Physiologic Factors Affecting the Circulatory Persistence of Copolymer Microbubbles and Comparison of Contrast-Enhanced Effects between Copolymer Microbubbles and Sonovue.

Ultrasound contrast agents have been widely used in clinical diagnosis. Knowledge of the physiologic factors affecting circulatory persistence is helpful in preparing long-lasting microbubbles (MBs) for blood perfusion and drug delivery research. In the study described here, we prepared copolymer MBs, compared their characteristics and contrast-enhanced effects with those of SonoVue and investigated the influence of external pressure, temperature, plasma components, renal microcirculation and cardiac motion on their circulatory persistence. The mean size of the copolymer MBs was 3.57 µm, larger than that of SonoVue. The copolymer MBs had longer circulatory persistence than SonoVue. At external pressures of 110 and 150 mm Hg, neither the quantity nor the morphology of the copolymer MBs changed. Further, their quantity and size were similar after incubation at 4°C and 39.4°C and when rabbit plasma and saline were compared. In vivo contrast-enhanced ultrasonography revealed a slightly larger area under the curve for the renal artery than for the renal vein. Thus, copolymer MBs exhibited good stability. However, the quantity of copolymer MBs decreased significantly after 180 s of circulation in an isolated toad heart perfusion model, indicating that cardiac motion was the main factor affecting their circulatory persistence.

Countercurrent extraction of sparingly soluble gases for membrane introduction mass spectrometry.

Membrane introduction mass spectrometry has been applied to inert gas measurements in blood and tissue, but gases with low blood solubility are associated with reduced sensitivity. Countercurrent extraction of inert gases from a blood sample into a water carrier phase has the potential to extract most of the gas sample while avoiding dependence of signal on blood solubility. We present the design of a membrane countercurrent exchange (CCE) device coupled with a conventional direct insertion membrane probe to measure partial pressure of low solubility inert gases in aqueous samples. A mathematical model of steady-state membrane CCB predicts that countercurrent extraction with appropriate selection of carrier and sample flow rates can provide a mass spectrometer signal nearly independent of variations in solubility over a specified range, while retaining a linear response to changes in gas partial pressure over several orders of magnitude. Experimental data are presented for sulfur hexafluoride and krypton in water samples. Optimal performance is dependent on adequate equilibration between the sample and carrier streams, and the large resistance to diffusion in the aqueous phase for insoluble gases presents a substantial challenge to the application of this principle.

Is nitric oxide released in oleic acid lung injury?

Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.

Role of molecular diffusion in conventional and high frequency ventilation.

The influence of molecular diffusion on gas-mixing during conventional mechanical ventilation (CMV) and high frequency ventilation (HFV) was studied by observing the wash-in of six poorly soluble, inert gases in arterial blood. Anesthetized dogs were ventilated either with CMV or HFV. Following a step change in inspired gas composition, the increase in arterial concentrations of hydrogen, helium, methane, ethane, isobutane, and sulfur hexafluoride was determined by gas chromatography. The relative gas diffusivities encompassed a range of almost one order of magnitude. Propane, present in inspired gas during both the control and wash-in phases, served as an internal reference for calculation of blood tracer concentrations. The wash-in of all six inert gases followed a single exponential time course during both CMV and HFV. The rate of wash-in of each gas decreased with increasing molecular weight (MW). The relationship of rate constants to a measure of relative diffusivity (MW-0.5) was significantly different than zero for both types of ventilation. The slope of this relationship was three times larger for CMV than HFV, indicating that molecular diffusion has a greater role in gas mixing during ventilation with large tidal volumes. Diffusion has a minor role in gas mixing during high frequency ventilation with small tidal volumes. Demonstration of the presence of gas separation secondary to molecular diffusion during HFV is enhanced by measuring wash-in, rather than wash-out, of inert gases because gas separation is likely to be obscured as exhaled gases pass through the well-mixed central airways during gas wash-out.

The sloping alveolar plateau of tracer gases washed out from mixed venous blood in man.

We have investigated the slope of the alveolar plateau for inert tracer gases that were washed out from mixed venous blood. Two pairs of tracer gases were used (He, SF6) and (C2H2, Freon 22). The gases of each pair share almost the same blood-gas partition coefficient but they have different diffusive properties in the gas phase. The experiments were performed in healthy subjects at rest and at three levels of exercise (75, 150, 225 W). Each experiment started with the alveolar washin of the tracer gases by adding these gases to inspired air. This washin was continued for several minutes in order to dissolve sufficient amounts of the tracer gases in the body tissues. Subsequently, the tracer gases were washed out. In this paper, the slopes of the alveolar plateaus are defined as the relative increase of the concentration per second. Steeper slopes were found for the heavier gases (SF6 and Freon 22) in comparison with those for the lighter gases of the two pairs (He and C2H2). This finding may be ascribed to the contribution of diffusion-limited gas mixing in the lung to the slope of the alveolar plateau. For each gas, the slope for the first expiration during washout (alveolar washout) was considerably smaller than that for the later part of washout (mixed venous washout), and the difference amounts to about 56% and 76% of the slope during mixed venous washout at rest and at the highest level of exercise, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Solubility of helium, argon, and sulfur hexafluoride in human blood measured by mass spectrometry.

A method has been developed to measure the solubility coefficients of gases in liquids by respiratory mass spectrometry. A sample (2.5 ml) pf the test liquid, equilibrated with a test gas mixture, is injected into a sealed flask (approximately 140 ml) for extraction by equilibration. The reequilibrated gas phase in the flask is analyzed by a mass spectrometer. Separately, an equal volume (2.5 ml) of the equilibrating test gas mixture is injected into a larger sealed flask (approximately ll liter) where it is mixed and then analyzed by the mass spectrometer. Solubility in the liquid is calculated from the ratio of mass spectrometer readings in both flasks and the ratio of flask volumes. The ratio of volumes of the small and the large flasks is made similar to the gas/liquid partition coefficient whereby the mass spectrometer readings in both become similar. With this approach, errors due to amplifier and mass spectrometer nonlinearity are greatly attenuated. The method was used to measure the solubility of helium, argon, and sulfur hexafluoride in distilled water, human plasma, and human blood.