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Biomedical subjects

J S Engle

Publications and source records attributed to J S Engle.

5 recordsLinked to original sources

TNF-alpha potentiates oxidant and reperfusion-induced endothelial cell injury.

Pulmonary edema following reperfusion is a major clinical problem. Changes in endothelial cell shape induced by oxidant injury may account for immediate capillary leakage associated with reperfusion injury. In these experiments we examined the role of tumor necrosis factor-alpha (TNF-alpha) in acute endothelial cell injury following ischemia-reperfusion. Sprague-Dawley rats were treated with a neutralizing antisera directed against TNF-alpha prior to production of distal ischemia. These rats demonstrated a significant reduction (P < 0.05) in acute lung edema in response to 4 hr of ischemia and 30 min of reperfusion when compared to rats undergoing the same procedure without antisera treatment. An in vitro model was developed to determine if TNF-alpha had a direct effect on endothelial cell response to ischemia-reperfusion. The effects of TNF-alpha and oxidant stress on the integrity of cultured endothelial cell monolayers was measured. Rat pulmonary artery endothelial cell monolayers reacted in vitro to oxidant stress by an increase in permeability. The cells changed shape and an increase in diffusion of 125I-albumin across cell monolayers resulted when these cells were exposed to 50 microM hydrogen peroxide (H2O2) or plasma from the ischemic hind limb of a Sprague-Dawley rat (50 microliters/ml). Pretreatment of cultured cells with low levels of recombinant mouse TNF-alpha significantly affected both the cell shape change and the increase in permeability (P < 0.05). Increased permeability of cell monolayers in vitro was not due to cell lysis as determined by media lactate dehydrogenase levels. The effect appeared to be due to cellular rounding and contraction seen using video time lapse microscopy. These data suggest a direct effect of TNF-alpha on endothelial cells, whereby the cells are rendered more susceptible to oxidant injury accompanying reperfusion.

Acute Disease

Effects of hemolysis and storage on quantification of hormones in blood samples from dogs, cattle, and horses.

Veterinary diagnostic endocrinology laboratories frequently receive hemolyzed plasma, serum, or blood samples for hormone analyses. However, except for the previously reported harm done by hemolysis to canine insulin, effects of hemolysis on quantification of other clinically important hormones are unknown. Therefore, these studies were designed to evaluate effects of hemolysis on radioimmunoassay of thyroxine, 3,5,3'-triiodothyronine, progesterone, testosterone, estradiol, cortisol, and insulin in equine, bovine, and canine plasma. In the first experiment, hormones were measured in plasma obtained from hemolyzed blood that had been stored for 18 hours. Blood samples were drawn from pregnant cows, male and diestrous female dogs, and male and pregnant female horses. Each sample was divided into 2 equal portions. One portion was ejected 4 times with a syringe through a 20-gauge (dogs, horses) or 22-gauge (cows) hypodermic needle to induce variable degrees of hemolysis. Two subsamples of the blood were taken before the first and after the first, second, and fourth ejections. One subsample of each pair was stored at 2 to 4 C and the other was stored at 20 to 22 C for 18 to 22 hours before plasma was recovered and stored at -20 C. The second portion of blood from each animal was centrifuged after collection; plasma was recovered and treated similarly as was blood. Concentrations of thyroxine in equine plasma, of 3,5,3'-triiodothyronine, estradiol, and testosterone in equine and canine plasma, and of cortisol in equine plasma were not affected by hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reduction in halothane MAC: comparison of morphine and alfentanil.

The anesthetic potency and effectiveness of alfentanil and morphine were established by determining the effects of increasing drug doses on the alveolar anesthetic requirement of halothane to maintain a constant anesthetic (MAC) level. Six selected doses of alfentanil and four of morphine were administered to groups of mechanically ventilated rats anesthetized with halothane. Alfentanil was given as a loading dose followed by an intravenous infusion of 0.01-100 micrograms X kg-1 X min-1, and morphine was administered as a subcutaneous dose of 4-20 mg/kg. The reduction in halothane requirement after morphine was biphasic, with a rapid linear increase occurring up to an 8 mg/kg subcutaneous dose, followed by a further, slower reduction in halothane requirement after doses of 8-20 mg/kg. At a 20 mg/kg dose, the halothane MAC was reduced approximately 84%. With alfentanil, a curvilinear reduction in halothane MAC occurred up to an alfentanil dose of 15 micrograms X kg-1 X min-1, where a 48% reduction was found. Larger doses produced severe truncal, chest wall, and abdominal rigidity, precluding adequate ventilation and the determination of MAC.

Adjuvants, Anesthesia

The decrease of the minimum alveolar anesthetic concentration produced by sufentanil in rats.

The anesthetic potency of sufentanil was established by determining its effect on the minimal alveolar anesthetic concentration (MAC) of halothane. Each of eight selected doses of sufentanil was administered to a group of four to five mechanically ventilated rats anesthetized with halothane. Sufentanil was administered as a constant infusion preceded by an intravenous bolus dose that was three times that of the infusion rate per minute. The tail-clamp technique was used to establish control MAC and the MAC of halothane with sufentanil. Increasing sufentanil dosages were nonlinearly related to reductions in the MAC of halothane. A sigmoidal dose-response curve was described. An abrupt, steep response follows the initial upward deflection of the curve with an additional 62% MAC reduction occurring between doses of 1 X 10(-5) mg X kg-1 X min-1 and 1 X 10(-4) mg X kg-1 X min-1. Essentially complete anesthesia was seen at the latter dosage. No significant adverse side effects were seen with sufentanil at doses up to 1 X 10(-2) mg X kg-1 X min-1.

Anesthesia, Inhalation