Acid-base disturbance during hemorrhage in rats: significant role of strong inorganic ions.

The present study tests the hypothesis that changes in the strong inorganic ion concentrations contribute significantly to the acid-base disturbance that develops during hemorrhage in the arterial plasma of rats in addition to lactate concentration ([Lac-]) increase. The physicochemical origins for this acid-base disorder were studied during acute, graded hemorrhage (10, 20, and 30% loss of blood volume) in three groups of rats: conscious, anesthetized with ketamine, and anesthetized with urethan. The results support the hypothesis examined: strong-ion difference (SID) decreased in the arterial plasma of all groups studied because of an early imbalance in the main strong inorganic ions during initial hemorrhagic phase. Moreover, changes in plasma [Lac-] contributed to SID decrease in a later hemorrhagic phase (after 10% hemorrhage in urethan-anesthetized, after 20% hemorrhage in ketamine-anesthetized, and after 30% hemorrhage in conscious group). Inorganic ion changes were due to both dilution of the vascular compartment and ion exchange with extravascular space and red blood cells, as compensation for blood volume depletion and hypocapnia. Nevertheless, anesthetized rats were less able than conscious rats to preserve normal arterial pH during hemorrhage, mainly because of an impaired peripheral tissue condition and incomplete ventilatory compensation.     

Factors influencing hydrogen ion concentration in muscle after intense exercise

To assess the importance of factors influencing the resolution of exercise-associated acidosis, measurements of acid-base variables were made in nine healthy subjects after 30 s of maximal exercise on an isokinetic cycle ergometer. Quadriceps muscle biopsies (n = 6) were taken at rest, immediately after exercise, and at 3.5 and 9.5 min of recovery; arterial and femoral venous blood were sampled (n = 3) over the same time. Intracellular and plasma inorganic strong ions were measured by neutron activation and ion-selective electrodes, respectively; lactate concentration ([La-]) was measured enzymatically, and plasma PCO2 and pH were measured by electrodes. Immediately after exercise, intracellular [La-] increased to 47 meq/l, almost fully accounting for a reduction in intracellular strong ion difference ([SID]) from 154 to 106 meq/l. At the same time, femoral venous PCO2 increased to 100 Torr and plasma [La-] to 9.7 meq/l; however, plasma [SID] did not change because of a concomitant increase in inorganic [SID] secondary to increases in [K+], [Na+], and [Ca2+]. During recovery, muscle [La-] fell to 26 meq/l by 9.5 min; [SID] remained low (101 and 114 meq/l at 3.5 and 9.5 min, respectively) due almost equally to the elevated [La-] (30 and 26 meq/l) and reductions in [K+] (from 142 meq/l at rest to 123 and 128 meq/l). Femoral venous PCO2 rose to 106 Torr at 0.5 min postexercise and fell to resting values at 9.5 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma osmolality and the strong ion difference predict respiratory adaptations in pregnant and nonpregnant women

This study tested the hypothesis that plasma osmolality and the strong ion difference ([SID]) predict PaCO2 during rest and during exercise in physically active pregnant (n = 22; gestational age 37.0 +/- 0.2 weeks) and nonpregnant (n = 17) women. Nonpregnant subjects were in varying stages of the menstrual cycle. Arterialized blood gases, hydrogen ion concentration, plasma osmolality, [SID], and circulating levels of progesterone were measured at rest and during upright cycling at work rates corresponding to 70 and 110% of the ventilatory threshold. Pooled data from the two groups at rest revealed significant correlations (P < 0.05) between PaCO2 with plasma osmolality, [SID], and progesterone. Progesterone was also significantly correlated with [SID] and osmolality. Also, changes in PaCO2 with exercise correlated significantly with changes in [SID]. The results support the hypothesis that plasma osmolality and [SID] are important factors in the modulation of respiratory sensitivity in healthy women. Also, the effects of progesterone on PaCO2 may be expressed, at least in part, through progesterone-induced changes in [SID] and osmolality.     

Cerebrospinal fluid ions in metabolic acidosis in dogs: effects of acetazolamide

We hypothesized that, during isosmotic isonatremic HCl acidosis with maintained isocapnia in cisternal cerebrospinal fluid (CSF), acetazolamide, by inhibiting carbonic anhydrase (CA) in the central nervous system (CNS), should produce an isonatric hyperchloric metabolic acidosis in CSF. Blood and CSF ions and acid-base variables were measured in two groups of anesthetized and paralyzed dogs with bilateral ligation of renal pedicles during 5 h of HCl acidosis (plasma [HCO3-] = 11 meq/l). Mechanical ventilation was regulated such that arterial PCO2 dropped and CSF Pco2 remained relatively constant. In group I (control group, n = 6), CSF [Na+] remained unchanged, [HCO3-] and strong ions difference (SID) fell, respectively, 6.1 and 5 meq/l, and [Cl-] rose 3.5 meq/l after 5 h of acidosis. In acetazolamide-treated animals, (group II, n = 7), CSF [Na+] remained unchanged, [HCO3-], and SID fell 11 and 7.1 meq/l, respectively, and [Cl-] rose 7.1 meq/l. We conclude that during HCl acidosis inhibition of CNS CA by acetazolamide induces an isonatric hyperchloric metabolic acidosis in CSF, which is more severe than that observed in controls.     

Hematological and acid-base changes in men during prolonged exercise with and without sodium-lactate infusion.

An emerging technique used for the study of metabolic regulation is the elevation of lactate concentration with a sodium-lactate infusion, the lactate clamp (LC). However, hematological and acid-base properties affected by the infusion of hypertonic solutions containing the osmotically active strong ions sodium (Na(+)) and lactate (Lac(-)) are a concern for clinical and research applications of LC. In the present study, we characterized the hematological and plasma acid-base changes during rest and prolonged, light- to moderate-intensity (55% Vo(2 peak)) exercise with and without LC. During the control (Con) trial, subjects were administered an isotonic, isovolumetric saline infusion. During LC, plasma lactate concentration ([Lac(-)]) was elevated to 4 meq/l during rest and to 4-7 meq/l during exercise. During LC at rest, there were rapid and transient changes in plasma, erythrocyte, and blood volumes. LC resulted in decreased plasma [H(+)] (from 39.6 to 29.6 neq/l) at the end of exercise while plasma [HCO(3)(-)] increased from 26 to 32.9 meq/l. Increased plasma strong ion difference [SID], due to increased [Na(+)], was the primary contributor to decreased [H(+)] and increased [HCO(3)(-)]. A decrease in plasma total weak acid concentration also contributed to these changes, whereas Pco(2) contributed little. The infusion of hypertonic LC caused only minor volume, acid-base, and CO(2) storage responses. We conclude that an LC infusion is appropriate for studies of metabolic regulation.     

Experimental determination of net protein charge, [A]tot, and Ka of nonvolatile buffers in bird plasma.

The quantitative mechanistic acid-base approach to clinical assessment of acid-base status requires species-specific values for [A]tot (the total concentration of nonvolatile buffers in plasma) and Ka (the effective dissociation constant for weak acids in plasma). The aim of this study was to determine [A]tot and Ka values for plasma in domestic pigeons. Plasma from 12 healthy commercial domestic pigeons was tonometered with 20% CO2 at 37 degrees C. Plasma pH, Pco2, and plasma concentrations of strong cations (Na, K, Ca), strong anions (Cl, L-lactate), and nonvolatile buffer ions (total protein, albumin, phosphate) were measured over a pH range of 6.8-7.7. Strong ion difference (SID) (SID5=Na+K+Ca-Cl-lactate) was used to calculate [A]tot and Ka from the measured pH and Pco2 and SID5. Mean (+/-SD) values for bird plasma were as follows: [A]tot=7.76+/-2.15 mmol/l (equivalent to 0.32 mmol/g of total protein, 0.51 mmol/g of albumin, 0.23 mmol/g of total solids); Ka=2.15+/-1.15x10(-7); and pKa=6.67. The net protein charge at normal pH (7.43) was estimated to be 6 meq/l; this value indicates that pigeon plasma has a much lower anion gap value than mammals after adjusting for high mean L-lactate concentrations induced by restraint during blood sampling. This finding indicates that plasma proteins in pigeons have a much lower net anion charge than mammalian plasma protein. An incidental finding was that total protein concentration measured by a multianalyzer system was consistently lower than the value for total solids measured by refractometer.     

Role of lungs and inactive muscle in acid-base control after maximal exercise

The pulmonary responses and changes in plasma acid-base status occurring across the inactive forearm muscle were examined after 30 s of intense exercise in six male subjects exercising on an isokinetic cycle ergometer. Arterial and deep forearm venous blood were sampled at rest and during 10 min after exercise; ventilation and pulmonary gas exchange variables were measured breath by breath during exercise and recovery. Immediately after exercise, ventilation and CO2 output increased to 124 +/- 17 1/min and 3.24 +/- 0.195 l/min, respectively. The subsequent decrease in CO2 output was slower than the decrease in O2 intake (half time of 105 +/- 15 and 47 +/- 4 s, respectively); the respiratory exchange ratio was greater than 1.0 throughout the 10 min of recovery. Arterial plasma concentrations of Na+, K+, and Ca2+ increased transiently after exercise. Arterial lactate ion concentration ([La-]) increased to 14-15 meq/l within 1.5 min and remained at this level for the rest of the study. Throughout recovery there was a positive arteriovenous [La-] difference of 4-5 meq/l, associated with an increase in the arteriovenous strong ion difference ([SID]) and by a large increase in the venous Pco2 and [HCO3-]. These findings were interpreted as indicating uptake of La- by the inactive muscle, leading to a fall in the muscle [SID] and increase in plasma [SID], associated with an increase in muscle PCO2. The venoarterial CO2 content difference was 38% greater than could be accounted for by metabolism of La- alone, suggesting liberation of CO2 stored in muscle, possibly as carbamate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma acid-base regulation above and below ventilatory threshold in late gestation.

Stewart's physicochemical approach was used to study the effects of pregnancy on acid-base regulation in arterialized blood. Responses of 15 healthy pregnant women (PG; gestational age, 37.1 +/- 0.2 wk) were compared with those of 15 nonpregnant controls (CG) at rest and during cycling at 70 and 110% of the ventilatory threshold (T(vent)). Hydrogen ion concentration ([H(+)]) was lower in the PG vs. CG at rest and during exercise (P < 0.05 at rest and 70% T(vent)). Exercise-induced changes in [H(+)] were similar between groups. Lower resting [H(+)] values in the PG vs. CG resulted from lower values for arterialized PCO(2) (Pa(CO(2))) and total weak acid ([A](tot)), which were partly offset by a lower strong-ion difference ([SID]). Reductions in [A](tot) and [SID] at rest were primarily the result of reductions in albumin [Alb] and sodium [Na(+)], respectively. In the transition from rest to 70% T(vent), small increases in Pa(CO(2)) and [A](tot) contributed to moderate increases in [H(+)] in both groups, however [SID] increased in the PG and decreased in the CG (P < 0.05 between groups). In the transition from rest to 110% T(vent), decreases in [SID] made a significantly greater contribution to changes in [H(+)] in the CG vs. PG. Exercise-induced increases in [H(+)] are similar in the pregnant vs. nonpregnant state, but there is a reduced contribution of [SID] both above and below T(vent) during pregnancy.     

Roles of CO2, O2, and acid in arteriovenous [H+] difference during muscle contractions

To determine the origins of the arteriovenous [H+] difference of muscle during contractions, arterial and muscle venous blood sample pairs were taken before and after 0.5, 5.0, and 30.0 min of 4/s isometric twitches of the gastrocnemius-plantaris muscle group of anesthetized dogs. These samples were analyzed for PO2, PCO2, and pH, the concentrations of O2, CO2, K+, Na+, La-, and Cl- in whole blood, and La-, K+, Na+, and Cl- in plasma. Whole blood was hemolyzed and analyzed for PO2, PCO2, and pH. Net O2 uptake, CO2 output, L, K+, Na+, and Cl- were calculated in addition to net output of non-CO2 acid (HA) and strong ion difference ([SID]) and common ion [SID] ([K+] + [Na+] - [Cl-] - [La-]). From these data we partitioned the origins of the arteriovenous [H+] difference via the common PCO2-pH diagram and via a [H+]-PCO2 diagram and determined whether true plasma arteriovenous [H+] differences reflect plasma and cell arteriovenous [H+] differences. The arteriovenous [H+] differences of plasma and hemolyzed blood were the same, showing that true plasma does reflect plasma and cells. K+ showed a small significant but transient output. Na+ was not significant, whereas Cl- showed a significant transient uptake. Lactate output and HA, calculated for dog blood acid-base, showed transient outputs and were the same. At 5.0 min when the arteriovenous difference was largest, CO2 alone would have increased [H+] 15.9 nmol/l whereas desaturation of Hb would have decreased [H+] 4.2 nmol/l and lactate could have raised [H+] 1.0 nmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

The roles of ion fluxes in skeletal muscle fatigue

Intense muscle contractions result in large changes in the intracellular concentrations of electrolytes. The purpose of this study was to examine the contributions of changes in intracellular strong ions to calculated changes in steady-state membrane potential (Em) and muscle intracellular H+ concentration ([H+]i). A physicochemical model is used to examine the origin of the changes in [H+]i during intense muscle contraction. The study used the isolated perfused rat hindlimb intermittently stimulated to contract at high intensity for 5 min. This resulted in significant K+ depletion of both slow (soleus) and fast (white gastrocnemius, WG) muscle fibers and a release of K+ and lactate (Lac-) into venous perfusate. The major contributor to a 12- to 14-mV depolarization of Em in soleus and WG was the decrease in intracellular K+ concentration ([K+]i). The major independent contributors to [H+]i are changes in the concentrations of strong and weak ions and in CO2. Significant decreases in the strong ion difference [( SID]i) in both soleus and WG contributed substantially to the increase in [H+]i during stimulation. In WG the model showed that the decrease in [SID]i accounted for 35% of the increase in [H+]i (133-312 nequiv/L; pHi = 6.88-6.51) at the end of stimulation. Of the main contributors to decreased [SID]i, increased [Lac-]i and decreased [K+]i contributed 40 and 60%, respectively, to increased [H+]i, whereas a decrease in [PCr2-]i contributed to reduced [H+]i. It is concluded that decreased muscle [K+]i during intense contractions is the single most important contributor to reduced Em and increased [H+]i. Depletion of PCr2- simultaneous to the changes in [Lac-]i and [K+]i prevents larger increases in [H+]i and helps maintain the intracellular acid-base state.     

Acid-base regulation and control of ventilation in human pregnancy

The purposes of this review were twofold: to apply modern physicochemical principles to explain changes in acid-base regulation and the control of ventilation in human pregnancy; and to demonstrate the value of pregnancy as a model for the study of endocrine effects on physiological control systems. Application of P.A. Stewart's approach (P.A. Stewart. Can. J. Physiol. Pharmacol. 61: 1444-1461, 1983) shows that lower values of plasma hydrogen ion concentration ([H+]) observed at rest and in association with exercise in pregnancy are the result of lower values for carbon dioxide tension (Pco2) and total weak acid ([A(tot)]). This effect is partly offset by a lower strong ion difference ([SID]). The ability to predict plasma [H+] at rest and following strenuous exercise in pregnancy (J.G. Kemp, F.A. Greer, and L.A. Wolfe. J. Appl. Physiol. 83: 644-651, 1997) supports the validity of Stewart's approach. Jennings and associates (D.B. Jennings. Can. J. Physiol. Pharmacol. 72: 1499-1512, 1994) have further demonstrated in animal models the involvement of plasma osmolality and circulating levels of angiotensin II (ANG II) and arginine vasopressin (AVP) in the chemical control of ventilation. We hypothesize that pregnancy-induced increases in respiratory sensitivity to carbon dioxide are the combined result of reduced plasma osmolality, reduced cerebrospinal fluid [SID], and augmented circulating levels of progesterone, ANG II, and AVP.     

Newborn puppy cerebral acid-base regulation in experimental asphyxia and recovery

We hypothesized that part of the newborn tolerance of asphyxia involves strong ion changes that minimize the cerebral acidosis and hasten its correction in recovery. After exposure of newborn puppies to 15 or 30 min experimental asphyxia (inhalation of gas with fractional concentration of CO2 and of O2 in inspired gas = 0.07-0.08 and 0.02-0.03, respectively), blood lactate increased to 13.2 and 23.4 mmol/l, respectively, brain tissue lactate increased to 14.4 and 19.7 mmol/kg, and cerebrospinal fluid (CSF) lactate increased to 7.6 and 14.4 mmol/l. We presume that the tissue lactate increase reflects increases in brain cell and extracellular fluid lactate concentration. The lactate increase, a change that will decrease the strong ion difference (SID), [HCO3-], and pH, was accompanied by increases in Na+ (plasma, CSF, brain), K+ (plasma, CSF), and osmolality without change in Cl-. After 60-min recovery, plasma and brain lactate decreased significantly, but CSF lactate remained unchanged. [H+] recovery was more complete than that of the strong ions due to hyperventilation-induced hypocapnia. We conclude that during asphyxia-induced lactic acidosis, changes in strong ions occur that lessen the decrease in SID and minimize the acidosis in plasma and CSF. To the extent that the increase in brain tissue sodium reflects increases in intra-and extracellular fluid sodium concentration, the decrease in SID will be less in these compartments as well. In recovery, CSF ionic values change little; plasma and brain tissue lactate decrease with a similar time course, and the [H+] is rapidly returned toward normal by hypocapnia even while the SID is below normal.     

Total weak acid concentration and effective dissociation constant of nonvolatile buffers in human plasma.

The strong ion approach provides a quantitative physicochemical method for describing the mechanism for an acid-base disturbance. The approach requires species-specific values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma nonvolatile buffers (K(a)), but these values have not been determined for human plasma. Accordingly, the purpose of this study was to calculate accurate A(tot) and K(a) values using data obtained from in vitro strong ion titration and CO(2) tonometry. The calculated values for A(tot) (24.1 mmol/l) and K(a) (1.05 x 10(-7)) were significantly (P < 0.05) different from the experimentally determined values for horse plasma and differed from the empirically assumed values for human plasma (A(tot) = 19.0 meq/l and K(a) = 3.0 x 10(-7)). The derivatives of pH with respect to the three independent variables [strong ion difference (SID), PCO(2), and A(tot)] of the strong ion approach were calculated as follows: dpH/dSID(+) = [1 + 10(pK(a)-pH)](2)/(2.303 x [SPCO(2)10(pH-pK'(1)[1 + 10(pK(a)-pH](2) + A(tot)10(pK(a)-PH]]; dpH/dPCO(2) = S10(-pK'(1)/[2.303[A(tot)10(pH)(10(pH + 10(pK(a))(-2) - SID(+)10(-pH)]], dpH/dA(tot) = -1/[2.303[SPCO(2)10(pH-pK'(1) + SID(+)10(pK(a)-pH)]], where S is solubility of CO(2) in plasma. The derivatives provide a useful method for calculating the effect of independent changes in SID(+), PCO(2), and A(tot) on plasma pH. The calculated values for A(tot) and K(a) should facilitate application of the strong ion approach to acid-base disturbances in humans.     

Plasma [H+] regulation and whole blood [CO2] in exercising ponies

The major objective was to determine in ponies whether factors in addition to changes in blood PCO2 contribute to changes in plasma [H+] during submaximal exercise. Measurements were made to establish in vivo plasma [H+] at rest and during submaximal exercise, and CO2 titration of blood was completed for both in vitro and acute in vivo conditions. In 19 ponies arterial plasma [H+] was decreased from rest 4.5 neq/l (P less than 0.05) during the 7th min of treadmill running at 6 mph, 5% grade (P less than 0.5). A 5.6-Torr exercise hypocapnia accounted for approximately 2.9 neq/l of this reduced [H+]. The non-PCO2 component of this alkalosis was approximately neq/l, and it was due presumably to a 1.7-meq/l increase from rest in the plasma strong ion difference (SID). Despite the arterial hypocapnia, mixed venous PCO2 was 2.7 Torr above rest during steady-state exercise. Nevertheless, mixed venous plasma [H+] was 1.2 neq/l above rest during exercise, which was presumably due to the increase in SID. Also studied was the effect of submaximal exercise on whole blood CO2 content (CCO2). In vitro, at a given PCO2 there was minimal difference in CCO2 between rest and exercise blood, but plasma [HCO3-] was greater for exercise blood than for rest blood. In vivo, during steady-state exercise, arterial plasma blood. In vivo, during steady-state exercise, arterial plasma [HCO3-] was unchanged or slightly elevated from rest, but CaCO2 was 4 vol% below rest.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between pH and the strong ion difference (SID) in body fluids

Acid-base balance evaluation according to the Henderson-Hasselbalch equation enable us to assess the contribution of respiratory (pCO2) and/or non-respiratory (metabolic, HCO3(-)) components to the acid-base balance status. A new approach to acid-base balance evaluation according to Stewart-Fencl, which is based on a detailed physical-chemical analysis of body fluids shows that metabolic acid-base balance disorders are characterized not only by [HCO3(-)]. According to this concept independent variables must be taken into an account. The abnormality of concentration of one or more of the independent variable(s) determines the pH of a solution. The independent variables are: 1. strong ion difference (SID); 2. total concentration of nonvolatile weak acids [A(tot)]; 3. in agreement with the Henderson-Hasselbalch concept also pCO2. Traditional evaluation of acid-base balance disorders is based on the pH of body fluids (though pH may be within normal range if several acid-base balance disturbances are present). In order to maintain this view and simultaneously to respect the Stewart-Fencl principle, we invented a new equation, which uses only the independent variables to define the pH of body fluids. This analysis shows that for a given value of pCO2, the pH of body fluids is determined by a difference between SID and [A(tot)-]. pH = 6.1 + log((SID - [A(tot)-])/(0.03pCO2)) or in itemized form: pH = 6.1 + log((([Na+] + [K+] + [Ca2+] + [Mg2+] - [Cl-] - [UA-]) - (k1[Alb] + k2[P(i)]))/(0.03 x pCO2)). Evaluation of the individual components of this equation enables us to detect, which of the independent variable (or a combination of independent variables) deviates from the normal range and therefore which one or ones is a cause of the acid-base balance disorder. At the end of this paper we give examples of a practical application of this equation.     

Physicochemical analysis of phasic menstrual cycle effects on acid-base balance

In accordance with Stewart's physicochemical approach, the three independent determinants of plasma hydrogen ion concentration ([H(+)]) were measured at rest and during exercise in the follicular (FP) and luteal phase (LP) of the human menstrual cycle. Healthy, physically active women with similar physical characteristics were tested during either the FP (n = 14) or LP (n = 14). Arterialized blood samples were obtained at rest and after 5 min of upright cycling at both 70 and 110% of the ventilatory threshold (T(Vent)). Measurements included plasma [H(+)], arterial carbon dioxide tension (Pa(CO(2))), total weak acid ([A(Tot)]) as reflected by total protein, and the strong-ion difference ([SID]). The transition from rest to exercise in both groups resulted in a significant increase in [H(+)] at 70% T(Vent) versus rest and at 110% T(Vent) versus both rest and 70% T(Vent). No significant between-group differences were observed for [H(+)] at rest or in response to exercise. At rest in the LP, [A(Tot)] and Pa(CO(2)) were significantly lower (acts to decrease [H(+)]) compared with the FP. This effect was offset by a reduction in [SID] (acts to increase [H(+)]). After the transition from rest to exercise, significantly lower [A(Tot)] during the LP was again observed. Although the [SID] and Pa(CO(2)) were not significantly different between groups, trends for changes in these two variables were similar to changes in the resting state. In conclusion, mechanisms regulating [H(+)] exhibit phase-related differences to ensure [H(+)] is relatively constant regardless of progesterone-mediated ventilatory changes during the LP.     

Relationship between plasma PGE2 level and changes in hemoglobin proportions during bleeding-induced anemia in adult rats

Reversion of hemoglobin proportions toward newborn values is a characteristic change found in blood of acutely bled adult rats. In this study, adult Sprague-Dawley rats were bled over a period of time until they became anemic by hematologic parameters. We measured plasma prostaglandin E2 levels of anemic and control rats using double-antibody technique. A significant increase was recorded in bled plasma, and the value returned to unbled level when anemia was corrected. Acetylsalicylic acid intake during bleeding-induced anemia abolished the process of reverse switching of hemoglobin, as well as inhibited the increase in plasma PGE2 levels. Changes in hemoglobin proportions due to phlebotomy were also blocked when acetylsalicylic acid was replaced by indomethacin. These observations are of significance in understanding, at least in part, the mechanism of reverse hemoglobin switching in adult rats undergoing erythropoietic stress.     

Interactive effects of anemia and muscle oxidative capacity on exercise endurance

We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls.     

Arterial acid-base status during digestion and following vascular infusion of NaHCO(3) and HCl in the South American rattlesnake, Crotalus durissus

Digestion is associated with gastric secretion that leads to an alkalinisation of the blood, termed the "alkaline tide". Numerous studies on different reptiles and amphibians show that while plasma bicarbonate concentration ([HCO(3)(-)](pl)) increases substantially during digestion, arterial pH (pHa) remains virtually unchanged, due to a concurrent rise in arterial PCO(2) (PaCO(2)) caused by a relative hypoventilation. This has led to the suggestion that postprandial amphibians and reptiles regulate pHa rather than PaCO(2). Here we characterize blood gases in the South American rattlesnake (Crotalus durissus) during digestion and following systemic infusions of NaHCO(3) and HCl in fasting animals to induce a metabolic alkalosis or acidosis in fasting animals. The magnitude of these acid-base disturbances were similar in magnitude to that mediated by digestion and exercise. Plasma [HCO(3)(-)] increased from 18.4+/-1.5 to 23.7+/-1.0 mmol L(-1) during digestion and was accompanied by a respiratory compensation where PaCO(2) increased from 13.0+/-0.7 to 19.1+/-1.4 mm Hg at 24 h. As a result, pHa decreased slightly, but were significantly below fasting levels 36 h into digestion. Infusion of NaHCO(3) (7 mmol kg(-1)) resulted in a 10 mmol L(-1) increase in plasma [HCO(3)(-)] within 1 h and was accompanied by a rapid elevation of pHa (from 7.58+/-0.01 to 7.78+/-0.02). PaCO(2), however, did not change following HCO(3)(-) infusion, which indicates a lack of respiratory compensation. Following infusion of HCl (4 mmol kg(-1)), plasma pHa decreased by 0.07 units and [HCO(3)(-)](pl) was reduced by 4.6 mmol L(-1) within the first 3 h. PaCO(2), however, was not affected and there was no evidence for respiratory compensation. Our data show that digesting rattlesnakes exhibit respiratory compensations to the alkaline tide, whereas artificially induced metabolic acid-base disturbances of same magnitude remain uncompensated. It seems difficult to envision that the central and peripheral chemoreceptors would experience different stimuli during these conditions. One explanation for the different ventilatory responses could be that digestion induces a more relaxed state with low responsiveness to ventilatory stimuli.     

Hypoproteinemia, strong-ion difference, and acid-base status in critically ill patients

Thepresent study was a prospective, nonrandomized, observationalexamination of the relationship among hypoproteinemia and electrolyteand acid-base status in a critical care population of patients. A totalof 219 arterial blood samples reviewed from 91 patients was analyzedfor arterial blood gas, electrolytes, lactate, and total protein.Plasma strong-ion difference ([SID]) was calculated from[Na⁺] + [K⁺]  [Cl]  [La].Total protein concentration was used to derive the total concentration of weak acid([A]_tot).[A]_tot encompassed arange of 18.7 to 9.0 meq/l, whereas [SID] varied from 48.1 to 26.6 meq/l and was directly correlated with[A]_tot. The decline in[SID] was primarily attributable to an increase in[Cl]. A directcorrelation was also noted betweenPCO₂ and [SID], but notbetween PCO₂ and[A]_tot. The decrease in [SID] and PCO₂ wassuch that neither [H⁺]nor [HCO₃] changedsignificantly with[A]_tot.