Tonometry is a minimally invasive method for estimating gastrointestinal intramural pH (pHi). Tissue pH is calculated by using the Henderson-Hasselbalch equation and measurements of arterial [HCO-3] and CO2 tension (PCO3) of saline contained in a Silastic balloon within the lumen of the gut. The validity of the method rests on two key assumptions: 1) PCO2 in saline in the tonometer balloon is similar to tissue PCO2 and 2) tissue and arterial [HCO-3] are similar. To validate this method, ileal pHi measured directly with a microelectrode was compared with pHi estimated tonometrically in four groups of anesthetized pigs. Group I (n = 4) were controls. In group II (n = 4), intestinal tissue acidosis was induced by total occlusion of the superior mesenteric artery (SMA). In group III (n = 5), acidosis was induced by partial occlusion of the SMA. In group IV (n = 4), tissue acidosis was induced by endotoxemia. Agreement was excellent between direct and tonometric measurements in groups I and IV and less good in groups II and III. Weighted mean correlation coefficients (rw) for the two measurement methods were 0.743 and 0.9447 in groups II and IV, respectively. Correlation coefficients for the individual animals in group III were more variable than the other groups and ranged from 0.547 to 0.990. The tonometric method for measuring GI pHi is invalid under conditions of zero flow and leads to error under conditions of low flow. However, the method is reliable in the setting of tissue acidosis induced by endotoxemia.
The effect of two chemically dissimilar cyclooxygenase inhibitors was studied in pentobarbital-anesthetized endotoxic pigs. Animals in groups II-IV were infused with Escherichia coli lipopolysaccharide (LPS, 150 micrograms/kg) and resuscitated with normal saline (1.2 ml.kg-1.min-1). Animals in group I (n = 4) were resuscitated as above but were not infused with LPS. Animals in group II (n = 7) served as endotoxic controls. Pigs in groups III (n = 6) and IV (n = 5) were pre- and posttreated with ibuprofen (10 mg/kg bolus then 10 mg.kg-1.h-1 and meclofenamate (5 mg/kg then 5 mg.kg-1.h-1, respectively. Ileal intramucosal hydrogen ion concentration [( H+]) was estimated tonometrically. In group I, cardiac index (CI), mean arterial pressure (MAP), superior mesenteric arterial perfusion (QSMA), and mesenteric O2 delivery (DO2) increased significantly, but other variables were unchanged. After infusion of LPS in group II, MAP and systemic vascular resistance index were markedly diminished but CI was well preserved. In this group, QSMA, systemic DO2, and mesenteric DO2 decreased, whereas systemic O2 uptake (VO2) and gut [H+] increased; mesenteric VO2 was unchanged. Compared with pigs in group II, pigs treated with ibuprofen or meclofenamate manifested improved systemic and mesenteric DO2. In groups III and IV, QSMA remained normal, increased systemic VO2 was not observed, and gut intramucosal acidosis was ameliorated. Increased intramucosal [H+] in group II suggests that QSMA was inadequate. The salutary effects of ibuprofen and meclofenamate suggest that inadequate mesenteric perfusion was mediated, at least in part, by cyclooxygenase-derived metabolites or arachidonic acid.
Infusing pigs with lipopolysaccharide (LPS) decreases superior mesenteric artery blood flow (Qsma), suggesting that mesenteric hypoperfusion may be responsible for LPS-induced alterations in gut mucosal permeability. To test this hypothesis, we studied four groups of anesthetized swine. Group 1 animals (N = 6) were infused with LPS (250 micrograms/kg over 1 hour beginning at 60 minutes) and continuously resuscitated with Ringer's lactate (48 mL/kg per hour). In group 2 (N = 5), Qsma was decreased by 50% by means of a mechanical occluder to mimic the LPS-induced alterations in Qsma observed in group I. Group 3 (N = 5) was included to document our ability to detect ischemia/reperfusion-induced alterations in mucosal permeability; in these pigs, Qsma was decreased in steps to zero flow (at 150 to 210 minutes) and then perfusion was restored (at 210 to 270 minutes). Pigs in group 4 (N = 6) served as normal controls; these animals were resuscitated with Ringer's lactate at the same rate as in group 1 but were not infused with LPS. To assess mucosal permeability, we measured plasma-to-lumen clearances for two markers, chromium 51-labeled edetic acid monohydrate (EDTA) and urea. Loading and maintenance infusions of the markers were given intravenously, and a 20-cm isolated segment of small intestine was continuously perfused at 2 mL/min with Ringer's lactate at 37 degrees C. Results were expressed as the ratio of the clearances for the two probes (CEDTA/CUREA). In group 3, CEDTA/CUREA was 999% +/- 355% of baseline at 270 minutes. In group 1, CEDTA/CUREA was 572% +/- 235% of baseline at 270 minutes. In groups 2 and 4, however, CEDTA/CUREA did not change significantly from the baseline value over the duration of the study. These data suggest that increased mucosal permeability after LPS is due to factors other than (or in addition to) mesenteric hypoperfusion.
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