Validation of oxygen consumption measurements during artificial ventilation.

We describe a system for the absolute calibration of indirect calorimeters, under the conditions of artificial ventilation and increased inspired O2 concentration, in which butane, at a measured flow rate, is burned downstream of an artificial lung. One milliliter of butane requires 6.4 ml O2 for its combustion, and the respiratory quotient is 0.615. With the closed-circuit O2-replenishment method there was no significant systematic error in the measurement of either O2 consumption or CO2 output and a random error with a SD of 8.3 ml/min for O2 consumption and 6.3 ml/min for CO2 output. There were no significant differences in the errors with inspired O2 concentrations between 23.8 and 59.5% and O2 consumptions between 89 and 366 ml/min.

Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen.

Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.

Regional quality control survey of blood-gas analysis.

We undertook an external quality control survey of blood-gas analysis in 16 laboratories at 13 hospitals. All samples were prepared in the laboratories under investigation by equilibration of blood or serum with gas mixtures of known composition. pH of serum was measured with no significant bias but with an SD of random error 0.026 pH units, which was almost twice the SD of the reference range (0.015). An acceptable random error (half SD of reference range) was not obtained in a longitudinal internal quality control suvey although there were acceptable results for buffer pH in both field and internal surveys. Blood PO2 was measured with no significant bias but with SD of random error 1.38 kPa which reduced to 0.72 kPa by excluding one egregious result. The latter value was just over half of the SD of the reference range (1.2 kPa). PCO2 of blood was also measured without significant bias but with a much smaller SD of random error of 0.28 kPa (by excluding one egregious result), which was again just over half the SD of the reference range (0.51 kPa). Measurements of blood PO2 and PCO2 seem generally acceptable in relation to their respective reference ranges but measurements of pH were unsatisfactory in both internal and external trials.

Anesthesia and the leucocyte.

Effective inhibition of cell division by anesthetics occurs only when cells are exposed to concentrations more than twice those required for anesthesia. Neutropenia following prolonged inhalation of nitrous oxide seems to be caused by a different mechanism, in which the cobalt in B12 is oxidised to the trivalent form by chemical reaction with nitrous oxide. B12 is thereby inactivated and this interferes with folate metabolism and thymidine synthesis: the effect may be detected after only a few hours in vivo exposure of mammals to 50% nitrous oxide. Unlike lymphocytes, the random motility of human neutrophils is not decreased by in vitro exposure to concentrations of halothane required for anesthesia. Similarly there is no effect on chemotaxis to casein and phagocytosis with exposure up to 2% halothane.

Cellular toxicity of anesthetics.

Inhalational anesthetics produce a range of side effects in addition to the production of narcosis. These are not uniform for all anesthetics, but show specificity. The side effects are not the result of uniform depression of all cell functions and are themselves highly specific. The basic mechanisms appear to be binding of the anesthetic to hydrophobic sites in macromolecules, with resulting conformational changes which may cause a change of properties. Examples are inactivation of enzymes, depolymerisation of polymers (such as microtubules) and paralysis of motile systems. These effects cause widespread changes such as interference with metabolic processes, cellular motility, micro structure and cell division. Cellular toxicity may also result from the action of biotransformation products including free radicals. These may disrupt membranes and result in autolysis of cells. Immune responses to anesthetics and their biotransformation products have been demonstrated but their clinical significance is not yet known.

Evolution of the atmosphere.

Planetary atmospheres depend fundamentally upon their geochemical inventory, temperature and the ability of their gravitational field to retain gases. In the case of Earth and other inner planets, early outgassing released mainly carbon dioxide and water vapour. The secondary veneer of comets and meteorites added further volatiles. Photodissociation caused secondary changes, including the production of traces of oxygen from water. Earth's gravity cannot retain light gases, including hydrogen. but retains oxygen. Water vapour generally does not pass the cold trap at the stratopause. In the archaean, early evolution of life, probably in hydrothermal vents, and the subsequent development of photosynthesis in surface waters, produced oxygen, at 3500 Ma or even earlier, becoming a significant component of the atmosphere from about 2000 Ma. Thereafter banded iron formations became rare, and iron was deposited in oxidized red beds. Atmospheric levels of carbon dioxide and oxygen have varied during the Phanerozoic: major changes may have caused extinctions. particularly the Permian/Triassic. The declining greenhouse effect due to the long-term decrease in carbon dioxide has largely offset increasing solar luminosity, and changes in carbon dioxide levels relate strongly to cycles of glaciation.