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R Engstrom

Publications and source records attributed to R Engstrom.

10 recordsLinked to original sources
PubMed1995

Pharmacokinetics of computer-controlled alfentanil administration in children undergoing cardiac surgery.

BACKGROUND: Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics of drugs. The purpose of this study was to model the pharmacokinetics of alfentanil in children undergoing cardiac surgery to provide accurate dosage titration intraoperatively as well as in the postoperative period. METHODS: Fourteen children (aged 3 months to 8 yr) undergoing cardiac surgery with CPB were administered alfentanil via a computer-controlled infusion pump. During surgery, the computer-controlled infusion pump was set to target plasma alfentanil concentrations of 500-2500 micrograms/ml. After surgery, the computer-controlled infusion pump was set to target plasma concentrations of 200-500 micrograms/ml. Parameters for children previously published by Goresky et al. were programmed into the device. Arterial blood samples were taken throughout the infusion. Plasma samples were assayed by radioimmunoassay. Alfentanil pharmacokinetics were estimated using a pooled-data approach with a simple weight-proportional, three-compartment mamillary model with parameters expressed in volumes and clearances as well as a CPB-adjusted, three-compartment model in which the parameters were allowed to change before, during, and after CPB. The accuracy of the three models was compared using cross-validation. RESULTS: Plasma alfentanil concentrations during computer-controlled infusion pump administration exceeded target concentrations for the first 10 min of drug administration, and from 300 min to the end of the study. The median absolute performance error was 33%. Pharmacokinetic modeling estimated a set of parameters for a simple three-compartment model with a median absolute weighted residual of 18.4%. A CPB-adjusted model nominally decreased the median absolute weighted residual to 17.0%. The performance of these models as measured by cross-validation performance was 18.9% median absolute performance error for the simple model and 18.4% median absolute performance error for the CPB-adjusted model. Parameters for the simple three-compartment model are: V1 = 19.2 ml.kg-1; V2 = 99 ml.kg-1; V3 = 2344 ml.kg-1; Cl1 = 2.5 ml.kg-1.min-1; Cl2 = 38 ml.kg-1.min-1; and Cl3 = 15 ml.kg-1.min-1. In the CPB-adjusted model V1, V2, and Cl2 changed with the onset of CPB. After CPB, V1 and Cl2 returned to the initial values, while V2 was described by a third value. CONCLUSIONS: The population pharmacokinetics of alfentanil in children undergoing cardiac surgery were well described by both a simple weight-proportional, three-compartment model and a weight-proportional, CPB-adjusted three-compartment model. Cross-validation estimated an expected median inaccuracy of approximately 18-20% with the estimated models in identical experimental circumstances. The flexible CPB-adjusted pharmacokinetic model could be used for modeling any drug with linear pharmacokinetics given in the context of CPB.

Alfentanil↗
PubMed1977

Inhaled nitrous oxide and cathepsin D activity in the lung.

Acute exposures of lungs to nitrous oxide in anesthetic concentration results in an initial lowered free activity of cathepsin D. Chronic exposures with either continuous or interrupted anesthetic exposure increases the free activity of this enzyme.

Anesthesia, Inhalation↗
PubMed1976

Cryoprotectant-treated myocardium evaluation.

Whole excis ed rat hearts were treated with 5, 10, or 15% (v/v) dimethyl sulfoxide/glycerol and then some were frozen in liquid nitrogen while the balance remained unfrozen. Freezing and thawing rates were approximately 30degreesC/min. Ventricular tissue was examined for histological damage, glycogen depletion, and enzyme sites, using histological, histochemical, and electron microscopy techniques. Early signs of cellular degeneration and ischemia were observed in all unfrozen groups; depletion of glycogen reserves, fuchsinophilic staining, vacuolization and granulation of the sarcoplasm were noted. Results from frozen groups were similar, but ultrastructural damage was more severe and extensive. Alkaline phosphatase and succinic dehydrogenase sites were abundant in unfrozen specimens and absent or markedly reduced in frozen specimens which also exhibited widespread nonspecific staining throughout intercellular spaces.

Animals↗
PubMed1975

Comparison of water immersion and saline infusion as a means of inducing volume expansion in man.

Although previous studies have demonstrated that water immersion to the neck (NI) results in both central hypervolemia and a significant natriuresis, it is unclear whether the magnitude of the "volume stimulus" of NI is comparable to that induced by the extracellular fluid volume expansion (ECVE) induced by acute saline administration. The present study was undertaken therefore to compare the natriuresis induced by these two different stimuli. All subjects were studied on four occasions while in balance on a diet containing 150 meq of sodium and 80 meq of potassium daily: seated control; seated immersion; and saline administration in both the seated and recumbent posture. The increment in UNaV during NI was indistinguishable from that of seated saline. Similarly, the kaliuretic response during NI was similar to that induced by seated saline infusion. In contrast, supine saline infusion resulted in a greater increment in UNaV than either NI or seated saline. The present data indicate that the "volume stimulus" of immersion is identical with that of standard saline-induced ECVE in normal seated subjects. Furthermore, the ability of NI to induce a natriuresis without a concomitant increase in total blood volume and with a decrease in body weight, rather than the increase which attends saline infusion, suggests that NI may be a preferred investigative tool for assessing the effects of ECVE in man.

Adolescent↗
PubMed1975

Dietary vitamin E and the effects of inhaled nitrogen dioxide on rat lungs.

Groups of rats were fed diets containing supplemented adequate, or deficient amounts of alpha-tocopherol. Some rats from each group were exposed for 2 h to high-level concentrations of nitrogen dioxide in their breathing air. A comparison of wet and dry lung weights did not indicate that exposure of the gas was a cause of edema. Proportion of lung weight to total body weight was increased in all animals with the lipid content diminishing according to the amount of dietary apha-tocopherol available. Dietary intake of the vitamin did not seem to protect the lipid content of lungs of the supplemented dietary group from oxidation. No difference in total peroxides was noted between any of the groups. Inflation and deflation compliance measurements were greater for both exposed and non-exposed supplemented animals when compared to the adequate and deficient groups.

Animals↗