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PubMed2000

Influence of an extracellular acidosis on excitatory synaptic transmission and long-term potentiation in the CA1 region of rat hippocampal slices.

The effects of extracellular acidification on the synaptic function and neuronal excitability were investigated on the hippocampal CA1 neurons. A decrease of extracellular pH from 7.4 to 6.7 did not alter either the resting membrane potential or the neuronal membrane input resistance. Extracellularly recorded field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were significantly reduced by acidosis. Additionally, the amplitude of presynaptic fiber volley was also reduced. The sensitivity of postsynaptic neurons to N-methyl-D-aspartate, but not to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, was depressed by acidosis. Lowering of extracellular pH did not significantly affect the magnitude of paired-pulse facilitation (PPF) of synaptic transmission. Acidosis also reversibly limited the sustained repetitive firing (RF) of Na(+)-dependent action potentials elicited by injection of depolarizing current pulses into the pyramidal cells. The limitation of RF by extracellular acidification was accompanied by the reduction of the maximal rate of rise (;V(max)) of the action potentials and the amplitude of afterhyperpolarization. Neither the Na (+)/H (+) antiporter blocker 5-(N -ethyl -N -isopropyl)-amiloride nor the selective adenosine A (1) receptor antagonist 1,3-dipropyl -8-cyclopentylxanthine, however, affected the acidosis -induced synaptic depression. It was also found that acidosis did not affect either the induction r maintenance of long -term potentiation (LTP) at Schaffer collateral -CA 1 synapses. These results suggest that the extracellular acidosis -induced synaptic depression is likely to result from an inhibition of presynaptic Na (+) conductance, thereby decreasing the amplitude of action potentials in individual afferent fibers or the number of afferent fiber activation to stimuli and then indirectly affecting the signaling processes contributing to trigger neurotransmitter release.

Acidosis↗
PubMed1978

Lactic acidosis and diffuse histiocytic lymphoma (DHL).

Four patients with advanced diffuse histiocytic lymphoma who developed lactic acidosis are described. All four patients demonstrated disturbed liver function tests. In two of the patients, the lactic acidosis was unresponsive to treatment. The third patient responded successfully to the early initiation of combination chemotherapy with achievement of a clinical remission and correction of the lactic acidosis. The fourth patient responded to the initiation of chemotherapy with abatement of his lactic acidosis, but expired probably as the result of a pulmonary embolus. It seems likely that extensive hepatic infiltration may be one of the factors contributing to lactic acidosis in patients with diffuse histiocytic lymphoma. The early initiation of antineoplastic therapy may be important in the management of patients with histiocytic lymphoma and lactic acidosis.

Acidosis↗
PubMed1998

Relevance of calcium homeostasis in glial cell swelling from acidosis.

Tissue acidosis from trauma or ischemia induces cytotoxic brain edema, mainly affecting astrocytes. In vitro, lactacidosis induces a dose-dependent swelling of glial cells. Activation of membrane transporters and channels, also involved in regulation of intracellular pH (pHi), has been identified as underlying mechanism, although details are poorly understood. We have currently studied whether Ca(2+)-ions play a role in acidosis-induced glial swelling and the associated intracellular acidification. The medium pH of a cell suspension (C6 glioma) was lowered from control (7.4) to 6.2 by lactic acid. Cell volume (CV) and pHi were assessed by flow cytometry. During acidosis in normal medium (2.2 mM Ca2+) CV reached a maximum of 125.1%. In a calcium-free medium swelling from acidosis was inhibited by 74%, while additional buffering of intracellular calcium (Ca2+i) by BAPTA-AM had no further effect. Buffering of Ca2+i alone did not affect the CV increase from acidosis at all. pHi which is decreasing during acidosis was not influenced by the above modifications. The present experiments indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while alterations of Ca2+i do not seem to be involved.

Acid-Base Equilibrium↗
PubMed1997

Role of calcium ions in acidosis-induced glial swelling.

Tissue acidosis occurring in cerebral ischemia and traumatic brain injury is a mediator of cytotoxic brain edema. In vitro, extracellular lactacidosis induces swelling of glial cells in a dose dependent manner. pH-regulatory membrane transporters and channels have been identified which are involved in the increase of the glial cell volume. Underlying mechanisms of their activation are poorly understood, however. We have, therefore, addressed the question, whether and how Ca(2+)-ions play a role in acidosis-induced glial swelling and intracellular acidification. For that purpose C6 glioma cells were suspended and the pH in the medium was lowered from 7.4 (baseline) to 6.2 by isotonic lactic acid. Cell volume and intracellular pH (pHi) were assessed by flow cytometry. In the presence of Ca(2+)-ions the cell volume reached a maximum of 125.1% from acidosis. In experiments using a calcium-free suspension medium, cell swelling from acidosis was inhibited by 74%. Additional buffering of intracellular calcium (Ca2+i) had no further inhibitory effect on acidosis-induced cell swelling, while buffering of Ca2+i by BAPTA-AM alone did not affect the glial volume increase secondary to administration of lactic acid. pHi which was decreasing from acidosis was not affected by the experimental modifications of the Ca(2+)-concentration in the medium or cytosol. The present data indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while release of Ca(2+)-ions from intracellular stores does not seem to be involved.

Acidosis↗
PubMed1983

Brain lactic acidosis and ischemic cell damage: quantitative ultrastructural changes in capillaries of rat cerebral cortex.

Excessive tissue lactic acidosis has earlier been shown to aggravate structural damage of both neurons and glial cells in the rat cerebral cortex. To study the reactions of cortical capillaries, light- and electronmicroscopic morphometry was used. Rats were subjected to severe incomplete ischemia (cerebral blood flow below 5% of normal) for 30 min by clamping their carotid arteries and by lowering the blood pressure. Lactate production during ischemia was modified by preischemic administration of either saline (low lactic acidosis group) or glucose (high lactic acidosis group). In the animals with low lactic acidosis, only minimal vascular changes were seen after both 5 min and 90 min recirculation. In the high lactic acidosis group, the endothelial cells were swollen after 5 min of recirculation, and the changes grew markedly worse during 90 min of recirculation. Nuclear chromatin coarsened and mitochondria swelled up. Morphometry showed that the lumen narrowed as a result of endothelial swelling. In spite of variable degree of perivascular astrocytic edema, the outer capillary diameter was little changed in the experimental groups. It seems likely that endothelial swelling hampers postischemic circulation in incomplete ischemia accompanied by high lactic acidosis.

Acidosis↗
PubMed1994

Effects of iron-induced lipid peroxidation and of acidosis on choline uptake by synaptosomes.

The effects of iron-induced lipid peroxidation and of lactic acidosis on [3H]choline uptake were investigated on crude synaptosomes prepared from rat cerebral cortices. Fe(2+)-induced lipid peroxidation as evidenced from the production of thiobarbituric acid reactives substances (TBARS) was correlated with a decrease in high-affinity choline uptake (HACU). Trolox C, a free radical scavenger, prevented both Fe(2+)-induced TBARS production and decrease in HACU. Lactic acidosis (pH 6.0 for 30 or 60 min) increased the TBARS production with concomitant decrease in HACU (-48%, -78%, respectively). The acidosis dependent decrease was not reversible following pH 7.4 readjustment after 60 min acidosis. It was not prevented by trolox C, although trolox C inhibited the acidosis-induced production of TBARS. The results suggest that the contribution of acidosis to peroxidative damages is probably of less importance in comparison to other cytotoxic mechanisms.

Acidosis, Lactic↗
PubMed1997

Effect of acidosis on contraction, intracellular pH, and calcium in the newborn and adult rabbit aorta.

This study investigated the effect of acidosis on intracellular pH (pHi), intracellular calcium concentration ([Ca]i), and vascular contraction in the aorta of the newborn and adult rabbit. Isometric tension, pHi, and [Ca]i were measured in an isolated ring preparation. After the vascular contraction was induced with 50mM KC1, the effect of respiratory acidosis produced by elevation of PCO2 was studied. Respiratory acidosis caused a transient depression followed by a recovery of contractile tension. The decrease in developed tension was greater in the newborn than in the adult. The decrease in pHi during acidosis was similar in the two age groups. [Ca]i increased during acidosis and the increase was greater in the newborn than in the adult. These data show that the vasorelaxant effect of acidosis in the newborn aorta is greater than that in the adult aorta. The greater vasodilation in the newborn cannot be explained by the difference in pHi or [Ca]i.

Acidosis, Respiratory↗
PubMed1997

Effects of acidosis on the distribution of processing of the beta-amyloid precursor protein in cultured hippocampal neurons.

Reported increases in brain lactate production in Alzheimer disease led us to test the hypothesis that lactic acid acidosis alters the processing of the beta-amyloid precursor protein, beta PP, in neurons. To test this proposition, embryonic rat hippocampal neurons were first cultures for 4 d in serum-free B27/neurobasal medium. Lactic acid at 0.5 and 1 mg/mL (pH 7.1 and, 6.9, respectively) caused a dose-dependent increase in cellular beta-amyloid immunoreactivity detected with antibody 4G8. Acidosis did not affect secretion of beta PP or its derivatives into the medium. The cytoplasmic production of beta PP was slightly reduced by acidosis without a differential effect on maturation or proteolytic processing. In the substrate-bound material, which was insoluble in nonionic detergent, acidosis caused increases in an N-terminal 75-kDa band, a C-terminal 72-kDa band, and potentially amyloidogenic bands at 35 and 38 kDa. Processing to the 4-kDa amyloid beta protein was not observed in these early pure rat neuronal cultures. These results suggest that mild acidosis id sufficient to alter neuronal processing to the amyloid precursor protein into potentially amyloidogenic forms and increase certain beta PP fragments bound to the substrate. If a similar process occurs in the presence of other cell types in the aging brain, acidosis may stimulate an extracellular deposition of amyloid and contribute to the pathogenesis of Alzheimer disease.

Acidosis, Lactic↗
PubMed1999

Incomplete renal tubular acidosis in 'primary' osteoporosis.

Chronic metabolic acidosis may increase alkali mobilization from bone and thus promote the development of osteoporosis. While it is undisputed that overt metabolic acidosis is associated with metabolic bone disease, renal acidification in patients with idiopathic osteoporosis has not been studied systematically. The purpose of this study was to investigate the prevalence of renal acidification defects in patients with 'primary' osteoporosis. Thirty-two women (including 10 premenopausal women) and 16 men who were referred to our department for investigation of osteoporosis were enrolled in this study. Patients with obvious or possible secondary osteoporosis were excluded. None of the patients had overt metabolic acidosis. In random urine samples 12 of the 48 patients had pH levels below 5.5 and were therefore considered to have normal renal acidification. The remaining 36 patients underwent further testing by a short-course oral ammonium chloride load. In this test nine of these 36 patients (7 men and 2 premenopausal women) failed to lower urinary pH below 5.5 despite the induction of systemic metabolic acidosis. In these patients, therefore, the diagnosis of incomplete distal renal tubular acidosis was made (RTA I). Patients with incomplete RTA I had significantly lower spontaneous plasma pH (7.38 +/- 0.0081 vs 7.41 +/- 0.004, mean +/- SEM, p = 0.002), a lower serum bicarbonate concentration (21.9 +/- 0.49 mmol/l vs 23.1 +/- 0.24 mmol/l, p = 0.034), a lower base excess (-2.33 +/- 0.42 mmol/l vs -0.55 +/- 0.21 mmol/l, p = 0.001) and lower Z-scores in bone densitometry (-2.18 +/- 0.27 vs -1.40 +/- 0.15, p = 0.028) than patients with normal renal acidification. In conclusion, a high prevalence of incomplete RTA I (in 44% of the male patients, 20% of the premenopausal female patients and 6% of all female patients) was found in patients with osteoporosis who, without testing, would have been diagnosed as having 'primary' osteoporosis. The mild metabolic acidosis observed in these patients may have contributed to loss of bone mass by a compensatory mobilization of alkali and calcium from bone. Because of possible therapeutic consequences (e.g., administration of alkali salts and high doses of vitamin D) we propose that measurements of urinary pH and, if necessary, ammonium chloride testing should be included in the diagnostic investigation especially of male and of premenopausal female patients with osteoporosis. Since referral bias, although unlikely, cannot be excluded in our study, the prevalence of RTA I in unselected patients with osteoporosis needs to be determined at primary screening institutions.

Absorptiometry, Photon↗
PubMed2002

Oxygen consumption and force development in turtle and trout cardiac muscle during acidosis and high extracellular potassium.

Relative to species such as rainbow trout, freshwater turtle shows a high tolerance to challenges involving acidosis and increases in extracellular K+. Therefore, the effects of acidosis or high K+ on twitch force and oxygen consumption were examined in ventricular ring preparations from these two species. The oxygen consumption associated with force development was estimated by net oxygen consumption (oxygen consumption during twitch force development minus that during rest). For turtle, elevation of CO2 from 2% (pH 7.7) to 12% (pH 6.9) in the gas equilibrating the muscle bath decreased twitch force by 20% without any effects on oxygen consumption. Decreasing pH from 7.7 to 6.9 with 22 mM lactic acid had similar effects. For trout, CO2-induced acidosis decreased twitch force by approximately 60%. Furthermore, force development became energetically less efficient as it fell disproportionately more than net oxygen consumption. This was not observed for lactic acidosis. For trout but not for turtle, acidosis resulted in an increase in oxygen consumption during rest. An increase in extracellular K+ from 2.5 mM to 10 mM depressed force and oxygen consumption proportionately for both species. Adrenaline (10 microM) increased twitch force for both species and oxygen consumption for trout; it attenuated the effects of high extracellular K+. Neither adrenaline nor high K+ influenced the ratio of force to net oxygen consumption. As opposed to high extracellular K+, acidosis appears to increase the energetic cost of contractility, particularly for the trout heart.

Acidosis↗
PubMed2003

Impact of hypercholesterolemia on acidosis-induced coronary microvascular dilation.

An increase in coronary flow conductance during acidosis is an important compensatory mechanism in various diseased conditions. On the other hand, hypercholesterolemia causes microvascular dysfunction as well as macrovascular disorders. We investigated the impact of hypercholesterolemia on the coronary microvascular response to acidosis. Coronary arterioles (< 150 microm) isolated from rabbit hearts were cannulated to micropipettes in a vessel chamber and the microvascular responses were observed. After preconstriction was established, the extravascular pH was gradually reduced from 7.4 to 7.0. The effects of glibenclamide, ATP-sensitive K(+) (K(ATP)) channel blocker, (1 microM, n = 4) or pertussis toxin (100 ng/mL, n = 7) on the acidosis-induced microvascular responses were examined. In another set of experiments, rabbits were randomly assigned to normal chow (NC group, n = 18) or high cholesterol (2 %) diet (HC group, n = 20). After 8 weeks of feeding, the responses of isolated coronary arterioles to acidosis, ADP, nitroprusside, and levcromakalim were examined in the two groups. Coronary arterioles significantly dilated as the pH was reduced and the dilation was significantly inhibited by glibenclamide or pertussis toxin. Acidosis-induced dilation in the HC group was significantly attenuated compared to the NC group (36.5 +/- 2.1 % vs 73.7 +/- 4.8 % at pH = 7.0 P < 0.05). There were no significant differences in the dilations by ADP, nitroprusside and levcromakalim between the two groups. In conclusion, acidosis-induced dilation of rabbit coronary arterioles is mediated by the activation of the pertussis toxin-sensitive G protein and K(ATP) channels, and the dilation of coronary arterioles is impaired in hypercholesterolemia. The impairment occurs upstream of K(ATP) channel opening.

Acidosis↗
PubMed2004

Effect of bicarbonate on retinal vasculature and acidosis-induced retinopathy in the neonatal rat.

BACKGROUND: Systemic acidosis induces preretinal neovascularization (NV) analogous to retinopathy of prematurity (ROP) in the neonatal rat. Sodium bicarbonate is used in human neonates to treat acidosis. The effects of alkali administration on the developing retinal vasculature and on acidosis-induced retinopathy (AIR) are unknown. We investigated the effect of sodium bicarbonate gavage on the retinal vasculature of normal and acidotic neonatal rats to determine (1) whether bicarbonate treatment is associated with preretinal NV and (2) whether AIR can be prevented with systemic bicarbonate treatment. METHODS: The extent of acidosis and alkalosis were initially determined from carotid arterial blood samples. In the bicarbonate-alone study, newborn rats were randomized into litters of 25 and received bicarbonate doses of 15 mmol/kg twice daily and 20 mmol/kg once daily from days 2 to 7. Control animals received saline gavage. In the AIR treatment study, acidosis was induced in neonatal rats by intraperitoneal injection of acetazolamide 200 mg/kg from days 2 to 7. Acetazolamide-treated rats received either additional bicarbonate gavage or no additional treatment. Eyes were enucleated on day 13, and the retinal vasculature was assessed for NV using ADPase staining techniques and light microscopy. RESULTS: Systemic alkalosis (peak pH 7.55+/-0.02; mean +/- SD) was confirmed with bicarbonate gavage, and partial reversal of acidosis was confirmed when acetazolamide-treated rats received bicarbonate. Surviving rats receiving bicarbonate 15 mmol/kg twice daily (28% survival) and 20 mmol/kg bicarbonate once daily (45% survival) had an incidence of preretinal NV of 9% and 8%, respectively. No NV was seen in saline-control rats. In the acetazolamide-treated rats, the incidence of preretinal NV in surviving rats was numerically lower in bicarbonate-treated rats than acetazolamide-only controls (8% versus 24%, p=0.065) but with only 19% survival in the bicarbonate-treated rats. CONCLUSIONS: In the neonatal rat, alkalosis induced by bicarbonate gavage is associated with a low incidence of mild, preretinal NV similar to ROP. Although treating acidotic rats with bicarbonate may reduce the incidence of preretinal NV, treatment was associated with an unacceptable mortality rate.

Acetazolamide↗
PubMed1993

The effect of hypoxia and acidosis on propranolol clearance in the isolated perfused rat liver preparation.

The effect of hypoxia and acidosis on the elimination of an oxidatively metabolized drug, S-propranolol, was examined in the single-pass isolated perfused rat liver (IPRL). The experiments (N = 6) consisted of four consecutive 30 min phases: normal pH (pH 7.4)/normal oxygen delivery, normal pH/hypoxia, hypercapnic acidosis (pH 7.1)/normal oxygenation and hypercapnic acidosis/hypoxia. Hypoxia and acidosis were produced by equilibrating the perfusate with appropriate mixtures of O2, N2 and CO2. With normal oxygen delivery there was no difference in hepatic clearance of propranolol between normal pH and acidosis (9.65 +/- 0.34 and 9.78 +/- 0.11 mL/min, respectively. P < 0.05). During hypoxia, propranolol clearance was impaired to a similar extent under both pH conditions (7.41 +/- 0.97 and 8.06 +/- 0.81 mL/min, respectively, P > 0.05). Therefore, respiratory acidosis does not affect the clearance of propranolol by the IPRL, nor does it influence the sensitivity of propranolol clearance to hypoxia. Neither acidosis nor hypoxia resulted in a significant reduction in bile flow compared with the normal pH/normal oxygen phase and there was no correlation between bile flow and perfusate bicarbonate concentration (P > 0.05).

Acidosis, Respiratory↗
PubMed1989

Effect of respiratory acidosis on hypoxic newborn myocardium.

We studied the effect of respiratory acidosis (pH = 6.8) on mechanical function, tissue adenosine triphosphate (ATP), and effluent creatine kinase (CK) in isolated arterially perfused hypoxic newborn and adult rabbit hearts. In the oxygenated muscle, acidosis reduced tension (T) and maximal tension first derivative [+ dT/dt (max)] in the adult more than in the newborn. In the adult hypoxic and reoxygenated hearts, acidosis during hypoxia (not reoxygenation) improved the recovery of T, + dT/dt (max) and tissue adenosine triphosphate (ATP) and reduced CK release and the rise in the resting tension. In the newborn heart, respiratory acidosis during hypoxia had no beneficial effects on recovery of mechanical function, tissue ATP and CK release. The buffering capacity and sarcolemmal H-Na exchange rate are both higher in the newborn heart than in the adult heart. This suggests that acidosis reduces the rise in intracellular Na and Ca, that is observed during hypoxia and reoxygenation, in the adult more than in the newborn and this may explain the beneficial effect of acidosis in the adult and not in the newborn.

Acidosis, Respiratory↗
PubMed1989

Effects of acidosis on anoxic and exocytotic noradrenaline release from the heart.

The effects of acidosis (pH 6.5) on the efflux of noradrenaline from the perfused heart of the rat have been studied. Acidosis does not influence the noradrenaline efflux induced by sympathetic nerve stimulation either in the presence or absence of neuronal uptake blockade. It is therefore unlikely that acidosis will contribute to the failure of nerve stimulation mediated noradrenaline release previously shown to occur during myocardial ischaemia. Acidosis exerts a biphasic effect on the noradrenaline efflux produced by substrate free anoxic perfusion with an inhibition of early noradrenaline overflow. Peak anoxic efflux of noradrenaline is greater when extracellular NaCl is replaced by Tris or sucrose in keeping with the hypothesis of carrier-mediated noradrenaline efflux. Marked early anoxic efflux occurs when extracellular NaCl is replaced by LiCl suggesting an additional mechanism of vesicular destabilization. Anoxic noradrenaline efflux is inhibited by amiloride (and ethylisopropyl amiloride) and it is proposed that the inhibitory effect of extracellular acidosis on early noradrenaline efflux also occurs by inhibition of the Na+ (Li+)/H+ antiporter leading to reduced Na+ (Li+) entry during the early phase of anoxia. At a later stage acidosis enhances anoxic noradrenaline efflux. This effect is postulated to be due to a reduction in the transvesicular pH gradient available for catecholamine storage within the storage vesicles.

Acidosis↗
PubMed1977

Metabolic acidosis in the vitamin D-deficient chick.

In vitamin D-deficient chicks raised from age 1 day on a vitamin D-deficient diet, hyperchloremic metabolic acidosis accurred at 3 wk and persisted. Within 24 hr of administration of vitamin D, the acidosis and hypocalcemia were attentuated; during the subsequent 72 hr the severity of the metabolic acidosis but not that of the hypocalcemia was further attenuated. That further attenuation occurred despite hypocalcemia of unchanging severity and presumed continuing secondary hyperparathyroidism suggests the possibility that vitamin D deficiency may be a requirement for the expression of metabolic acidosis. Since in vitro and in vivo studies suggest that subphysiologic values of media and blood pH, respectively, are attended by reduced production of 1,25-(OH2D3, the most biologically active vitamin D metabolite known, the occurrence of acidosis in vitamin D deficiency may compound its metabolic consequences. The possible effects of acidosis must be considered in interpreting results of investigations of vitamin D metabolism in vitamin-D-deficient chicks.

Acidosis↗
PubMed1979

Pathogenesis of acidosis in hereditary fructose intolerance.

An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.

Acid-Base Imbalance↗
PubMed1979

Role of PCO2 as determinant of CSF [HCO-3] in metabolic acidosis.

To study regulation of CSF [HCO-3] in metabolic acidosis and in particular the role of CSF PCO2 in establishing CSF bicarbonate level, acute metabolic acidosis was induced by the intravenous infusion of HCl in three groups of anesthetized dogs for six hours when PaCO2 was changed at different rates. Plasma [HCO-3] was lowered to 12 +/- 2 meq/L within one hour and maintained at that level thereafter in all groups. (I) Seven dogs were kept isocapnic while metabolic acidosis was induced. The cisternal CSF [HCO-3] fell by only 2.6 meq/L after six hours and was not significantly different from control. (II) In 11 dogs metabolic acidosis was induced while the dogs breathed spontaneously. There was a gradual drop in PaCO2 accompanied by a similar drop in CSF PCO2 of 14.5 torr. CSF [HCO-3] fell significantly by 6.1 meq/L at 6 hours and in parallel with the fall in CSF PCO2. (III) In order to show interdependence of the rate of fall in CSF [HCO-3] with rate of fall in cisternal PCO2 six dogs were mechanically hyperventilated and PaCO2 reduced to 21 torr rapidly and maintained there for six hours. CSF PCO2 followed PaCO. CSF bicarbonate fell rapidly and by 5 meq/L. In groups II and III the fall in cisternal [HCO-3] paralleled the drop in PCO2. Therefore, in metabolic acidosis the rate of the fall in cisternal bicarbonate appears to be a function of the rate of fall in CSF PCO2. It is speculated that the coupling of CSF [HCO-3] reduction in metabolic acidosis to CSF PCO2 fall is primarily for the benefit of CNS H+ homeostasis.

Acidosis↗