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J B Antonsson

Publications and source records attributed to J B Antonsson.

10 recordsLinked to original sources
PubMed1995

Changes in gut intramucosal pH and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage.

OBJECTIVE: To establish the relationship between gut intramucosal pH and blood flow to the gut, gut oxygen delivery, and gut oxygen extraction ratio in a porcine model of peritonitis and hemorrhage. DESIGN: Prospective, controlled study. SETTING: Experimental laboratory in a university teaching hospital. SUBJECTS: Thirty pigs of both sexes, weighing 15 to 22 kg. INTERVENTIONS: Animals were anesthetized, intubated, and mechanically ventilated. A flow probe was placed around the superior mesenteric artery for registration of blood flow. A tonometer was placed in the lumen of midileum for calculation of gut intramucosal pH. Hourly, for 5 hrs, blood samples were taken from mixed venous, mesenteric venous, and arterial blood. Five animals served as controls, ten animals had peritonitis induced by fecal instillation in the abdominal cavity, five were bled stepwise, five were bled rapidly (to a mean arterial pressure of 30 mm Hg), and five were bled rapidly and reinfused after 3 hrs. MEASUREMENTS AND MAIN RESULTS: Both peritonitis and hemorrhage caused decreases in gut blood flow and intramucosal pH. In mild peritonitis, the intramucosal pH decrease preceded that of blood flow. In all experimental groups, oxygen delivery decreased over time; in both mild and severe peritonitis, this decrease was preceded by a decrease of intramucosal pH. Intramucosal pH correlated well with gut oxygen extraction ratio in peritonitis (r2 = .86). In hemorrhage, there was a correlation of r2 = .66, but in intramucosal pH of < 7.12, a further decrease was accompanied only by minor changes in extraction ratio. CONCLUSIONS: Since a reduction in blood flow was preceded by a decrease in intramucosal pH, low intramucosal pH in peritonitis cannot be explained by low flow alone. Gut oxygen delivery proved to be a poor indicator of gut acidosis (i.e., low intramucosal pH). In peritonitis, a decreasing intramucosal pH was associated with an increasing oxygen extraction ratio. In hemorrhage, this association had a sharp deflection point below which a further decrease in intramucosal pH occurred concomitantly with an unchanged gut oxygen extraction ratio. Increased extraction ratio was not sufficient, not even initially, to maintain aerobic metabolism (i.e., unchanged intramucosal pH).

Animals↗
PubMed1995

Gut intramucosal pH and intraluminal PO2 in a porcine model of peritonitis or haemorrhage.

The tonometric method of detecting decreased gut intramucosal pH (pHi) is based on the fact that carbon dioxide can diffuse through the wall of the silastic balloon of the tonometer. By using deoxified saline and measuring PO2 as well as PCO2 this study aimed to follow changes in mucosal PO2 and relate them to changes in pHi in peritonitis versus haemorrhage. Twenty five pigs were used. Five were controls, in 10 peritonitis was induced by the instillation of faeces in the abdominal cavity, and 10 were bled, half of them stepwise during three hours, and half of them rapidly down to a mean (SEM) arterial pressure of 30 (10) mm Hg. The drop in pHi correlated well with decreasing intraluminal PO2 (r = 0.63 (0.13)) in haemorrhage. In peritonitis this drop occurred within a very limited change in intraluminal PO2 (r = 0.06 (0.17)). Thus oxygen seemed to be present in the mucosa at the same time as there were signs of anaerobic metabolism as evidenced by a low intramucosal pH. Impaired oxygen extraction or utilisation, or both, is proposed as an explanation to this seemingly paradoxical situation.

Animals↗
PubMed1994

Gut perfusion in experimental shock.

The gut seems to play a very important role in the shock syndrome, since it is an organ that is early and profoundly affected by insufficient tissue perfusion. Once affected by inadequate oxygenation, the gut can also act as a "motor of shock" by the release of toxic mediators and through the translocation of bacteria and bacterial endotoxins. It thus would be of benefit to monitor the gut during shock, and this can be accomplished by tonometry, a method to calculate the intramucosal pH (pHi). As hypoxia results in anaerobic metabolism and accumulation of acid metabolites, tissue acidosis is a sign of insufficient oxygenation. However, recent experiments have shown that, in septic states, a decreased pHi cannot be explained by decreased regional blood flow alone.

Animals↗
PubMed1993

Subcutaneous and gut tissue perfusion and oxygenation changes as related to oxygen transport in experimental peritonitis.

Peritonitis and septic shock may lead to tissue hypoxia, but this risk is not identical in all organ systems. This study was undertaken to measure changes in tissue oxygenation and perfusion in the gut wall and subcutaneous tissue, respectively, and to examine their relation to oxygen delivery and consumption. Twelve pigs were anesthesized and mechanically ventilated. An ultrasonic flow probe was placed around the superior mesenteric artery for registration of blood flow. A mesenteric vein was cannulated for blood sampling. For calculation of gut intramural pH (pHi), a Silastic balloon (Tonomitor) was placed in the lumen of the midileum. pHi was calculated from tonometrically measured PCO2 and arterial bicarbonate concentration. The subcutaneous PO2 was measured by means of an oxygen-permeable Silastic tube implanted in the subcutis of the abdominal wall. Oxygen delivery (DO2) and consumption (VO2) were determined for the gut as well as for the whole body. In six randomly allocated animals, peritonitis was induced after a stabilization period of at least 1 hr, by instillation of autologous faeces into the abdominal cavity, while the other six animals served as controls. The animals were then followed for 5 hr. pHi remained stable in the control group, whereas a drop from 7.37 to 7.02 took place in the peritonitis group. In the test group, subcutaneous oxygen tension (PscO2) already began to fall 1 hr after the induction of peritonitis, and gained the minimum at the end of the study. In peritonitis, a moderate correlation was seen between pHi and DO2 (r = 0.51 +/- 0.16); no statistical difference was noted if pHi was correlated to gut DO2 (r = 0.56 +/- 0.18).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Increased intestinal permeability in endotoxic pigs. Mesenteric hypoperfusion as an etiologic factor.

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.

Acidosis↗
PubMed1991

Leukotriene C4 induces mesenteric hypoperfusion and intestinal intramural acidosis in pigs.

We examined the effect of intravenous infusion of graded doses of authentic leukotriene (LT) C4 on several physiological variables in pentobarbital-anesthetized immature swine. Mesenteric blood flow (Qsma) was measured using an ultrasonic flow probe and ileal intramucosal hydrogen ion concentration ([H+]I) was estimated tonometrically. Three groups were studied. Pigs in Group I (n = 6) were infused beginning at t = 0 min with increasing doses (0.03-1.0 microgram/kg-min) of LTC4, each dose being administered for 10 min. Pigs in Group II (n = 6) were infused with LTC4 as above, but were pre- and post-treated with a specific sulfidopeptide LT receptor antagonist, LY203647 (30 mg/kg bolus and then 10 mg/kg-hr) beginning at t = -20 min. Pigs in Group III (n = 4) received only normal saline (5 ml/kg-h). Infusing LTC4 significantly decreased Qsma and mesenteric oxygen uptake and significantly increased ileal [H+]I. These changes were prevented by LY203647. These data support the idea that sulfido-peptide LT are capable of causing mesenteric ischemia and that this phenomenon can be blocked by LY203647.

Acetophenones↗
PubMed1991

Delayed treatment with an LTD4/E4 antagonist limits pulmonary edema in endotoxic pigs.

We used a selective leukotriene (LT) D4/E4 receptor antagonist (LY 203647) to investigate the role of cysteinyl LTs as mediators of several important pathophysiological events in a porcine model of endotoxic shock. Pentobarbital-anesthetized pigs (11.8-17.5 kg) were mechanically ventilated with 100% O2. Pigs in groups I (n = 10), IIA (n = 10), and IIB (n = 5) were infused with Escherichia coli lipopolysaccharide (LPS; 250 micrograms/kg) from time (t) = 0-20 min. Pigs in group III (n = 3) were normal controls. All pigs were resuscitated from t = 0-240 min with Ringer lactate (0.8 ml.kg-1.min-1). Pigs in group I received no further treatment. At t = 30 min, groups IIA and IIB were injected with LY 203647 (30 mg/kg) and were started on an infusion of the compound at 10 (group IIA) or 30 mg.kg-1.h-1 (group IIB). Delayed treatment with LY 203647 significantly (P less than 0.05) and persistently ameliorated LPS-induced pulmonary hypertension. The compound also abrogated LPS-induced pulmonary edema, as assessed by gravimetrically determined lung extravascular wet-to-dry weight ratios. Despite its beneficial effect on pulmonary edema, delayed treatment with LY 203647 did not improve arterial oxygenation. Delayed treatment with LY 203647 transiently improved mesenteric perfusion. These data suggest that cysteinyl LTs are important mediators in porcine endotoxicosis.

Acetophenones↗
PubMed1991

Beneficial effects of LY203647, a novel leukotriene C4/D4 antagonist, on pulmonary function and mesenteric perfusion in a porcine model of endotoxic shock and ARDS.

The sulfidopeptide leukotrienes (LT) have been implicated as important pathophysiological mediators in septic shock. To further define the role of these compounds, we utilized a porcine endotoxicosis model to study the effects of pre- and concurrent treatment with LY203647, a novel LT receptor antagonist. Pentobarbital-anesthetized pigs (13-20 kg) were mechanically ventilated with 100% O2. Superior mesenteric arterial flow (Qsma) was measured using an ultrasonic flow probe. Ileal intramucosal hydrogen ion concentration, [H+]1, was estimated tonometrically. Pigs in groups I and II were infused with endotoxin (250 micrograms/kg) and resuscitated with saline (1.2 ml/kg min). Group I (n = 8) were controls; Group II (n = 8) were pretreated with LY203647 (30 mg/kg bolus, then 10 mg/kg h). Treatment with LY203647 persistently and significantly (P less than .05) improved post-LPS pO2 and transiently improved Qsma. Treatment with LY203647 did not affect [H+]1. Lung extravascular wet-to-dry weight ratios were 7.13 +/- .33 and 5.43 +/- .09 in groups I and II, respectively (P less than .001). These data suggest that sulfidopeptide LT are important mediators of key pathophysiologic events in this porcine model of endotoxic shock and the adult respiratory distress syndrome (ARDS).

Acetophenones↗
PubMed1990

Validation of tonometric measurement of gut intramural pH during endotoxemia and mesenteric occlusion in pigs.

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.

Animals↗