PubMed Health⌕ Search

Biomedical subjects

L R Engelking

Publications and source records attributed to L R Engelking.

At least 37 records · Page 2Linked to original sources
PubMed1987

Antipyrine and lidocaine are cleared faster in horses than in humans: acetaminophen may be handled similarly.

The following studies were designed to evaluate plasma elimination kinetics of intravenously administered antipyrine, acetaminophen and lidocaine among 9 healthy adult horses and 9 healthy drug-free humans (3 each per drug group), in order to compare potential species differences in drug-metabolizing ability. Acetaminophen is largely biotransformed in humans by hepatic glucuronide and sulfate conjugation, whereas both antipyrine and lidocaine are oxidized by hepatic microsomal mixed-function oxidases. Thus, plasma clearances of these drugs are thought to reflect differences in hepatic oxidative and conjugative activity, and possibly hepatic blood flow in the case of lidocaine. Results showed that mean (+/- SD, n = 3) acetaminophen clearance was similar in both horses (4.84 +/- 0.637 ml/min/kg) and humans (4.68 +/- 0.691 ml/min/kg). However, antipyrine clearance was 10 times greater in horses (5.83 +/- 2.21 ml/min/kg) than in humans (0.536 +/- 0.110 ml/min/kg), which may reflect enhanced hepatic microsomal activity in horses. Although lidocaine clearance in humans was similar to estimated hepatic blood flow (20.6 +/- 5.81 ml/min/kg), clearance in horses was more than 2 times greater (52.0 +/- 11.7 ml/min/kg). The cause of the higher clearance of lidocaine in horses (like dogs) remains unexplained, and may involve significant metabolism of lidocaine at extrahepatic, extravascular sites, for intravascular degradation and renal excretion of intact lidocaine in horses was negligible. Although precise biochemical mechanisms underlying pharmacokinetic parameters for these drugs in horses were not determined, it is nonetheless concluded from antipyrine results that horses may have an enhanced ability (compared with humans) to clear drugs from the circulation that are primarily metabolized in the liver by phase I oxidative reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1985

Enhanced biliary bilirubin excretion after heparin-induced erythrocyte mass depletion.

The effect of large-dose heparin therapy on erythrocyte mass depletion in ponies was investigated to determine whether stimulation of reticuloendothelial cell activity and catabolic function would be evidenced by enhanced catabolism of heme to bilirubin. Ponies with chronic external biliary fistula were used to examine biliary excretion of bilirubin both before and after heparin loading (107 U/kg, IV, plus 320 U/kg, subcutaneously) and at maintenance dosages of 320 U/kg given (subcutaneously) at 12 and 24 hours after initial loading with heparin. Results indicated that by 48 hours after ponies were first treated with heparin, catabolism of heme increased, resulting in a 35% increase in plasma bilirubin concentration and a 65% enhancement in biliary bilirubin excretion. During this period, both hematocrit and blood hemoglobin concentrations decreased by 35%. After the last heparin treatment at 24 hours after initial heparin loading, all measured variables returned toward base line within 48 hours. These studies indicated that heparin augments phagocytosis of erythrocytes, resulting in enhanced plasma bilirubin concentration and biliary bilirubin excretion.

Animals↗
PubMed1985

Hepatobiliary transport of indocyanine green and sulfobromophthalein in fed and fasted horses.

Fasting is associated with unconjugated hyperbilirubinemia in several species, including the horse. Studies in ponies showed that a 3-day fast decreased plasma clearance of bilirubin, cholic acid, and sulfobromophthalein (BSP). Since these organic anions are conjugated with different substrates, it is possible that observed differences in plasma clearance result from a general decrease in hepatic conjugating capacity during the animals' fasting. To test this hypothesis, the effects of a 3-day fast on plasma clearance of IV injected BSP (4.4 to 5.1 mg/kg), which is conjugated to glutathione, and indocyanine green (ICG; 0.8 to 1.1 mg/kg), which is not conjugated, were studied in 10 healthy horses and 2 ponies with diverted enterohepatic circulations (indwelling T tubes). Blood samples were obtained for 30 minutes after injection, and bile samples from ponies were obtained for 3 hours. Fasting increased plasma bilirubin concentration in all animals studied (from 1.03 +/- 0.337 mg/dl in control animals to 3.49 +/- 1.01 mg/dl in fasted animals). Kinetic values of ICG disappearance were determined from single exponential functions, and those for BSP were determined from both single and curvilinear (2-exponential) functions. Plasma clearance of BSP in fed horses (8.65 +/- 1.02 ml X min-1 X kg-1) was greater than clearance of ICG (3.54 +/- 0.67 ml X min-1 X kg-1), results similar to those reported in dogs, cats, rats, and persons. Fasting significantly decreased fractional plasma disappearance rate of both BSP (-36%) and ICG (-58%) and similarly reduced plasma clearance (BSP,-48%; ICG,-55%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of plasma sample storage on blood ammonia, bilirubin, and urea nitrogen concentrations: cats and horses.

Ten horses, a pony, and 13 cats were used to evaluate base-line blood ammonia, bilirubin, and urea nitrogen concentrations and to determine The effects of prolonged cold storage (-20 degrees C) before assay. Base-line plasma ammonia concentrations in cats (0.992 +/- 0.083 [SE] micrograms/ml) did not change significantly after 48 hours of storage (0.871 +/- 0.073 micrograms/ml); however, they were increased 4.2- and 13-fold after 168 and 216 hours of storage, respectively. In contrast to base-line plasma-ammonia values in cats, those of horses were significantly (0.265 +/- 0.044 micrograms/ml) lower, and significantly increased from base-line values after 48 hours of storage (0.861 +/- 0.094 micrograms/ml) and continued to increase 25.6-fold at 168 hours and 18.4-fold at 216 hours. Plasma urea nitrogen concentrations in cats (25.8 +/- 1.06 mg/dl) and horses (11.2 +/- 0.749 mg/dl) did not change significantly during 168 hours of storage. Total plasma bilirubin values from both cats (0.19 +/- 0.049 mg/dl) and horses (0.75 +/- 0.064 mg/dl) also did not change significantly during storage. These results indicate that feline plasma samples for ammonia determinations may be stored at -20 degrees C for up to 48 hours, whereas equine plasma ammonia values tend to increase during that time. The reason for the increase remains unexplained. Both feline and equine plasma urea nitrogen and total bilirubin are stable for at least 168 hours of storage at -20 degrees C.

Ammonia↗
PubMed1984

Essential role of sodium and chloride for theophylline-induced choleresis in the isolated perfused rat liver.

Active secretion of electrolytes by hepatocytes is believed to be responsible for bile acid-independent canalicular bile flow (BAICF). Theophylline, which enhances BAICF, has been shown to enhance electrogenic Cl- secretion in a number of other epithelia. Such transport is dependent on Na+ and Cl-. Thus, the mechanism of theophylline choleresis may also involve stimulation of electrogenic Cl- secretion of the liver. This hypothesis was tested by studying the effect of ion substitution on theophylline choleresis in isolated perfused rat livers. Addition of theophylline (0.1 mmol) and dibutyryl cAMP (0.05 mmol) to 100 ml perfusate, in a single dose, increased bile flow and biliary secretion of Na+ and Cl- reversibly. These effects of theophylline were virtually abolished when perfusate Na+ (146 mM) was replaced by Li+ (146 mM) or choline+ (120 mM), and when Cl- (127 mM) was replaced by 120 mM NO-3, acetate- or isethionate-. Since even the permeable ions like Li+ and NO-3 could not substitute for Na+ and Cl-, these results show that the effect of theophylline on BAICF is specifically dependent on the presence of Na+ and Cl- in the perfusate. We propose, by analogy to other epithelia, that an electrogenic Cl- secretion mechanism is present in the liver. Theophylline, acting via cAMP, stimulates this transport process, thereby enhancing BAICF.

Animals↗
PubMed1984

Effects of halothane anesthesia on equine liver function.

Effects of halothane anesthesia were investigated in ponies prepared surgically with chronic external biliary fistulas (T tubes) to determine the effects on liver function and biliary excretion during 2 hours of anesthesia. Four studies were performed on 2 ponies, 2 to 6 months after surgery with the enterohepatic circulation held intact between studies. Intravenous bile acid infusion was used to maintain steady-state bile flow, bilirubin, and bile acid excretion during each study. Compared with the immediate 2-hour preanesthesia values (base line), halothane caused a 138% increase in bilirubin excretion, a 60% increase in biliary bilirubin concentration, and a 43% increase in PCV. Halothane anesthesia also caused a 16% reduction in plasma bilirubin, a 46% reduction in biliary bile acid concentration, and a 27% reduction in bile acid excretion. The bile acid independent fraction of bile flow appeared to increase. Plasma aspartate transaminase concentration did not change during anesthesia. The ratio of conjugated bilirubin fractions in bile [82% to 83% disconjugates of glucuronide and glucoside (2 forms) and 17% to 18% monoconjugates of glucoside, glucuronide, and xyloside] did not change during anesthesia and less than 1% was excreted unconjugated. Halothane anesthesia did not appear to affect adversely the activity of the transferase-conjugating enzymes in the presence of an increased bilirubin load. Seemingly, greatly increased conjugated bilirubin excretion observed during halothane anesthesia was most likely the result of a combination of increased hepatic clearance from plasma and increased hepatic bilirubin production from turnover of free hepatic heme or heme from the induced cytochrome P-450 system.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗
PubMed1984

Effects of isoflurane anesthesia on equine liver function.

The acute 2-hour effects of isoflurane anesthesia on liver function and biliary excretion were examined in 2 ponies prepared surgically with chronic external biliary fistulas (T-tubes). Studies were conducted 2 to 8 months postoperatively with the enterohepatic circulation held intact between studies. Bile acid infusion IV (8.1 to 8.8 mumol/min) helped maintain bile flow and bile acid and bilirubin excretion during complete biliary diversion throughout each study. Following 3-hour control periods, anesthesia was induced and maintained at 1.3 to 1.5 minimal alveolar concentration plus O2 (spontaneous breathing) for 2 hours. Compared with the immediate 2-hour preanesthesia values, isoflurane caused significant increases in PCV (27%) and biliary bilirubin excretion (24%). However, no significant differences were detected in plasma or biliary bilirubin concentrations, biliary bile acid concentration or excretion, bile flow, or plasma aspartate aminotransferase concentrations between preanesthesia control and anesthesia periods. The results indicate that although isoflurane anesthesia enhanced hepatic bilirubin excretion, its effects on hepatic bilirubin formation and/or clearance are modest, compared with effects of halothane anesthesia which have previously been shown to enhance equine bilirubin excretion by 138% and reduce bile acid excretion by 27%. Isoflurane anesthesia in ponies does not appear to affect hepatic bile acid transport or bile formation significantly.

Anesthesia, Inhalation↗
PubMed1982

Effect of glucose administration on equine fasting hyperbilirubinemia.

The effects of several treatments and their routes of administration on the reduction of hyperbilirubinemia in 9 pony mares after a 3-day fast were studied. Treatments were as follows: glucose given at doses of 1.2, 2.4, and 3.7 mg/min/kg of body weight; refeeding the base-line diet; feeding straw; and IV administration of taurocholic acid at a dosage of 0.07 mumol/min/kg. The 3 glucose dosages were each given by 3 different routes: IV, intraduodenal, and intragastric. The smallest dosage of glucose given by IV route reduced the plasma bilirubin concentration only 7%, even though other measured values associated with fasting returned toward their base line; increased free fatty acid concentration was reduced by 50%; plasma insulin increased above base-line values. Except for the smallest glucose dose given by IV route, the effects of the routes of administration (IV less than intraduodenal less than intragastric) and of the doses of glucose were not significantly different. Taurocholic acid (given IV) was ineffective in reducing the plasma fasting bilirubin concentration. Refeeding the base-line diet reduced the hyperbilirubinemia by 66% in 12 hours, which was a significantly greater reduction than the effect of all other treatments except the largest dose of glucose given by intragastric route. Feeding straw was less effective than refeeding, causing only about a 30% reduction.

Animal Feed↗
PubMed1980

Determination of the pool size and synthesis rate of bile acids by measurements in blood of patients with liver disease.

1. A simplified technique for the measurement of bile-acid pool size and synthesis rate has been developed in patients with liver disease. Isotope dilution studies in blood and bile were performed after intravenous injection of [24-14C]cholic acid with radioimmunoassay for the measurement of the bile-acid concentration. The interpolated pool sizes and synthesis rates, determined from results from both blood and bile, were not significantly different. The concentration of bile acids in the blood of healthy controls was not sufficiently elevated to permit application of this technique. 2. Three out of six patients with cirrhosis had a markedly reduced pool size compared with that of controls, whereas those with cholestasis had an unchanged pool size. The daily synthesis rate was reduced in both groups. Liver disease caused a redistribution (0.5-16%) of the bile-acid pool to the blood, which was associated with enhanced urinary excretion of cholic acid and its metabolites.

Adult↗
PubMed1980

Within-day fluctuations in serum bile-acid concentrations among normal control subjects and patients with hepatic disease.

Under carefully controlled conditions in a clinical research ward, conjugated primary bile-acid concentrations were measured by a 125I-radioimmunoassay every eight hours for four days in seven healthy control subjects and ten patients with hepatic disease (five with cirrhosis, three with primary biliary cirrhosis and two with sclerosing cholangitis). Two meals of approximately equal composition were consumed daily at 10 A.M. and 6 P.M., and blood was drawn at 4 A.M., 12 noon and 8 P.M.. With the exception of one patient, all subjects had greater postprandial than fasting serum bile-acid concentrations, with all healthy control subjects and most of those with hepatic disease showing evening values equal to or greater than the noon values. For the healthy control subjects, the mean values were 0.8, 1.4 and 1.9 microM, and for those with hepatic disease, 108, 140 and 133 microM. There were large fluctuations in serum bile acids (up to sevenfold) among patients with hepatic disease. These fluctuations were independently validated by finding corresponding changes in serum radioactivity derived from injection of a tracer (24-14C cholic acid) at the start of each study. To be consistent, especially for serial measurements, bile acids should be measured in blood taken at the same time of the day and at the same time relative to meals.

Analysis of Variance↗
PubMed1980

Direct measurement of biliary bilirubin excretion in ponies during fasting.

Biliary excretion of bilirubin, including the conjugate composition, was studied during feeding and during a 2.5-day fast of three pony mares with chronic external biliary (T-tube) fistulas. Fasting bilirubin excretion (1.96 +/- 0.74 microgram/min/kg of body weight), after establishing a new steady state, was not different from excretion during feeding (1.99 +/- 0.45 microgram/min/kg). Hyperbilirubinemia of fasting resulted from a reduced removal of plasma bilirubin rather than from an increased input of bilirubin into the plasma. Relative plasma excretion of the individual conjugate fractions of biliary bilirubin was not changed by fasting.

Animals↗
PubMed1980

Effect of dehydrocholic, chenodeoxycholic, and taurocholic acids on the excretion of bilirubin.

The effects of IV bile acid infusion (at approx 20% of normal excretion rate) on the biliary excretion of 3-alpha-hydroxy bile acids and bilirubin were investigated in ponies prepared surgically with chronic external biliary fistulas. Endogenous bile acid excretion (approx 45 mumol/min) decreased to the hepatic synthesis rate (approx 1.5 mumol/min) during the initial 4 to 5 hours of bile drainage. In type 1 studies, both chenodeoxycholic and taurocholic acid infusion (8 to 9 mumol/min) increased bilirubin excretion by 58% to 82% following 5 hours of biliary diversion. During type 2 studies, 3-hour IV infusions (10.5 mumol/mon) of dehydrocholic acid, 4 hours following biliary diversion, increased bile flow by 45% to 62% and excretion of 3-alpha-hydroxy bile acid by 34% to 36% above preinfusion (hepatic synthesis) levels. Bilirubin excretion was not significantly changed during those increases in bile flow and bile acid excretion. Immediately after dehydrocholic acid infusion, taurocholic acid infusion (8.1 mumol/min) greatly increased bilirubin excretion for 1 hour (a reversal of hepatic storage identical to that found during type 1 studies), prolonged excretion (mg/2 hours) being two to three times that caused by dehydrocholic acid infusion. Bilirubin excretion appeared to correlate with the micelle-forming capacity of endogenous bile acids as opposed to the nonmicelle-forming characteristic of synthestic dehydrocholic acid.

Animals↗
PubMed1979

Bile acid clearance in sheep with hereditary hyperbilirubinemia.

The disappearance of IV injected [24-14C]cholic acid from plasma was studied in normal and mutant Corriedale and Southdown sheep exhibiting hereditary defects in hepatic organic anion transport. Hepatic cholic acid clearance was determined from the integral of the 40-minute disappearance curves fit to the sums of two exponential functions. Cholic acid clearance among Corriedale sheep was significantly less (P less than 0.05) for mutant sheep (8.44 +/- 0.86 SEM ml/minute/kg of body weight) than for normal sheep (12.7 +/- 0.58 ml/minute/kg). Cholic acid clearance in the Southdown mutant (1.97 +/- 0.59 ml/minute/kg) was less than 15% of normal clearance rate (13.3 +/- 2.2 ml/minute/kg). Clearance of [14C]taurocholic acid (curves fit to three exponential function) in the Southdown mutant (10.8 +/- 0.4 ml/minute/kg) was significantly greater (P less than 0.01) than cholic acid clearance, yet was not significantly different (P greater than 0.05) from normal taurocholate clearance (17.8 +/- 2.5 ml/minute/kg). Hepatic regurgitation of conjugated bile acid was not detected after [14C]cholic acid injection. Both the mutant Corriedale and Southdown sheep, which exhibited inherited defects in hepatic bilirubin transport similar to Dubin-Johnson syndrome and Gilbert's disease in man, exhibited defects in hepatic bile acid clearance.

Animals↗
PubMed1976

Effect of bile acid on hepatic excretion and storage of bilirubin in ponies.

Endogenous bilirubin uptake from plasma and biliary bilirubin excretion were determined in ponies with chronic biliary T-tube fistulas. Excreted bile was quantitatively recovered. Uptake was calculated from the plasma disappearance of 14C-labeled bilirubin. Biliary bilirubin excretion was determined directly in excreted bile. When bile acid excretion was low (during continuous drainage without bile acid replacment), bilirubin excretion was 37% less than uptake. Uptake and excretion were essentially identical when taurocholic acid was infused to replace bile acids. After depletion of the bile acid pool, replacement of bile acids (by taurocholic acid infusion) greatly increased both bilirubin excretion and its biliary concentration for approximately 1 hour. After this initial increase, bilirubin excretion was maintained at a rate approximately 30% greater than the preinfusion rate. Bile acid excretion was found to be essential for normal, endogenous bilirubin excretion.

Animals↗
PubMed1976

Plasma bile acid elevation following CCI4 induced liver damage in dogs, sheep, calves and ponies.

Plasma bile acid concentration was determined in normal dogs,sheep, calves and ponies for three days before and six days after liver damage, induced by carbon tetrachloride. In all species, a significant increase in plasma bile acid concentration was associated with a concomitant significant increase in plasma sorbitol dehydrogenase and transferase activity. Plasma bilirubin also significantly increased in all animals except the dogs. Results suggested that plasma bile acid levels could be used to test liver function in domestic animals.

Animals↗
PubMed1975

Bile acid kinetics and bile secretion in the pony.

Bile acid pool size and synthesis rate were determined by both isotope-dilution and washout methods in ponies with chronic external biliary fistulas. Bile acid pool size (10.9 mumol/kg) and synthesis rate (11.2 mumol/day per kg) estimated by the isotope-dilution method did not differ significantly from pool size (9.4 mumol/kg) and synthesis rate (9.5 mumol/day per kg) estimated by washout method. Bile acid-dependent and -independent fractions of bile flow, determined by a method that circumvents any inevitable correlation of flow to bile acid secretion due to common factors in both parameters, did not differ from those values obtained by linear regression of bile flow versus bile acid secretion. The choleretic effect of infused chenodeoxycholic acid was higher than that of both endogenous bile acid and infused taurocholic acid.

Animals↗