ELECTROLYTE STATE OF CANINE RED BLOOD CELLS DURING HYPOTHERMIC STORAGE WITH THE ADDITION OF N-ACETYLCYSTEINE

It is a well known fact that the thiazide derivatives and their analogues produce more or less metabolic alkalosis in the subjects treated with them. Concerning the relationship of acidbase equilibrium to the regulation of blood pressure, however, we have had only a few reports. Since this prblem seems to be important to elucidate the hypotensive mechanism of the thiazide derivatives, the author attempted in the present study to determine the influence of metabolic alkalosis induced by intravenous in-fusion of sodium bicarbonate solution on blood pressure in the hypertensive subjects. Materials and Methods One hundred and fifty ml of 7 per cent sodium bicarbonate solution was infused intravenously in 10 hypertensive subjects. Blood pressure was estimated before and every 5 minutes after the infusion of bicarbonate solution, for I hour. Arterial blood pH, sodium, potassium, chloride and bicarbonate concentrations in plasrna, and sodium and potassium concentrations in the red blood cells were estimated before and 30 minutes and I hour after the infusion. Results Arterial blood pH markedly rose after the intravenous infusion of 7 per cent of sodium bicarbonate solution. Systolic and diastolic blood pressures progressively fell in all subjects. Both systolic and diastolic blood pressures showed minimum levels 30 minutes after the infusion and then gradually returned to near the pre-infusion levels. Only the decrease in diastolic pressure was significant statistically 30 and 35 minutes after the infusion. Sodium concentration in plasma slightly increased whereas potassium concentration showed a gradual decrease. These changes, however, were not significant. Bicarbonate concentration significantly increased and chloride concentration decreased but the latter change was not significant. Sodium concentration in the red blood cells slightly increased and the ratio of plasma sodium to sodium in the red blood cells decreased. But both changes were not significant. Potassium concentration in the red blood cells had no change. The ratio of potassium in the red blood cells to plasma potassium increased though its increase was not significant. Discussion DRIPPS and COMROE have reported that respiratory acidosis induced by the inhalation of C2 gas raise blood pressure in normal subjects. This finding is contrary to PAGE & OLMSTED'S observation that it lower blood pressure in normal dogs. On the other hand, WALDON and GOLDSTEIN and WELLER have noted a tendency of respiratory acidosis in the patients with essential hypertension. Because of these conflicting information, it is interesting to investigate the relationship of the alteration in acid-base equilibrium to blood pressure, especially with reference to the hypotensive mechanism of the thiazide derivatives which often disturb acid-base equilibrium to some extent. In the present study it was demonstrated that metabolic alkalosis induced by intravenous infusion of sodium bicarbonate solution lower systolic and diastolic blood pressures in the hypertensive subjects. It is, however, difficult to say whether the decrease of blood pressure following the infusion of bicarbonate solution is induced directly by metabolic alkalosis itself or indirectly through the alterations in electrolytes distribution accompanied by alkalosis. So far it would appear likely that metabolic alkalosis itself lowered blood pressure directly, since the alterations in electrolytes distribution induced by alkalosis were significant. Summary Intravenous infusion of sodium bicarbonate raised arterial blood pH and lowered gradually systolic and diastolic blood pressures in hypertensive subjects. Alterations of electrolytes distribution were not significant.

In a previous paper the author reported that the acid-base equilibrium plays an important role in the mechanism of hemodynamics in hypertension. It was concluded that in metabolic acidosis systolic and diastolic blood pressures did not show any change, but total peripheral resistance elevated moderately, while in metabolic alkalosis systolic and diastolic blood pressures indicated a significant decrease in normotensive and hypertensive subjects. From the point of the electrolyte distribution of plasma and red cells it seems to be important to elucidate the mechanism of the changes of hemodynamics in hypertension induced by the acid-base equilibrium. In this report, therefore, the author has attempted to determine the influences of metabolic acidosis on the electrolyte distributions in plasma and red cells and investigate their relationships to the hemodynamics in normotensive and hypertensive subjec〓s. Materials and Methods The study was done on 33 subjects, of whom 16 were normotensives and 17 had apparent essential hypertension without evidences of cardiac or renal failures. Three hundred ml of 0.01 N hydrochloric acid solution was infused intravenously to induce metabolic acidosis and one hundred and fifty ml of 7 per cent bicarbonate solution to induce metabolic alkalosis. Sodium, potassium, chloride and bicarbonate concentrations in plasma, and sodium and potassium concentrations in the red blood cells were measured before and after the infusion. The red blood cells were separated by centrifugation at 3, 600 g for 30 minutes. Results Serial electrolyte changes in metabolic acidosis and their relationship to hemodynamics : Arterial blood pH fell after the intravenous infusion of 0.01 N hydrochloric acid in normotensive and hypertensive subjects. Sodium concentration in plasma decreased slightly in both groups after the influsion. Potassium concentration rose in normotensives and conversely fell in hypertensives, but the differences between them were not significant. Plasma concentration of chloride did not change after the infusion in normotensives while it was elevated insignificantly in hypertensives. Bi-carbonate concentration rose in both groups, but a statistical significance was noted only in the hypertensive group. Since sodium concentration in red blood cells slightly decreased in both groups of patients, the ratio of plasma sodium to sodium in red blood cells, Nae/Nai, increased insignificantly. Potassium concentration in the red blood cells increased slightly in both groups and the ratio of plasma potassium to potassium in red blood cells, Ki/Ke, had no remarkable change in the normotensive group but showed a mild increase in the hypertensive groups. Interestingly there was a close relationship between changes in systolic blood pressure and/or total peripheral resistance and Ki/Ke in the hypertensive group.

AFTER the administration of large doses of DCA or ACTH there is a fall L in the concentrations of sodium and chloride in thermal sweat (1–4). If nonhormonal factors which effect the electrolyte composition are controlled, the concentrations of sodium and chloride in thermal sweat represent reliable indices of the level of adrenocortical activity (1–3). The Na+/K+ concentration ratio has been employed in a similar manner (5–8). Unfortunately, adequate data regarding the change in concentration of potassium during heightened adrenocortical activity is lacking, and this ratio in thermal sweat has not been evaluated in normal individuals under controlled conditions. Although previous investigators have emphasized the effect of the nonhormonal factors on these electrolyte concentrations in sweat (1, 3, 9,) numerous clinical studies (2, 5, 6, 7, 8, 10) have used the concentrations of sodium, potassium and chloride as indices of adrenocortical activity without adequate control of these factors. Skin and air temperature, method of collection, rate and duration of sweating, and the interval between the onset of sweating and its collection all have demonstrable effects on the electrolyte composition of thermal sweat (3, 11–17).

To evaluate the effect of fetal tracheal occlusion on sodium and chloride concentrations in amniotic and tracheal fluid. Intrauterine tracheal occlusion has been proposed to reverse pulmonary hypoplasia, an important prognostic factor in congenital diaphragmatic hernia. In early human trials, technical failure of the obstructive device has been reported. Eight fetal lambs (gestational age = 95 days) were subjected to fetal tracheoscopy, and amniotic and tracheal fluid samples were taken. In multiple pregnancies (n = 6), amniotic fluid was also sampled from the contralateral amniotic sac and used as a control. Subsequently, endotracheal obstruction, using a detachable balloon, was performed. After 14 days, all fetuses were delivered, and sodium and chloride concentrations in amniotic and tracheal fluid were measured again. Statistical analysis was done using a two-tailed Student's t test, paired or unpaired as appropriate. In controls, between 95 and 109 days gestational age, no significant changes occurred in sodium or chloride concentrations in amniotic or tracheal fluid. After 2 weeks of tracheal obstruction, however, chloride and sodium concentrations in amniotic fluid decreased (chloride = 76.7 mEq/L vs. 107.6 mEq/L, p = 0.0003; sodium = 109.6 mEq/L vs. 125.9 +/- 5.2 mEq/L, p = 0.019). A concomitant increase in chloride and sodium concentration was observed in tracheal fluid (chloride = 145.4 mEq/L vs. 130.0 mEq/L, p = 0.047; sodium = 153.1 mEq/L vs. 142.9 mEq/L, p = 0.051). When comparing groups at 109 days, chloride and sodium concentrations in amniotic fluid were markedly lower in the treated group versus controls (p = 0.0004 and p = 0.05 for chloride and sodium, respectively). Complete tracheal occlusion in ovine fetuses results in a significant decrease of amniotic fluid sodium and chloride concentrations.

Background: Oxidative damage is one of the main causes of Red blood cell (RBC) storage lesion which can reduce RBC survival during RBC storage in blood bank condition. In this study, we evaluate the effect of N-acetyl cysteine (NAC) as an anti-oxidant compound on RBC oxidative damage and RBC metabolism during storage of this product. Methods: In this experimental study, 10 bag of packed RBC were provided to the Iranian Blood Transfusion Organization's Innovation Center were randomly selected and effect of NAC was investigated on metabolism, oxidative status and hematologic variables of RBC during RBC storage. The results of this study were compared between two groups of NAC treated RBC and untreated RBC (without NAC). All of the data were analyzed with SPSS statistical program (version 22). Results: In this study, the concentration of lactate and LDH enzyme activity in the NAC treated RBC were lower than the control group (without NAC). The concentration of malondialdehyde (MDA) as a lipid peroxidation marker in the NAC treated RBC was lower increase than the untreated RBC. Also antioxidant capacity was so higher in the NAC - RBC than in the control group, especially in the 28th day of RBC storage (Pday28 <0.05). Conclusion: The results of this study indicated that the use of NAC as an additive solution could decrease oxidative damage via maintaining of the RBC oxidant capacity during RBC storage. In the future NAC may be used as an additive for maintaining of the RBC survival and RBC quality during storage of RBC in blood bank condition.

Ackerman, Hans C. MD, DPhil, MSc; Beaudry, Steven D. BS; Fairhurst, Rick M. MD, PhD Author Information

In six of seven healthy males 6 days of hydrochlorothiazide (HCT), 50 mg twice daily, without potassium supplements resulted in a rise in red blood cell (RBC) sodium concentration. Serum potassium concentration fell in all subjects. Four days after discontinuing HCT, intracellular sodium and extracellular potassium concentrations had normalized. Throughout the evaluation period the course of mean relative intracellular sodium was almost a mirror image of mean relative extracellular potassium. Thus, either the decline of serum potassium or of HCT (because of its inhibitory effect on Na-K-ATPase activity) might have diminished Na-K-ATPase-dependent active RBC sodium efflux with a resultant rise in erythrocyte sodium concentration. RBC potassium and serum sodium concentrations were not affected by short-term exposure to HCT.

The mineral and water composition of human red blood cells in diabetic acidosis and during recovery with special reference to changes in potassium content.

Objectives To evaluate the influence of heart disease and heart failure on 9 parameters: the serum sodium, potassium, chloride, creatinine and urea concentrations, heart rate, vaso-vagal tonus index (VVTI), red cell number and hematocrit. Background Previous studies have demonstrated that heart disease, heart failure and their treatment are associated with changes in laboratory and electrocardiographic parameters. Animals, materials and methods Data were retrieved from 92 client-owned dogs with naturally occurring heart disease. Dogs were classified according to the severity of their heart disease and or the presence of heart failure. The effects of heart disease, the progression into heart failure, the initiation of successful therapy and the administration of diuretics on these parameters were determined. Results Worse heart failure was characterized by the following changes: a significant fall in serum sodium and chloride concentrations and VVTI, and a significant increase in the serum urea concentration and heart rate. The onset of heart failure was characterized by a fall in VVTI and chloride concentration. The successful treatment of heart failure was characterized by a fall in heart rate, an increase in creatinine and sodium concentrations. Dogs receiving diuretics had higher heart rates, lower VVTI, higher urea concentrations, lower potassium, sodium and chloride concentrations. Conclusions Numerous complex alterations in some of the studied parameters are associated with heart disease, heart failure and their treatment. Further consideration of these changes may improve our skills in diagnosis, prognostication and treatment.

For neonates and preterm infants, in whom a transfusion dose is low, the use of red blood cells (RBC) from cord blood appears to be feasible. Standardisation of fractionation and identification and assessment of quality control parameters for such RBC are still lacking. We describe the process used to obtain RBC from cord blood for transfusion purposes, including quality controls to evaluate fractionation performance and the effects of storage. The cord RBC, to which SAG-M was added, were sampled on the day of fractionation, and 7 and 14 days (end of storage) later in order to measure the complete blood count, biochemical parameters and residual white blood cells. We also assessed microbial contamination. Data relative to 279 cord blood units were evaluated. The median gestational age at collection was 40 weeks (interquartile range [IQR] 39.1-40.7) and the median volume was 90 mL (IQR 81-103). Units were subjected to automated fractionation with Compomat, and packed RBC were suspended in SAG-M solution. The median volume of the SAG-M-suspended units was 31 mL (IQR 24.0-38.1) and the median haematocrit was 54.2% (IQR 49.4-59.5). The median volume after leukoreduction was 22 mL (IQR 17-28), with the volume decrease being similar in units leukoreduced before (n=75) or after (n=204) storage. The haematocrit of leukoreduced units was higher than that of buffy coat-depleted units. Storage at 2-6 °C for 14 days was accompanied by an increase of potassium levels and percentage of haemolysis. Microbial cultures were positive for 2.9% of the collected units. Fractionation of whole cord blood can provide RBC concentrates with similar baseline characteristics as units from adults. The transfusion dose and quality of the units appear safe and suitable for clinical use in neonates, with a satisfactory haematocrit and residual white blood cell content, despite a very variable collection volume.

Red blood cells (RBCs) are routinely stored and transfused worldwide. Recently, metabolomics have shown that RBCs experience a three-phase metabolic decay process during storage, resulting in the definition of three distinct metabolic phenotypes, occurring between Days 1 and 10, 11 and 17, and 18 and 46. Here we use metabolomics and stable isotope labeling analysis to study adenine metabolism in RBCs. A total of 6 units were prepared in SAGM or modified additive solutions (ASs) containing 15 N5 -adenine. Three of them were spiked with 15 N5 -adenine on Days 10, 14, and 17 during storage. Each unit was sampled 10 times spanning Day 1 to Day32. At each time point metabolic profiling was performed. We increased adenine concentration in the AS and we pulsed the adenine concentration during storage and found that in both cases the RBCs' main metabolic pathways were not affected. Our data clearly show that RBCs cannot consume adenine after 18 days of storage, even if it is still present in the storage solution. However, increased levels of adenine influenced S-adenosylmethionine metabolism. In this work, we have studied in detail the metabolic fate of adenine during RBC storage in SAGM. Adenine is one of the main substrates used by RBCs, but the metabolic shift observed during storage is not caused by an absence of adenine later in storage. The rate of adenine consumption strongly correlated with duration of storage but not with the amount of adenine present in the AS.

The ovine model is frequently utilized to extrapolate data regarding fetal and amniotic fluid dynamics to human pregnancy. The ovine amnion is highly vascularized, facilitating intramembranous exchange of water and solutes between the amniotic fluid and fetal plasma. In comparison, the relatively avascular human amniotic membrane may have a reduced potential for intramembranous absorption. In view of these anatomical differences, we hypothesized that comparison of human and ovine amniotic fluid composition would provide insight into differences in the mechanisms of amniotic fluid exchange. Amniotic fluid was sampled from 43 patients upon hospital admission, and from 27 ovine ewes at five days following amniotic fluid catheter placement. Both human (32 to 39 weeks' gestation) and ovine pregnancies (125 to 136 days' gestation) were sampled during the last 20% of gestation. Samples were analyzed for osmolality and sodium, potassium and chloride concentrations. The contribution of electrolytes to amniotic fluid osmolality and changes in osmolality and electrolyte composition versus gestational age were assessed by regression and covariance analysis. Mean (+/-SEM) amniotic fluid sodium concentration (134.6+/-1.9 vs. 127.1+/-2.0 mEq/1) was greater and potassium (4.6+/-0.1 vs. 6.1+/-0.6 mEq/l) and osmolality (263.9+/-3.7 vs. 285.1+/-1.6 mOsm/kg) less in human than sheep. The range of amniotic fluid osmolality was greater in human (223 to 336 mOsm/kg) than in sheep (274 to 298 mOsm/kg). Human amniotic fluid osmolality was highly correlated with amniotic fluid sodium (r = 0.97) and chloride (r = 0.96) while ovine amniotic fluid osmolality was only weakly correlated with amniotic fluid sodium (r = 0.75) and chloride (r = 0.51). The slope of the regression line of amniotic fluid sodium and osmolality was greater for human than for sheep amniotic fluid (P < 0.0001). The percent of amniotic fluid osmolality accounted for by sodium, chloride and potassium concentrations was greater for human (97%) than for sheep (86%; P < 0.0001). The results suggest that human amniotic fluid osmolality is comprised almost entirely of the major electrolytes while alternative solutes (e.g., fructose) contribute to ovine amniotic fluid osmolality. Extrapolation of fetal and amniotic fluid dynamics from ovine models to humans should incorporate differences in amniotic fluid osmolality and electrolyte composition.

The ovine model is frequently utilized to extrapolate data regarding fetal and amniotic fluid dynamics to human pregnancy. The ovine amnion is highly vascularized, facilitating intramembranous exchange of water and solutes between the amniotic fluid and fetal plasma. In comparison, the relatively avascular human amniotic membrane may have a reduced potential for intramembranous absorption. In view of these anatomical differences, we hypothesized that comparison of human and ovine amniotic fluid composition would provide insight into differences in the mechanisms of amniotic fluid exchange.Amniotic fluid was sampled from 43 patients upon hospital admission, and from 27 ovine ewes at five days following amniotic fluid catheter placement. Both human (32 to 39 weeks' gestation) and ovine pregnancies (125 to 136 days' gestation) were sampled during the last 20% of gestation. Samples were analyzed for osmolality and sodium, potassium and chloride concentrations. The contribution of electrolytes to amniotic fluid osmolality and changes in osmolality and electrolyte composition versus gestational age were assessed by regression and covariance analysis.Mean (+/-SEM) amniotic fluid sodium concentration (134.6+/-1.9 vs. 127.1+/-2.0 mEq/1) was greater and potassium (4.6+/-0.1 vs. 6.1+/-0.6 mEq/l) and osmolality (263.9+/-3.7 vs. 285.1+/-1.6 mOsm/kg) less in human than sheep. The range of amniotic fluid osmolality was greater in human (223 to 336 mOsm/kg) than in sheep (274 to 298 mOsm/kg). Human amniotic fluid osmolality was highly correlated with amniotic fluid sodium (r = 0.97) and chloride (r = 0.96) while ovine amniotic fluid osmolality was only weakly correlated with amniotic fluid sodium (r = 0.75) and chloride (r = 0.51). The slope of the regression line of amniotic fluid sodium and osmolality was greater for human than for sheep amniotic fluid (P < 0.0001). The percent of amniotic fluid osmolality accounted for by sodium, chloride and potassium concentrations was greater for human (97%) than for sheep (86%; P < 0.0001).The results suggest that human amniotic fluid osmolality is comprised almost entirely of the major electrolytes while alternative solutes (e.g., fructose) contribute to ovine amniotic fluid osmolality. Extrapolation of fetal and amniotic fluid dynamics from ovine models to humans should incorporate differences in amniotic fluid osmolality and electrolyte composition.

The promoting activities of low and high sodium or potassium ion concentrations, under conditions of neutral as well as elevated urinary pH, in urinary bladder carcinogenesis, were investigated in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Male Wistar rats were given 0.05% BBN in their drinking water for 4 weeks and then treated for 32 weeks with either control diet (group 1) or this diet supplemented with equimolar amounts of the following minerals: 2.34% NaCl (group 2), 2.98% KCl (group 3), 3.36% NaHCO3 (group 4), 1.68% NaHCO3 + 2% KHCO3 (group 5), or 4% KHCO3 (group 6). The alkalizing salts NaHCO3 and KHCO3 induced comparable increases in urinary pH and elevated urinary sodium or potassium ion concentrations respectively. The combination of NaHCO3 + KHCO3 similarly caused an elevation of the urinary pH and less increased sodium and potassium ion concentrations. In the groups fed NaHCO3 and KHCO3 either alone or in combination, the incidences of papillary/nodular hyperplasia, papillomas and carcinomas in the urinary bladder had increased as compared to controls. NaCl and KCl also induced high urinary sodium or potassium ion concentrations without alteration of urinary pH. This was accompanied by increased incidences of simple hyperplasia, papillary/nodular hyperplasia, and/or papillomas but no carcinomas. The present results indicate that the potassium ion is as potent as the sodium ion in promoting urinary bladder carcinogenesis under conditions of elevated urinary pH, and that both the sodium and potassium ions may exert weak promoting activity under conditions of neutral urinary pH.

To evaluate the tear film osmolality and electrolyte composition in healthy horses. 15 healthy adult horses. Each horse was manually restrained, and an ophthalmic examination, which included slit-lamp biomicroscopy, indirect ophthalmoscopy, and a Schirmer tear test, was performed. Tear samples were collected from both eyes with microcapillary tubes 3 times at 5-minute intervals. The tear samples for each horse were pooled, and the osmolality and electrolyte concentrations were measured. The mean (SD) was calculated for each variable to establish preliminary guidelines for tear film osmolality and electrolyte composition in healthy horses. The mean (SD) tear film osmolality was 283.51 (9.33) mmol/kg, and the mean (SD) sodium, potassium, magnesium, and calcium concentrations were 134.75 (10), 16.3 (5.77), 3.48 (1.97), and 1.06 (0.42) mmol/L, respectively. The sodium concentration in the tear film was similar to that in serum, whereas the potassium concentration in the tear film was approximately 4.75 times that of serum. Results provided preliminary guidelines with which tear samples obtained from horses with keratopathies can be compared. Measurement of tear film osmolality in these horses was easy and noninvasive. The tear film concentration of divalent cations was greater than expected and was higher than the divalent cation concentrations in the tear films of rabbits and humans. These data may be clinically useful for the diagnosis and monitoring of hyperosmolar ocular surface disease in horses.