Pulmonary vascular pressures of thoroughbred horses exercised 1, 2, 3 and 4 h after furosemide administration.

Furosemide premedication of horses 4 h prior to exercise significantly attenuates exercise-induced pulmonary capillary hypertension which may help diminish the severity of exercise-induced pulmonary haemorrhage. As pulmonary hemodynamic effects of furosemide may be mediated via a reduction in plasma volume (which is most pronounced 15-30 min postfurosemide administration, with plasma volume recovering thereafter), we hypothesized that administration of furosemide at intervals shorter than 4 h before exertion may be more effective in attenuating the exercise-induced rise in pulmonary capillary blood pressure. Thus, our objective was to determine whether furosemide-induced attenuation of exercise-induced pulmonary arterial, capillary and venous hypertension would be enhanced when the drug is administered at intervals shorter than 4 h before exercise. Using established techniques, right atrial, and pulmonary arterial, capillary and wedge (venous) pressures were ascertained in seven healthy, sound, exercise-trained Thoroughbred horses in a randomized split-plot experimental design. Measurements were made at rest and during exercise performed at maximal heart rate (217 +/- 3 beats/min) in the control (no medications) experiments and following furosemide administration (250 mg intravenously (i.v.)) at 1, 2, 3 and 4 h before exercise. Sequence of treatments was randomized and 7 days were allowed between experiments on each horse. Although furosemide administration in the four treatment groups caused only insignificant changes in the pulmonary arterial, capillary and wedge pressures of standing horses, furosemide-induced reduction in mean right atrial pressure achieved statistical significance in the 2 h postfurosemide experiments. In the control studies, exercise was attended by statistically significant increments in mean right atrial, as well as pulmonary arterial, capillary and wedge pressures. Although exercise in each of the four furosemide experiments was also attended by significant increments in right atrial as well as pulmonary vascular pressures, in the 1, 2 and 3 h postfurosemide experiments, mean right atrial pressure increased to a significantly lower value than in the control study. Exercise-induced changes in pulmonary vascular pressures in the 1 h postfurosemide experiments were not different from the pressures in the control study. There was a significant attenuation of exercise-induced pulmonary capillary and venous hypertension in the 2, 3 and 4 h postfurosemide experiments, but significant differences among these treatments were not found. Thus, these data did not support the contention that administration of furosemide at intervals shorter than 4 h before exercise is more effective in attenuating exercise-induced pulmonary capillary or venous hypertension in Thoroughbred horses.

A review of 5-hydroxymethylfurfural (HMF) in parenteral solutions.

The chemical formation, toxicity, and pharmacokinetics of 5-hydroxymethylfurfural (HMF) and certain other decomposition products found in parenteral solutions are reviewed. Heat sterilization-induced hexose decomposition to furan derivatives is promoted at low pH. Based upon infusion studies with rats and dogs, HMF does not appear to be acutely toxic at concentrations ordinarily encountered in parenteral infusion solutions (e.g., 10 mg/liter). Dosages of parenterally administered HMF exceeding 75 mg/kg body wt have led to some toxic effects, including increased activity of hepatic enzymes, altered serum-protein fractions, increased relative spleen weight, and hepatic fatty degeneration. Approximately 50% of parenterally administered HMF is oxidized and eliminated by the kidneys. From a clinical standpoint, the amount of HMF formed as a result of the heat sterilization of parenteral solutions containing hexoses does not seem to pose any significant toxicologic problem.

Comment on the carcinogenic potential of di(2-ethylhexyl) phthalate.

Analysis of the carcinogen bioassay of di(2-ethylhexyl) phthalate (DEHP) has shown that the designated maximum tolerated dose was exceeded in the low- and high-dose groups of male rats, in the high-dose group of female rats, and in the low- and high-dose groups of female mice. Significant differences in tumor incidence among small populations of laboratory animals within the testing facility further confounded interpretation of the bioassay. Critical data on food consumption, nutritional status, clinical signs, clinical pathology, and intestinal microorganisms are lacking. This review concludes that because of major deficiencies in the available data, the studies cannot be interpreted as showing a carcinogenic effect due to DEHP alone. Epigenetic mechanisms to explain the biologic effects are examined.