Intracellular bicarbonate of skeletal muscle under different metabolic states.

Intracellular bicarbonate of single muscle fibers in vivo was measured by a direct electrometric method simultaneously with the membrane PD in rats under seven different metabolic states. From the measured intracellular bicarbonate values and the PCO2, the bicarbonate equilibrium potential and the intracellular pH were calculated. The mean intracellular [HCO3-] under normal control conditions was 10.3 +/- 0.7 mM (SE). The intracellular bicarbonate fell significantly in both chronic metabolic acidosis and chronic K+ depletion. In contrast, intracellular bicarbonate was elevated in chronic metabolic alkalosis, K+ loading, and Na+ depletion. Taking intracellular pH as an index of the acid-base status of cells, we find that whereas the calculated cell pH decreased along with the cell bicarbonate in both chronic metabolic acidosis and K+ depletion, cell pH increased along with the bicarbonate only in chronic metabolic alkalosis. Cell pH was unchanged in both chronic K+ loading and Na+ depletion.     

Renal contribution to acid-base regulation during the menstrual cycle

Menstruating women exhibit a light but sustained hypocapnia during the luteal phase. To elucidate whether the hypocapnia results primarily from a respiratory or renal mechanism, we measured the rate of urinary excretion of acid at intervals during the menstrual cycle in five subjects. The acid-base composition of arterial blood in three subjects and end-tidal PCO2 in the remaining two subjects were also determined. During the follicular phase, the acid-base composition of blood and the rate of net acid excretion remained virtually constant. After ovulation, significant decreases in PaCO2 (3.5 mmHg), [HCO3]p (2 meq/liter), and net acid excretion (2 meq/h) occurred in the first 4-6 days of the luteal phase (14 days long). Following this, net acid excretion returned to the preovulatory level. PaCO2 and [HCO3]p, however, remained decreased for 3 more days. At the end of the luteal phase, restoration of PaCO2 proceeded faster than that of [HCO3]p. The acid-base changes in blood and urine observed during the luteal phase were comparable to those occurring during adaptation and recovery from sustained hypocapnia, suggesting that hypocapnia during the luteal phase is primarily respiratory in origin.     

Effect of arterial pH and PCO2 on biliary HCO3- secretion in the pig

The purpose of the present study was to examine the effect of changes in arterial pH and PCO2 on biliary HCO3- secretion. This was done in order to further characterize the various ion transport mechanisms considered responsible for biliary HCO3- secretion in the pig. Experiments were performed on two groups of six pigs. In both groups arterial pH was varied in steps from pH 7.40 to 7.00, both at PCO2 5.5 kPa and PCO2 10 kPa. In group I (n = 6), data were obtained on the effect of arterial pH and PCO2 on ductular HCO3- secretion in bile acid depleted (cholestyramine pretreated), secretin-infused pigs. In group II (n = 6), the effect of pH and PCO2 on canalicular HCO3- secretion was studied in ursodeoxycholic acid (UDCA)-infused pigs (3 mumol min-1 kg-1 body wt). In group I, biliary HCO3- secretion exhibited PCO2-dependent, positive straight line relationships to arterial pH. An increment in biliary HCO3- secretion of 17 (11-24)% was seen during high PCO2 at pH 7.40. In group II, biliary HCO3- secretion exhibited PCO2-dependent, positive curvilinear relationships to arterial pH. A median increment in HCO3- secretion of 37 (20-62)% was seen during elevated PCO2 at arterial pH 7.40. The linear dependence of ductular HCO3- secretion on arterial pH and the effect of elevated PCO2 on HCO3- secretion fit well with findings in other epithelia, where proton transport is thought be driven by a proton pump. A computer simulation provided evidence suggesting that secretin-dependent HCO3- secretion does not involve the action of a Na+/H+ ion exchanger--in contrast to UDCA-dependent HCO3- secretion. It is concluded that ductular and canalicular HCO3- secretion could be mediated by a proton pump and a Na+/H+ ion exchanger in addition to canalicular HCO3- secretion due to solvent drag and diffusion, respectively.     

Distribution of H+ and HCO3 minus between CSF and blood during respiratory alkalosis in dogs.

Anesthetized, paralyzed dogs after a control period at normal pHa were hyperventilated to produce a hypocapnic alkalosis. The pH, PCO2, (HCO3 minus), and (lactate) in cisternal and lumbar CSF and arterial blood were determined at normal conditions (control) shortly after induction of respiratory alkalosis (time 0) and 3, 4.5, and 6 h thereafter. These values along with measurements of the CSF/plasma DC potential (E) allowed calculations of the electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus. After 6 h of hypocapnic alkalosis, muH+ and muHCO3 minus had returned to minus 0.7 and minus 1.0 mV of control at the cistern and to minus 1.0 and +0.4 mV of control for lumbar CSF. This return of mu is compatible with a passive distribution of these ions though active ion regulation is not ruled out. Assuming passive distribution, differences in deltaE/DELTApHa between metabolic and respiratory acid-base changes determined the extent of CSF pH homeostasis during compensated acid-base derangements.     

Effect of induced metabolic alkalosis on sweat composition in men

To determine whether induced metabolic alkalosis affects sweat composition, 10 males cycled for 90 min at 62.5 +/- 1.3% peak oxygen uptake, on two separate occasions. Subjects ingested either empty capsules (placebo) or capsules containing NaHCO3- (0.3 g kg-1 body mass; six equal doses) over a 2-h period, which commenced 3 h prior to exercise. Arterialized-venous blood samples were drawn prior to and after 15, 30, 60 and 90 min of exercise. Sweat was aspirated at the end of exercise from a patch located on the right scapula region. NaHCO3- ingestion elevated blood pH, [HCO3-] and serum [Na+], whereas serum [Cl-] and [K+] were reduced, both at rest and during exercise (P < 0.05). Sweat pH was greater in the NaHCO3- trial (6.24 +/- 0.18 vs. 6.38 +/- 0.18; P < 0.05), whereas sweat [Na+] (49.5 +/- 4.8 vs. 50.2 +/- 4.3 mEq L-1), [Cl-] (37.5 +/- 5.1 vs. 39.3 +/- 4.2 mEq L-1) and [K+] (4.66 +/- 0.19 vs. 4.64 +/- 0.34 mEq L-1) did not differ between trials (P > 0.05). Sweat [HCO3-] (2.49 +/- 0.58 vs. 3.73 +/- 1.10 mEq L-1) and [lactate] (8.92 +/- 0.79 vs. 10.51 +/- 0.32 mmol L-1) tended to be greater after NaHCO3- ingestion, although significance was not reached (P=0.07 and P=0.08, respectively). These data indicate that induced metabolic alkalosis can modify sweat composition, although it is unclear whether the secretory coil, reabsorptive duct, or both are responsible for this alteration.     

Control of rectal gland secretion by blood acid-base status in the intact dogfish shark (Squalus acanthias)

In order to address the possible role of blood acid-base status in controlling the rectal gland, dogfish were fitted with indwelling arterial catheters for blood sampling and rectal gland catheters for secretion collection. In intact, unanaesthetized animals, isosmotic volume loading with 500 mmol L-1 NaCl at a rate of 15 mL kg-1 h-1 produced a brisk, stable rectal gland secretion flow of about 4 mL kg-1 h-1. Secretion composition (500 mmol L-1 Na+ and Cl-; 5 mmol L-1 K+; <1 mmol L-1 Ca2+, Mg2+, SO(4)2-, or phosphate) was almost identical to that of the infusate with a pH of about 7.2, HCO3- mmol L-1<1 mmol L-1 and a PCO2 (1 Torr) close to PaCO2. Experimental treatments superimposed on the infusion caused the expected disturbances in systemic acid-base status: respiratory acidosis by exposure to high environmental PCO2, metabolic acidosis by infusion of HCl, and metabolic alkalosis by infusion of NaHCO3. Secretion flow decreased markedly with acidosis and increased with alkalosis, in a linear relationship with extracellular pH. Secretion composition did not change, apart from alterations in its acid-base status, and made negligible contribution to overall acid-base balance. An adaptive control of rectal gland secretion by systemic acid-base status is postulated-stimulation by the "alkaline tide" accompanying the volume load of feeding and inhibition by the metabolic acidosis accompanying the volume contraction of exercise.     

Correction of CSF HCO 3 − after its experimental increase in normocapnia

In anesthetized normocapnic dogs CSF [HCO ₃ ^– ] was increased to 33 mmol/l by perfusing the brain ventricles for 45 min with a mock CSF containing a high [HCO ₃ ^– ]. In dogs with normal plasma [HCO ₃ ^– ], CSF [HCO ₃ ^– ] fell by ca. 7 mmol/l in 2 h following the end of the perfusion. Lowering plasma [HCO ₃ ^– ] to 11 mmol/l by infusing HCl intravenously was without effect but increasing plasma [HCO ₃ ^– ] to 36 mmol/l by infusing Na₂CO₃ limited the CSF [HCO ₃ ^– ] fall to 2.8 mmol/l. It is concluded that correction of CSF [HCO ₃ ^– ] is partially dependent on a sufficiently low plasma [HCO ₃ ^– ]. The small and persistent fall of CSF [HCO ₃ ^– ] which at high plasma [HCO ₃ ^– ] occurs against a concentration gradient with blood suggests moreover the contribution of more specific mechanism(s) for lowering CSF [HCO ₃ ^– ] after its experimental increase.     

Dependence of cell pH and buffer capacity on the extracellular acid-base change in the skeletal muscle of bullfrog

Intracellular pH was measured with single- or double-barreled liquid ion-exchanger microelectrodes in the bullfrog sartorius muscle perfused in vitro. A neutral carrier ligand was used for pH sensor of microelectrodes. Average slopes of the single-barreled microelectrodes were -56.4 +/- 1.34 mV/pH (n = 30) and the double-barreled -52.6 +/- 1.34 mV/pH (n = 65). While changing acid-base parameters of bathing media (pHe from 6.7 to 8.4, PCO2 from 3.7 to 37 mmHg, and HCO3- concentrations from 5 to 75 mM), paired muscle cell pH (pHi) and membrane potential (EM) values were determined at 23 degrees C. In control conditions (pHe = 7.6, HCO3- = 15 mM, PCO2 = 11 mmHg), pHi and EM (n = 20) averaged 6.99 +/- 0.04 (S.E.) and -69.2 +/- 2.2 mV, respectively. A negative correlation was observed between pHi and EM (correlation coefficient r = -0.564, p less than 0.002). The change in EM per unit pH change was approximately -30mV, indicating that the H+ distribution across the cell membrane only incompletely obeys the Donnan rule. The pHi varied more or less with pHe. Namely, changes in pHe and PCO2 at constant HCO3- produced relatively large changes in pHi, but elevation of pHe and HCO3- at constant PCO2 produced relatively minor rise in pHi. The stability of pHi or the size of buffer capacity were proportional to external HCO3- concentrations. These data suggested that a transmembrane distribution of buffer pairs depends largely on non-ionic diffusion of CO2-HCO3- buffer system and partly on ion fluxes of HCO3- or H+.     

The distribution and movements of carbon dioxide, carbonic acid and bicarbonate between blood and milk in the goat.

1. A-V differences and milk concentrations of respiratory gases, pH, HCO3 and H2CO3 have been measured in lactating goats and cows. 2. The pH and [HCO3 minus] of milk were significantly lower than those of plasma while milk PCO2 was virtually identical to that of mammary venous blood. [H2CO3+ dissolved CO2] was similar in milk and blood. 3. 14-C (from injected [14-C]HCO3 minus was found to cross the mammary epithelium in both directions. 14-C also passed across the duct epithelium and since this epithelium has previously been shown to be impermeable to ions it is argued that 14-C crossed in an unionized form, i.e. as CO2 and/or H2CO3. 4. Hourly milking with the aid of oxytocin raised milk pH, [HCO3 minus], [H2CO3], [Na] and E1Cl], and lowered [K], [lactose] and [phosphate]. These effects are discussed in relation to the hypothesis proposed previously for the action of oxytocin on milk composition. 5. A scheme for the distribution and movements of CO2, H2CO3 and HCO3 minus between extracellular fluid and milk is suggested, and discussed in relation to Cl minus transport.     

Physiological mechanisms of hyperventilation during human pregnancy

This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid-base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM(3); 36.3+/-1.0 weeks gestation; mean+/-S.D.) and again 20.2+/-7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO(2) (PaCO(2)) and [H(+)]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P(4)]) and 17beta-estradiol ([E(2)]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P(4)] and [E(2)], ventilation and V CO(2) increased, whereas PaCO(2) and the central chemoreflex ventilatory recruitment threshold for PCO(2) (VRTCO(2)) decreased from PP to TM(3) (all p<0.01). The reductions in PaCO(2) were not related to the increases in [P(4)] and [E(2)]. The alkalinizing effects of reductions in PaCO(2) and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H(+)] was still reduced in TM(3) vs. PP (all p<0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, V CO(2) and cerebral blood flow account for the reductions in PaCO(2), [H(+)] and VRTCO(2). This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid-base balance, metabolic rate and cerebral blood flow.     

pH effect on osmotic response of collecting tubules to vasopressin and 8-CPT-cAMP

The effect of peritubular and luminal pH changes on hydraulic conductance, (Lp, 10(-7) cm X s-1 X atm-1) in the isolated perfused rabbit cortical collecting tubule (CCT) was tested at 37 degrees C before and after administration of 20 microU/ml vasopressin or 10(-4) M 8-[p-chlorophenylthio]-adenosine cyclic monophosphate (8-CPT-cAMP). In vasopressin experiments when bath pH was changed from 7.58 to 7.16 or from 7.58 to 6.70, mean Lp decreased from 249 +/- 32 to 199 +/- 23 (n = 5; P less than 0.01) and from 231 +/- 38 to 201 +/- 36 (n = 5; NS), respectively. In contrast, in 8-CPT-cAMP experiments when bath [HCO3] was kept constant while CO2 was elevated the hydroosmotic response was increased. Using 2.5 mM HCO3, Lp at 0.4% CO2 was 275 +/- 15 and at 6% CO2 it was 352 +/- 50 (n = 4; paired t test; P less than 0.05). At 8.5 and 21.5 mM HCO3 raising CO2 from 2 to 13% and from 4 to 32% increased Lp from 237 +/- 71 to 410 +/- 32 (n = 4; paired t test; P less than 0.05) and from 282 +/- 45 to 449 +/- 63 (n = 6; paired t test; P less than 0.001), respectively. Reducing luminal pH from 7.40 to 5.40 had no effect on either vasopressin- or cAMP-induced changes in Lp. Accordingly, lowering the bath pH by increasing the PCO2 at constant [HCO3] markedly stimulates the response to 8-CPT-cAMP, whereas lowering the bath pH by reducing [HCO3] inhibits the vasopressin response.     

Distribution of H+ and HCO3 minus between CSF and blood during respiratory acidosis in dogs.

To evaluate the regulation of (H+) and (HCO3 minus) in brain extracellular fluid during respiratory acidosis, the changes in cisternal and lumbar CSF acid-base state were assessed in six anteshetized, paralyzed, mechanically ventilated dogs rendered hypercapnic by increase in FIco2. Arterial (HCO3 minus) was held constant. The electrochemical potential difference (mu) between CSF and blood for H+ and HCO3 minus was calculated from values for (H+) and (HCO3 minus) in CSF and arterial plasma and the simultaneously measured CSF/plasma DC potential difference. Measurements were made at pHa equal to 7.40, after stable arterial values of pHa of about 7.2 were attained and 3, 4.5, and 6 h thereafter. A steady state for ion distribution was attained by 4.5 h. Values of mu for H+ and HCO3 minus at 6 h had returned to +0.7 and minus 0.7 mV of control for cisternal CSF and +1.3 and minus 0.6 mV of control for lumbar CSF. The attainment of steady-state values for mu close to control is comparable with passive distribution of these ions between CSF and blood.     

Potential role of nitric oxide in the pathophysiology of experimental bacterial meningitis in rats.

We have investigated the possible role of nitric oxide (NO) in the pathophysiology of bacterial meningitis (BM) by using the rat model of experimental BM. The nitrite concentration in cerebrospinal fluid (CSF) was used as a measure of NO production in vivo since NO rapidly degrades to nitrite and nitrate. Rats were inoculated intracisternally with live bacteria (5 x 10(6) CFU of Haemophilus influenzae type b strain DL42 or Rd-/b+/O2), with bacterial endotoxin (20 ng of DL42 lipooligosaccharide [LOS] or 200 ng of Escherichia coli lipopolysaccharide), or with a saline control vehicle. CSF samples were collected preinoculation and at the time of maximal alteration in blood-brain barrier permeability (BBBP). CSF [nitrite] was quantified by measuring A550 after addition of the Greiss reagent and comparison to a standard curve of sodium nitrite. Rats inoculated with either DL42, Rd-/b+/O2, LOS, or lipopolysaccharide demonstrated a significantly elevated mean peak CSF [nitrite] (8.34, 15.62, 10.75, and 10.44 mM, respectively) versus the concentration prior to treatment and/or those in saline-treated animals (5.29 and 5.33 mM, respectively; P < 0.05 for each comparison). We then determined if there was a correlation between CSF [nitrite] and percent BBBP (%BBBP) at various time points postinoculation with Rd-/b+/O2. %BBBP was defined as the concentration of systemically administered 125I-labeled bovine serum albumin in the CSF divided by the level of 125I-labeled bovine serum albumin in serum multiplied by 100. The mean %BBBP increased in tandem with the mean CSF [nitrite] (R = 0.84, P = 0.018), which peaked at 18 h in the absence of a change in the serum [nitrite]. Systemic administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester demonstrated a significant reduction of mean CSF nitrite production (0.95 versus 6.0 mM in controls; P = 0.02) when administered intravenously to animals which had been inoculated intracisternally with 20 ng of LOS. Suppression of mean leukocyte pleocytosis (3,117 versus 11,590 leukocytes per mm3 in control LOS-challenged rats; P = 0.03) and mean alterations of BBBP (2.11 versus 6.49% in control LOS-challenged rats; P = 0.009) was observed concomitantly with decreased CSF [nitrite]. These results support the hypothesis that NO contributes to increased %BBBP in experimental BM.     

Mathematical formulation of CO2 dissociation curve and buffer line of human blood at rest

The CO2 content and pH of tonometered blood were measured in nine healthy subjects. The CO2 content in the whole blood (Cb) was found to be expressed by an exponential function of PCO2 including only one parameter (B) as follows: Cb = 1.15 . B-2.548 . PBCO2. The B value was specific to the sampled blood and ranged from 0.4 to 0.45 in the deoxygenated and from 0.45 to 0.52 in the oxygenated blood. The relationship between pH and log PCO2 was also expressed by using one characteristic parameter (D) as follows: for the deoxygenated blood, log PCO2 = 2.144-D . (pH-7.045), and for the oxygenated blood, log PCO2 = 2.037-D . (pH-7.085). The D values were in a range of 1.38 to 1.58. The linear relation between log [HCO3-] and pH was also expressed by using only one parameter. Next, between Cb and [HCO3-] obtained at the same PCO2 of 40 mmHg, a high correlation was observed: the regression line was given, independently of O2 saturation, by Cb40 = 1.942 . [HCO3-]40-3.193, where [HCO3-] was expressed in mM. Using the above equations, it was possible to evaluate the approximate B and D values from a pair of pH and PCO2 measurements and subsequently to depict the CO2 dissociation curve as well as the buffer line in the true plasma.     

Serum potassium and acid-base parameters in severe dialysis-associated hyperglycemia treated with insulin therapy

We analyzed the changes in serum potassium concentration ([K]) and acid-base parameters in 43 episodes of dialysis-associated hyperglycemia (serum glucose level > 33.3 mmol/L), 22 of which were characterized as diabetic ketoacidosis (DKA) and the remaining 21 as nonketotic hyperglycemia (NKH). All episodes were treated with insulin therapy only. Age, gender, initial and final serum values of glucose, sodium, chloride, tonicity and osmolality did not differ between DKA and NKH. At presentation, serum values of [K] (DKA 6.2 +/- 1.3 mmol/L; NKH 5.2 +/- 1.5 mmol/L) and anion gap [AG] (DKA 27.2 +/- 6.4 mEq/L; NKH 15.4 +/- 3.5 mEq/L) were higher in DKA, whereas serum total carbon dioxide content [TCO2 ] (DKA 12.0 +/- 4.6 mmol/L; NKH 22.5 +/- 3.1 mmol/L), arterial blood pH (DKA 7.15 +/- 0.09; NKH 7.43 +/- 0.07) and arterial blood PaCO2 (DKA 26.2 +/- 12.3 mm Hg; NKH 34.5 +/- 6.7 mm Hg) were higher in NKH. At the end of insulin treatment, serum values of [K] (DKA 4.0 +/- 0.7 mmol/L, NKH 4.0 +/- 0.5 mmol/L), [AG] (DKA 16.3 +/- 5.4 mEq/L, NKH 14.9 +/- 3.0 mEq/L), [TCO2 ] (DKA 23.5 +/- 5.0 mmol/L, NKH 24.1 +/- 4.2 mmol/L), arterial blood pH (DKA 7.42 +/- 0.09, NKH 7.51 +/- 0.14) and arterial blood PaCO2 (DKA 31.8 +/- 6.7 mm Hg, NKH 34.2 +/- 8.3 mm Hg) did not differ between the two groups. Linear regression of the decrease in serum [K] value during treatment, (Delta[K]), on the presenting serum [K] concentration,([K]2 ), was: DKA, Delta[K] = 2.78 - 0.81 x [K]2 , r = -0.85, p < 0.001; NKH, Delta[K] = 2.44 - 0.71 x [K]2 , r = -0.90, p < 0.001. The slopes of the regressions were not significantly different. Stepwise logistic regression including both DKA and NKH cases identified the presenting serum [K] level and the change in serum [TCO2 ] value during treatment as the predictors of Delta[K] (R2 = 0.81). Hyperkalemia is a feature of severe hyperglycemia (DKA or NKH) occurring in patients on dialysis. Insulin administration brings about correction of DKA and return of serum [K] concentration to the normal range in the majority of the hyperglycemic episodes without the need for other measures. The initial serum [K] value and the change in serum [TCO2 ] level during treatment influence the decrease in serum [K] value during treatment of dialysis-associated hyperglycemia with insulin.     

Autoregulation of cerebral blood flow and its relation to cerebrospinal fluid pH.

Internal carotid artery blood flow (IFBF) was determined in each of nine Macaca mulatta by means of a flow transducer implanted around an internal carotid artery. The monkeys were lightly anesthetized, intubated, and paralyzed. Normoxia and normocarbia were maintained stable throughout the experiment. ICBF was monitored while mean arterial blood pressure (MABP) was lowered by withdrawal of blood. MABP was kept within the known limits of autoregulation in order not to compromise CBF. Cerebrospinal fluid (CSF) from the cisterna magna was analyzed for pH PCO2, and PO2 before and after a 30-min hypotensive period in which MABP was lowered from 116 +/- 4 to 70 +/- 2 mmHg (mean +/- SE). Corresponding HCO3- concentrations were calculated. The decrease in MABP did not result in a significant reduction in ICBF but elicited a 37% reduction in calculated cerebrovascular resistance, indicating normal autoregulation. Mena CSF pH was not significantly decreased (P less than 0.05); it changed from 7.320 +/- 0.010 to 7.317 +/- 0.010 after the induced hypotensive period. Thus CSF pH does not appear to have a significant role in cerebral blood flow autoregulation.     

Assessing acid-base status in circulatory failure. Differences between arterial and central venous blood

To assess arteriovenous differences in acid-base status, we measured the pH and partial pressure of carbon dioxide (PCO2) in blood drawn simultaneously from the arterial and central venous circulations in 26 patients with normal cardiac output, 36 patients with moderate and 5 patients with severe circulatory failure, and 38 patients with cardiac or cardiorespiratory arrest. The patients with normal cardiac output had the expected arteriovenous differences: venous pH was lower by 0.03 unit, and venous PCO2 was higher by 0.8 kPa (5.7 mm Hg). These differences widened only slightly in those with moderate cardiac failure. Additional simultaneous determinations in mixed venous blood from pulmonary arterial catheters were nearly identical to those in central venous blood. In the five hypotensive patients with severe circulatory failure there were substantial differences between the mean arterial and central venous pH (7.31 vs. 7.21) and PCO2 (5.8 vs. 9.0 kPa [44 vs. 68 mm Hg]). Large arteriovenous differences were present during cardiac arrest in patients whose ventilation was mechanically sustained, whether sodium bicarbonate had been administered (pH, 7.27 vs. 7.07; PCO2, 5.8 vs. 8.6 kPa [44 vs. 65 mm Hg]) or not (pH, 7.36 vs. 7.01; PCO2, 3.7 vs. 10.2 kPa [28 vs. 76 mm Hg]). By contrast, in patients with cardiorespiratory arrest, large arteriovenous differences were noted only when sodium bicarbonate had been given (pH, 7.24 vs. 7.01; PCO2, 9.5 vs. 16.9 kPa [71 vs. 127 mm Hg]). We conclude that both arterial and central venous blood samples are needed to assess acid-base status in patients with critical hemodynamic compromise. Although information about arterial blood gases is needed to assess pulmonary gas exchange, in the presence of severe hypoperfusion, the hypercapnia and acidemia at the level of the tissues are detected better in central venous blood.     

Altered [3H]imipramine and 5-HT2 but not [3H]paroxetine binding sites in platelets from depressed patients.

BACKGROUND: Serotonergic system alterations were studied in 51 depressed patients classified according to DSM-III-R criteria for major depression with melancholia compared to 31 healthy controls. METHOD: [3H]Imipramine and [3H]paroxetine binding sites and the 5HT2 receptor were simultaneously determined in blood platelet membranes. RESULTS: A significantly lower maximum binding in [3H]imipramine binding was observed in depressed patients compared to controls (1134+/-74 vs. 1712+/-106 fmol/mg protein, P<0.0001) without changes in the equilibrium dissociation constant (1.10+0.05 vs. 1.25-/+0.09 nM). [3H]Paroxetine binding did not differ between the two groups (Bmax, 1441+/-55 vs. 1280+/-81 fmol/mg protein; Kd, 0.060+/-0.002 vs. 0.062+/-0.002 nM). The K(d) value of 5HT2 binding was lower in depressed patients than controls (0.95+/-0.04 vs. 1.15+/-0.09 nM, P<0.039) without changes in maximum binding (140+/-11 vs. 127+/-14 fmol/mg protein). CONCLUSIONS: Taken together, these results suggest that [3H]imipramine and 5HT2 receptors may be good biological markers for serotonergic dysfunction in depressive disorders.     

Additivity of adrenaline and contractions on hormone-sensitive lipase,but not on glycogen phosphorylase,in rat muscle

AIM: Hormone-sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. METHODS: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 microm, 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. RESULTS: Hormone-sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 +/- 0.03 (SE) m-unit mg protein(-1) (basal), 0.65 +/- 0.02 (adrenaline), 0.65 +/- 0.03 (contractions), 0.78 +/- 0.03 (adrenaline and contractions); EDL: 0.18 +/- 0.01, 0.30 +/- 0.02, 0.26 +/- 0.02, 0.32 +/- 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 +/- 4 (a/a + b)% vs. 46 +/- 3 (P < 0.05); EDL: 60 +/- 5 vs. 39 +/- 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 +/- 3 (a/a + b)%] was identical to and in EDL [45 +/- 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. CONCLUSIONS: In slow-twitch oxidative as well as in fast-twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.     

Effects of the infusion mode on bicarbonate balance in on-line hemodiafiltration

BACKGROUND: Electrolyte and acid-base balance may be differently affected by the infusion mode in on-line hemodiafiltration (HDF). We studied the effects of the different infusion modes on bicarbonate transport across the dialyzer membrane, and thus on the final bicarbonate balance of the HDF sessions. METHODS: Instantaneous HCO3- transfer across the dialyzer membrane, blood bicarbonate profile and the total balance of the sessions were studied in six dialysis patients under the same operating conditions over 36 HDF sessions, in order to compare the effects of predilution HDF (pre-HDF), postdilution HDF (post-HDF), and mixed HDF on the final bicarbonate balance. RESULTS: The final HCO3- balance was more positive in post-HDF vs pre-HDF (142 +/- 36 vs 99 +/- 41 mmol/session, p<0.05), with a final blood HCO3- concentration of 26.6 +/- 1.0 vs 25.4 +/- 1.1 mmol/L, (p<0.05). Mixed HDF yielded intermediate results (balance: 119 +/- 42 mmol/session, final HCO3- 26.2 (1.2 mmol/L). These differences were seen to result from the increased HCO3- concentration of blood entering the filter in predilution, due to the infused HCO3-, enhancing convective loss and reducing the driving force for diffusive HCO3- gain. CONCLUSIONS: Bicarbonate concentration in dialysate-reinfusate is critical in order to obtain an adequate end of session HCO3- balance in on-line HDF. The predilution method produced the lowest cumulative net HCO3- gain between the three studied infusion modes. Our data suggest that, under the same operating conditions and excluding the effect of ultrafiltration, dialysate HCO3- should be increased by about 2 mmol/L in pre-HDF, and 1 mmol/L in mixed HDF, to yield the same final balance as in post-HDF.