ABSTRACT
Obstructive jaundice was produced in 11 dogs by common bile duct ligation for 4 weeks, then biliary decompression was performed by bilioenteric anastomosis. Animals were regularly studied over the 2 months after decompression by the following methods: (1) serum biochemistry was monitored; (2) light microscopic changes in serial liver biopsies were graded; (3) the respiratory characteristics of isolated hepatic mitochondria, obtained by open liver biopsy, were studied using an oxygen micro-electrode system; (4) in vivo handling of an hepatobiliary imaging agent (diisopropyl iminodiacetic acid) was studied by dynamic liver scintiscanning. None of these liver assessments were normalized after 7 to 10 days of biliary decompression. Our study suggests that biliary decompression of patients with extrahepatic biliary obstruction requires long periods of time to enable major recovery of the abnormal liver function induced by biliary obstruction.
Subject(s)
Cholestasis/surgery , Liver/metabolism , Anastomosis, Surgical , Animals , Cholestasis/diagnostic imaging , Cholestasis/metabolism , Cholestasis/pathology , Dogs , Female , Gallbladder/surgery , Jejunum/surgery , Liver/diagnostic imaging , Liver/pathology , Mitochondria, Liver/metabolism , Oxygen Consumption , Radionuclide ImagingABSTRACT
Peritoneal fluid may be the source of multi-system failure during the initial stages of acute pancreatitis. The toxicity of human pancreatic ascitic fluid (HPAF) collected under sterile conditions from 12 patients with acute pancreatitis was investigated with the use of an in vitro preparation of mitochondria. Hepatocyte mitochondria from Sprague-Dawley rats were prepared by standard techniques. Mitochondrial oxidative activity was determined in glutamate-malate medium, with micromodification of the YSI Model 53 (Yellow Springs, Ohio) oxygen electrode system. The oxygen uptake of 150 to 200 microliter samples of mitochondria suspension (20 to 25 mg/ml) was monitored for 3 minutes, after which 3 microliter of 0.1 M adenosine diphosphate (ADP) was added to the chamber to induce state 3 respiration. Two minutes after the oxygen trace returned to state 4 respirations, 20, 40, or 80 microliter of the HPAF sample was introduced into the reaction vessel and the oxygen measurement continued for an additional 3 minutes. After this, 3 microliter of 0.1 M ADP again was added to the reaction chamber and the oxygen measurement continued. Control runs were made with reconstituted pooled human serum used in place of the HPAF samples. A significant (p less than 0.05) increase in state 4 respiration occurred in all 12 samples of HPAF. Addition of ADP showed a significant decline (p less than 0.05) in respiratory control ratio in all specimens. A dose-response curve was observed in 8 of 12 HPAF samples tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Ascitic Fluid/metabolism , Mitochondria, Liver/metabolism , Pancreatitis/metabolism , Acute Disease , Adenosine Diphosphate/metabolism , Adenosine Triphosphate/metabolism , Animals , Female , Humans , Oxygen Consumption , Rats , Rats, Inbred StrainsABSTRACT
In order to quantitate possible time-related changes in the viability of rat hypothalamic tissue slices, tissue oxygen consumption was measured after incubation periods ranging from 0-4 hours. There were no significant differences in mean tissue oxygen consumption between the various incubation periods; nor was there any trend indicating that oxygen consumption gradually decreases over time. Moreover, no regional differences were observed among the various rostral hypothalamic slices. One obvious trend, however, was that during the first two hours of each experiment, tissue oxygen consumption decreased briefly and then returned to normal higher levels. The exact occurrence of this transitory decrease varied from experiment to experiment; but the subsequent recovery in oxygen consumption was always complete by two hours of incubation. This initial transient decrease in tissue oxygen consumption may reflect the initial period of electrophysiological inactivity reported in several in vitro studies.
Subject(s)
Hypothalamus, Anterior/metabolism , Oxygen Consumption , Animals , In Vitro Techniques , Male , Preoptic Area/metabolism , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
Acute hemorrhagic pancreatitis (AHP) involves multiple organ failure probably caused by the toxic factor(s) released in pancreatitis-associated ascitic fluid (PAAF). We found that PAAF interferes with hepatic mitochondrial respiration resulting in severe disturbances in respiratory control (RCR) and ADP/O ratios. Pancreatitis was induced in dogs by retrograde pancreatic duct infusion and the resultant PAAF was centrifuged, filtered, and frozen until used. Two human PAAFs collected from AHP patients were treated in a similar manner. Rat liver mitochondrial oxygen uptake was measured at 30 degrees C before and after addition of ADP and PAAF. Paired control runs were made using pooled heat-inactivated dog serum. Tests with nine canine PAAFs showed a mean increase of 120% in state 4 respiration (P less than 0.0001). After exposure to PAAF, addition of ADP to previously coupled mitochondria did not induce state 3 respiration. The human PAAFs both showed significant increases in state 4 respiration (P less than 0.01) and a marked decrease in RCR. Dose-response tests with human and canine PAAFs showed a positive correlation between percentage increase in state 4 respiration and the concentration of PAAF used. These results confirm the presence in PAAF of mitotoxic substance(s) which cause irreversible mitochondrial damage. Inhibition of coupled mitochondrial respiration by PAAF with the resultant fall in ATP may be the causative agent for the tissue and organ damage observed in AHP.
Subject(s)
Ascites/physiopathology , Mitochondria, Liver/physiology , Pancreatitis/physiopathology , Animals , Dogs , Hydrogen-Ion Concentration , Oxidative Phosphorylation , Oxygen Consumption , Pancreatitis/complications , Toxins, BiologicalSubject(s)
Liver/metabolism , Oxygen Consumption , Pancreatitis/physiopathology , Animals , Ascites/physiopathology , Dogs , Female , Humans , Rats , Rats, Inbred Strains , Trypsin/metabolismSubject(s)
Oxygen/analysis , Polarography , Animals , Catalase/analysis , Computers , Electrodes , Enzymes, Immobilized , Glucose/analysis , Glucose Oxidase , Hydrogen Peroxide , Mitochondria/metabolism , Oxidoreductases , Oxygen Consumption , Partial Pressure , Polarography/instrumentation , Polarography/methods , Solubility , Solutions , Spectrophotometry , TemperatureABSTRACT
When a free-standing emergency clinic (FEC) unexpectedly opened in Montgomery County, Maryland, the local emergency medical services council thought the FEC's operational plan was in conflict with the community concept of emergency medical services (EMS). Because there were no agreed upon factual guidelines with which to judge the FEC, the council established a task force to study the problem and to develop standards and guidelines. This article is based on that report. We recommend that if a facility physically separate from a hospital uses the words "emergency" in offering medical services, it means at least 24 hours of operation with standards at least equal to those offered by the local EMS system.