Deferoxamine induces hypotension in experimental gram-negative septicemia.

Multiple organ system failure may result from tissue damage caused by activated neutrophils or endotoxin. A significant part of this tissue damage is due to peroxidation induced by oxygen-free radicals and requires iron as a co-factor. Iron chelation has been shown to prevent tissue damage in some models. This experiment was carried out to determine whether iron chelation with deferoxamine (DFO) would prevent lung damage in a swine model of Gram-negative septicemia. Fifteen animals were randomized to control, Pseudomonas aeruginosa infusion at a rate of 2 x 10(7) colony forming units/20 kg/min (septic group), or Pseudomonas infusion combined with DFO pretreatment at a dose of 80 mg/kg/h (septic-treated group). Three of six septic-treated animals became severely hypotensive and died during the course of the experiment as opposed to none of six septic animals. Surviving septic-treated animals were significantly hypotensive (60 +/- 24 mmHg mean arterial pressure) compared to septic (122 +/- 9 mmHg) and control (109 +/- 8 mmHg) animals. DFO did not improve respiratory function (e.g., pO2) or morphology in septic animals. We conclude that iron-chelation therapy with DFO at the above dosage results in a significant deterioration in cardiovascular function in septic swine. Lung damage was not prevented.

PC-based system for collection and analysis of physiological data.

A personal computer based system for data acquisition and analysis appropriate to physiological experiments is described in detail. The system is independent of the details of the analog signal generation. The software, written in C, is modular and easily portable to other PC systems. The system is capable of: (a) sampling many analog signals at an appropriate rate (100 Hz), (b) storing large quantities of digitized data, (c) analysing digitized waveforms to obtain signal parameters, and (d) storing signal parameters in a format suitable for statistical analysis. Computer processed cardiopulmonary data are compared with data derived from standard ICU equipment.

Cardiopulmonary responses to Pseudomonas septicemia in swine: an improved model of the adult respiratory distress syndrome.

Bacteremia with resultant damage to multiple organ systems remains a serious problem in intensive care of human patients. We have developed a clinically relevant swine model of sepsis-induced adult respiratory distress syndrome (ARDS). Twenty-three animals were given various doses of Pseudomonas aeruginosa intravenously. Low cardiac output septic shock was prevented with massive fluid infusion. It was found that a dose of 1.0 X 10(7) colony forming units per 20 kg/min for 2 hours reliably produced respiratory failure in a setting of hyperdynamic sepsis which meets the diagnostic criteria of human ARDS.

A model-free method for mass spectrometer response correction.

A new method for correction of mass spectrometer output signals is described. Response-time distortion is reduced independently of any model of mass spectrometer behavior. The delay of the system is found first from the cross-correlation function of a step change and its response. A two-sided time-domain digital correction filter (deconvolution filter) is generated next from the same step response data using a regression procedure. Other data are corrected using the filter and delay. The mean squared error between a step response and a step is reduced considerably more after the use of a deconvolution filter than after the application of a second-order model correction. O2 consumption and CO2 production values calculated from data corrupted by a simulated dynamic process return to near the uncorrupted values after correction. Although a clean step response or the ensemble average of several responses contaminated with noise is needed for the generation of the filter, random noise of magnitude less than or equal to 0.5% added to the response to be corrected does not impair the correction severely.

Central venous bubbles and mixed venous nitrogen in goats following decompression.

Decompression of awake goats from saturation at 1, 2, and 3 ATA of air has been carried out using ultrasonic Doppler bubble detection, central venous blood inert gas measurement, and cardiac output measurement. The results of these experiments indicate that the decrease in nitrogen elimination rate as an apparent result of decompression cannot be due to excessive cardiac output or mass transport of a large amount of inert gas to the lungs as bubbles. Rather, the rapid drop in mixed venous nitrogen content is consistent with a generalized decrease in tissue-to-blood nitrogen elimination. This in turn appears to be due to a cardiovascular response to the decompression insult as was previously reported for dogs (D'Aoust et al., J. Appl. Physiol. 41: 348--355, 1976) at 1, 2, and 3 ATA; addition of ultrasonic Doppler monitoring and cardiac output in the present studies allowed measurement of the degree of latency in the appearance of bubbles at a central venous location. This time period includes that required for bubble formation, growth, and vascular transport of the bubbles to the Doppler detector. All results of these studies are consistent with the interpretation that due to a decompression insult, which probably includes bubble formation, some degree of hemostasis, and other hematologic sequelae, the transport of tissue inert gas to the capillary venous blood is retarded, thus providing the rapid apparent decrease in mixed venous blood inert gas content. These results demonstrate what is most likely a general response to a severe but not crucial decompression by the cardiovascular system.

Prlonged bubble production by transient isobaric counter-equilibration of helium against nitrogen.

The production of systemic gas bubbles by isobaric counter-equilibration of helium against 5 atmospheres saturated nitrox (0.3 ATA O2 in both mixes) in awake goats was demonstrated. Sixteen animal exposures (8 dives, 2 animals per dive) to a sudden isobaric gas switch from saturation on N2 to He were conducted; 8 saturations occurred at 132 fsw and 8 at 198 fsw. Central venous bubbles were detected acoustically by means of a Doppler ultrasonic cuff surgically implanted around the inferior vena cava of each animal. Bubbles occurred from 20 to 60 min after the switch in both the 132 fsw and 198 fsw exposures, but were not always present in the 132 fsw exposure, and did not persist for as long. Bubbles or other Doppler events were often detected for the entire isobaric period-12 h-following the gas switch in the 198 fsw exposures. Decompressions were conducted according to the USN saturation tables and were uneventful, with only occasional bubbles. Supersaturation ratios calculated to have occurred for a considerable period after the gas switch were approximately 1.15 (tissue gas tension pi, divided by ambient hydrostatic pressure, P) with maxima at 1.26 for the faster tissues. These values are limiting ones in USN decompression only for the slower tissues. In general, therefore, these results argue for reducing the permissible ascent criteria for the faster tissues-assuming bubbles are to be avoided-and allowing more time at stops for non-saturation decompression. Gas switches from a more soluble to a less soluble and/or more rapidly diffusing gas should therefore be avoided until physiological limits are well worked out.

Venous gas bubbles: production by transient, deep isobaric counterdiffusion of helium against nitrogen.

When awake goats were subjected to isobaric gas switching from saturation (17 hours) on 4.7 atmospheres of nitrogen (0.3 atmosphere of oxygen) to 4.7 atmospheres of helium (0.3 atmosphere of oxygen), bubbles detected by 5-megahertz Doppler ultrasound in the posterior vena cava 20 to 60 minutes after the switch continued for 4 hours. Similar experiments carried out at 6.7 atmospheres of inert gas and 0.3 atmosphere of oxygen produced more bubbles for as long as 12 hours after the gas switch. This is believed to be the first objective demonstration of the phenomenon of deep isobaric supersaturation under transient operational diving conditions at relatively shallow diving depths. Detection of bubbles by Doppler ultrasound confirms the potential importance of the phenomenon to shallow saturation diving and holds promise for better quantitification of its effects as well as those of its counterpart, isobaric undersaturation, which can confer a decompression advantage.

Decompression-induced decrease in nitrogen elimination rate in awake dogs.

Formulation of safe decompression procedures still requires unproven assumptions regarding both gas equilibration rates and the associated ascent criteria. Although the assumption of symmetry of uptake and elimination rates has been suspect for several years, few data are available. Measurements of actual mixed venous blood nitrogen content [vN2] during compression and following decompression in chronically catheterized awake dogs have clearly demonstrated that desaturation is markedly slower than saturation, and that this effect can be imposed by decompression. The disappearance of arteriovenous nitrogen concentration differences during desaturation following a decompression that produced decompression sickness indicates that cardiopulmonary and cardiovascular changes induced by mechanisms associated with decompression per se can potentiate its deleterious effects. Current US practices do not provide for such asymmetry, while those used in the UK have incorporated this in their models for the last decade.