, cCa2+ varied from 0.16 mmol l-1 per pH unit to 0.52 mmol l-1. The regression slope of cCa2+ on pH was made steeper by decreasing erythrocyte volume fraction and by increasing temperature and the concentrations of HCO3, calcium or albumin. The metabolic acid-base alterations were produced by HCl or NaHCO3 at a constant gas flow, cCA2+ changes per pH unit were 0.70 mmol l-1 in plasma and 1.04 mmol l-1 in whole blood. The different results found in plasma and in erythrocyte fluids may be explained by their different buffering capacity. Haemoglobin may buffer hydrogen ions, and the formation of HCO3- is catalysed by carbonic anhydrase from the red cells.     

Comparison of external jugular and peripheral venous administration of sodium bicarbonate in puppies

We compared the administration of sodium bicarbonate via a catheter inserted in the external jugular and extending to the junction with the subclavian vein (group 1) and a peripheral hindpaw vein (group 2) in puppies. During spontaneous cardiac activity, the increases in pH (0.12 +/- 0.04 in group 1 vs. 0.08 +/- 0.04 in group 2) and PCO2 (11 +/- 2.8 torr in group 1 vs. 6 +/- 3.2 torr in group 2) in blood from the right atrium 10 sec after the injection of bicarbonate differed significantly. However, the increases in pH (0.31 +/- 0.07 in group 1 vs. 0.30 +/- 0.15 in group 2) and PCO2 (86 +/- 33 torr in group 1 vs. 72 +/- 35 torr in group 2) in blood from the right atrium during closed chest CPR were similar in the two groups. We found that the sodium bicarbonate reached the central circulation more rapidly when administered in the external jugular vein as compared to a peripheral site, but this difference was small and did not reach the level of significance during CPR. Our findings do not provide evidence of any advantage to obtaining central venous access (a potentially complicated procedure) in children with cardiac arrest in regard to the delivery of medications to the heart.     

Hypertonic sodium bicarbonate versus intravenous lipid emulsion in a rabbit model of intravenous flecainide toxicity: no difference,no sink

Context. The use of intravenous lipid emulsion (ILE) as an antidote in non-local, anaesthetic drug toxicity has generated considerable interest. Flecainide is a lipophilic anti-arrhythmic with a significant cardiotoxic profile, with blockade of sodium and potassium channels causing arrhythmias and shock in severe toxicity. ILE has been proposed as a treatment option in severe flecainide toxicity refractory to other modalities. Objective. We compared the effects of ILE and hypertonic sodium bicarbonate in a rabbit model of flecainide toxicity. Materials and methods. Twenty sedated and ventilated New Zealand White Rabbits received flecainide infusion titrated to a mean arterial pressure (MAP) of 60% baseline, which was defined as toxicity. The rabbits then received either sodium bicarbonate or ILE, and the flecainide infusion was reduced in an attempt to model ongoing enteric absorption. MAP and heart rate were recorded every minute for 15 min and plasma flecainide concentration was measured at toxicity and 15 min. ECG QRS duration was recorded at baseline, toxicity and at 5, 10 and 15 min post-toxicity. Results. No difference was observed in heart rate (p = 0.2804), MAP (p = 0.1802) or QRS duration (p = 0.7471) between groups. The immediate rate of rise in MAP was greatest in the bicarbonate group in the 5 min immediately post-toxicity. Conclusions. In this study, no differences were observed between an active control of hypertonic sodium bicarbonate and ILE for the primary endpoint of MAP at 15 min nor for QRS duration at any timepoint. There was a transient rapid increase in blood pressure seen in the sodium bicarbonate group that was not sustained. No increase was seen in blood concentration of flecainide in the ILE group, suggesting no ‘lipid sink’ for flecainide in this model. More research is warranted to define any role for ILE in flecainide toxicity.     

Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.

The effects of changes in peritubular pH, carbon dioxide tension (PCO2), and HCO3- concentration on net HCO3- transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3- concentration and pH by reciprocal replacement of HCO3- with Cl-, significantly stimulated net HCO3- absorption. Lowering peritubular HCO3- concentration and pH, by substitution of HCO3- with gluconate, while keeping Cl- concentration constant, also stimulated net HCO3- absorption. Raising peritubular HCO3- concentration and pH, by reciprocal replacement of Cl- with HCO3-, inhibited net HCO3- absorption (or stimulated net HCO3- secretion). When the tubule was cooled, raising peritubular HCO3- concentration had no effect on net HCO3- transport, suggesting these results are not due to the passive flux of HCO3- down its concentration gradient. The effect of changes in ambient PCO2 on net HCO3- transport were also studied. Increasing the ambient PCO2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3- transport. Similarly, lowering ambient PCO2 to 14 mmHg had no effect on net HCO3- transport. Simultaneously increasing peritubular HCO3- concentration and PCO2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3- secretion to the same degree as nonisohydric increases in peritubular HCO3- concentration. Likewise, isohydric lowering of peritubular HCO3- concentration and PCO2 stimulated net HCO3- absorption. We conclude that: acute changes in peritubular HCO3- concentration regulate acidification in the CCT and these effects are mediated by a transcellular process; acute changes in ambient PCO2 within the physiologic range have no effect on HCO3- transport in the in vitro perfused CCT; and acute in vitro regulation of CCT acidification is independent of peritubular pH.     

56例嗜铬细胞瘤病人尿中儿茶酚胺的定量分析

目的 :为实验诊断嗜铬细胞瘤疾病 ,建立高效液相色谱法快速测定尿中去甲肾上腺素 (NE)、肾上腺素 (E)和多巴胺 (DA)三种儿茶酚胺类物质的方法。方法 :流动相选用柠檬酸 -柠檬酸三钠 -甲醇 -离子对试剂 -EDTA -Na2 混合液 (pH 4 2 ) ;色谱柱采用 3 0× 3mmC18柱 ,并以自制的固相萃取柱作标本的预处理 ,以电化学检测器检测。结果 :对 5 6例嗜铬细胞瘤病人的 3种儿茶酚胺进行了测定和统计分析 ,结果发现与正常相比 ,5 6例嗜铬细胞瘤病人的NE、E均明显增高 ,其中 2 4例病人以NE明显增高 (P<0 0 1) ,18例病人以E明显增高 (P <0 0 1) ,14例以NE、E明显增高 (P <0 0 1)。结论 :该方法对于嗜铬细胞瘤疾病的实验诊断具有重要意义 ,并有助于肿瘤的定位。     

Bone marrow involvement is predictive of infusion-related reaction during rituximab administration in patients with B cell lymphoma

Purpose

The purpose of this study is to evaluate risk factors for infusion-related reaction (IRR) following rituximab administration in patients with B cell non-Hodgkin lymphoma.

Methods

A retrospective analysis was conducted of patients with newly diagnosed B cell lymphoma who have received rituximab-included immunochemotherapy with appropriate premedication and commonly used schedule of infusion rate. IRRs were graded by review of the patients’ electronic medical record according to the Common Terminology Criteria for Adverse Events version 4.0.

Results

One hundred and sixty-nine patients were included in the analysis and most of the patients (150; 88.8 %) had diffuse large B cell lymphoma (DLBCL). Thirty-six patients (21.3 %) had any grade of IRRs: 23 patients were grade (G) 1 (13.6 %), 13 had ≥G2 IRRs (7.7 %), and only 4 had ≥G3 IRRs (2.4 %). All except one patient had IRR during the first cycle and only two had repetitive IRR thereafter. Bone marrow (BM) involvement was the strongest risk factor for IRR in multivariable analysis (odds ratio 4.06, 95 % confidence interval 1.67–9.89; p?=?0.002). A subgroup analysis confined to patients with DLBCL showed very similar results when compared with the entire population, and patients with DLBCL who had ≥G2 IRR showed shorter event-free and overall survival when compared to those who did not.

Conclusions

BM involvement is predictive of occurrence of IRR during rituximab administration in patients with B cell lymphoma. More intensive premedication and careful observation for IRR during rituximab administration are required for patients with B cell lymphoma who have BM involvement.     

The association of emergency department administration of sodium bicarbonate after out of hospital cardiac arrest with outcomes

Background

Sodium bicarbonate administration is mostly restricted to in-hospital use in Taiwan. This study was conducted to investigate the effect of sodium bicarbonate on outcomes among patients with out-of-hospital cardiac arrest (OHCA).

Regulation of cell pH by ambient bicarbonate, carbon dioxide tension, and pH in the rabbit proximal convoluted tubule.

To study the regulation of cell pH by ambient pH, carbon dioxide tension (PCO2), and bicarbonate (HCO3), cell pH was measured in the isolated, in vitro microperfused rabbit proximal convoluted tubule using the fluorescent dye (2',7')-bis-(carboxyethyl)-(5,6)-carboxyfluorescein. For the same changes in external pH, changes in [HCO3] and PCO2 affected cell pH similarly ([HCO3]: pHi/pHe = 0.67, PCO2: pHi/pHe = 0.64, NS). Isohydric changes in extracellular [HCO3] and PCO2 did not change cell pH significantly. Changes in peritubular [HCO3] elicited larger changes in cell pH than changes in luminal [HCO3], which were enhanced by peritubular 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate (SITS). The cell pH defense against acute increases and decreases in PCO2 was inhibited by sodium, but not by chloride removal. Peritubular SITS inhibited the cell pH defense against increases and decreases of PCO2, whereas luminal amiloride inhibited cell pH defense against increases in PCO2. Conclusions: (a) Steady-state cell pH changes in response to changes in extracellular [HCO3] and PCO2 are quantitatively similar for a given change in extracellular pH; (b) the rate of the basolateral Na/(HCO3)3 cotransporter is a more important determinant of cell pH than the rate of the apical membrane mechanism(s); (c) cell pH defense against acute changes in PCO2 depends on the basolateral Na/(HCO3)3 cotransporter (acid and alkaline loads) and the luminal Na/H antiporter (acid loads).