A perfluorochemical loss/restoration (L/R) system for tidal liquid ventilation.

Tidal liquid ventilation is the transport of dissolved respiratory gases via volume exchange of perfluorochemical (PFC) liquid to and from the PFC-filled lung. All gas-liquid surface tension is eliminated, increasing compliance and providing lung protection due to lower inflation pressures. Tidal liquid ventilation is achieved by cycling fluid from a reservoir to and from the lung by a ventilator. Current approaches are microprocessor-based with feedback control. During inspiration, warmed oxygenated PFC liquid is pumped from a fluid reservoir/gas exchanger into the lung. PFC fluid is conserved by condensing (60-80% efficiency) vapor in the expired gas. A feedback-control system was developed to automatically replace PFC lost due to condenser inefficiency. This loss/restoration (L/R) system consists of a PFC-vapor thermal detector (+/- 2.5%), pneumatics, amplifiers, a gas flow detector (+/- 1%), a PFC pump (+/- 5%), and a controller. Gravimetric studies of perflubron loss from a flask due to evaporation were compared with experimental L/R results and found to be within +/- 1.4%. In addition, when L/R studies were conducted with a previously reported liquid ventilation system over a four-hour period, the L/R system maintained system perflubron volume to within +/- 1% of prime volume and 11.5% of replacement volume, and the difference between experimental PFC loss and that of the L/R system was 1.8 mL/hr. These studies suggest that the PFC L/R system may have significant economic (appropriate dosing for PFC loss) as well as physiologic (maintenance of PFC inventory in the lungs and liquid ventilator) impact on liquid ventilation procedures.

Perfluorochemical elimination from the lungs: effect of initial dose.

Liquid-assisted ventilation with perfluorochemical (PFC) has been beneficial in a variety of respiratory diseases in animals and humans. Although PFC evaporation from the lungs is in part dependent on ventilation strategy and positioning, guidelines for initial and replacement dosing are unclear. We hypothesized that PFC evaporative loss over time is dependent on the size of the initial dose. Juvenile rabbits (n = 18) were ventilated using constant animal position and ventilator strategy. PFC (perflubron: LiquiVent ) was instilled endotracheally, using four groups with initial doses of 2, 6, 12, and 17 mL/kg. A previously described thermal detector that measures PFC in expired gas was used to calculate loss rate, residual perflubron in the lung, and volume loss as a % of initial fill volume. There was a significant dose, time, and dose-time interaction such that evaporative loss was dependent on initial PFC volume and time after fill (P < 0.05). Evaporative loss rate decreased earlier at lower doses. The percentage of initial volume lost to evaporation over time was inversely related to dose and could not be predicted by decreasing % PFC saturations, independent of dose. Evaporative loss should be considered to optimize both the application of PFC to the lung and replacement dosing during partial liquid ventilation.

On-line techniques for perfluorochemical vapor sampling and measurement.

The authors developed a compact gas sampling and perfluorochemical (PFC) measuring system for use in total and partial liquid ventilation systems, based on a precision two-thermistor thermal detector (TD). They describe the sensitivity and linearity of their on-line method for PFC analysis of expired gases and show how it may be used in partial liquid ventilation studies for determining PFC saturation and loss. Gas is sampled for a short time from a breathing circuit through a heated tube at a selectable point in the breathing cycle. Inspiration is sensed by a pressure transducer. The sample of gas is pulled into the heated (48 degrees C) thermistor chamber by suction and held there while the cooling effect of the vapor changes the thermistor temperature. Dry air in another chamber affects a second thermistor, and the difference of these responses is amplified. The raw signal is corrected for the effects of varying O2 levels by a fuel cell. This signal is sampled and held and displayed on a front panel display. Calibration is performed in percentage saturation at 37 degrees C using the PFC in use at that temperature, or another standard such as O2. In-vitro testing showed a linear response in the thermal detector device (R2 = 0.99) over the range of vapor pressures tested (0-14) mmHg) and was reproducible to within 3%. When electronically corrected for changes in O2 concentration, there was less than a 2% change in PFC saturation. The TD responses to CO2 (R2 = 0.99) and water vapor (R2 = 1.0) were linear and approximately equal and opposite over the normal operating ranges of expired gases. In-vivo results in rabbits showed a significant (R2 = 0.73; p < 0.01) correlation between the auto-sampler and manual collection modes for determination of PFC in expired gas.

Intravital fluorescence microscopy: impact of light-induced phototoxicity on adhesion of fluorescently labeled leukocytes.

Alterations in leukocyte/endothelium interaction due to phototoxic effects of the fluorescent dyes acridine orange (AO) and rhodamine 6G (Rh6G) were studied by intravital microscopy using the dorsal skinfold model in awake Syrian golden hamsters. AO (0.5 mg/kg/min; constant IV infusion) and Rh6G (0.1 micromol/kg; bolus IV) were administered via an indwelling venous catheter. Five to seven arterioles (35-55 microm) and postcapillary venules (30-65 microm) were investigated in each animal. Vessels were exposed four times for 30 sec to continuous light of the appropriate excitation wavelength with a 10-15-min time interval between exposures. Animals were randomly assigned to five experimental groups (five distinct light energy levels). AO and Rh6G induced leukocyte rolling/sticking in postcapillary venules and arterioles when exposed to high light energy levels. AO, but not Rh6G, induced arteriolar vasospasm when exposed to high light energies. The potential phototoxic effect of AO and Rh6G is demonstrated, as assessed by the stimulation of leukocyte-endothelium interaction and arteriolar vasospasm in vivo. This study underscores the necessity to optimize microscopic set-ups for intravital microscopy, to reduce the excitation light energy level significantly, and to perform stringent control experiments, ruling out an artificial phototoxicity-induced stimulation of leukocyte adhesion.

Intraoperative venous dilation and subsequent development of deep vein thrombosis in patients undergoing total hip or knee replacement.

This patient study was based on the observation of characteristic intimal lesions in jugular and femoral veins removed from dogs a few hours following total hip replacement. The lesions, small localized intimal tears, suggested that smooth muscle and connective tissue, might have dilated beyond the ability of intima to accommodate. Intraoperative venous dilation correlated with the incidence of intimal lesions. It was postulated that surgical trauma resulted in circulating vasoactive substances which caused venous dilation and that dilation of smooth muscle and connective tissue beyond the yield point of intima resulted in intimal rupture. Similar intraoperative dilation and lesions, in patients might predispose to development of deep vein thrombosis (DVT). Total hip (THR) and total knee (TKR) replacement patients were selected for study because: (a) of the high incidence of DVT and (b) blood circulation is present in THR but not in TKR patients during operation. Ultrasound was used to monitor cephalic vein diameter during the perioperative period. Development of DVT postoperatively was compared with intraoperative venous dilation. In THR patients, intraoperative venous dilation ranged from 6%-56%. One of nine patients with dilation less than or equal to 17% developed DVT while 12 patients with dilation of greater than or equal to 22% developed DVT, giving a correct prediction of 95%. Of four patients in the intermediate range (19%, 20%), two developed DVT and two did not. The sharp demarcation was to be expected because of abrupt rupture of viscoelastic material when the critical point of elongation is exceeded.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of ultrasound for noninvasive study of blood vessel responsiveness.

To provide a noninvasive means for studying individual macroscopic blood vessels, an ultrasound scanner was modified to provide a recording of blood vessel diameter. The instrument has A- and B-modes of signal display. The B-mode is used to position the probe and the A-mode to measure vessel diameter. The A-mode has two electronic gates for tracking the echo from each of two structures, i.e., near and far wall of vessel. The front gate was modified to pick up the falling rather than rising edge of a peak generated by the vessel wall. An analog signal proportional to the distance between gates was derived for recording with a strip-chart recorder. Probe holders were constructed to optimize positioning and holding of probe. Stability was excellent (reading varied 0.05 mm over 1 h). Axial resolution was between 0.3 and 0.73 mm. Discrepancy of measurements of plastic tubing made by ocular and ultrasound varied from 1.1 to 4.6%. Discrepancy with lightly fixed vessels was 2.7-8.2%. Ex vivo measurements on vessels with viable smooth muscle were more variable, perhaps because of actual change during measurements. Changes in vessel diameter induced by change in hydrostatic pressure and exposure to histamine were recorded.

Rapid assessment of ventricular function in acute volume overload using opaque myocardial markers.

Radiopaque markers, implanted in the myocardium, have been used to analyze ventricular function. However, the inordinate time involved in measuring marker motion limited widespread use. This work describes the application of a marker recognition system, which provides automatic recording and storage of marker locations. Use of the system was demonstrated by repeated measurements of ventricular performance in a canine model of acute volume overload.