Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Hypoxia silences retrotrapezoid nucleus respiratory chemoreceptors via alkalosis.

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.

Urine anion gap can differentiate respiratory alkalosis from metabolic acidosis in the absence of blood gas results.

INTRODUCTION: Low plasma bicarbonate concentration due to chronic respiratory alkalosis may be misdiagnosed as metabolic acidosis and mistreated with administration of alkali therapy, particularly when arterial blood gas is not available. METHODS: We measured urine anion gap [urine (Na+ + K+ ) - (Cl- )], as a surrogate of renal ammonium excretion in 15 patients presenting with hyperventilation and low serum bicarbonate concentration to distinguish chronic respiratory alkalosis (CRA) from metabolic acidosis (MA) when blood gas was unavailable. RESULTS: Hyperventilation and low serum bicarbonate concentrations were associated with urine pH above 5.5 and positive urine anion gap in all, suggesting CRA. The diagnosis was later confirmed by obtaining capillary blood gas, which showed a decrease in PCO2 and high normal pH values. CONCLUSION: The use of urine anion gap can help to differentiate between chronic respiratory alkalosis and metabolic acidosis, especially when arterial blood gas is not obtained.

Renal acidification responses to respiratory acid-base disorders.

Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are expressed as primary changes in the arterial carbon dioxide tension (PaCO2). An increase in PaCO2 (hypercapnia) acidifies body fluids and initiates the acid-base disturbance known as respiratory acidosis. By contrast, a decrease in PaCO2 (hypocapnia) alkalinizes body fluids and initiates the acid-base disturbance known as respiratory alkalosis. The impact on systemic acidity of these primary changes in PaCO2 is ameliorated by secondary, directional changes in plasma [HCO3¯] that occur in 2 stages. Acutely, hypercapnia or hypocapnia yields relatively small changes in plasma [HCO3¯] that originate virtually exclusively from titration of the body's nonbicarbonate buffers. During sustained hypercapnia or hypocapnia, much larger changes in plasma [HCO3¯] occur that reflect adjustments in renal acidification mechanisms. Consequently, the deviation of systemic acidity from normal is smaller in the chronic forms of these disorders. Here we provide an overview of the renal acidification responses to respiratory acid-base disorders. We also identify gaps in knowledge that require further research.

Teaching acid/base physiology in the laboratory.

Acid/base homeostasis is one of the most difficult subdisciplines of physiology for medical students to master. A different approach, where theory and practice are linked, might help students develop a deeper understanding of acid/base homeostasis. We therefore set out to develop a laboratory exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical students that had participated in this laboratory exercise. The acquired data showed very consistent and solid findings after the development of both metabolic acidosis and respiratory alkalosis. All results were consistent with the appropriate diagnosis of the acid/base disorder. Not one single group failed to obtain data that were compatible with the diagnosis; it was only the degree of acidosis/alkalosis and compensation that varied.

The standard strong ion difference, standard total titratable base, and their relationship to the Boston compensation rules and the Van Slyke equation for extracellular fluid.

A general formalism for calculating physiological acid-base balance in multiple compartments is extended to the combined interstitial, plasma, and erythrocyte multicompartment system in humans using the Siggaard-Andersen approximation for interstitial fluid. The resulting equations for total titratable base and strong ion difference reproduce the experimental in vivo carbon dioxide titration curve as well as the experimental strong ion difference value of the interstitial, plasma, and erythrocyte system in normal man. The "Boston rules" for compensation in acute respiratory acidosis and alkalosis are then derived analytically from the model. The Van Slyke equation for the interstitial, plasma, and erythrocyte system is also derived and shown to approximate the Van Slyke equation for standard base excess.

Effects of various sodium bicarbonate loading protocols on the time-dependent extracellular buffering profile.

Although much research has investigated the types of exercise that are enhanced with sodium bicarbonate (NaHCO3) ingestion, to date, there has been limited research on the dosage and timing of ingestion that optimizes the associated ergogenic effects. This study investigated the effects of various NaHCO3 loading protocols on the time-dependent blood-buffering profile. Eight male volunteers (age, 22.4 +/- 5.7 yr; height, 179.8 +/- 9.6 cm, body mass, 76.3 +/- 14.1 kg) completed Part A, measures of alkalosis throughout 120 minutes after ingestion of various single NaHCO3 dosages (0.3 gxkg-1, 0.2 gxkg-1, 0.1 gxkg-1, and placebo); and Part B, similar profiles after alternative NaHCO3 loading protocols (single morning dosage [SMD], single evening dosage [SED], and dosages ingested on 3 consecutive evenings [CED]). Results from Part A are as follows. Blood buffering in the 0.1 gxkg-1 condition was significantly lower than the 0.2 g.kg-1 and 0.3 gxkg-1 conditions (p < 0.002), but there was no significant differences between the 0.2 gxkg -1and 0.3 g.kg-1 conditions (p = 0.34). Although the blood buffering was relatively constant in the 0.1 and 0.2 conditions, it was significantly higher at 60 minutes than at 100 minutes and 120 minutes in the 0.3 gxkg-1 condition (p < 0.05). Results from Part B are as follows. Blood buffering for SMD was significantly higher than for SED and CED (p < 0.05). Blood buffering in the SMD condition was significantly lower at 17:00 hours than at 11:00 hours (p = 0.007). The single 0.2 and 0.3 gxkg-1 NaHCO3 dosages appeared to be the most effective for increasing blood-buffering capacity. The 0.2 gxkg-1 dosage is best ingested 40 to 50 minutes before exercise and the 0.3 gxkg-1 dosage 60 minutes before exercise.

Exaggerated compensatory response to acute respiratory alkalosis in panic disorder is induced by increased lactic acid production.

BACKGROUND: In acute respiratory alkalosis, the severity of alkalaemia is ameliorated by a decrease in plasma [HCO(3)(-)] of 0.2 mEq/L for each 1 mmHg decrease in PaCO(2). Although hyperventilation in panic disorder patients is frequently encountered in outpatients, the drop in plasma [HCO(3)(-)] sometimes surpasses the expectation calculated from the above formula. The quantitative relationship between reduced PaCO(2) and plasma [HCO(3)(-)] in acute respiratory alkalosis has not been studied in panic disorder patients. Our objective was to provide reference data for the compensatory metabolic changes in acute respiratory alkalosis in panic disorder patients. METHODS: In 34 panic disorder patients with hyperventilation attacks, we measured arterial pH, PaCO(2), plasma [HCO(3)(-)] and lactate on arrival at the emergency room. RESULTS: For each decrease of 1 mmHg in PaCO(2), plasma [HCO(3)(-)] decreased by 0.41 mEq/L. During hypocapnia, panic disorder patients exhibited larger increases in serum lactate levels (mean +/- SD; 2.59 +/- 1.50 mmol/L, range; 0.78-7.78 mmol/L) than previously reported in non-panic disorder subjects. Plasma lactate accumulation was correlated with PaCO(2) (P < 0.001). CONCLUSIONS: These results suggest that the compensatory metabolic response to acute respiratory alkalosis is exaggerated by increased lactic acid production in panic disorder patients. Here, we call attention to the diagnosis of acid-base derangements by means of plasma [HCO(3)(-)] and lactate concentration in panic disorder patients.

Relationship of metabolic alkalosis, azotemia and morbidity in patients with chronic obstructive pulmonary disease and hypercapnia.

BACKGROUND: Exacerbation of chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality, but the effect of metabolic compensation of respiratory acidosis (RA) on mortality is not fully understood. OBJECTIVE: To investigate the relationship between metabolic compensation and mortality in COPD patients with RA. METHODS: We prospectively investigated all COPD patients with RA admitted to the respiratory intensive care unit between February 2001 and March 2007. Two hundred and thirteen patients (159 male, 54 female; mean age 65 +/- 10.8 years) were divided into three groups (71 patients each) according to base excess (BE) levels: (1) low BE, (2) medium BE, and (3) high BE. H(+) concentration was calculated according to their standard formula and BE was calculated according to the Van Slyke equation. RESULTS: The overall mortality rate was 24.9%. The group mortality rates were 32, 17 and 25% in the low, medium and high BE groups, respectively (p = 0.001). When patients were divided into three groups according to the HCO(3)(-) levels, the group mortality rate was 59.1% in the low HCO(3)(-) group and 19.8% in the high HCO(3)(-) group. Based on univariate analysis, six factors affecting mortality were identified. However, multivariate analysis showed that the levels of serum HCO(3)(-) (p = 0.013; OR: 0.552; CI: 0.345-0.882) and creatinine (p = 0.019; OR: 2.114; CI: 1.132-3.949) had an independent effect. CONCLUSION: In patients with COPD exacerbation and hypercapnia, the development of sufficient metabolic compensation and adequate renal function significantly decreases mortality.

Diagnosis and treatment of simple acid-base disorders.

The ability to diagnose and treat acid-base disorders is an important component in the practice of the nutrition support clinician. A complete understanding of the basic principles of metabolic and respiratory disorders allows the practitioner to formulate educated decisions regarding fluids, parenteral nutrition salts, and the management of electrolytes. This review will discuss the diagnosis and treatment of common metabolic and respiratory disorders encountered in nutrition support practice.

Delivery dependence of early proximal bicarbonate reabsorption in the rat in respiratory acidosis and alkalosis.

In the intact rat kidney, bicarbonate reabsorption in the early proximal tubule (EP) is strongly dependent on delivery. Independent of delivery, metabolic acidosis stimulates EP bicarbonate reabsorption. In this study, we investigated whether systemic pH changes induced by acute or chronic respiratory acid-base disorders also affect EP HCO3- reabsorption, independent of delivery (FLHCO3, filtered load of bicarbonate). Hypercapnia was induced in rats acutely (1-3 h) and chronically (4-5 d) by increasing inspired PCO2. Hypocapnia was induced acutely (1-3 h) by mechanical hyperventilation, and chronically (4-5 d) using hypoxemia to stimulate ventilation. When compared with normocapneic rats with similar FLHCO3, no stimulation of EP or overall proximal HCO3 reabsorption was found with either acute hypercapnia (PaCO2 = 74 mmHg, pH = 7.23) or chronic hypercapnia (PaCO2 = 84 mmHg, pH = 7.31). Acute hypocapnia (PaCO2 = 29 mmHg, pH = 7.56) did not suppress EP or overall HCO3 reabsorption. Chronic hypocapnia (PaCO2 = 26 mmHg, pH = 7.54) reduced proximal HCO3 reabsorption, but this effect was reversed when FLHCO3 was increased to levels comparable to euvolemic normocapneic rats. Thus, when delivery is accounted for, we could find no additional stimulation of proximal bicarbonate reabsorption in respiratory acidosis and, except at low delivery rates, no reduction in bicarbonate reabsorption in respiratory alkalosis.

Regulation of net bicarbonate transport in rabbit cortical collecting tubule by peritubular pH, carbon dioxide tension, and bicarbonate concentration.

The effects of changes in peritubular pH, carbon dioxide tension (PCO2), and HCO3- concentration on net HCO3- transport was examined in in vitro perfused cortical collecting tubules (CCTs) from unpretreated New Zealand white rabbits. Lowering peritubular HCO3- concentration and pH by reciprocal replacement of HCO3- with Cl-, significantly stimulated net HCO3- absorption. Lowering peritubular HCO3- concentration and pH, by substitution of HCO3- with gluconate, while keeping Cl- concentration constant, also stimulated net HCO3- absorption. Raising peritubular HCO3- concentration and pH, by reciprocal replacement of Cl- with HCO3-, inhibited net HCO3- absorption (or stimulated net HCO3- secretion). When the tubule was cooled, raising peritubular HCO3- concentration had no effect on net HCO3- transport, suggesting these results are not due to the passive flux of HCO3- down its concentration gradient. The effect of changes in ambient PCO2 on net HCO3- transport were also studied. Increasing the ambient PCO2 from 40 mmHg to either 80 or 120 mmHg, allowing pH to fall, had no effect on net HCO3- transport. Similarly, lowering ambient PCO2 to 14 mmHg had no effect on net HCO3- transport. Simultaneously increasing peritubular HCO3- concentration and PCO2, without accompanying changes in peritubular pH, i.e., isohydric changes, stimulated net HCO3- secretion to the same degree as nonisohydric increases in peritubular HCO3- concentration. Likewise, isohydric lowering of peritubular HCO3- concentration and PCO2 stimulated net HCO3- absorption. We conclude that: acute changes in peritubular HCO3- concentration regulate acidification in the CCT and these effects are mediated by a transcellular process; acute changes in ambient PCO2 within the physiologic range have no effect on HCO3- transport in the in vitro perfused CCT; and acute in vitro regulation of CCT acidification is independent of peritubular pH.

The relationships between arterial oxygen flow rate, oxygen binding by hemoglobin, and oxygen utilization after myocardial infarction.

The interrelationships of arterial oxygen flow rate index, oxygen binding by hemoglobin, and oxygen consumption have been examined in patients with acute myocardial infarction. Proportional extraction of oxygen increased in close association with decreasing oxygen flow rate, and hence, whole body oxygen consumption was constant over nearly a three-fold variation in arterial oxygen flow rate. A reduction in hemoglobin-oxygen affinity at in vivo conditions of pH. Pco(2) and temperature also occurred in proportion to the reduction in arterial oxygen flow rate. Therefore, the increased proportional removal of oxygen from arterial blood at low oxygen flow rates, required to maintain oxygen consumption, may have been facilitated by the reduced affinity of hemoglobin for oxygen at in vivo conditions. However, the decrease in affinity did not appear to explain more than 30-40% of the increased extraction. Respiratory alkalosis was a frequent occurrence in these patients and 2,3-diphosphoglycerate was positively associated with blood pH as well as with the time-averaged proportion of deoxyhemoglobin in arterial and venous blood.Hemoglobin-oxygen affinity measured at standard conditions and the mixed venous oxygen saturation were equally good indicators of reduced arterial oxygen flow rate in patients without shock. However, Svo(2) is more easily measured and is a more useful indicator of reduced oxygen flow rate, since its relationship to oxygen flow appears to be independent of affinity changes and time.

Influence of steady-state alterations in acid-base equilibrium on the fate of administered bicarbonate in the dog.

Previous workers have shown that metabolic acidosis increases the apparent space through which administered bicarbonate is distributed. This finding has been ascribed to the accompanying acidemia and to the consequent availability of a large quantity of hydrogen ion that accumulates on nonbicarbonate tissue buffers during the development of acidosis. To test this hypothesis, bicarbonate space was measured in dogs with a broad range of steady-state plasma [HCO-3] in association with alkalemia as well as with acidemia. Appropriate combinations of pH and plasma [HCO-3] were achieved by pretreating the animals to produce graded degrees of each of the four cardinal, chronic acid-base disorders. Metabolic acidosis (n = 15) was produced by prolonged HCl-feeding; metabolic alkalosis (n = 17) by diuretics and a chloride-free diet; and respiratory acidosis (n = 9) and alkalosis (n = 8) by means of an environmental chamber. Animals with normal acid-base status (n = 4) were also studied. Sodium bicarbonate (5 mmol/kg) was infused over 10 min to the unanesthetized animals; observations were carried out over 90 min. The results obtained from animals with metabolic acid-base disturbances demonstrated an inverse relationship between bicarbonate space and initial plasma pH, confirming the previous findings of others. By contrast, the results obtained in animals with respiratory acid-base disturbances demonstrated a direct relationship between bicarbonate space and initial plasma pH. The pooled data revealed that bicarbonate space is, in fact, quite independent of the initial pH but is highly correlated with the initial level of extracellular [HCO-3]; dogs with low extracellular [HCO-3] (congruent to 10 meq/liter) whether acidemic or alkalemic, have a bicarbonate space that is 25% larger than normal and some 50% larger than in dogs with high extracellular [HCO-3] (congruent to 50 meq/liter). We conclude from these results that the increased bicarbonate space in metabolic acidosis (and respiratory alkalosis) does not reflect the availability of more hydrogen ions for release during bicarbonate administration, but merely evidences the wider range of titration (delta pH) of nonbicarbonate buffers that occurs during alkali loading whenever plasma [HCO-3] is low.

Respiratory alkalosis may impair the production of vitamin D and lead to significant morbidity, including the fibromyalgia syndrome.

Hyperventilation caused by physical and/or psychological stress may lead to significant respiratory alkalosis and an elevated systemic pH. The alkalotic pH may in turn suppress the normal renal release of phosphate into the urine, thereby interrupting the endogenous production of 1,25-dihydroxyvitamin D (calcitriol). This could cause a shortfall in its normal production, leading to a variety of adverse consequences. It might partially explain the pathogenesis of acute mountain sickness, a treatable disease characterized by severe hyperventilation secondary to the hypoxia of high altitude exposure. Milder degrees of hyperventilation due to different forms of stress may produce other conditions which share characteristics with acute mountain sickness. One of these may be the fibromyalgia syndrome, a chronic painful disorder for which no satisfactory treatment exists. Should fibromyalgia and acute mountain sickness have a common etiology, may they also share a common form of treatment? Evidence is presented to support this hypothesis.

Interrelationships among hypoxia-inducible factor biology and acid-base equilibrium.

In this article, we try to summarize the most important novel biological information on the complex interrelationships between acid-base alterations and hypoxia-inducible factor (HIF) signaling. Extracellular and intracellular acid-base alterations affect HIF signaling in part independently of hypoxia, and involve, among others, effects on cytoprotection and apoptosis. Conversely, HIF signaling may affect systemic and local acid production rates and has been implicated in the mechanism of the acute hyperventilatory response (ie, respiratory alkalosis) in response to hypoxia as well as for hypoxia-induced pulmonary artery hypertension (PAH), although the latter data are quite preliminary and can be explained by alternative mechanisms. Thus, this review calls attention to these relationships for renal physiologists and nephrologists to stimulate focused clinical observations and specific investigative efforts as proposed in this overview.

TRPV1 deletion exacerbates hyperthermic seizures in an age-dependent manner in mice.

Febrile seizures (FS) are the most common seizure disorder to affect children. Although there is mounting evidence to support that FS occur when children have fever-induced hyperventilation leading to respiratory alkalosis, the underlying mechanisms of hyperthermia-induced hyperventilation and links to FS remain poorly understood. As transient receptor potential vanilloid-1 (TRPV1) receptors are heat-sensitive, play an important role in adult thermoregulation and modulate respiratory chemoreceptors, we hypothesize that TRPV1 activation is important for hyperthermia-induced hyperventilation leading to respiratory alkalosis and decreased FS thresholds, and consequently, TRPV1 KO mice will be relatively protected from hyperthermic seizures. To test our hypothesis we subjected postnatal (P) day 8-20 TRPV1 KO and C57BL/6 control mice to heated dry air. Seizure threshold temperature, latency and the rate of rise of body temperature during hyperthermia were assessed. At ages where differences in seizure thresholds were identified, head-out plethysmography was used to assess breathing and the rate of expired CO2 in response to hyperthermia, to determine if the changes in seizure thresholds were related to respiratory alkalosis. Paradoxically, we observed a pro-convulsant effect of TRPV1 deletion (∼4min decrease in seizure latency), and increased ventilation in response to hyperthermia in TRPV1 KO compared to control mice at P20. This pro-convulsant effect of TRPV1 absence was not associated with an increased rate of expired CO2, however, these mice had a more rapid rise in body temperature following exposure to hyperthermia than controls, and the expected linear relationship between body weight and seizure latency was absent. Based on these findings, we conclude that deletion of the TRPV1 receptor prevents reduction in hyperthermic seizure susceptibility in older mouse pups, via a mechanism that is independent of hyperthermia-induced respiratory alkalosis, but possibly involves impaired development of thermoregulatory mechanisms, although at present the mechanism remain unknown.

Gymnocypris przewalskii decreases cytosolic carbonic anhydrase expression to compensate for respiratory alkalosis and osmoregulation in the saline-alkaline lake Qinghai.

Naked carp (Gymnocypris przewalskii), endemic to the saline-alkaline Lake Qinghai, have the capacity to tolerate combined high salinity and alkalinity, but migrate to spawn in freshwater rivers each year. In this study, the full-length cDNA of the cytosolic carbonic anhydrase c isoform of G. przewalskii (GpCAc) was amplified and sequenced; mRNA levels and enzyme activity of GpCAc and blood chemistry were evaluated to understand the compensatory responses as the naked carp returned to the saline-alkaline lake after spawning. We found that GpCAc had a total length of 1400 bp and encodes a peptide of 260 amino acids. Comparison of the deduced amino acid sequences and phylogenetic analysis showed that GpCAc was a member of the cytosolic carbonic anhydrase II-like c family. Cytosolic-carbonic-anhydrase-c-specific primers were used to analyze the tissue distribution of GpCAc mRNA expression. Expression of GpCAc mRNA was found in brain, gill, liver, kidney, gut, and muscle tissues, but primarily in the gill and posterior kidney; however, none was evident in red blood cells. Transferring fish from river water to lake water resulted in a respiratory alkalosis, osmolality, and ion rise in the blood, as well as significant decreases in the expression and enzyme activity of GpCAc in both the gill and kidney within 96 h. These results indicate that GpCAc may play an important role in the acclimation to both high salinity and carbonate alkalinity. Specifically, G. przewalskii decreases cytosolic carbonic anhydrase c expression to compensate for a respiratory alkalosis and to aid in osmoregulation during the transition from river to saline-alkaline lake.

Pulmonary blood transit time and impaired arterial oxygenation in patients with chronic liver disease.

BACKGROUND: Contrast-enhanced echocardiography (CEE) using agitated saline can detect intrapulmonary vasodilatation (IPVD) in patients with hepatopulmonary syndrome (HPS). We estimated the pulmonary transit time of erythrocytes (PTT) by CEE, using microbubbles, and studied its relationship to arterial oxygenation in chronic liver disease. METHODS: Sixteen patients with chronic liver disease and seven healthy subjects were studied. PTT was defined as the time between opacification of the right atrium and left atrium on CEE, using human serum albumin-air microbubble complexes with a mean diameter of 4 microm (Albunex). IPVD was detected by CEE with agitated saline. Arterial blood gases were analyzed with patients in the supine position, and while they were seated. Cardiac output (CO) was determined by Doppler echocardiography. RESULTS: The mean PTT value for all of the patients was 4.0 +/- 1.4 s. One of the 3 patients who showed IPVD was normoxemic. Mild orthodeoxia was observed in the patients with abnormal alveolar-arterial oxygen difference (A-aDO2) values (>15 mmHg), but not in those with normal A-aDO2 values, or in the healthy subjects. PTT was correlated with PaO2 (r = 0.52; P < 0.05; n = 16) and A-aDO2 (r = -0.54; P < 0.05; n = 16) in the seated position. CO was significantly correlated with PTT (r = -0.62; P < 0.05; n = 15), but not with PaO2 and A-aDO2, in both positions. CONCLUSIONS: PTT may be a useful parameter for evaluating arterial oxygenation in patients with chronic liver disease with early HPS.