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KEY POINTS We investigated the influence of arterial PCO2 ( PaCO2 ) with and without acute experimental metabolic alkalosis on neurovascular coupling (NVC). We assessed stepwise iso-oxic alterations in PaCO2 prior to and following intravenous NaHCO3 to acutely elevate arterial pH and [HCO3- ]. The NVC response was not altered following NaHCO3 between stepwise PaCO2 stages; therefore, NVC is acutely mediated by PaCO2 rather than the prevailing arterial [H+ ]/pH. The NVC response was attenuated by 27-38% with -10 mmHg PaCO2 and the absolute peak change was reduced by -19% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ]. The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively) likely indicating an influence of resting cerebrovascular tone on NVC responsiveness. ABSTRACT Elevations in cerebral metabolism necessitate appropriate coordinated and localized increases in cerebral blood flow (i.e. neurovascular coupling; NVC). Recent pre-clinical work indicates that arterial PCO2 ( PaCO2 ) mediates NVC independently of arterial/extracellular pH; this has yet to be experimentally tested in humans. The goal of this study was to investigate the hypotheses that: (1) the NVC response would be unaffected by acute experimentally elevated arterial pH; rather, PaCO2 would regulate any changes in NVC; and (2) stepwise respiratory alkalosis and acidosis would each progressively reduce the NVC response. Ten healthy males completed a standardized visual stimulus-evoked NVC test during matched stepwise iso-oxic alterations in PaCO2 (hypocapnia: -5, -10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following intravenous NaHCO3 (8.4%, 50 mEq/50 ml) that elevated arterial pH (7.406 ± 0.019 vs. 7.457 ± 0.029; P 0.05) irrespective of the higher pH (P = 0.002) at each matched stage of PaCO2 (P = 0.417). The absolute peak change was reduced by -19 ± 41% with +10 mmHg PaCO2 irrespective of acutely elevated arterial pH/[HCO3- ] (stage post hoc: P = 0.022). The NVC kinetics (i.e. time to peak) were markedly slower with hypercapnia versus hypocapnia (24 ± 5 vs. 7 ± 5 s, respectively; stage effect: P

KEY POINTS We investigated the influence of arterial PCO2 (PaCO2 ) with and without experimentally altered pH on cerebral blood flow (CBF) regulation at sea level and with acclimatization to 5050 m. At sea level and high altitude, we assessed stepwise alterations in PaCO2 following metabolic acidosis (via 2 days of oral acetazolamide; ACZ) with and without acute restoration of pH (via intravenous sodium bicarbonate; ACZ+HCO3- ). Total resting CBF was unchanged between trials at each altitude even though arterial pH and [HCO3- ] (i.e. buffering capacity) were effectively altered. The cerebrovascular responses to changes in arterial [H+ ]/pH were consistent with the altered relationship between PaCO2 and [H+ ]/pH following ACZ at high altitude (i.e. leftward x-intercept shifts). Absolute cerebral blood velocity (CBV) and the sensitivity of CBV to PaCO2 was unchanged between trials at high altitude, indicating that CBF is acutely regulated by PaCO2 rather than arterial pH. ABSTRACT Alterations in acid-base balance with progressive acclimatization to high altitude have been well-established. However, how respiratory alkalosis and the resultant metabolic compensation interact to regulate cerebral blood flow (CBF) is uncertain. We addressed this via three separate experimental trials at sea level and following partial acclimatization (14 to 20 days) at 5050 m; involving: (1) resting acid-base balance (control); (2) following metabolic acidosis via 2 days of oral acetazolamide at 250 mg every 8 h (ACZ; pH: Δ -0.07 ± 0.04 and base excess: Δ -5.7 ± 1.9 mEq⋅l-1 , trial effects: P < 0.001 and P < 0.001, respectively); and (3) after acute normalization of arterial acidosis via intravenous sodium bicarbonate (ACZ + HCO3- ; pH: Δ -0.01 ± 0.04 and base excess: Δ -1.5 ± 2.1 mEq⋅l-1 , trial effects: P = 1.000 and P = 0.052, respectively). Within each trial, we utilized transcranial Doppler ultrasound to assess the cerebral blood velocity (CBV) response to stepwise alterations in arterial PCO2 (PaCO2 ), i.e. cerebrovascular CO2 reactivity. Resting CBF (via Duplex ultrasound) was unaltered between trials within each altitude, indicating that respiratory compensation (i.e. Δ -3.4 ± 2.3 mmHg PaCO2 , trial effect: P < 0.001) was sufficient to offset any elevations in CBF induced via the ACZ-mediated metabolic acidosis. Between trials at high altitude, we observed consistent leftward shifts in both the PaCO2 -pH and CBV-pH responses across the CO2 reactivity tests with experimentally reduced arterial pH via ACZ. When indexed against PaCO2 - rather than pH - the absolute CBV and sensitivity of CBV-PaCO2 was unchanged between trials at high altitude. Taken together, following acclimatization, CO2 -mediated changes in cerebrovascular tone rather than arterial [H+ ]/pH is integral to CBF regulation at high altitude.

NEW FINDINGS What is the central question of this study? The pathophysiology of acute mountain sickness (AMS), involving the respiratory, renal and cerebrovascular systems, remains poorly understood. How do the early adaptations in these systems during a simulated altitude of 5000 m relate to AMS risk? What is the main finding and its importance? The rate of blood alkalosis and cerebral artery dilatation predict AMS severity during the first 10 h of exposure to a simulated altitude of 5000 m. Slow metabolic compensation by the kidneys of respiratory alkalosis attributable to a brisk breathing response together with excessive brain blood vessel dilatation might be involved in early development of AMS. ABSTRACT The complex pathophysiology of acute mountain sickness (AMS) remains poorly understood and is likely to involve maladaptive responses of the respiratory, renal and cerebrovascular systems to hypoxia. Using stepwise linear regression, we tested the hypothesis that exacerbated respiratory alkalosis, as a result of a brisk ventilatory response, sluggish renal compensation in acute hypoxia and dysregulation of cerebral perfusion predict AMS severity. We assessed the Lake Louise score (LLS, an index of AMS severity), fluid balance, ventilation, venous pH, bicarbonate, sodium and creatinine concentrations, body weight, urinary pH and cerebral blood flow [internal carotid artery (ICA) and vertebral artery (VA) blood flow and diameter], in 27 healthy individuals (13 women) throughout 10 h exposures to normobaric normoxia (fraction of inspired O2 = 0.21) and normobaric hypoxia (fraction of inspired O2 = 0.117, simulated 5000 m) in a randomized, single-blinded manner. In comparison to normoxia, hypoxia increased the LLS, ventilation, venous and urinary pH, and blood flow and diameter in the ICA and VA, while venous concentrations of both bicarbonate and creatinine were decreased (P

Background: The strong ion model (SIM) is an alternative paradigm in the characterization of acid‐base disturbances particularly in complex disorders. Hypothesis/Objectives: To compare the acid‐base changes in dogs with parvoviral enteritis (PE) using the Henderson‐Hasselbalch (HH) approach, with 2 strong ion approaches. Animals: Forty‐four dogs with PE, and 16 age‐matched control dogs. Methods: Prospective controlled observational study. Acid‐base status was evaluated using the HH model, Fencl‐Stewart (FS) approach and a validated strong ion model (VDM). The acid‐base changes according to each model were classified and compared. Statistical correlations between pH, CO2, and various SIM variables were performed, as well as between the sum of effects (SOE) of the SIM and the individual variables comprising the SOE. Results: The HH model identified acid‐base disorders in 31/44 cases of which 16/31 were mixed with metabolic acidosis and concurrent respiratory alkalosis the most common (10/31). Using the FS approach, metabolic changes were present 36/42 cases, with changes in free water (FW), chloride, and unmeasured anions (UA) being the most prevalent. Both FW and UA correlated well with pH; however, UA were most consistently abnormal in severe acidemia. Similarly to the HH, the VDM detected acid‐base disturbances in 28/44 cases. Major contributors to the acid‐base changes were hyponatremia, hypochloremia, and Atot acidosis because of elevated globulins and increased UA. Conclusions and Clinical Importance: Acid‐base changes are common and complex in dogs with PE, and were easier to understand using a SIM paradigm. Increases in UA have not been documented in PE in dogs.

KEY POINTS It was unknown whether respiratory alkalosis impacts the global cerebral metabolic response as well as the cerebral pro-oxidation and inflammatory response in passive hyperthermia. This study demonstrated that the cerebral metabolic rate was increased by ∼20% with passive hyperthermia of up to +2°C oesophageal temperature, and this response was unaffected by respiratory alkalosis. Additionally, the increase in cerebral metabolism did not significantly impact the net cerebral release of oxidative and inflammatory markers. These data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, but it does markedly increase the cerebral metabolic rate, independently of PaCO2 . ABSTRACT There is limited information concerning the impact of arterial PCO2 /pH on heat-induced alteration in cerebral metabolism, as well as on the cerebral oxidative/inflammatory burden of hyperthermia. Accordingly, we sought to address two hypotheses: (1) passive hyperthermia will increase the cerebral metabolic rate of oxygen (CMRO2 ) consistent with a combined influence of Q10 and respiratory alkalosis; and (2) the net cerebral release of pro-oxidative and pro-inflammatory markers will be elevated in hyperthermia, particularly in poikilocapnic hyperthermia. Healthy young men (n = 6) underwent passive heating until an oesophageal temperature of 2°C above resting was reached. At 0.5°C increments in core temperature, CMRO2 was calculated from the product of cerebral blood flow (ultrasound) and the radial artery-jugular venous oxygen content difference (cannulation). Net cerebral glucose/lactate exchange, and biomarkers of oxidative and inflammatory stress were also measured. At +2.0°C oesophageal temperature, arterial PCO2 was restored to normothermic values using end-tidal forcing. The primary findings were: (1) while CMRO2 was increased (P

BACKGROUND We aim to assess symptoms, laboratory findings, and radiological abnormalities in patients diagnosed with inherited metabolic disorders (IMDs) in the neonatal intensive care unit (NICU). METHODS A total of 6,150 newborns treated in a 3rd level NICU between 2012 and 2020 in Turkey were screened, of which 195 consulted with a suspicion of metabolic disease based on their clinical, laboratory, or radiological findings were included in the present study. RESULTS The prevalence of IMDs was 1:94.6 in the patients. Those consulted in the department of pediatric metabolism were divided into two groups, with the 65 diagnosed with IMDs assigned as Group I, and the 130 patients who were not diagnosed with IMDs as Group II. The most common IMDs were organic acidemias (29.23%) and urea cycle disorders (UCDs) (26.15%). The rates of consanguinity marriage (75.3% vs. 37.6%, p

The high metabolic demand of cerebral tissue requires that local perfusion is tightly coupled with local metabolic rate (neurovascular coupling; NVC). During chronic altitude exposure, where individuals are exposed to the antagonistic cerebrovascular effects of hypoxia and hypocapnia, pH is maintained through renal compensation and NVC remains stable. However, the potential independent effect of acute hypocapnia and respiratory alkalosis on NVC remains to be determined. We hypothesized that acute steady‐state hypocapnia via voluntary hyperventilation would attenuate the magnitude of NVC. We recruited 17 healthy participants and insonated the posterior cerebral artery (PCA) with transcranial Doppler ultrasound. NVC was elicited using a standardized strobe light stimulus (6 Hz; 5 × 30 s on/off) where absolute delta responses from baseline (BL) in peak, mean, and total area under the curve (tAUC) were quantified. From a BL end‐tidal (PET)CO2 level of 36.7 ± 3.2 Torr, participants were coached to hyperventilate to reach steady‐state hypocapnic steps of Δ‐5 Torr (31.6 ± 3.9) and Δ‐10 Torr (26.0 ± 4.0; p, We assessed the NVC response to a visual stimulus, under conditions of normocapnia and two steps of hypocapnia via voluntary hyperventilation.

This study investigated the secondary stress responses of Paralichthys orbignyanus exposed to ammonia and nitrite and after recovery. Fish were exposed to 0.12, 0.28, and 0.57 mg NH₃‐N/L, or 5.72, 10.43, and 15.27 mg NO₂‐N/L for 10 d followed by the same time length for recovery. Ammonia‐ and nitrite‐free water was used as a control treatment. Blood samples were collected after 1, 5, and 10 d of exposure and after recovery. Fish exposed to ammonia presented lower and higher glucose levels after 10 d of exposure and recovery, respectively. Ammonia induced initial and transient ionic disturbances and metabolic alkalosis. Nitrite exposure caused hyperglycemia, increased plasma K⁺ levels, and respiratory alkalosis, whereas metabolic acidosis was observed after recovery. Increased proportion of monocytes and/or granulocytes and reduced number of lymphocytes were demonstrated in fish exposed to 0.28 mg NH₃‐N/L (Day 1) and 10.43 mg NO₂‐N/L (Day 5) and after recovery in the 0.28 and 0.57 mg NH₃‐N/L treatments. Exposure to ammonia decreased the proportion of granulocytes on Day 5. In conclusion, exposure to concentrations at 0.12 mg NH₃‐N/L and 5.72 mg NO₂‐N/L provoked physiological disorders in Brazilian flounder. Nonetheless, fish exposed to 5.72 mg NO₂‐N/L following a 10‐d recovery period showed complete resumption of homeostasis.

Aims In acute heart failure (AHF) patients, pulmonary oedema and low tissue perfusion may lead to changes in the acid–base balance, which may be associated with worse outcomes. Methods and results In this prospective nationwide cohort study from 24 academic hospitals, arterial blood gas (ABG) was measured in 1982 AHF patients at hospital admission. Acidosis was defined as pH 7.44. Mortality was stratified according to ABG results. Overall, 19% had acidosis, 37% had normal pH, and 44% had alkalosis. The most common type of acidosis was the mixed type (42%) followed by metabolic acidosis (40%), and the most common type of alkalosis was respiratory alkalosis (58%). At 12 months' follow-up 304 patients (15%) died. Patients with acidosis had higher mortality (acidosis 19.5%, neutral pH 13.7%, alkalosis 14.9%; P = 0.007). In the Cox proportional-hazards regression model, acidosis was a significant predictor of mortality (hazard ratio 1.93; 95% confidence intervals 1.27–2.93) along with N-terminal pro-brain type natriuretic peptide (NT-proBNP), among others. In contrast, alkalosis was not associated with increased mortality. pH had an incremental prognostic value over NT-proBNP (net reclassification improvement 30%; P < 0.001), and ABG analysis identified extra patients at increased risk for mortality among patients with an NT-proBNP level less than the median (12-month mortality 17.5% vs. 9.9%; P = 0.009). Conclusion In high-risk AHF patients, the most common acid–base imbalance is respiratory alkalosis. Acidosis is observed in every fifth patient and is a significant predictor of mortality. pH provides an additional prognostic value and may be used to optimize risk stratification in high-risk AHF patients.

Objective To compare the diagnostic performance of the traditional approach to acid–base analysis with the Stewart approach and a semiquantitative approach. Design Prospective cohort study. Setting University teaching hospital. Animals A total number of 84 dogs and 14 cats presenting to a university teaching hospital emergency room. Procedures All dogs and cats in which venous blood samples for acid–base, lactate, and serum biochemical analysis were all collected within 60 minutes of each other, over a 5-month enrollment period. Acid–base analysis was performed using the traditional approach, Stewart approach, and a semiquantitative approach. Results Traditional acid–base analysis identified respiratory acid–base abnormalities in 14/98 animals and metabolic acid–base abnormalities in 67/98. A mixed disorder of metabolic acidosis and respiratory alkalosis was most common occurring in 29/98 patients. The Stewart approach identified metabolic abnormalities in 82/98 patients; strong ion difference abnormalities were evident in 68/98 cases; an increased strong ion gap acidosis was identified in 49/98 cases; and changes in the quantity of weak acids in 25/98 cases. The semiquantitative approach identified abnormalities in all cases evaluated. Of the 14 patients with a primary respiratory acid–base abnormality, the Stewart approach identified metabolic abnormalities in 9 and the semiquantitative approach found abnormalities in all animals. Conclusions and Clinical Relevance The physicochemical approaches diagnosed more acid–base abnormalities in this population than the traditional approach although many of the abnormalities identified were small and of unknown clinical relevance. The physicochemical approaches may provide greater insight as to the underlying etiology of abnormalities, which maybe of particular relevance to cases with changes in albumin and/or phosphorus concentration.

Introduction Chronic idiopathic hyperventilation (CIH) is a form of dysfunctional breathing that has proven hard to treat effectively. Objectives To perform a preliminary test of the hypothesis that by periodically inducing normocapnia over several weeks, it would be possible to raise the normal resting level of CO2 and achieve a reduction of symptoms. Methods Six CIH patients were treated 2 h a day for 4 weeks with a novel breathing mask. The mask was used to induce normocapnia in these chronically hypocapnic patients. Capillary blood gases and acid/base parameters [capillary CO2 tension (PcapCO2), pH, and standard base excess (SBE)] were measured at baseline and once each week at least 3 h after mask use, as well as spirometric values, breath-holding tolerance and hyperventilation symptoms as per the Nijmegen Questionnaire (NQ). Results The mask treatment resulted in a significant increase of resting PcapCO2 (+0.45 kPa, P = 0.028), a moderate increase in SBE (+1.4 mEq/L, P = 0.035) and a small reduction in daily symptoms (−3.8 NQ units, P = 0.046). The effect was most pronounced in the first 2 weeks of treatment. Conclusion By inducing normocapnia with the breathing mask 2 h a day for 4 weeks, the normal resting CO2 and acid/base levels in chronically hyperventilating patients were partially corrected, and symptoms were reduced.

Febrile seizures are the most common type of convulsive events in children. It is generally assumed that the generalization of these seizures is a result of brainstem invasion by the initial limbic seizure activity. Using precollicular transection in 13-day-old rats to isolate the forebrain from the brainstem, we demonstrate that the forebrain is not required for generation of tonic-clonic convulsions induced by hyperthermia or kainate. Compared with sham-operated littermate controls, latency to onset of convulsions in both models was significantly shorter in pups that had undergone precollicular transection, indicating suppression of the brainstem seizure network by the forebrain in the intact animal. We have shown previously that febrile seizures are precipitated by hyperthermia-induced respiratory alkalosis. Here, we show that triggering of hyperthermia-induced hyperventilation and consequent convulsions in transected animals are blocked by diazepam. The present data suggest that the role of endogenous brainstem activity in triggering tonic-clonic seizures should be re-evaluated in standard experimental models of limbic seizures. Our work sheds new light on the mechanisms that generate febrile seizures in children and, therefore, on how they might be treated.

SUMMARY Purpose: Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid–base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS. Methods: We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco2 were measured immediately on admission to the hospital. Key Findings: Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco2 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco2 37.7 ± 4.3 mmHg; p < 0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE-admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p < 0.005). Significance: The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid–base status.

Arterial and venous blood were analysed at rest and post exercise for pH, PCO2, and PO2, and bicarbonate ([HCO3-]), base excess (BE), and strong ion difference (SID) were calculated in response to a 10 day sojourn to 3800 m. Pulmonary artery pressures (PAP) were measured at rest. Post exercise samples were restricted to venous blood. The equids (n = 6) experienced a profound hypoxia-hypocapnia and a respiratory alkalosis. PaO2 decreased 42% and PaCO2 41%. PaCO2 increased to 80% of initial values after 8 days at altitude. Arterial [HCO3-] decreased by 34%; however, it returned to normal by Day 4. Base excess decreased initially, but increased at altitude with time. Strong ion difference was decreased during the altitude exposure and continued to be depressed even after return to low altitude. Pulmonary artery pressure increased 63% on Day 1 of exposure (from 27.9 +/- 2 to 45.4 +/- 3 mmHg); Days 2 and 6 averaged 36.3 +/- 3 and 37.5 +/- 3 mmHg. Thirty-six hours after return to 225 m, most variables (except [SID] and post exercise BE) returned to normal. The most profound changes in the indicators of gas exchange, at altitude, occurred during the first 3 days and only [HCO3-] returned to normal during the subsequent acclimatization to altitude.

— Although it has been established that liver failure is associated with arterial hypocapnia and alkalaemia (i.e., respiratory alkalosis), the influence of liver failure on mixed venous acid-base status has not yet been studied. Thus, arterial and mixed venous acid-base status were simultaneously measured in controls and in a large series of patients with cirrhosis. Grade B patients (n = 28) or Grade C patients (n = 21) had significantly lower arterial and mixed venous carbon dioxide tensions than controls (n = 29). Grade B or Grade C patients also had significantly higher arterial, mixed venous pH, and lower mixed venous bicarbonate concentrations than controls. Among Grade A patients (n = 27), those with the lowest Pugh's score (i.e., equal to five) had significantly lower mixed venous carbon dioxide tension than controls. The other arterial and mixed venous acid-base values did not differ significantly between Grade A patients with the lowest Pugh's score and controls. Grade A patients with a Pugh's score equal to six and Grade B patients had similar acid-base disorders. No significant differences were found between groups concerning the anion gap and plasma chloride concentrations. In conclusion, this study shows that in Grade B or C patients, respiratory alkalosis was responsible for mixed venous hypocapnia, alkalaemia and hypobicar-bonataemia. In addition, in Grade A patients with the lowest Pugh's score (equal to five), analysis of arterial and mixed venous blood revealed that mixed venous hypocapnia was the sole anomaly of the acid-base status. This last finding suggests that mixed venous hypocapnia might be an early event preceding the onset of arterial hypocapnia.

Rationale and objectives: In conscious mammals, hypoxia produces respiratory alkalosis which is assumed to silence central respiratory chemoreceptors (CRCs). We tested this theory by examining how ...

Pseudohypoparathyroidism is a heterogeneous group of disorders characterised by hypocalcaemia, hyperphosphataemia, increased serum parathormone and insensitivity to the biological activity of parathormone. These patients may present for incidental surgery, procedures related to kidney stones, cataract removals and renal transplants. No particular anaesthetic agent or technique is indicated except that respiratory alkalosis should be avoided as it may further decrease ionised calcium levels and thereby precipitate tetany. In this report, we present the peri-operative management of three patients with this rare condition and describe an unusual presentation of hypocalcaemic extra-ocular muscle spasm.

Climbing Mt. Everest without supplementary oxygen presents a fascinating physiological challenge because, at the summit, humans are very near the limit of tolerance to hypoxia. It was not until 1978 that the feat was accomplished, and this was after many unsuccessful attempts over a period of more than 50 years, and several physiological studies that suggested that it would be impossible. An analysis shows that the critical factors for reaching the summit are the enormous hyperventilation which is necessary to maintain the alveolar Po2 at viable levels, the fact that the barometric pressure is substantially higher than predicted by the Standard Atmosphere, and the severe respiratory alkalosis that assists loading of oxygen by the blood in the lung. Even so the maximal oxygen consumption on the summit is extremely low with the result that climbers are critically vulnerable to unexpected setbacks such as changes in the weather.

The purpose of this study was to examine the effects of respiratory alkalosis on human skeletal muscle metabolism at rest and during submaximal exercise. Subjects exercised on two occasions for 15 min at 55 % of their maximal oxygen uptake while either hyperventilating (R-Alk) or breathing normally (Con). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to R-Alk. In the first minute of exercise, there was a delayed activation of pyruvate dehydrogenase (PDH) in R-Alk compared with Con, resulting in a reduced rate of pyruvate oxidation. Also, glycogenolysis was higher in R-Alk compared with Con, which was attributed to a higher availability of the monoprotonated form of inorganic phosphate (P(i)), resulting in an elevated rate of pyruvate production. The mismatch between pyruvate production and its oxidation resulted in net lactate accumulation. These effects were not seen after 15 min of exercise, with no further differences in muscle metabolism between conditions. The results from the present study suggest that respiratory alkalosis may play an important role in lactate accumulation during the transition from rest to exercise in acute hypoxic conditions, but that other factors mediate lactate accumulation during steady-state exercise.

Experimental data show that elevation of intracellular pH leads to severe lesions of brain cells. Acidification of intracellular fluid by accumulation of lactate may compensate the effect of respiratory alkalosis. Increased serum pH, and low PCO2, associated with hyperlactataemia (sometimes incorrectly called ‘acidosis’) have been reported in children with Leigh syndrome (LS). The aim of the study was to determine whether respiratory alkalosis is characteristic of patients with LS due to SURF1 mutations. All venous blood gas data (88 samples) of 18 spontaneously breathing LS patients with recently established SURF1 mutations, hospitalized during 1986–2000, were retrospectively reviewed. The data of an affected boy who survived on a respirator for more than 3 months (79 daily samples) were analysed separately. In spontaneously breathing patients, the data indicated that the patients had compensated or partially compensated respiratory alkalosis (pH 7.388 ± 0.060, PCO2 29.2 ± 5.7 mmHg, HCO− 3 17.4 ± 3.0 mmol/L, BE −6.7 ± 3.2 mmol/L). Bicarbonate excretion was detected in urine of two examined LS cases in spite of decreased serum HCO− 3. In the affected child maintained on a respirator, simple manipulation of the inspired CO2 tension to establish a normal pressure of 35–45 mmHg automatically caused an increase of serum HCO− 3 concentration to a normal value of 26.3 ± 2.9 mmol/L (and BE to +2.2 ± 3.1 mmol/L), in spite of cytochrome oxidase (COX) deficiency due to a confirmed SURF1 mutation. We suggest that respiratory alkalosis (hypocapnia) of Leigh syndrome patients with SURF1 mutations results from compulsory hyperventilation and speculate that hypocapnia may contribute to Leigh-like brain damage in the SURF1-deficient patients as well as in other patients presenting with Leigh-like syndrome. The supposition that accumulation of lactate may protect the brain of LS patients from alkalosis-related damage requires further study. Avoidance of any factors stimulating hyperventilation of LS patients and caution when attempting to correct low plasma bicarbonate are suggested.

Thirty-four dogs suffering from severe babesiosis caused by Babesia canis rossi were included in this study to evaluate acid-base imbalances with the quantitative clinical approach proposed by Stewart. All but 3 dogs were severely anemic (hematocrit

In the time it has taken medicine to develop the techniques to describe the circulatory changes of severe infections, both pattern and process have been profoundly influenced by the use of intravenous fluids, vasopressors, antibiotics, steroids, mechanical ventilation and haemoflltration. Constant features of severe sepsis include a reduction in peripheral vascular tone on both the arterial and venous sides of the circulation, a defect in oxygen utilisation resulting in lactic acidosis, and varying degrees of myocardial dysfunction. These events have a temporal progression, the precise pattern observed depending on the tempo of the infection, the influence of therapeutic manoeuvres, the age and comorbidities of the patient, and the time the observations are made in the course of events. Early sepsis is accompanied by a decrease in systemic vascular resistance and a metabolic acidosis. The clinical picture includes fever, tachycardia, tachypnoea, respiratory alkalosis and an increased cardiac output with warm, dry peripheries and a bounding pulse. Advanced sepsis involves varying degrees of venous and myocardial contractile failure, and is characterised by progressive acidaemia, respiratory failure and marked sympathetic adrenergic activation. In the absence of vigorous fluid resuscitation, the cardiac output is decreased and the patients are cold, clammy peripherally shut down, and frequently confused, obtunded or comatose. In infections with a silent primary focus (predominantly involving Gram-negative organisms), this stage is frequently the first to attract the attention of attending staff. Late sepsis is characterised by profound acidaemia, vascular hypo-responsiveness, multiple organ failure and death.

Although significant pulmonary hypertension can occur in patients treated with either hypocapnic alkalosis or "permissive" hypercapnic acidosis, the effects of sustained alkalosis or acidosis on subsequent vasodilator responses have not been established. This study measured the effects of 60-100 min of sustained alkalosis or acidosis on endothelium-independent and -dependent vasodilation with inhaled nitric oxide (iNO) and acetylcholine (ACh) in isolated lungs from 1-week-old piglets. After stabilization, lungs were divided into control (pH 7.40, PaCO(2) 40 torr, n = 5), alkalotic (pH 7.60, PaCO(2) 25 torr, n = 6), or acidotic (pH 7.25, PaCO(2) 65 torr, n = 5) groups and ventilated with 21% O(2) for 40 min. Acute hypoxic pulmonary vasoconstriction (HPV) was then induced with 4-6% O(2). After a stable pressor response had occurred (approximately 20 min), pulmonary artery dose-response relationships to increasing concentrations of iNO were measured. The iNO was then stopped and after a stable hypoxic pressure had again been reestablished (approximately 20 min), dose-responses to increasing concentrations of ACh were measured. Hypoxic pulmonary vascular resistance (PVR) was similar in all groups. Pulmonary artery pressure dose-response relationships to iNO and ACh were blunted in the alkalosis group, suggesting that both endothelium-independent and -dependent vasodilation were reduced during sustained hypocapnic alkalosis. In contrast, sustained acidosis did not alter subsequent vasodilator responses. Future studies must elucidate the mechanisms underlying blunted pulmonary vasodilation during sustained alkalosis and examine the consequences of sustained alkalosis therapy on subsequent vasodilator responses in clinical practice.

We report a case of stunned myocardium induced by coronary vasospasm which was associated with spontaneous pneumothorax. A 72-year-old woman with a sudden onset of chest pain was transferred to our hospital by an ambulance. Electrocardiography on admission suggested evidence of myocardial ischemia, and chest radiography disclosed a right pneumothorax. After right chest drainage was carried out, the findings of myocardial ischemia on electrocardiography persisted. Therefore, emergency coronary angiography was performed, which demonstrated coronary vasospasm on an acetylcholine loading test. Left ventriculography revealed akinesis in a portion of the anterior wall that normalized on echocardiography two days later. We made a diagnosis of stunned myocardium associated with pneumothorax. The severe chest pain and respiratory alkalosis were conseqences of the coronary vasospasm. It is known that the electrocardiographic characteristics of pneumothorax are similar to those of myocardial ischemia. In patients with pneumothorax and ST-T changes on electrocardiography, coronary vasospasm should be considered.

Inhaled nitric oxide (NO) is currently used as an adjuvant therapy for a variety of pulmonary hypertensive disorders. In both animal and human studies, inhaled NO induces selective, dose-dependent pulmonary vasodilation. However, its potential interactions with other simultaneously used pulmonary vasodilator therapies have not been studied. Therefore, the objective of this study was to determine the potential dose-response interactions of inhaled NO, oxygen, and alkalosis therapies. Fourteen newborn lambs (age 1–6 days) were instrumented to measure vascular pressures and left pulmonary artery blood flow. After recovery, the lambs were sedated and mechanically ventilated. During steady-state pulmonary hypertension induced by U46619 (a thromboxane A2 mimic), the lambs were exposed to the following conditions: Protocol A, inhaled NO (0, 5, 40, and 80 ppm) and inspired oxygen concentrations (FiO2) of 0.21, 0.50, and 1.00; and Protocol B, inhaled NO (0, 5, 40, and 80 ppm) and arterial pH levels of 7.30, 7.40, 7.50, and 7.60. Each condition (in randomly chosen order) was maintained for 10 min, and all variables were allowed to return to baseline between conditions. Inhaled NO, oxygen, and alkalosis produced dose-dependent decreases in mean pulmonary arterial pressures (P 5 ppm, alkalosis induced further dose-independent decreases in mean pulmonary arterial pressure, while oxygen did not. We conclude that in this animal model, oxygen, alkalosis, and inhaled NO induced selective, dose-dependent pulmonary vasodilation. However, when combined, a systemic arterial pH >7.40 augmented inhaled NO-induced pulmonary vasodilation, while an FiO2 >0.5 did not. Therefore, weaning high FiO2 during inhaled NO therapy should be considered, since it may not diminish the pulmonary vasodilating effects. Further studies are warranted to guide the clinical weaning strategies of these pulmonary vasodilator therapies. Pediatr Pulmonol. 1999; 28:3–11. © 1999 Wiley-Liss, Inc.

In a study using a heated chamber for induction of experimental febrile seizures (eFS) in rat pups, ictal activity was shown to be precipitated by a respiratory alkalosis (Schuchmann et al., 2006). In sharp contrast to this, in a recent review Dubé et al., (2007) suggest that the respiratory alkalosis is model specific, and that no increase in respiratory rate is observed in the widely used "hair dryer model" of eFS. The data in the present work, based on well-established techniques for measuring respiratory rates in rat pups, show a pronounced increase in the "hair dryer model" with values that are slightly higher than those recorded in the heated chamber model. Hence, a temperature-evoked increase in respiration is a common feature of these two models of eFS.

A 23-year-old, 467-kg Palomino mare was examined for evaluation of sudden onset severe ataxia and depression. The mare had been found down in a pasture and was unable to rise. She was observed, by her owner, to be normal 24 hours earlier. This mare had resided with this owner for approximately 1.5 years, had always lived out on pasture, and had experienced numerous episodes of colic since the time she was purchased. Recent reported feed changes included introduction of new hay. Upon arrival at the hospital, the mare was severely ataxic in all 4 limbs and extremely disoriented. She head-pressed several times during the course of the evaluation and yawned repeatedly. The mare was tachycardic, with a heart rate of 98 beats per minute, and tachypneic, with a respiratory rate of 60 breaths per minute, and the mucous membranes were hyperemic and purple, with a capillary refill time of greater than 3 seconds. The mare was blind bilaterally, as indicated by absence of both menace and pupillary light responses. She had bilateral facial nerve paralysis and decreased hypoglossal nerve function. She was able to prehend, but was dysphagic with decreased tongue tone and movement. Analysis of the venous blood revealed metabolic acidosis and respiratory alkalosis with a normal pH of 7.38 (reference range 7.32–7.44), HCO3 of 13 mEq/L (reference range 25–30 mEq/L), PCO2 of 21.2 mmHg (reference range 36–46 mmHg), and BE of -12 mEq/L (reference range -1-1 mEq/L).a It also revealed a low blood urea nitrogen concentration of 8 mg/dL (reference range 11–27 mg/dL) and a high blood glucose concentration of 263 mg/dL (reference range 63–134 mg/dL).a Both packed cell volume and total solids were high at 52% (reference range 32–53%), and 8 g/dL (reference range 5.8–7.7 g/dL), respectively. The blood ammonia concentration was 120 μmol/L (reference range 18–78 μmol/L)b.

Ear lobe blood pHa, PaCo2, PaO2, and O2 saturation (SaO2) were measured in healthy Caucasians and Sherpas at 3400 m (Namche Bazaar, Nepal, n = 4/5), 5050 m (Pyramid Laboratory, Lobuche, Nepal, n = 20/5) and 6450 m (Camp II of Mt Everest, n = 11/7). In the investigated altitude range, pHa increased progressively with altitude from 7.463 +/- 0.005 (mean +/- SE) to 7.496 +/- 0.006 in Caucasians whereas it remained essentially constant (7.45-7.46) in Sherpas. At all altitudes, PaCO2 was higher in Sherpas than in Caucasians (P < 0.02). By contrast, PaO2 and SaO2 were the same in Caucasians and Sherpas at all investigated altitudes. Moreover, in Caucasians sojourning for 3 weeks at 5050 m, PaCO2 kept decreasing whereas pHa, PaO2 and SaO2 remained constant. These data suggest that; (1) respiratory alkalosis was a common finding both in Caucasians and Sherpas; (2) at 6450 m. Sherpas were less alkalotic due to higher PaCO2 than Caucasians, possibly a consequence of a blunted ventilatory response; (3) at 6450 m, SaO2 and PaO2 were the same in Caucasians and Sherpas despite different PaCO2 values. The latter finding could be the consequence of one or more of the following adjustments in Sherpas: (1) an increased efficiency of alveolar O2 transfer, i.e. smaller alveolar-arterial O2 gradient; (2) a decreased (arterial-mixed venous) O2 difference possibly due to increased cardiac output; (3) a reduced increase of the [2,3-DPG]/[Hb] ratio; but not (4) an elevated gas exchange ratio (R). It is concluded that both physiological and biochemical variables contribute to optimize the O2 transport at altitude. Apparently a more efficient adaptation to hypoxia allows Sherpas to limit alkalosis through a lower ventilatory drive and to maintain SaO2 at the same PaO2 by decreasing the [2,3-DPG]/[Hb] ratio.

Recent investigations have demonstrated that rainbow trout cope with acute high pH (pH > 9.0) exposure (lasting 3–8 days) through their ability to counteract high-pH-induced disturbances to ammonia excretion (JAmm), acid-base homeostasis, and electrolyte balance. In the present investigation our goal was to establish how these physiological processes were modulated during chronic (28-day) high pH (pH = 9.5) exposure. Chronic high pH led to minimal mortality, and there were no long-term changes in stress indicators levels, such as cortisol or glucose. JAmm was initially reduced by 40% at high pH but rapidly recovered and fluctuated around control rates, thereafter. Decreased JAmm was associated with an initial 2.5-fold increase in plasma ammonin concentrations (TAmm), followed by a return toward pre-exposure levels after 3 days. Overall, plasma TAmm was slightly higher (40–80%) in the treatment fish, and this likely led to plasma PNH3s that were sufficient to sustain JAmm at high pH. White muscle TAmm stores were also chronically elevated, by 50–100%. There was a transient, twofold elevation of JUrea immediately following high-pH exposure, but by 3 days JUrea had returned to control rates and stabilized thereafter. Plasma ion balance was well maintained at high pH, despite a chronic depression of Na+ influx. Even though there was a persistent respiratory alkalosis at alkaline pH, blood pH was effectively regulated by a simultaneous metabolic acid load, which was not associated with increased lactic acid production. White muscle intracellular pH (pHi) was unaltered during high pH exposure. We conclude that the long-term survival of rainbow trout in alkaline environments is facilitated by higher steady-state internal ammonia concentrations, the development of a sustained, compensatory metabolic acidosis which offsets decreased plasma PCO2, and the effective regulation of plasma electrolyte balance. © 1996 Wiley-Liss, Inc.

In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.

Summary Ventilatory and metabolic compensation to acid-base disturbances is reviewed. The mechanisms for compensation as well as the values obtained from several studies using normal dogs and dogs with experimentally induced diseases are provided. Compensation is not the same in dogs and human beings. Dogs have a better ability to adapt to most respiratory disorders, and human beings adapt better to metabolic acidosis. In metabolic alkalosis and chronic respiratory acidosis there is no difference in compensation between these species. Ventilatory compensation for metabolic disorders in dogs is the same whether they have metabolic acidosis or metabolic alkalosis, whereas metabolic compensation in respiratory disturbances is less effective in acidosis. Values for the expected changes in PCO2 in dogs with metabolic acidosis and metabolic alkalosis, and for bicarbonate concentration (HCO3-) in dogs with acute and chronic respiratory alkalosis and acidosis are presented.

In order to better understand the basis for the euryhalinity of the flounder, Platichthys flesus, which tolerates large variations in water salinity, experiments have been designed to characterize the time course of extracellular ionic and acid-base adjustments under hypo- or hyperosmotic conditions. Abrupt transfer from sea water (SW) to fresh water (FW) provokes a transient decrease in the plasma osmolality (Posm) and a concomitant transient metabolic alkalosis (whole blood pH 7.78 in SW and 8.04 five days after FW transfer) associated with a marked, persistent hypercapnia. After 33 days in FW, Posm and whole blood pH are not significantly different from those in SW, but whole blood Pco2 and plasma bicarbonate concentration are always higher than SW values. Opposite transitory fluctuations, i.e. a metabolic acidosis associated with a respiratory alkalosis, occur when flounder long-acclimated to FW are again exposed to SW. The mechanisms involved in these salinity-dependent acid-base disturbances are rather complex and remain to be elucidated. These observations attest to the importance of the extracellular acid-base changes that may be (i) linked to extracellular anisosmotic regulation and/or to cellular metabolic adjustments, and (ii) compensated partially by ventilatory adjustments.

UNLABELLED A full-term female offspring of a first and uneventful pregnancy presented at 60 h of life with irritability, tachypnea and respiratory alkalosis progressing to deep coma with clinically dominant circulatory failure, tachycardia and hypotension. Diagnosis of ornithine transcarbamylase (OTC) deficiency was made on the basis of hyperammonaemia, hypocitrullinaemia and extreme hyperexcretion of orotic acid. The baby was treated with peritoneal dialysis, arginine hydrochloride and adequate energy supply. DNA analysis revealed an as of yet unidentified missense mutation in the 6th exon of the OTC gene, resulting in a change of lysine to glutamine at position 210 (K210Q). Her parents were not found to carry this mutation, implying that this mutation may have occurred either de novo in the patient or in a parental germ cell. CONCLUSION An acute neonatal form of OTC deficiency should be considered in the differential diagnosis of coma in female newborns.

Travel to high altitude for the lowland dweller unmasks a complicated array of physiological mechanisms responsible for acclimatization (Dempsey & Forster, 1982). First, the reduction in both the barometric pressure and the arterial partial pressure for oxygen () stimulates an increase in ventilation, the magnitude of which depends upon the individual ventilatory sensitivity to hypoxia. Then, the arterial partial pressure for carbon dioxide () is decreased due to hypoxic hyperventilation resulting in respiratory alkalosis. As time at altitude increases over the next 1–2 weeks, acid–base balance is normalized by renal excretion of bicarbonate, and is improved by increases in the ventilatory sensitivity to hypoxia and polycythaemia. This simplified overview of altitude acclimatization highlights two major controlling factors for cerebral blood flow (CBF): (1) changes in arterial blood gases (i.e. and ) and (2) changes in pH. The brain, notably a vital organ, relies upon an adequate supply of blood and delivery of oxygen for its normal operation. Therefore, CBF is regulated not only to maintain oxygen delivery but also to maintain cerebral tissue pH (or cerebral spinal fluid (CSF) pH). Interestingly, the cerebral circulation is relatively insensitive to hypoxia, only increasing CBF when reaches levels

De¢ciency of ornithine carbamoyltransferase (OCT, EC 2.1.3.3; McKusick 311250) is an X-linked disorder of the urea cycle. Symptomatic carriers present with a wide range of symptoms due to hyperammonaemic encephalopathy (Brusilow and Horwich 1995). We present a case of OCT de¢ciency in an 11-month-old female with the unusual feature of transient chorea as the primary neurological symptom, an association not previously reported. A previously healthy caucasian girl presented to our hospital at 11 months of age with an impaired level of consciousness and chorea. She had cryptosporidial diarrhoea six weeks prior to presentation, which resolved, and a mild upper respiratory tract infection ¢ve days prior to admission. There was no vomiting at any stage. She was found at 02:00 with her back arched, making unusual movements of her upper limbs. A general practitioner diagnosed seizures. On arrival at our emergency department she had an impaired level of consciousness, typical choreiform movements of all four limbs and intermittent back arching. Normal tendon re£exes and £exor plantar responses were noted, as was tachypnoea (70 breaths per minute) with minimal eiort. There was no hepatomegaly. Intravenous (IV) diazepam was associated with brief, but unsustained, improvement of the chorea. A CT head scan, full blood count, ionized calcium, sodium, potassium, chloride, urea and creatinine were all normal. Arterial blood gas showed a respiratory alkalosis (pH 7.55, pCO2 17 mmHg, HCO3 15.1 mmol/L). Plasma ammonium, measured after this result, was signi¢cantly elevated at 565 mmol/L (reference 20^80). IV dextrose was increased to 10 mg/kg per min and she was treated with IV sodium benzoate and L-arginine. Her ammonium fell to 96 mmol/L over the next 3 h, then remained stable, and oral sodium phenylbutyrate was introduced. Her ammonium then fell to 46 mmol/L and remained in the normal range. Gradual reduction, then resolution, of her chorea parallelled the drop in ammonium. Three hours after starting benzoate therapy, she displayed abnormal mouthing movements but had no limb chorea. After 6 h of therapy, the mouthing J. Inherit. Metab. Dis. 23 (2000) 843^844 # SSIEM and Kluwer Academic Publishers. Printed in the Netherlands.

Acute percutaneous salicylate intoxication is a rare event in children but can happen with a skin disease where salicylic acid, used as a keratolytic ointment, can be absorbed transcutaneously. Until now, few cases of transcutaneous salicylate intoxication have been reported in the literature. Our case report is about a 5-year-old girl with lamellar ichthyosis and an acute salicylate transcutaneous intoxication after the application of a skin ointment. The child had a fever, hyperpnoea with respiratory alkalosis, comatose state and oculogyric crisis. We would like to emphasize the danger of applying salicylic acid in children with extensive skin diseases and, therefore, it is advisable to measure the plasma salicylic levels so as to prevent eventual salicylate toxicity.

Treatment for hypoglycaemia with glucagon and IV glucose improved consciousness in a 28-year-old male diabetic. He remained confused, however, which was thought to be the result of prolonged hypoglycaemia and he was treated with mannitol and IV insulin. Twenty-four hours after admission he was lucid and a CT scan performed 24 hours later was normal.

Received 6 March 1989, accepted 20 April 1989. ISSN 0001–6772. Department of Physiology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala, Sweden. Mhdtabolic and respiratory alkalosis were produced in goathd with the primary aim of studying possible influence of a reduced blood hydrogen ion concentration on aldosterone secretion. Metabolic alkalosis was induced by I h i. v. infusion of hypertonic tris(hydroxy-methyl)aminomethane (THAM) solution. The infusion was associated with a significant reduction in plasma aldosterone concentration (PA). It occurred in the absence of a detectable fall in plasma K or obvious change in plasma renin activity, but simultaneously with a moderate increase in plasma cortisol concentration and a significant reduction of plasma Na concentration. It suggests that changes of the primary aldosterone regulators were not the cause of the fall in PA, but leaves open the possibility that either the decreased blood hydrogen ion concentration as such or THAM-induced blood hypertonicity reduced the aldosterone secretion. Thde respiratory alkalosis was due to heat polypnoea elicitehd by 2 h exposure of the goats to 45°C. Here, no obvious change in PA was observed during the alkalotic period, which, however, was associated with a rise in plasma K. Increased K stimulation may therefore have masked a possible inhibitory influence of the alkalosis upon the aldosterone secretion.

A rise in fetal Paco2 was observed after elective cesarean section in patients anesthetized both with a barbiturate and with nitrous oxide/oxygen. Epidural analgesia seemed to be a good alternative in order to attain better blood gas values in the newborn infant. Fourteen healthy mothers and their infants were studied in connection with elective cesarean section. Epidural analgesia with plain bupivacaine 0.75% was used. Doses varied between 90 and 120 mg. The time between the epidural injection and delivery was around 50 min. In six cases the fetal heart rate was registered continuously. Most of the mothers were sedated with diazepam intravenously or fully anesthetized, after delivery. The mothers were interviewed later. The respiratory adaptation of the infants was studied by blood gas and acid-base measurements in repeated arterial samples during the first 3 hours of life. A comparison was made with a group previously studied, where general anesthesia with a barbiturate, nitrous oxide/oxygen was the method used. The present material showed no differences concerning Pao2 and Paco2 but clearly indicated a tendency towards an earlier normalization of the initial metabolic acidosis. Mothers showed a respiratory alkalosis which was overcompensated by the metabolic component. Maternal blood pressure falls were observed in four cases, and fetal effects could be detected. Although epidural analgesia has a more favorable effect upon the newborn's metabolic component, both the compared methods allow good respiratory adaptation provided they are used correctly. Mothers can be given the opportunity to choose between being conscious or asleep when their child is delivered.

Summary. Arterial blood gases were analysed from eight patients with clinically typical hyperventilation syndrome (HVS^ and with no signs of organic diseases, and from eight control patients with no cardiopulmonary or metabolic disease; the blood samples were drawn at rest, during an orthostatic test and during and 10 min after maximal exercise. In all stages of the tests the arterial oxygen tension of the HVS patients was at a high normal level. By the end of the orthostatic test, during maximal exercise and 10 min after the exercise every HVS patient had moderate to marked hypocapnia. At every stage of the tests the arterial Pco2 of the HVS patients was significantly lower than that of the control patients; during standing and after exercise the arterial pH was significantly higher in the HVS group than in the control group. Either during the orthostatic test or 10 min after the exercise or at both situations all of the HVS patients, but none of the controls, showed respiratory alkalosis. The results indicate that standing up and heavy exercise can markedly stimulate the HVS patients to hyperventilate. Thus, orthostatic and exercise tests combined with blood gas analyses seem to be useful in diagnosing the HVS.

There is a postexercise acidosis in the coconut crab, Birgus latro, which is initially due to an elevation in the hemolymph P, and a metabolic acidosis which is only partially due to lactic acid. Hyperventilation following exercise causes a respiratory alkalosis that helps to restore acid-base balance. The ventilatory receptors appear to be internally located, and ventilation is stimulated by a drop in the hemolymph pH or [HCO], but not by P or P. Amelioration of the metabolic acidosis in normal crabs occurs in 1 hour despite elevated lactate levels. Crabs with their gills removed showed only a transient lag in both respiratory and metabolic recovery from acidosis, indicating the dominance of the branchial lung of Birgus in gas exchange. The data suggest that intra- and extracellular transfers may be significant in acid-base regulation.

Pulmonary functions were studied in 188 asymptomatic children with bronchial asthma and 272 healthy children. Ventilatory function was measured by the spirogram and maximum expiratory flow volume (MEFV) curve. Although the forced vital capacity (FVC) and peak expiratory flow rate (PEFR) were of the same values in normal and asthmatic subjects, the maximal mid-expiratory flow rate (MMF), the maximal flow rate at 50% (V50) and that at 25% (V25) of vital capacity were definitely lower in asthmatic children than those in healthy children, particularly in children with severe asthma. Arterial blood gas tensions and pH were measured in 180 asthmatic children with various clinical symptoms and 102 asthmatic children with disturbance of consciousness. Hypocapnia was detected even in the asymptomatic state, and carbon dioxide tensions (Pco2) were markedly high values only on very severe attacks. There was a linear fall in arterial oxygen tension (Po2) and oxygen saturation (So2) with increasing severity of attack. A complication of metabolic acidosis was frequent in the subjects who suffered from severe attacks. Children with severe asthma had small airways obstruction even in the asymptomatic state. This pulmonary disturbance appears to induce mild sustained hypocapnia and respiratory alkalosis as acceleration of ventilatory drive. Therefore, the development of hypercapnia, even if it is mild, may be considered to represent somewhat severe impairement of the pulmonary function in children with bronchial asthma.

Gill ventilation, blood gas and acid-base values, Mo,, Mc.02 and the gas exchange ratio have been measured before, during, and after exposure to hypoxia in the channel catfish, Zctalurus punctatus. Z.punctatus maintains M,,, at control levels to a PI,, as low as 60 mm Hg, through a profound branchial hyperventilation. Concomitantly, however, a lactic acidosis usually develops, indicating a significant anaerobic glycolysis. Both a metabolic acidosis and respiratory alkalosis occur inzctalurus during hypoxic exposure, with the former usually predominating. MCo, doubles and the gas exchange ratio (R,) increases from 0.8 at control levels to 2.0 at hypoxic levels, indicating that, in addition to anaerobic glycolysis, nonglycolytic pathways producing CO, also oper- ate during hypoxic exposure. Analysis reveals that at least half of the increased MCo2 during hypoxic exposure is due strictly to lactate acidification of the tissue HCO,- pool, rather than from metabolic production of molecular CO,. Thus, the actual respiratory quotient (RQ) only rises to 1.5 during hypoxic exposure. Within one hour of a return to air saturated water, a large lactate "flush" and severe plasma acidosis occur, and control levels for these and other values are not reachieved for 2-6 hours after hypoxic exposure. Complete analysis of 0, and CO, exchange in the catfish exposed to short-term hypoxia thus must consider both the time course of acid-base disturbance and the evolution of CO, from the acidified tissue bicarbonate pool. Limitation of oxygen delivery to the tissues, whether due to the increased demands of exer- cise or the reduced supply during envi- ronmental hypoxia, is a physiological problem encountered at some time by almost every fish species. While extensive investigation has cen- tered on adjustments and adaptations evoked to maintain oxygen delivery in the face of po- tential 0, limitations, it is also generally ac- knowledged that various tissues of many fishes can sustain considerable levels of anaerobic metabolism by which the minimum energy re- quirements of the animal are alternatively satisfied. Evidence for anaerobiosis is often presented in the form of increased blood, tissue, or urine levels of lactate, one of the major metabolic end-products of vertebrate anaerobic gly- colosis. Thus, elevations in lactate during or following environmental hypoxia have been at- tributed to a progressive shift towards anaerobic glycolysis in many fresh water and marine fishes (Leifestad et al., '57; Heath and Pritchard, '65; Holeton and Randall, '67; Ban- durski et al., '68; Caillouet, '68; Wittenberger, '68; Hunn, '69; Burton, '70a, b; Burton, '71; Bur- ton and Spehar, '7 l; Hughes and Johnston, '78). However, nonglycolytic anaerobic pathways resulting in the evolution of CO, and end- products other than lactate, apparently also operate during hypoxic or anoxic exposure in fishes (see Blazka, '58; Burton and Spehar, '71; Hochachka and Somero, '73). Increases in lactate and other anaerobic end-products in fish offer an indication that anaerobic metabolism is occurring-they can- not, however, provide quantitative information on the time course of development of anaerobiosis or on the anaerobiclaerobic met- abolic balance during acute hypoxic expo

Hemolymph O2 and CO2 levels and pH were measured in lobsters (H. vulgaris) as they settled in normoxic conditions and during prolonged exposure to moderately hypoxic seawater. Initial handling and transfer to the experimental conditions resulted in a marked acidosis. Complete recovery took from 24 to 48 hours. Samples of hemolymph taken after 48 hours yielded “settled” normoxic levels for O2 CO2 and pH. Subsequent exposure to moderately hypoxic water caused an initial respiratory alkalosis associated with pronounced hyperventilation. The induced pH change was sufficient to cause a marked increase in the oxygen affinity of the hemocyanin, allowing almost complete saturation of post-branchial (arterial) hemolymph despite a 3-fold decrease in hemolymph oxygen tension. Prolonged exposure to hypoxia resulted in an attenuation of the hyperventilation response but hemolymph bicarbonate levels rose substantially and may have maintained pH high and thus kept oxygen affinity above the normoxic level. On return to normoxic water both ventilation volume and hemolymph carbon dioxide decreased and pH and oxygen affinity returned to normoxic levels.