Luminal PCO2 Research Articles

The gaseous gastrointestinal tract of a seawater teleost, the English sole (Parophrys vetulus)

There has been considerable recent progress in understanding the respiratory physiology of the gastrointestinal tract (GIT) in teleosts, but the respiratory conditions inside the GIT remain largely unknown, particularly the luminal PCO2 and PO2 levels. The GIT of seawater teleosts is of special interest due to its additional function of water absorption linked to HCO3− secretion, a process that may raise luminal PCO2 levels. Direct measurements of GIT PCO2 and PO2 using micro-optodes in the English sole (Parophrys vetulus; anaesthetized, artificially ventilated, 10–12 °C) revealed extreme luminal gas levels. Luminal PCO2 was 14–17 mmHg in the stomach and intestinal segments of fasted sole, considerably higher than arterial blood levels of 5 mmHg. Moreover, feeding, which raised intestinal HCO3− concentration, also raised luminal PCO2 to 34–50 mmHg. All these values were higher than comparable measurements in freshwater teleosts, and also greater than environmental CO2 levels of concern in aquaculture or global change scenarios. The PCO2 values in subintestinal vein blood draining the GIT of fed fish (28 mmHg) suggested some degree of equilibration with high luminal PCO2, whereas subintestinal vein PO2 levels were relatively low (9 mmHg). All luminal sections of the GIT were virtually anoxic (PO2 ≤ 0.3 mmHg), in both fasted and fed animals, a novel finding in teleosts.

110 - Emerging adults – a challenge for an integrated psychosomatic approach

There has been considerable recent progress in understanding the respiratory physiology of the gastrointestinal tract (GIT) in teleosts, but the respiratory conditions inside the GIT remain largely unknown, particularly the luminal PCO2 and PO2 levels. The GIT of seawater teleosts is of special interest due to its additional function of water absorption linked to HCO3− secretion, a process that may raise luminal PCO2 levels. Direct measurements of GIT PCO2 and PO2 using micro-optodes in the English sole (Parophrys vetulus; anaesthetized, artificially ventilated, 10–12 °C) revealed extreme luminal gas levels. Luminal PCO2 was 14–17 mmHg in the stomach and intestinal segments of fasted sole, considerably higher than arterial blood levels of 5 mmHg. Moreover, feeding, which raised intestinal HCO3− concentration, also raised luminal PCO2 to 34–50 mmHg. All these values were higher than comparable measurements in freshwater teleosts, and also greater than environmental CO2 levels of concern in aquaculture or global change scenarios. The PCO2 values in subintestinal vein blood draining the GIT of fed fish (28 mmHg) suggested some degree of equilibration with high luminal PCO2, whereas subintestinal vein PO2 levels were relatively low (9 mmHg). All luminal sections of the GIT were virtually anoxic (PO2 ≤ 0.3 mmHg), in both fasted and fed animals, a novel finding in teleosts.

0597. The relation between intestinal intramucosal ph and stress hormones in pig hemorrhagic shock model

Measurements: Jejunal pHi was calculated by the luminal PCO2, obtained with a balloon tonometer, and arterial bicarbonate concentration. Arterial blood samples were taken for analysis of adrenaline (ADR), noradrenaline (NA), angiotensin II (Ang II) and arterial blood gas. SMV blood samples were taken for analysis of lactate/ pylvate acid (sma L/P), and blood gas (PsmvCO2). Results At shock phase, SMA flow decreased to 40% from the baseline (p < 0.01) and pHi decreased from 7.4 ± 0.2 to

Tonometry as a predictor of inadequate splanchnic perfusion in an intra-abdominal hypertension animal model

BackgroundThe gastrointestinal system is the most sensitive to the presence of intra-abdominal hypertension. We aimed to assess the early prognostic value of gastric air tonometry as a predictor of inadequate splanchnic perfusion and determine its relation with abdominal perfusion pressure (APP). MethodsTwenty-five Large White swine were used for this study. A control group and two study groups were included, in which intra-abdominal pressure (IAP) was elevated with Co2 to 20 and 30 mmHg during 5 h. We measured the intramucosal gastric pH (pHim) and determined gastric luminal PCO2 (PgCO2) and PgCO2gap (gastric luminal CO2–arterial CO2) to evaluate gastric acidity. APP was indirectly obtained through IAP and mean arterial pressure. Additionally, histopathologic samples of small intestine were obtained and analyzed. ResultspHim showed a decrease in IAP groups, with statistical significance in the 30 mmHg group, 90 min after stabilization period (P < 0.01). Serum lactate showed delayed alteration when compared with pHim, with significant increase, 180 min after stabilization (P < 0.05). The values of PgCO2 and PCO2gap were increased in IAP groups, being statistically significant in the 30 mmHg group, 120 and 150 min, respectively, after stabilization. In increased IAP groups, there was a time progressive decrease of APP, with statistically significant differences observed between groups at 20 min (P < 0.001). The histopathology study revealed parenchymal injury of the intestine at 30 mmHg. ConclusionsTonometry is sensitive to the increase in IAP and relates to the reduction of APP generated by splanchnic hypoperfusion.

Effects of inhibition of epithelial ion transport and carbonic anhydrase on CO 2 ‐induced intracellular acidification in mouse duodenal villous cells

Epithelial ion transporters and carbonic anhydrase (CA) participate in the regulation of intracellular pH (pHi) in duodenal villous cells. Luminal acid or elevated luminal pCO2 (CO2 stress) acidifies duodenal epithelial cells. The Na/H exchange-1 (NHE-1) inhibitor dimethyl amiloride (DMA) or the Na:HCO3− cotransport (NBC) inhibitor DIDS enhances cellular acidification, whereas the CA inhibitors methazolamide (MTZ) or benzolamide (BNZ) abrogates acidification. We examined the effects of these inhibitors on pHi under CO2 stress in mouse duodenum. Mouse duodenal villous cells were exposed and loaded with a pH-sensitive fluorescence dye BCECF, and pHi was measured with in vivo fluorescent microscope. Duodenal mucosa was exposed to high CO2 solution (pH 6.4, pCO2 260 Torr) with or without DMA (0.1 mM), DIDS (1 mM), MTZ (1 mM), BNZ (1 μM) or novel cell-impermeant CA inhibitor sulfonamide compounds. CO2−stress rapidly acidified the cells followed by pHi recovery to the baseline after CO2 removal. DMA enhanced CO2-induced pHi decrease, whereas DIDS and MTZ reduced the acidification. BNZ and the cell-impermeant CA inhibitors had no effect. The divergent effects of DMA and DIDS on pHi suggest that NHE-1 is more important than is NBC for pHi regulation. Compared with complete inhibition of CO2−induced acidification by MTZ or BNZ in rat duodenum, MTZ was less effective, and the impermeant CA inhibitors had no effect in mouse duodenum, consistent with a marked species difference between rat and mouse for pHi regulation by CA and by plasma membrane acid-base transporters.

Low carbon dioxide permeability of the apical epithelial membrane of guinea‐pig colon

We have investigated the apical membrane permeability for CO2 of intact epithelia of proximal and distal colon of the guinea pig. The method used was the mass spectrometric 18O-exchange technique previously described. In a first step, we determined the intraepithelial carbonic anhydrase (CA) activity by studying vital isolated colonocytes before and after lysis with Triton X-100. Intraepithelial CA activity was found to be 41,000 and 900 for proximal and distal colon, respectively. Then 18O-exchange measurements were done with stripped intact epithelial layers, which on their apical side were exposed to the reaction solution containing 18O-labelled CO2 and HCO3-. The mass spectrometric signals in these measurements are determined by the intracellular epithelial CA activity, and by the apical membrane permeabilities for CO2 and HCO3-, P(CO2) and P(HCO3). From the signals, we calculated the two permeabilities while inserting the CA activities obtained from isolated colonocytes. From layers of intact colon epithelium, the apical P(CO2) was determined to be 1.5 x 10(-3) cm s(-1) for proximal and 0.77 x 10(-3) cm s(-1) for distal colon. These values are > or =200 times lower than the P(CO2) of the human red cell membrane as studied with the same technique (0.3 cm s(-1)). We conclude that the apical membrane offers a significant resistance towards CO2 diffusion, which implies that a major drop in CO2 partial pressure (pCO2) will occur across the apical membrane when luminal pCO2 is higher than basolateral or capillary pCO2. In view of the very high pCO2 that can occur in the colonic lumen, this property of the apical membrane constitutes a significant protection of the cell against the high acid load associated with high pCO2.

Subcutaneous gas tensions closely track ileal mucosal gas tensions in a model of endotoxaemia without anaerobism

Few comparative data exist on the responses of the subcutaneous and splanchnic circulations to evolving endotoxic shock. We therefore compared continuous subcutaneous pO(2) (pO(2sc)) and pCO(2) (pCO(2sc)) with simultaneous continuous gut luminal pCO(2) (pCO(2gi)) in an animal model of endotoxaemia and examined whether changes in gas tensions track tissue energy charge (EC). Prospective observational study. Fourteen anaesthetized rats, 7 controls and 7 experimental. Controls were injected with saline, the experimental group with 20 mg/kg Klebsiella endotoxin. pCO(2sc), pO(2sc), and pCO(2gi) were measured continuously. Plasma lactate concentrations were measured at defined periods during the study. After 2 h ileal segments were snap frozen and assayed for tissue EC. Endotoxaemia resulted in a significant decrease in mean arterial blood pressure (132+/-9 to 71+/-20 mmHg) and pO(2sc) (71+/-23 to 33+/-22 torr) and a significant increase in pCO(2gi) (58+/-10 to 90+/-20 torr) and pCO(2sc) (56+/-6 to 81+/-25 torr). During endotoxaemia pCO(2gi) was directly correlated with pCO(2sc) (R (2)=0.5) and inversely correlated with pO(2sc) (R (2)=0.63). Plasma lactate concentrations were significantly elevated from baseline in the endotoxin limb. The mean EC was not significantly different in the two groups. Both subcutaneous tissue gas tensions and intestinal luminal carbon dioxide tensions are rapidly responsive during evolving hypodynamic endotoxic shock. Alterations in tissue gas tensions were not associated with dysoxia.

Gut mucosal damage during endotoxic shock is due to mechanisms other than gut ischemia.

Whether the gut alterations seen during sepsis are caused by microcirculatory hypoxia or disturbances in cellular metabolic pathways associated with mitochondrial respiration remains controversial. We hypothesized that hypoperfusion or hypoxia and local production of nitric oxide might play an important role in the development of gut mucosal injury during endotoxic shock and investigated their roles by using differing levels of fluid resuscitation and occlusion of the superior mesenteric artery (SMA). Anesthetized New Zealand rabbits were allocated to group I (sham, n = 8); group II [low-dose endotoxin (LPS, Escherichia coli-055:B5, 150 microg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group III [high-dose LPS (1 mg/kg)/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 8]; group IV [high-dose LPS (1 mg/kg)/hypovolemia (4 ml x kg-1 x h(-1) fluids); n = 8]; and group V [SMA ligation/fluid resuscitation (12 ml x kg(-1) x h(-1)); n = 4]. Luminal gut lactate concentrations and PCO2 gap increased in groups IV and V (P < 0.05), reflecting alterations in gut perfusion. Interestingly, significant histological alterations were observed in all LPS groups but not in group V. Blood and luminal gut nitrate/nitrite concentrations increased only in group IV. The mechanism of gut injury in endotoxic shock seems unrelated to hypoxia and release of nitric oxide. Gut dysfunction may occur as a result of so-called "cytopathic hypoxia."

Quantitative Assessment of Motility-Associated Changes in Gastric and Duodenal Luminal pH in Humans

Background: Interdigestive pain relieved by food is a common feature of ulcer disease. We tested the hypothesis that the duodenal bulb is intermittently acidified in association with phase III of the interdigestive motility cycle, and tried to quantify the balance between acid and duodenal bicarbonate secretion during this particular period. Methods: The experiments were performed in Helicobacter- negative healthy volunteers. Gastric and duodenal luminal pH was measured with a triple antimon electrode before, during, and after phase III of the migrating motor complex. Gastric acid secretion rate was measured in real time with a perfusion system and duodenal bicarbonate secretion was estimated from a continuous recording of the transmucosal potential difference (PD) in the duodenal bulb. Results: No significant changes in bulb pH occurred before, during, or after phase III. During the studied time window, the stomach produced 2.24 ± 0.55 mmol of acid at a peak pH of 1.74 ± 0.10. Basal HCO3 secretion calculated from bulb PD was 0.82 ± 0.12 mmol × 30 min−1 to which was added 0.47 ± 0.07 mmol of HCO3− during duodenal phase III. The contribution of retroperistalsis-driven HCO3− reflux was small (0.08 ± 0.02 mmol). Conclusions: Both the pH recording and the quantitative assessment of secretion rates show that in healthy subjects, fasting gastric acid production and duodenal bicarbonate secretion are of similar magnitude and dynamically coordinated. The mechanism behind the linkage may be reflex activation by motor activity, or a luminal PCO2 rise during phase III activity.

Transient mesenteric ischaemic episodes tracked by continuous jejunal PCO2 monitoring during liquid feeding.

To test the effect of liquid feeds on the responses to splanchnic ischaemia of a continuous rapid response PCO2 sensor inserted in the jejunum. Prospective experimental animal study in a university research laboratory. Adult male Wistar rats. Adult male Wistar rats (285-425 g) were anaesthetised with sodium pentobarbitone 60 mg/kg i.p. and ventilated with 100% oxygen and isoflurane via tracheostomy to a PaCO2 of 30-40 mmHg. A sensor was inserted into the mid-jejunum to record PCO2 every second. Distal aortic pressure was transduced. Four control rats received no feeds whilst in another four rats liquid feed was infused into the proximal jejunum at 3 ml/h. In each rat five episodes of splanchnic ischaemia were induced by 2-min elevations of an aortic sling to a mean distal aortic pressure of 30 mmHg. PCO2 elevations were always detectable, usually less than a minute from the onset of splanchnic ischaemia in both fed and unfed rats, with no difference in mean times to detectable response. In the fed rats there was a small but significant increase in the time to peak sensor response (196+/-16 vs. 180+/-12 s) and a trend towards an elevated mean baseline luminal PCO2 (67+/-9 vs. 55+/-4 mmHg). Brief episodes of splanchnic ischaemia were tracked successfully by a rapid response jejunal continuous PCO2 sensor during the infusion of a proprietary liquid feed preparation despite minor changes in PCO2 response characteristics and a possible elevation in baseline luminal PCO2.

Effects of motility on epithelial transport in the human descending duodenum.

The aim of the study was to determine how motility affects the balance between absorptive and secretory ion transport in the proximal human small intestine. Thirty-two healthy subjects and 16 patients (eight with villus atrophy, eight with normal duodenal biopsies) were studied. The absorptive sodium flux was estimated by measurement of bicarbonate absorption with a double-lumen perfusion technique. The secretory chloride flux was calculated from the ratio between the continuously recorded transmural potential difference (PD) and the epithelial parallel resistance, which was measured in forceps biopsies by square-wave current analysis. Graded variations in contraction frequency were obtained by recording during defined time periods before, during and after phase III of the migrating motor complex (MMC). Bicarbonate was absorbed by a process that led to CO2 formation, and both bicarbonate absorption and luminal PCO2 increased with contraction frequency. The motility-related PCO2 rise was reduced in patients with villus atrophy and by removal of bicarbonate from the perfusate. A higher motor activity was also associated with a larger PD (more lumen negative). Both the absorptive and the secretory fluxes were thus enhanced by motility. The estimated absorptive flux was approximately twice as large as the secretory flux during periods of low motor activity, and four times as large during submaximal motor activity. We conclude that motor activity affects both absorptive and secretory mucosal function in a quantifiable manner. Information about the behaviour of the respective linkage functions may make it possible to model the intestinal absorption process in vivo.

Gastric tonometry: where do we stand?

Gastric tonometry has proved to be a sensitive but not specific predictor of outcome in the critically ill. The data accumulated to date indicate that those patients able to achieve or maintain a normal gastric mucosal pH do better than those who do not. In addition, therapy aimed at improving an abnormal gastric mucosal pH has proved to be less successful. These findings may simply indicate that tonometry identifies those "responders" and "nonresponders," as becomes increasingly apparent in populations of critical care patients receiving interventional therapy. Gastric tonometry has undergone a number of methodologic changes over the last decade, seeing a switch from saline to automated gas tonometry. Along with this switch of methodology has come a deeper scrutiny of the indices used to assess gut perfusion. Most studies (including all the interventional ones) have used gastric mucosal pH. The newer indices of gut luminal PCO2 (PgCO2) referenced to arterial CO2 (PgCO2-PaCO2) or end tidal CO2 (PgCO2-PeCO2), although relatively well validated, remain to be proven as predictors of outcome or guides to interventional therapy. If we take a fresh look at the interventional trials in intensive care patients, there is a very definite trend toward benefit in the protocol groups, although they are generally reported as negative studies. There is much to be accomplished, however, before we accept the gastric tonometer as a routine tool with which to guide therapy based on gastrointestinal perfusion, including a greater understanding of gastrointestinal physiology and, as ever, the call for an adequately powered prospective randomized controlled trial to evaluate the clinical utility of gas tonometry.

Low gastric luminal pCO2 due to a malmanufactured tonometer catheter

Low gastric luminal pCO2 due to a malmanufactured tonometer catheter

Blood in the gastrointestinal tract delays and blunts the PCO2 response to transient mucosal ischaemia.

To determine whether the presence of blood in the gastrointestinal tract impairs the detection of splanchnic mucosal ischaemia by reducing the rate and magnitude of rise in gut luminal PCO2. Prospective observational study. University Research Laboratory. Four adult male Wistar rats with four controls from a concurrent study. Four adult male Wistar rats were anaesthetised with sodium pentobarbitone and ventilated with oxygen and isoflurane to an initial PaCO2 of 30-40 torr. Electrochemical-fiberoptic gas sensors inserted into silastic tubing placed in the ileal lumen measured luminal PCO2 at 1-s intervals. Distal aortic pressure was monitored continuously. Six 2-min episodes of aortic hypotension were induced in each rat to a mean pressure of 30 mmHg by intermittent elevation of a silk sling placed around the proximal aorta. Before the last three episodes in each rat 0.75-1.0 ml blood was injected into the ileal lumen via a 25-gauge needle. Four control rats from a concurrent experiment were treated in an identical fashion except that the rats were subjected to five ischaemic episodes, and there was no intraluminal injection of blood, although a 20-gauge cannula was placed in the proximal ileal lumen. The presence of blood in the lumen significantly decreased the ischaemic deltaPCO2 response from 33 +/- 8 to 15 +/- 4 torr (P < 0.001) and also significantly increased the peak response time from 188 +/- 12 to 227 +/- 24 s (P < 0.001). The corresponding measurements in the concurrent controls differed only from the values after blood injection in the experimental group. In this animal model the presence of intraluminal blood significantly delayed the rate and the amplitude of luminal PCO2 increases in response to transient ischaemia. This raises questions about the validity of luminal CO2 measurements as an indicator of splanchnic ischaemia in the presence of gastrointestinal haemorrhage.

Directly measured tissue pH is an earlier indicator of splanchnic acidosis than tonometric parameters during hemorrhagic shock in swine

To compare tissue pH in the stomach, bowel, and abdominal wall muscle during hemorrhagic shock and recovery using tissue electrodes; also, to compare tissue electrode pH measurements to gastric intramucosal pH (pHi), gastric luminal PCO2, and PCO2 gap (gastric luminal CO2--arterial CO2) measured with an air-equilibrated tonometer. Prospective animal study. University animal research laboratory. Eight anesthetized, mechanically ventilated Yorkshire swine. Hemorrhagic shock was initiated by withdrawing blood over a 15-min period to lower systolic blood pressure to 45 mm Hg. Shock was maintained for 45 mins and was followed by a 5-min resuscitation to normal blood pressure with a blood/lactated Ringer's (1:2) mixture. Recovery was monitored for 60 mins. pH was measured with electrodes in the submucosa of the stomach, the submucosa of the small bowel, and the abdominal wall muscle. Gastric luminal PCO2 was measured with an air-equilibrated tonometer and pHi and PCO2 gap were calculated. Each organ showed a different sensitivity to shock and resuscitation. The bowel pH responded most rapidly to the onset of hemorrhagic shock and had the largest change in tissue pH. The bowel also showed the most rapid recovery during resuscitation. The submucosal pH of the stomach responded more slowly than the bowel, but faster than the abdominal wall muscle pH, gastric PCO2 gap, or pHi. The smallest changes in organ pH as a result of hemorrhagic shock were seen in the abdominal wall muscle and the stomach as assessed by gastric tonometry. Direct measurement of tissue pH indicates that intra-abdominal organ pH varies during hemorrhagic shock. The small bowel pH changes the most in magnitude and rapidity compared with stomach pH or abdominal wall muscle pH. Tonometrically derived parameters were not as sensitive in the detection of tissue acidosis during shock and resuscitation as pH measured directly in the submucosa of the stomach or small bowel.

Subcutaneous oxygen tensions provide similar information to ileal luminal CO2 tensions in an animal model of haemorrhagic shock.

The cutaneous and splanchnic circulations undergo early vasoconstriction in shock. Methodological problems and insufficient information on subcutaneous carbon dioxide partial pressures limit the usefulness of previous studies on splanchnic and subcutaneous gas tensions in shock. Little comparative data exist on the responses of these tissues to shock and resuscitation. We therefore compared continuous subcutaneous PO2 (PO2sc) and PCO2 (PCO2sc) with simultaneous continuous gut luminal PCO2 (PCO2gi) in an animal model of haemorrhagic shock and resuscitation. Prospective observational study. Intensive care laboratory in a teaching hospital. Five anaesthetised rats. Electrochemical-fiberoptic gas sensors inserted into Silastic tubing placed in the subcutaneous tissue and in the ileal lumen measured PCO2sc, PO2sc and PCO2gi continuously in five anaesthetised rats. After steady state conditions, hypotension [mean arterial blood pressure (MAP) 40 mmHg] was induced by controlled haemorrhage. The rats were allowed to remain hypotensive for 15 min and then resuscitated with shed blood and crystalloids. Arterial plasma lactate concentrations were measured at defined periods during the study. Hypovolaemia resulted in a significant decrease in PO2sc (P < 0.01) and a significant increase in PCO2gi and PCO2sc (P < 0.05). These values returned to baseline with resuscitation. PO2sc appeared to respond to haemorrhage earlier than PCO2gi and PCO2sc (P = 0.02). PO2sc was inversely correlated with PCO2gi (r2 0.7, P < 0.001). There were no significant changes in arterial plasma lactate concentrations. In our rat model, subcutaneous oxygen tension provided similar information to ileal luminal PCO2 and was more rapidly responsive than subcutaneous carbon dioxide tensions and arterial lactate during evolving haemorrhagic shock and resuscitation.

Gastrointestinal luminal PCO2 tonometry: an update on physiology, methodology and clinical applications

Gastrointestinal luminal PCO2 tonometry: an update on physiology, methodology and clinical applications

Gastrointestinal PCO2 tonometry in 1998

Gastrointestinal luminal tonometry is a minimally invasive monitoring technique for critically ill patients. It is not widely accepted yet, possibly because of uncertainties with respect to physiologic background, methodology, and clinical usefulness. This review discusses recent developments, including automated air tonometry, that might render tonometry easier to apply by replacing the laborious and error-prone manual saline technique, the value of the blood-intragastric PCO2 gap versus the intramucosal pH, the need for gastric acid suppression during tonometry in the stomach, the sources of error for fluid PCO2 tonometry, and the luminal PCO2 in parts of the gastrointestinal tract other than the stomach. Finally, new clinical investigations are reviewed.

Enteral feed delays response times of a tissue PCO2 sensor

Real time assessment of gut luminal PCO2 is possible with rapidly responsive tissue CO2 sensors [1]. The impact of the presence of feeds in the gut on the rapidity of response of the sensor to a change in mucosal CO2 tension has not been evaluated.

Does enteral feeding potentially alter the PCO2 gap and pHi?

Measurement of pHi or the mucosal-arterial PCO2 gap is advocated to detect splanchnic ischaemia and covert shock. Nasogastric feeding may significantly affect these measurements. We used a previously described animal model [1] to evaluate the effect of enteral feeds on the luminal PCO2 response to intermittent splanchnic ischaemia.