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PubMed1996

Differential effects of short-term hypoxia and hypercapnia on N-methyl-D-aspartate-induced cerebral vasodilatation in piglets.

BACKGROUND AND PURPOSE: Recent studies in piglets show that either asphyxia or global cerebral ischemia, which combines effects of hypoxia and hypercapnia, transiently attenuates N-methyl-D-aspartate (NMDA)-induced pial arteriolar dilation. The purpose of this study was to determine individually the effects of hypoxic hypoxia and normoxic hypercapnia on NMDA-dependent cerebrovascular reactivity. In addition, we examined mechanisms involved in reduced cerebral vascular dilation to NMDA. METHODS: In anesthetized piglets, we examined pial arteriolar diameters using a cranial window and intravital microscopy. Arteriolar responses to topically applied NMDA were determined under control conditions and after arterial hypoxia or arterial hypercapnia. In addition, arteriolar responses to NMDA were examined in animals given indomethacin (10 mg/kg IV) or superoxide dismutase (100 U/mL, topical application) before hypoxia. RESULTS: Under control conditions, application of NMDA produced a dose-related dilation of pial arterioles (eg, 9 +/- 1% to 10(-5), 15 +/- 2% to 5 x 10(-5), and 28 +/- 5% to 10(-4) mol/L NMDA above baseline, respectively, in the hypoxic group; n = 6, P < .05). After transient exposure to 15 minutes of hypoxic hypoxia, arteriolar responses to NMDA were reduced at 30 minutes and at 60 minutes (10(-4) mol/L NMDA dilated by 12 +/- 5% and 18 +/- 5%, respectively; n = 6, P < .05). Five minutes of hypoxic hypoxia also reduced dilatation to NMDA. Indomethacin or superoxide dismutase preserved arteriolar responses to NMDA after 15 minutes of hypoxia. Pial arteriolar responses to NMDA remained unimpaired during and after hypercapnia. CONCLUSIONS: Short-term severe hypoxic hypoxia and reventilation impair the NMDA-induced dilatation of pial arterioles. Respiratory acidosis alone does not modify pial arteriolar reactivity to NMDA. The reduced responsiveness of the cerebral blood vessels to NMDA caused by hypoxia appears to be due to action of oxygen radicals.

Acute Disease↗
PubMed1999

Gastric mucosal pH and blood flow during weaning from mechanical ventilation in patients with chronic obstructive pulmonary disease.

To determine if gastric intramucosal pH changes during weaning from mechanical ventilation are related to gastric mucosal blood flow modifications, we studied 16 ventilator-supported patients with chronic obstructive pulmonary disease (COPD) who tolerated a 2-h trial of spontaneous breathing with pressure support ventilation and were successfully extubated and 11 patients with COPD who failed such a trial. Gastric mucosal perfusion was assessed using gastric intramucosal pH (pH(i)) by tonometry and laser-Doppler flowmetry. During the weaning attempt, the failure weaning group developed a rapid, shallow breathing pattern with acute respiratory acidosis. The pH(i) was lower and gastric intramucosal PCO(2) (PCO(2)im) was higher in the failure weaning group than in the successful weaning group (p < 0.05). No change in gastric intramucosal-arterial PCO(2) difference was observed and a linear correlation was found between arterial PCO(2) and PCO(2)im (r(2) = 0.70; p < 0.001). Cardiac index increased in the failure group (p < 0.05) and remained stable in the success group whereas gastric mucosal blood flow decreased in the failure group (H(120) (min): -22 +/- 11% from baseline; p < 0.05) and increased in the success group (H(120) (min): 85 +/- 27% from baseline; p < 0.05). We conclude that gastric intramucosal pH changes during a 2-h weaning trial are mainly due to arterial PCO(2) variations. Nevertheless, gastric mucosal blood flow changes do occur and differ according to the weaning success or failure.

Acid-Base Equilibrium↗
PubMed2000

Time course of diaphragm injury and calpain activity during resistive loading.

The purpose of this study was to determine the time course of arterial blood gas (ABG) deterioration, increased calpain activity, and diaphragm injury during 4 d of resistive loading. Adult Sprague- Dawley rats were divided into control (C) animals and groups that were tracheally banded (TB) for 1 d (TB1), 2 d (TB2), 3 d (TB3), and 4 d (TB4). In TB rats, the carotid artery was cannulated and the trachea was banded during anesthesia. TB groups (TB1, TB2, TB3, and TB4) had a 67% smaller internal cross-sectional area of the trachea than did C animals. ABG samples from awake rats showed a decreased arterial oxygen tension (Pa(O(2))) and a respiratory acidosis in the TB1, TB2, and TB3 groups. Calpain activity was higher in the diaphragm of TB than of C rats; calpainlike activities in soluble fractions of diaphragm tissue were greater in all TB groups than in C rats, whereas those in bound fractions were greater in the TB2 and TB3 groups. Point counting of hematoxylin and eosin-stained cross-sections showed that the area fraction (A(A)) of normal diaphragm was lower and the A(A) of abnormal muscle and connective tissue was higher in TB3 than in C rats. Increased resistive loading induced by tracheal banding was associated with hypercapnic ventilatory failure, increased calpain activity, and diaphragm injury. Ventilatory failure in response to resistive loading may be due to diaphragm injury and/or to decreased minute ventilation.

Airway Obstruction↗
PubMed1988

Pulmonary angiotensin-converting enzyme activity in the oxygen-toxic sheep.

Despite the potential utility of endothelial metabolic substrates for the early clinical detection of acute lung injury, the relationship between lung capillary injury and pulmonary endothelial metabolic function remains incompletely understood. Previous studies have shown that lung capillaries are damaged by oxygen toxicity in the sheep; however, metabolic functions of the pulmonary endothelium have not been examined in this otherwise well-characterized animal model of lung injury. Therefore, we studied the activity of pulmonary endothelial angiotensin-converting enzyme (ACE) in five unanesthetized adult sheep that breathed 100% O2 via tracheostomy for 3 days and in four other sheep that breathed compressed air. In contrast to the sheep that breathed air, the sheep that breathed O2 developed substantial arterial hypoxemia and hypercapnia, an increased alveolar-to-arterial O2 gradient and a slight respiratory acidosis. Morphological examination of lungs from sheep that breathed O2 revealed a multifocal distribution of injury, including interstitial edema, capillary endothelial damage, and alveolar epithelial damage. Indicator-dilution methods were used to assess first-pass pulmonary metabolism of the ACE substrate [3H]Benzoyl-Phe-Ala-Pro (BPAP) and the apparent kinetics (KM and Vmax) of ACE activity. Pulmonary metabolism of BPAP exhibited saturability, was reduced by an ACE inhibitor (enalaprit), and did not result from the activity of circulating plasma ACE. There was no difference between the 2 groups of sheep in the percent metabolism of either 0.1 mumol BPAP/kg or 1.0 mumol BPAP/kg or in the KM of BPAP metabolism. In both groups, the Vmax and Vmax/KM decreased as a result of reductions in cardiac output and volume distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Is the association between inhaled beta-agonist use and life-threatening asthma because of confounding by severity?

We have previously reported an increasing dose-response relationship between the regular use of beta-agonist inhalers and the risk of asthma death and near death among a cohort of 12,301 subjects who had been dispensed 10 or more prescriptions of asthma drugs from January 1980 to April 1987. That analysis was based solely on information obtained from linkable computerized data bases. Such an association might be explained in part by the tendency of patients with more severe asthma, that is, those at greatest risk for an adverse outcome, to use more beta-agonist medication. To further examine this potential confounding by severity, we gathered clinical information independently from the field on the 129 case patients and their 655 control patients from the matched case-control analysis of 12,301 subjects. In 68% of the control patients with a life-threatening episode and 75% of the matched control subjects, we obtained a valid questionnaire from at least one physician who had seen the patient during the previous 2 yr. Acceptable information on hospitalizations because of asthma was obtained in 87% of those hospitalized. Clinical features associated with an increased risk of fatal and near-fatal asthma were: a history of loss of consciousness or seizures during a previous asthma attack (odds ratio, 10.2; 95% CI, 3.9 to 26.7), a history of attacks of asthma precipitated by eating certain foods (odds ratio, 5.1; 95% CI, 2.4 to 11.1), a clinical score designed to reflect the severity of prior attacks of asthma leading to hospitalization, and prior respiratory acidosis among those in whom a blood gas determination was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1984

Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus.

Hyperglycemia has been shown to induce arterial hypoxemia in the chronically catheterized fetal sheep. To investigate the mechanism behind this glucose-induced hypoxemia, eight pregnant ewes and their fetuses were studied. Fetal glucose infusion (11.9 +/- 0.6 mg glucose/kg per min) was associated with a doubling of the fetal plasma glucose concentration with concomitant elevation of the umbilical vein-distal arterial O2 content difference by 24 h of infusion (P less than 0.01). Calculated fetal O2 consumption increased from 8.1 +/- 0.4 ml/kg per min in the control period to a maximum value of 10.6 +/- 0.3 ml/kg per min by third infusion day (P less than 0.01), which is an increase of approximately 30%. The degree of stimulation of fetal O2 consumption was related to the degree of fetal hyperglycemia but not to the degree of fetal hyperinsulinemia. The increase in fetal O2 consumption was accompanied by a significant increase in fetal O2 extraction with no change in either fetal O2 delivery or fetal blood O2 affinity. In addition, fetal hypercapnea with a mild fetal respiratory acidosis was induced by fetal hyperglycemia. The increase in fetal arterial PCO2 was linearly related (P less than 0.001) to the magnitude of increase in fetal O2 consumption. These studies suggest that chronic fetal hyperglycemia induces a state of accelerated fetal oxidative metabolism and may be important in explaining the etiology behind certain unusual findings in human infants of diabetic mothers.

Animals↗
PubMed1989

Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD.

Adult↗
PubMed1990

2,4-Dienoyl-coenzyme A reductase deficiency: a possible new disorder of fatty acid oxidation.

Several inherited disorders of fatty acid beta-oxidation have been described that relate mainly to saturated precursors. This study is the first report of an enzyme defect related only to unsaturated fatty acid oxidation and provides the first in vivo evidence that fat oxidation in humans proceeds by the reductase-dependent pathway. The patient was a black female, presenting in the neonatal period with persistent hypotonia. Biochemical studies revealed hyperlysinemia, hypocarnitinemia, normal organic acid profile, and an unusual acylcarnitine species in both urine and blood. The new metabolite was positively identified by mass spectrometry as 2-trans,4-cis-decadienoylcarnitine, derived from incomplete oxidation of linoleic acid. In spite of dietary therapy, the patient died of respiratory acidosis at four months of age. Samples of liver and muscle from the autopsy were assayed for 2,4-dienoyl-coenzyme A reductase activity. Using the substrate 2-trans,4-cis-decadienoylcoenzyme A, the reductase activity was 40% of the control value in liver and only 17% of that found in normal muscle. It is suggested that unsaturated substrates should be used for in vitro testing to cover the full range of potential beta-oxidation defects and that acylcarnitine species identification be used for in vivo detection of this disorder.

Fatty Acid Desaturases↗
PubMed2006

A common cardiac sodium channel variant associated with sudden infant death in African Americans, SCN5A S1103Y.

Thousands die each year from sudden infant death syndrome (SIDS). Neither the cause nor basis for varied prevalence in different populations is understood. While 2 cases have been associated with mutations in type Valpha, cardiac voltage-gated sodium channels (SCN5A), the "Back to Sleep" campaign has decreased SIDS prevalence, consistent with a role for environmental influences in disease pathogenesis. Here we studied SCN5A in African Americans. Three of 133 SIDS cases were homozygous for the variant S1103Y. Among controls, 120 of 1,056 were carriers of the heterozygous genotype, which was previously associated with increased risk for arrhythmia in adults. This suggests that infants with 2 copies of S1103Y have a 24-fold increased risk for SIDS. Variant Y1103 channels were found to operate normally under baseline conditions in vitro. As risk factors for SIDS include apnea and respiratory acidosis, Y1103 and wild-type channels were subjected to lowered intracellular pH. Only Y1103 channels gained abnormal function, demonstrating late reopenings suppressible by the drug mexiletine. The variant appeared to confer susceptibility to acidosis-induced arrhythmia, a gene-environment interaction. Overall, homozygous and rare heterozygous SCN5A missense variants were found in approximately 5% of cases. If our findings are replicated, prospective genetic testing of SIDS cases and screening with counseling for at-risk families warrant consideration.

Adult↗
PubMed2006

SIDS: genetic and environmental influences may cause arrhythmia in this silent killer.

In this issue of the JCI, Bowers et al. show that the common polymorphism of the cardiac voltage-gated sodium channel, type Valpha (SCN5A), designated S1103Y, found in African Americans is associated with an increased risk of sudden infant death syndrome (SIDS). Wild-type and mutant SCN5A channels both functioned typically under normal conditions in vitro, but exposure to acidic intracellular pH levels such as those found in respiratory acidosis--a known risk factor for SIDS--produced abnormal gain-of-function late reopenings of S1103Y channels, behavior that is often associated with cardiac arrhythmias. These pathologic late reopenings were suppressed by low levels of the channel-blocking drug mexiletine. These findings provide an excellent illustration of a causal relationship between the interaction of the environment and genetic background in SIDS and also raise interesting questions about the linkage of a genetic abnormality with a clinical phenotype.

Arrhythmias, Cardiac↗
PubMedDate not supplied

Current concepts of malignant hyperthermia.

Malignant hyperthermia (MH) is a chemically induced, genetic myopathy characterized by metabolic and respiratory acidosis, arrhythmias, hyperpyrexia, and muscular rigidity usually occurring during or within 24 hours postanesthesia. It is initiated by some anesthetic drugs, muscle relaxants, and possibly by catecholamines produced by stress. The incidence of the disease is 1:15,000 in populations who have received a general anesthetic. A recently developed platelet bioassay test allows for rapid identification of the susceptible individual, while medication with dantrolene sodium can usually prevent or reverse the syndrome.

Adult↗
PubMed2003

Airway surface pH in subjects with cystic fibrosis.

The cystic fibrosis (CF) transmembrane conductance regulator protein can transport bicarbonate and may therefore regulate airway surface (AS) pH. Disturbances of AS pH could contribute to the pathophysiology of CF lung disease. Five studies were carried out including the following: study 1) nasal pH measurements were made in 25 CF and 10 non-CF adults using an antimony pH probe. Mean nasal pH was significantly lower in the CF group. Nasal potential difference may have been a confounding factor; study 2) in a fresh cohort of CF and non-CF subjects, no significant difference was found between the two groups using a gold pH probe; study 3) simultaneous nasal pH measurements were made in 15 CF and 15 non-CF adults using both probes. In the CF group, there was a trend for the antimony probe to read lower than the gold probe. In the non-CF group, the antimony probe read higher. The pH difference noted in study 1 related to technical factors; study 4) the effect of acute changes in serum acid/base balance on nasal pH was assessed in five non-CF adults. Nasal pH was not altered by either acute respiratory acidosis or alkalosis; study 5) nasal and lower airway pH was measured in five CF and six non-CF children. No difference was found between the groups. There was a correlation between nasal and lower airway pH. The authors conclude that airway surface pH does not differ between cystic fibrosis and noncystic fibrosis subjects and therefore, cystic fibrosis transmembrane conductance regulator may not play a major role in airway surface pH in vivo.

Adolescent↗
PubMed2006

Metabolic and blood gas dependence on digestive state in the Savannah monitor lizard Varanus exanthematicus: an assessment of the alkaline tide.

A large alkaline tide (up to 20 mmol l(-1) increase in bicarbonate concentration [HCO3-] with an accompanied increase in blood pH) has previously been reported for some carnivorous reptiles within 24 h after ingesting a large meal. This phenomenon has been attributed to the secretion of large amounts of H+ ions into the stomach, which is required for digestion of large prey items. To test the generality of this phenomenon in carnivorous reptiles, this study quantified the metabolic and acid-base status of the Savannah monitor lizard, Varanus exanthematicus, during digestion at 35 degrees C. Following a meal of approximately 10% of body mass, V(O2) and V(CO2) were measured continuously and arterial pH, blood gases and strong ions were measured every 8 h for 5 days. During peak digestion (24 h post feeding), V(O2) and V(CO2) increased to approximately threefold fasting values (V(O2), 0.95-2.57 ml min(-1) kg(-1); V(CO2) 0.53-1.63 ml min(-1) kg(-1)) while respiratory exchange ratio (R) remained constant (0.62-0.73). During digestion, arterial P(CO2) increased (from 4.6 kPa to 5.8 kPa), and [HCO3-] also increased (from 24.1 mmol l(-1) to 40.3 mmol l(-1)). In contrast to early studies on crocodilians, arterial pH in V. exanthematicus remained relatively stable during digestion (7.43-7.56). Strong ions contributed little to the acid-base compensation during the alkalosis. Collectively the data indicate that the metabolic alkalosis associated with H+ secretion (as indicated by increased plasma bicarbonate) is partially compensated by a respiratory acidosis.

Animal Feed↗
PubMed2006

A critical analysis of carbonic anhydrase function, respiratory gas exchange, and the acid-base control of secretion in the rectal gland of Squalus acanthias.

We compared in vivo responses of rectal gland secretion to carbonic anhydrase (CA) inhibition (10(-4) mol l(-1) acetazolamide) in volume-loaded dogfish with in vitro responses in an isolated-perfused gland stimulated with 5 x 10(-6) mol l(-1) forskolin and removed from systemic influences. We also measured respiratory gas exchange in the perfused gland, described the acid-base status of the secreted fluid, and determined the relative importance of various extracellular and intracellular acid-base parameters in controlling rectal gland secretion in vitro. In vivo, acetazolamide inhibited Cl(-) secretion and decreased pHi in the rectal gland, but interpretation was confounded by an accompanying systemic respiratory acidosis, which would also have contributed to the inhibition. In the perfused gland, M(CO(2)) and M(O(2)) increased in linear relation to increases in Cl(-) secretion rate. CA inhibition (10(-4) mol l(-1) acetazolamide) had no effect on Cl(-) secretion rate or pHi in the perfused gland, in contrast to in vivo, but caused a transitory 30% inhibition of M(CO(2)) (relative to stable M(O(2))) and elevation in secretion P(CO(2)) effects, which peaked at 2 h and attenuated by 3.5-4 h. Secretion was inhibited by acidosis and stimulated by alkalosis; the relationship between relative Cl(-) secretion rate and pHe was almost identical to that seen in vivo. Experimental manipulations of perfusate pH, P(CO(2)) and HCO(3)(-) concentration, together with measurements of pHi, demonstrated that these responses were most strongly correlated with changes in pHe, and were not related to changes in P(CO(2)), extracellular HCO(3)(-), or intracellular HCO(3)(-) levels, though changes in pHi may also have played a role. The acid-base status of the secreted fluid varied with that of the perfusate, secretion pH remaining about 0.3-0.5 units lower, and changing in concert with pHe rather than pHi; secretion HCO(3)(-) concentrations remained low, even in the face of greatly elevated perfusate HCO(3)(-) concentrations. We conclude that pH effects on rectal gland secretion rate are adaptive, that CA functions to catalyze the hydration of CO(2), thereby maintaining a gradient for diffusive efflux of CO(2) from the working cells, and that differences in response to CA inhibition likely reflect the higher perfusion-to-secretion ratio in vitro than in vivo.

Acetazolamide↗
PubMed1986

Acid-base regulation and ion transfers in the carp (Cyprinus carpio): pH compensation during graded long- and short-term environmental hypercapnia, and the effect of bicarbonate infusion.

To study both temporal and quantitative effects of hypercapnia on the extent of pH compensation in the arterial blood, specimens of carp (Cyprinus carpio) were exposed to a PCO2 of about 7.5 mmHg (1 mmHg = 133.3 Pa) (1% CO2) in the environmental water for several weeks, and a second group of animals was subjected to an environmental PCO2 of about 37 mmHg (5% CO2) for up to 96 h. A third series of experiments was designed to test the possibility that infusion of bicarbonate would increase the extent of plasma pH compensation. Dorsal aortic plasma pH, PCO2 and [HCO3-], as well as net transfer of HCO3- -equivalent ions, NH4+, Cl- and Na+, between fish and ambient water, were monitored throughout the experiments. Exposure to environmental PCO2 of 7.5 mmHg resulted in the expected respiratory acidosis with the associated drop in plasma pH, and subsequent compensatory plasma [HCO3-] increase. The compensatory increase of plasma bicarbonate during long-term hypercapnia continued during 19 days of exposure with plasma bicarbonate finally elevated from 13.0 mmoll-1 during control conditions to 25.9 mmoll-1 in hypercapnia, an increase equivalent to 80% plasma pH compensation. Exposure to 5% hypercapnia elicited much larger acid-base effects, which were compensated to a much lesser extent. Plasma pH recovered to only about 45% of the pH depression expected at constant bicarbonate concentration. At the end of the 96-h exposure period, plasma [HCO3-] was elevated by a factor of 2.5 to about 28.2 mmoll-1. The observed increase in plasma bicarbonate concentration during 5% hypercapnic exposure was attributable to net gain of bicarbonate equivalent ions from (or release of H+-equivalent ions to) the environmental water. Quantitatively, the gain of 15.6 mmol kg-1 was considerably larger than the amount required for compensation of the extracellular space, suggesting that acid-base relevant ions were transferred for compensation of the intracellular body compartments. The uptake of bicarbonate-equivalent ions from the water was accompanied by a net release of Cl-and, to a smaller extent, by a net uptake of Na+, suggesting a 75% contribution of the Cl-/HCO-3 exchange mechanism. Infusion of bicarbonate after 48 h of exposure to 7.5 mmHg PCo2 had only a transient effect on further pH compensation. The infused bicarbonate was lost to the ambient water, and pre-infusion levels of bicarbonate were reattained within 24 h. Repetition of the infusion did not result in a notable improvement of the acid-base status.(ABSTRACT TRUNCATED AT 400 WORDS)

Acid-Base Equilibrium↗
PubMed1988

Acid-base regulation and blood gases in the anuran amphibian, Bufo marinus, during environmental hypercapnia.

Specimens of Bufo marinus were exposed to aerial and aquatic hypercapnia (5% CO2) in a closed, water recirculation system to evaluate mechanisms involved in the compensation of a respiratory acidosis in these animals. Arterial PCO2 was elevated from about 9 mmHg (1 mmHg = 133.3 Pa) to 35 (1 h) and 37 mmHg (2 h), and gradually approached about 40 mmHg (24 h of hypercapnia). The typical hypercapnia-induced reduction in plasma pH from about 7.9 to below 7.4 was partially offset, at least during the first hours of hypercapnia, by a reduction in the inspired/arterial PCO2 difference, presumably brought about by pulmonary hyperventilation. The predominant contributor to extracellular pH compensation, however, was a net gain of bicarbonate from the environment, mainly facilitated by ammonia excretion. Bicarbonate originating from the environment was accumulated in the body fluids, increasing the plasma concentration from the control of about 9 to 36 mmol l-1 after 24 h. Extracellular pH was compensated to only about 30% of the shift expected at constant bicarbonate level and, according to the steady reduction of pH, non-bicarbonate buffering of CO2 also contributed significantly to the elevation of bicarbonate. This relatively poor pH compensation (compared with fishes) could not be improved either by direct administration of bicarbonate into the bloodstream or by increased environmental ion concentrations. It is concluded that the availability of bicarbonate is not a limiting factor for pH compensation during hypercapnia, and that the inability of Bufo to accumulate bicarbonate to concentrations sufficient for better hypercapnia compensation is based on a constitutional 'bicarbonate threshold' of the resorbing and retaining structures for acid-base-relevant ions.

Acid-Base Equilibrium↗