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PubMed1985

Effects and interrelationships of PTH, Ca2+, vitamin D, and Pi in acid-base homeostasis.

Chronic administration of 1,25(OH)2D or PTH increases the set point at which plasma bicarbonate concentration is regulated by the kidney and thereby maintains metabolic alkalosis in a variety of species. The renal mechanism(s) responsible for the chronic acid excretory response to 1,25(OH)2D and PTH administration have not been defined, but indirect evidence suggests effects on distal nephron segments. With either hormone in dogs, but not in rats, metabolic alkalosis is generated in part by extrarenal mechanisms. Contrary to the variable finding of hyperchloremic acidosis in human primary hyperparathyroidism, a steady state of mild metabolic alkalosis of renal origin is achieved in normal human subjects infused chronically with PTH. The multiple potential mechanisms responsible for this discrepancy will require careful consideration in future investigations. The acute and chronic effects of plasma calcium concentration on both renal and extrarenal acid-base homeostasis are incompletely understood and require extensive further investigation. Studies in rats have suggested that phosphate depletion results in important counterbalancing renal acidosis and extrarenal alkalosis-producing effects. Chronic hypophosphaturia in the absence of appreciable hypophosphatemia can also result in impaired renal acidification by virtue of phosphate's property as a luminal buffer.

Acid-Base Equilibrium↗
PubMed1982

Effect of pH on sensation and vastus lateralis electromyogram during cycling exercise.

Six male subjects performed 30 min of cycling exercise: 15 min at 50% of maximum oxygen consumption (VO2 max) and 15 min at 80% VO2 max. On random days subjects ingested 300 mg/kg body wt of NH4Cl to induce acidosis, NaHCO3 to induce alkalosis, or CaCO3 as a placebo during a 3-h preexercise period. Blood pH at the onset of exercise was 7.238 in acidosis, 7.435 in alkalosis, and 7.394 in the placebo control. A direct ratio scaling technique was employed to measure the sensation of how hard exercise felt. Sensory intensity increased twofold after 15 min at 50% VO2max (P less than 0.01). There was no effect of pH on how hard exercise felt during 50% VO2max bouts. Sensory intensity at the end of heavy exercise increased 20% more in acidosis but was not different in alkalosis compared with placebo (P less than 0.05). There was no difference in integrated electromyogram (EMG) between conditions, but there was an average 13% integrated EMG increase by the end of exercise (P less than 0.05). Plasma lactate was lower in acidosis and higher in alkalosis than placebo at 80% VO2max. These data indicate that during heavy exercise acidotic pH accelerates the change in sensory intensity, but this phenomenon is not necessarily associated with changes in the integrated surface EMG.

Acidosis↗
PubMed1985

Influence of chronic respiratory acid-base disorders on acute CO2 titration curve.

We have recently shown that background presence of chronic metabolic acid-base disorder markedly alters in vivo acute CO2 titration curve. These studies were carried out to assess the influence of chronic respiratory acid-base disorders on response to acute hypercapnia and to explore whether the chronic level of plasma pH is the factor responsible for alterations in the CO2 titration curve. We compared whole-body responses to acute hypercapnia of dogs with preexisting chronic respiratory alkalosis (n = 8) with that of normal animals (n = 4) and animals with chronic respiratory acidosis (n = 13). Chronic respiratory alkalosis and acidosis, as well as the acute CO2 titrations, were produced in unanesthetized dogs within a large environmental chamber. For comparison with our data on chronic metabolic acidosis and alkalosis, plasma bicarbonate levels, which are secondarily altered in chronic respiratory acid-base disorders, were used as an index of chronic acid-base status of the animals. Results indicate that, as with chronic metabolic acid-base disorders, a larger increment in plasma bicarbonate occurs during acute hypercapnia when steady-state plasma bicarbonate is low (respiratory alkalosis) than when it is high (respiratory acidosis). Yet, in further analogy with the metabolic studies, plasma hydrogen ion concentration is better defended at higher plasma bicarbonate levels in accordance with mathematical relationships defined by the Henderson-Hasselbalch equation. Combined results demonstrate that the influence of chronic acid-base status on whole-body response to acute hypercapnia is independent of initial plasma pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed2001

Effects of hypercapnia and hypocapnia on [Ca2+]i mobilization in human pulmonary artery endothelial cells.

The hydrogen ion is an important factor in the alteration of vascular tone in pulmonary circulation. Endothelial cells modulate vascular tone by producing vasoactive substances such as prostacyclin (PGI2) through a process depending on intracellular Ca2+ concentration ([Ca2+]i). We studied the influence of CO2-related pH changes on [Ca2+]i and PGI2 production in human pulmonary artery endothelial cells (HPAECs). Hypercapnic acidosis appreciably increased [Ca2+]i from 112 +/- 24 to 157 +/- 38 nmol/l. Intracellular acidification at a normal extracellular pH increased [Ca2+]i comparable to that observed during hypercapnic acidosis. The hypercapnia-induced increase in [Ca2+]i was unchanged by the removal of Ca2+ from the extracellular medium or by the depletion of thapsigargin-sensitive intracellular Ca2+ stores. Hypercapnic acidosis may thus release Ca2+ from pH-sensitive but thapsigargin-insensitive intracellular Ca2+ stores. Hypocapnic alkalosis caused a fivefold increase in [Ca2+]i compared with hypercapnic acidosis. Intracellular alkalinization at a normal extracellular pH did not affect [Ca2+]i. The hypocapnia-evoked increase in [Ca2+]i was decreased from 242 +/- 56 to 50 +/- 32 nmol/l by the removal of extracellular Ca2+. The main mechanism affecting the hypocapnia-dependent [Ca2+]i increase was thought to be the augmented influx of extracellular Ca2+ mediated by extracellular alkalosis. Hypercapnic acidosis caused little change in PGI2 production, but hypocapnic alkalosis increased it markedly. In conclusion, both hypercapnic acidosis and hypocapnic alkalosis increase [Ca2+]i in HPAECs, but the mechanisms and pathophysiological significance of these increases may differ qualitatively.

Acidosis, Respiratory↗
PubMed2003

Intracellular alkalinization augments capacitative Ca2+ entry in platelets.

In order to elucidate the significance of intracellular alkalinization in signal transduction of platelets, we investigated the effects on capacitative Ca(2+) entry (CCE) of intracellular alkalinization that was induced by NH(4)Cl. Addition of NH(4)Cl (10 mM) to the medium resulted in an elevation of intracellular pH by about 0.35, which was eliminated by simultaneous addition of propionate (20 mM), an inducer of intracellular acidification, to the medium. CCE was induced by an extracellular addition of Ca(2+) to platelets in which Ca(2+) stores had been depleted by stimulation with thapsigargin in nominally Ca(2+)-free medium. NH(4)Cl markedly augmented CCE and subsequent platelet aggregation, both of which were abolished in the presence of SKF-96365, an inhibitor of capacitative Ca(2+) entry in non-excitable cells such as platelets. The augmentation of CCE and subsequent aggregation by NH(4)Cl was not observed in the presence of propionate or SKF-96365. Extracellular alkalosis induced by Tris also markedly augmented CCE and subsequent aggregation. These augmenting effects of extracellular alkalosis by Tris were significantly but incompletely inhibited by simultaneous addition of propionate (20 mM), which completely eliminated elevation of intracellular pH elicited by Tris. Thus, the augmenting effect of extracellular alkalosis on CCE was in part mediated by intracellular alkalosis. These findings suggest that intracellular alkalinization is a potent signal that augments CCE in platelets.

Alkalosis↗
PubMedDate not supplied

Lusitropic changes induced by acid base alterations in cat papillary muscles.

The present work investigates the effects of acid-base alterations upon myocardial relaxation. Experiments were performed in cat papillary muscles contracting isometrically at constant frequency (0.2 Hz) and temperature (29 degrees C). To induce intracellular alkalosis at constant pH0, 20 mM NH4Cl were added to the perfusate. Alkalosis at variable pH0 was induced by switching from the control solution (5% CO2-95% O2, pH0 7.40) to a solution identical to the control one, equilibrated with 3% CO2-97% O2. Acidosis was induced by switching the control perfusate to a solution equilibrated with 12% CO2-88% O2 in which pH0 was either allowed to change or kept constant by manipulation of bicarbonate concentration. Alkalosis produced a negative lusitropic effect either when pH0 was kept constant or when it was allowed to increase. For an increase in myocardial contractility of 30%, half relaxation tme (T50) and time to peak tension (TTP) were prolonged 9.4 +/- 5% and 5.4 +/- 2% respectively at constant pH0 and 6.8 +/- 0.8 and 4.7 +/- 1% respectively at variable pHo. It is suggested that this negative lusitropic effect of alkalosis can be attributed to an increase in myofilament sensitivity to calcium. Either at constant or at variable pHo acidosis decreased myocardial contractility by approximately 50%. This decrease in contractility was accompanied by a positive lusitropic action only when pHo was allowed to decrease, or when acidosis at constant pHo was evoked in the presence of EIPA, a specific inhibitor of the Na+/H+ exchanger.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1995

Low CO2 stimulates inositol phosphate turnover and increased inositol 1,4,5-trisphosphate levels in piglet cerebral microvascular smooth muscle cells.

In contrast to hypercapnic dilation, hypocapnia-induced cerebral vasoconstriction does not involve prostanoids in newborn pigs. The hypothesis that increased pH or decreased CO2 tension increases inositol phosphate turnover in piglet cerebral microvascular smooth muscle (SM) cells was addressed to begin to assess the possibility that this second-messenger system is involved in hypocapnia-induced cerebral vasoconstriction. Cerebral microvascular SM cells in primary culture prelabeled with [3H]-myoinositol were stimulated for 30 sec with artificial cerebrospinal fluid of increased or normal pH, (7.80 vs 7.40), constant PCO2 36 mm Hg. Following extraction from cells, radiolabeled inositol phosphates were separated by HPLC. These metabolic alkalosis studies were repeated using an inositol 1,4,5-trisphosphate (Ins[1,4,5]P3 protein-binding assay (PBA). Respiratory alkalosis using aCSF with pH 7.60, PCO2 20 mm Hg versus control pH 7.40, PCO2 36 mm Hg was similarly tested with PBS measurement of Ins(1,4,5)P3. aCSFs of control pH 7.40, and PCO2s of 70, 36, or 25 mm Hg were studied both by [3H]-myoinositol (HPLC) and PBA to further determine the importance of CO2 tension, in the presence of fixed pH, on Ins(1,4,5)P3 production. When PCO2 was constant, inositol phosphate turnover (as measured by [3H]-Ins[1,4,5]P3 accumulation) increased when pH was increased from 7.40 to 7.80 at 30 sec of stimulation. Mean [3H]-Ins(1,4,5)P3 accumulation at pHs of 7.40 and 7.80, constant PCO2 of 36 mm Hg, were 2.9 +/- 0.7 and 4.1 +/- 0.8 cpm/micrograms protein, respectively. Ins(1,4,5)P3 levels for pH of 7.40 or 7.80 and constant PCO2 of 36 mm Hg, were 25.4 +/- 1.8 and 38 +/- 8 pmol/well, respectively, by PBA. Respiratory alkalosis also increased Ins(1,4,5)P3 levels. For pH of 7.40, PCO2 36 mm Hg and pH 7.60, PCO2 20 mm Hg, Ins(1,4,5)P3 levels were 37.6 +/- 16 and 64.1 +/- 25 pmol/well, respectively. Decreasing CO2 tension (from 70 mm Hg to 25 mm Hg) in the presence of fixed pH 7.40 failed to increase Ins(1,4,5)P3 levels. The present data demonstrate that decreased CO2 tension stimulates an increase in Ins(1,4,5)P3 production in piglet cerebral microvascular smooth muscle cells. Increasing pH via lower PCO2 increases the level of Ins(1,4,5)P3 even more than increasing pH with fixed base, but extracellular pH appears to be important since decreased PCO2 without changing extracellular pH had no effect. We conclude that the inositol phosphate second messenger system in cerebral microvascular smooth muscle responds appropriately to acute alkalosis to be involved in hypocapnia-induced cerebral vasoconstriction.

Alkalosis, Respiratory↗
PubMed1992

[Renal adaptations to acid-base disorders].

Alterations in acid-base status affect renal hemodynamics and tubular function. GFR is reduced both in acute acidosis and alkalosis. Tubular functional adaptation to acute acidosis includes an acceleration in proximal acidification, induced by the increase in Pco2 and luminal bicarbonate concentration and a stimulated ammonia production, induced by low pH. Alteration in distal bicarbonate reabsorption is also an important determinant of the net acid excretion. Renal functional alterations in acute alkalosis include a reduction in GFR and a stimulated bicarbonate secretion in the cortical collecting duct. Proximal acidification is almost unchanged during acute alkalosis but reportedly accelerates after at least 3 weeks of maintained alkalosis. Renal adaptation during chronic phase of acid-base disorders differs from that during the acute phase.

Acidosis↗
PubMedDate not supplied

Acid-base balance in heart failure.

In end-stage heart failure, various acid-base disorders can be discovered due to the renal loss of hydrogen ions and hydrogen ion movements into cells, the reduction of the effective circulating volume, hypoxemia and renal failure. This justifies the occurrence of metabolic alkalosis, metabolic acidosis, respiratory alkalosis, as well as respiratory acidosis alone or in combination. Several studies have been published on the acid-base state in heart failure. In a 1951 study, Squires et al analyzed the distribution of body fluid in congestive heart failure by taking into consideration the abnormalities in serum electrolyte concentration and in acid-base equilibrium. A recent study by Milionis et al, analyzed 86 patients with congestive heart failure receiving conventional treatment; the majority of these patients exhibited hypokalemia, hyponatremia, hypocalcemia and hypophosphatemia. Disorders in acid-base balance were noted in 37.2% of patients. In a recent study, 70 patients with severe congestive heart failure before heart transplantation showed high-normal pH, slightly reduced pCO 2 and a slight loss of hydrogen ions. After heart transplantation, stability of blood pH and hydrogen ion concentrations was found. In contrast, bicarbonate and pCO 2 increased significantly. The data led us to formulate the diagnosis of a mixed acid-base disorder that includes respiratory alkalosis and metabolic alkalosis before heart transplantation. In heart failure, the presence of acid-base imbalance associated with the activation of mechanisms that lead to salt and water retention reveals evidence concerning the pivotal role of the kidney in determining the outcome of these patients.

Acid-Base Equilibrium↗
PubMed1990

[Tetany as a sole manifestation in a patient with Bartter's syndrome and a successful treatment with indomethacin].

37 year-old man presented to our clinic because of tetany that occurred during driving a car in the morning. He had no anorexia, chronic diarrhea or vomiting. He was normotensive and no edema was noted. On neurological examination, he was rather apprehensive and Trousseau sign was mildly positive. No muscle weakness was noted except for the moderate atrophies of bilateral anterior tibial muscles as a sequela of Guillain-Barré syndrome that he suffered at the age of 7. The results of laboratory studies included hypokalemia, metabolic alkalosis, hyperuricemia, increased plasma renin activity, increased plasma aldosterone concentration, reduced pressor response to infusion of angiotensin II. Based on these clinical and laboratory findings, the diagnosis of Bartter's syndrome was made. As far as we know, it is extremely rare that Bartter's syndrome manifests tetany alone as in the present case. The exacerbation of preexisting alkalosis by hyperventilation during driving might be the cause of tetany. Tetany was easily provoked by hyperventilation, during which serum ionized calcium remained in normal level despite the exacerbation of alkalosis. The results suggest that alkalosis per se can cause tetany in Bartter's syndrome. Indomethacin, 75 mg daily, effectively prevented tetany from recurring for nearly 4 years without any side effect.

Adult↗
PubMed1980

[The influence of arterial partial pressure of CO2 and of the arterial value of pH on the oxygen consumption of the whole body during extracorporal circulation (author's transl)].

134 patients with coronary heart disease, with defects of the cardiac values or with inborn heart diseases were studied referring to the influences of the arterial partial pressure of CO2 and the arterial value of pH on oxygen consumption of the whole body during total hypothermic extracorporal circulation. Oxygen consumption of the whole body increases during respiratory or metabolic alkalosis whereas respiratory or metabolic acidosis decreases oxygen consumption significantly. These typical changes of oxygen consumption of the whole body during extraorporal circulation due to alkalosis or acidosis may be explained by different facts. Within the cellular area glycolysis is in relation of value for pH, and phosphofructokinase-reaction slows up due to ATP-level also in relationship of value for pH. In addition to cellular parameters hemodynamic parameters may explain the changes of oxygen consumption due to alkalosis and acidosis. Alkalosis effects a decrease of the total peripheral resistane whereas acidosis effects an increase of the total peripheral resistance. Peripheral oxygen consumption vaires in addition to other parameters in inverse proportion of the level of totalperipheral resistance.

Acid-Base Equilibrium↗
PubMed2000

Phenotypic variability in Bartter syndrome type I.

Limited phenotypic variability has been reported in patients with Bartter syndrome type I, with mutations in the Na-K-2Cl cotransporter gene (BSC). The diagnosis of this hereditary renal tubular disorder is usually made in the antenatal-neonatal period, due to the presence of polyhydramnios, premature delivery, hypokalemia, metabolic alkalosis, hypercalciuria, and nephrocalcinosis. Among nine children with hypercalciuria and nephrocalcinosis, we identified new mutations consistent with a loss of function of the mutant allele of the BSC gene in five. Three of the five cases with BSC gene mutations were unusual due to the absence of hypokalemia and metabolic alkalosis in the first years of life. The diagnosis of incomplete distal renal tubular acidosis was considered before molecular evaluation. Three additional patients with hypokalemia and hypercalciuria, but without nephrocalcinosis in the first two and with metabolic acidosis instead of alkalosis in the third, were studied. Two demonstrated the same missense mutation A555T in the BSC gene as one patient of the previous group, suggesting a single common ancestor. The third patient presented with severe hypernatremia and hyperchloremia for about 2 months, and a diagnosis of nephrogenic diabetes insipidus was hypothesized until the diagnosis of Bartter syndrome type I was established by molecular evaluation. We conclude that in some patients with Bartter syndrome type I, hypokalemia and/or metabolic alkalosis may be absent in the first years of life and persistent metabolic acidosis or hypernatremia and hyperchloremia may also be present. Molecular evaluation can definitely establish the diagnosis of atypical cases of this complex hereditary tubular disorder, which, in our experience, may exhibit phenotypic variability.

Amino Acid Sequence↗
PubMed2003

Effect of low oxygen inhalation on changes in blood pH, lactate, and ammonia due to exercise.

The present study examined the effect of hypoxia-induced respiratory alkalosis on exercise-induced metabolic acidosis and increases in plasma lactate and ammonia levels. Six male subjects underwent exercise of increasing intensity until exhaustion: (1) in normoxia (20.9% O(2)) (=MAX), (2) in hypoxia (12% O(2)) (=HP) in which hypoxic condition had been maintained from 60 min before to 30 min after exercise, and (3) the same intensity of exercise as HP in normoxia (=SUB). Arterialized blood was drawn from a superficial vein. Post-exercise blood pH was significantly higher in HP than in MAX ( P<0.05), although plasma lactate was at the same level. For hypoxia as compared to normoxia, regression analysis confirmed a parallel shift of plasma lactate to higher pH levels indicating the effect of respiratory alkalosis ( P<0.01). After exercise plasma levels of ammonia were lower in HP than in MAX ( P<0.05). Regression analysis between ammonia and pH revealed nearly identical changes in hypoxia and normoxia at low pH. From these results, we conclude that: (1) hypoxia-induced respiratory alkalosis attenuated exhaustive exercise-induced metabolic acidosis, (2) plasma lactate concentration was determined by the relative exercise intensity, (3) the maximum plasma ammonia concentration under exhaustive exercise was reduced at hypoxia because of respiratory alkalosis.

Adult↗
PubMed2001

Extracellular pH affects platelet aggregation associated with modulation of store-operated Ca(2+) entry.

The pH dependence of store-operated Ca(2+) influx (SOCI) into human platelets, as well as its physiological consequence, aggregation, was studied. In Ca(2+)-free medium, thapsigargin (1 microM) induced a small increase in intracellular free-Ca(2+) ([Ca(2+)](i)), which was not affected by changes in extracellular pH. The addition of Ca(2+) (0.5-3 mM) after Ca(2+) store depletion caused by thapsigargin resulted in concentration-dependent increases in [Ca(2+)](i) (SOCI), which were strongly inhibited by SKF-96365 (100 microM), an inhibitor of receptor-mediated Ca(2+) entry. SOCI was inhibited by acidosis (pH 6.9) and augmented by alkalosis (pH 7.9). The addition of Ca(2+) (0.5-3 mM) to platelets, which were kept in Ca(2+)-free medium, slightly but significantly increased [Ca(2+)](i). This Ca(2+) leak entry was also decreased and increased by extracellular acidosis (pH 6.9) and alkalosis (pH 7.9), respectively, but not affected by SKF-96365. Neither thapsigargin (1 microM) stimulation in Ca(2+)-free solution nor elevation of extracellular Ca(2+) alone was sufficient to induce platelet aggregation. In contrast, the addition of Ca(2+) (1 mM) to platelets activated by thapsigargin resulted in aggregation, which was markedly inhibited by SKF-96365 (100 microM). Platelet aggregation associated with SOCI was also inhibited by extracellular acidosis (pH 6.9) and augmented by extracellular alkalosis (pH 7.9). These results suggest that acidosis-induced inhibition, as well as alkalosis-induced promotion of platelet aggregation, involve pH effects on SOCI.

Blood Platelets↗
PubMed1996

Acid-base and electrolyte disturbances in patients with diabetic ketoacidosis.

We undertook the present study to examine the acid-base and electrolyte disturbances in relation to hydration status in patients with diabetic ketoacidosis (DKA). A total of 40 insulin-dependent diabetes mellitus patients (22 male, 18 female), aged 18-61 years with DKA admitted to our hospital during the last 2 years, were studied. The duration of diabetes averaged 9 +/- 2 years. In all cases a detailed investigation of the acid-base status and electrolyte parameters was performed. Twenty-one patients had a pure metabolic acidosis with an increased serum anion gap, seven had DKA combined with hyperchloremic metabolic acidosis, nine had DKA coexisting with metabolic alkalosis, while three had DKA with a concurrent respiratory alkalosis. Hydration status as evidenced by the ratio of urea/creatinine seems to play an important role in the development of mixed acid-base disorders (detected by changes in the ratios delta anion gap/delta bicarbonate (delta AG/delta HCO3) and sodium/chloride (Na/Cl)). In fact, hyperchloremic acidosis developed in the patients with the better hydration status. However, contradictorily, the severely dehydrated patients who experienced recurrent episodes of vomiting developed DKA with a concurrent metabolic alkalosis. Finally, patients with pneumonia or gram-negative septicemia exhibited DKA combined with a primary respiratory alkalosis. We conclude that patients with DKA commonly develop mixed acid-base disorders, which are partly dependent on patients' hydration status.

Adolescent↗
PubMed1978

Acid-base balance and neostigmine antagonism of pancuronium neuromuscular blockade.

In 40 cases anesthetized with chloralose and urethane, pancuronium was infused i.v. at a constant rate to produce and maintain 90% depression twitch tension of the anterior tibialis muscle following supramaximal stimulation of the peroneal nerve. Neither respiratory alkalosis nor metabolic acidosis influenced the infusion rate required to produce 90% depression of twitch tension or antagonism of this depression yb neotigmine. Respiratory acidosis (pH 7.15; PaCO2 10 kPa) did not alter the required infusion rate but did prevent complete antagonism by neostigmine. Metabolic alkalosis (pH 7.65; PaCO2 4.8 kPa) reduced both the required infusion rate and prevented complete restoration of twitch tension by neostigmine. The duration of neostigmine antagonism was shortened by metabolic alkalosis. We conclude that respiratory acidosis and metabolic alkalosis prevent antagonism of pancuronium by neostigmine.

Acid-Base Equilibrium↗
PubMed1993

Actions of extracellular chloride ion substitution on contractility of isolated ventricular myocardium.

OBJECTIVE: Replacement of extracellular chloride ions by some other anions exerts a positive inotropic effect on isolated cardiac muscle preparations. The aim of this study was to determine whether the increase of force was mediated by an intracellular alkalosis. METHODS: Isometric tension development was measured using guinea pig papillary muscles during replacement of superfusate Cl- with isethionate ions. Intracellular pH and L-type Ca2+ currents were measured in isolated myocytes using epifluorescence microscopy and a switch-clamp technique respectively. RESULTS: Reduction of extracellular Cl- increased tension, a phenomenon which was partially inhibited with the anion exchange blocker SITS. Force was also increased by reducing superfusate PCO2. Reduction of superfusate [Cl-] and PCO2 both produced concentration dependent intracellular alkalosis. The relationship between the changes to tension and intracellular pH was different when either the superfusate [Cl-] or PCO2 was reduced, less pronounced when the [Cl-] was reduced. An increase of the L-type Ca2+ current was produced in low [Cl-] solutions which could be attributed to the accompanying intracellular alkalosis. CONCLUSIONS: The positive inotropic effect of superfusate Cl- removal can only partially be explained by intracellular alkalosis. Other, as yet unknown, changes must determine the remainder of the inotropic response.

Animals↗
PubMed2000

Effects of respiratory and metabolic pH changes and hypoxia on ropivacaine-induced cardiotoxicity in dogs.

We have studied the effects of acute changes in acid-base status and hypoxia on the cardiotoxic effects of intracoronary injection of ropivacaine in anaesthetized dogs. The effects of intracoronary ropivacaine were compared when ropivacaine was administered during eucapnia and during each of another nine states in random order: hypocapnia, hypercapnia, hypoxia, metabolic alkalosis, metabolic acidosis, combined metabolic acidosis and hypocapnia, combined metabolic alkalosis and hypercapnia, combined hypoxia and hypercapnia, and combined metabolic acidosis and hypoxia. Hypocapnic alkalosis consistently reduced the cardiotoxic effects of intracoronary ropivacaine (P < 0.01). Our findings indicate that induction of hypocapnic alkalosis may provide a useful adjunct to standard resuscitative measure after inadvertent administration of amide local anaesthetic agents.

Acid-Base Imbalance↗