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Coronary collateral development during chronic ischemia: serial assessment using harmonic myocardial contrast echocardiography.

OBJECTIVES: We sought to characterize collateral development in an experimental model of chronic myocardial ischemia by using myocardial contrast echocardiography (MCE). BACKGROUND: Coronary collaterals maintain myocyte viability during myocardial ischemia. The natural history and determinants of collateral development are difficult to study serially in vivo. METHODS: The left anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with a hydraulic occluder and ameroid constrictor to enable reversible and gradual total LAD occlusion, respectively. Myocardial contrast echocardiography was performed using intravenous injection of perfluorocarbon gas-containing microbubbles during two-dimensional harmonic echocardiographic imaging. Myocardial contrast echocardiography images and radiolabeled microsphere flow measurements were obtained during transient LAD occlusion on day 0. Over the ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day intervals. RESULTS: Myocardial contrast echocardiography risk area size (expressed as a percent of the left ventricular short axis slice) decreased over the course of six weeks (32%+/-3% on day 0, 21% +/-3% at day 10, 5+/-3% at day 20, 1%+/-1% at day 30 and 1%+/-1% at day 42, p< or =0.001 vs. day 0). Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow, correspondingly increased between day 0 and day 42 (0.14+/-0.02 to 0.90+/-0.07, p<0.02). CONCLUSIONS: Collateral development occurs relatively early and rapidly in this chronic canine model. Myocardial contrast echocardiography using harmonic imaging and intravenous injection of microbubbles can uniquely track the spatial and temporal course of collateral growth, and may be a powerful tool for noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.

Animals↗

Real-time perfusion imaging with low mechanical index pulse inversion Doppler imaging.

OBJECTIVES: We sought to determine how successful pulse inversion Doppler (PID) imaging would be in detecting myocardial perfusion defects during dobutamine stress echocardiography. BACKGROUND: By transmitting multiple pulses of alternating polarity (PID) at a low mechanical index, myocardial contrast enhancement from intravenously injected microbubbles can be detected using real-time frame rates. Pulse inversion Doppler imaging was performed in 117 patients during dobutamine stress echocardiography by using an intravenous bolus of a perfluorocarbon-filled, albumin-(Optison: n = 98) or liposome- (Definity: n = 19) encapsulated microbubble and a mechanical index of <0.3. The visual identification of myocardial contrast defects and wall motion abnormalities was determined by blinded review. Forty of the patients had quantitative angiography (QA) performed to correlate territorial contrast defects with stenosis diameter >50%. RESULTS: There was a virtual absence of signal from the myocardium before contrast injections in all patients. Bright myocardial opacification at peak stress was observed in at least one coronary artery territory at frame rates up to 25 Hz in 114 of the 117 patients during dobutamine stress echocardiography. Regional myocardial contrast defects at peak stress were observed in all 30 patients with >50% stenosis in at least one vessel (13 with single-vessel and 17 with multivessel disease). Contrast defects were observed in 17 territories subtended by >50% diameter stenosis that had normal wall motion at peak stress. Overall agreement between QA and myocardial contrast enhancement on a territorial basis was 83%, as compared with 72% for wall motion. CONCLUSIONS: Pulse inversion Doppler imaging allows the detection of myocardial perfusion abnormalities in real-time during stress echocardiography and will further add to the quality and sensitivity of this test.

Albumins↗

Visualization of risk-area myocardium as a high-intensity, hyperenhanced "hot spot" by myocardial contrast echocardiography following coronary reperfusion: quantitative analysis.

OBJECTIVES: We examined whether delayed post-injection imaging of a new ultrasound contrast agent (BR-14) could produce prolonged opacification and hyperenhancement of myocardium subjected to coronary occlusion/reperfusion. BACKGROUND: We hypothesized that ultrasound exposure destroyed BR-14 and eliminated visualization of sustained myocardial opacification from retained microbubbles. METHODS: We studied eight open-chest dogs with 3 h of left anterior descending coronary artery (LAD) occlusion followed by 3 h of reperfusion. Myocardial contrast echocardiography (MCE) was performed before occlusion and 120 min after the onset of both occlusion and reperfusion. Ultrasound imaging was initiated 15 min after injection. Myocardial blood flow (MBF) was assessed by microspheres. RESULTS: Pre-occlusion images revealed uniform opacification of left ventricular myocardium greater than that of the cavity, with a mean intensity of the LAD bed of 8.66 +/- 1.38 dB. During occlusion, MCE resulted in the appearance of a perfusion defect in the LAD risk area (intensity 2.08 +/- 1.10 dB). After 120 min of reperfusion, the LAD risk-area myocardium manifested dense opacification of a higher intensity ("hot spot") than baseline (13.7 vs. 8.7 dB), but with reduced MBF consistent with accumulation of a high concentration of microbubbles. Increased MCE intensity was associated with a greater myeloperoxidase score. CONCLUSIONS: These data establish that contrast opacification by BR-14 may be selectively retained within the perfusion bed of a coronary artery subjected to occlusion/reperfusion. Such opacification exhibits defects with occlusion, manifests hyperenhanced intensity (hot spot) with reperfusion, is associated with the level of myeloperoxidase activity, and conforms to the area of myocardium subjected to altered flow.

Animals↗

Hemodynamic characteristics, myocardial kinetics and microvascular rheology of FS-069, a second-generation echocardiographic contrast agent capable of producing myocardial opacification from a venous injection.

OBJECTIVES: We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. BACKGROUND: FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection. METHODS: Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular findings of FS-069 can explain its echocardiographic behavior during direct coronary injections. RESULTS: There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gamma-variate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification. CONCLUSIONS: FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.

Albumins↗

Dissolution of thrombotic arterial occlusion by high intensity, low frequency ultrasound and dodecafluoropentane emulsion: an in vitro and in vivo study.

OBJECTIVES: We examined the effectiveness of the microbubbles of an echo contrast agent, dodecafluoropentane (DDFP) emulsion, to enhance low frequency ultrasound clot disruption in vitro and in vivo. BACKGROUND: Ultrasound is reported to facilitate clot dissolution, and microbubbles could theoretically enhance ultrasound clot dissolution by augmenting cavitational effects. METHODS IN VITRO STUDIES: The disruption rate of fresh human clots by ultrasound (24 kHz, 2.9 W/cm2) was examined in saline and DDFP emulsion. In vivo studies: Using a rabbit iliofemoral thrombotic occlusion model, recanalization rate and histopathologic findings were compared among groups treated with DDFP emulsion alone, transcutaneous ultrasound (20 kHz, 1.5 W/cm2) alone and with DDFP emulsion and ultrasound combined. RESULTS: The ultrasound clot disruption rate was significantly (p < 0.01) increased, from 72 +/- 18% (mean +/- SD) in saline to 98 +/- 4% in DDFP emulsion in 3 min in vitro. No vessel was recanalized by DDFP emulsion alone (0%), and only a single artery was patent after ultrasound treatment alone (9%). In contrast, 82% of iliofemoral arteries were angiographically recanalized after ultrasound treatment with DDFP emulsion. Histologically, the patent arteries had only minimal focal mural thrombus, with no evidence of vessel wall damage. However, substantial damage was observed in rabbit dermis and subcutaneous tissue. CONCLUSIONS: 1) DDFP emulsion, an echo contrast agent, significantly enhances the clot-disrupting effect of low frequency ultrasound in vitro and in an in vivo rabbit iliofemoral occlusion model. 2) This simple combination therapy has potential for clinical application in patients with thrombotic arterial occlusions.

Animals↗

Three-dimensional myocardial contrast echocardiography: validation of in vivo risk and infarct volumes.

OBJECTIVES: The aim of this study was to determine whether three-dimensional (3D) myocardial contrast echocardiography (MCE) could provide an accurate in vivo assessment of risk and infarct volumes. BACKGROUND: MCE has been shown to accurately define risk area and infarct size in single tomographic slices. The ability of this technique to measure risk and infarct volumes by using three-dimensional echocardiography (3DE) has not been determined. METHODS: Fifteen open chest dogs underwent variable durations of coronary artery occlusion followed by reperfusion. At each stage, MCE was performed by using left atrial injection of AIP201, a deposit microbubble with a mean diameter of 10 +/- 4 microm and a mean concentration of 1.5 x 10(7) x ml(-1). Images were obtained over a 180 degree arc with use of an automated rotational device and were stored in computer as a 3D data set. Postmortem risk area and infarct size were measured in six to eight left ventricular short-axis slices of equal thickness using technetium-99m autoradiography and tissue staining, respectively. MCE images corresponding to these planes were reconstructed off-line. RESULTS: A close linear relation was noted between the volume of myocardium not showing contrast enhancement on 3D MCE during coronary occlusion and postmortem risk volume (y = 1.2x - 3.0, r = 0.83, SEE = 5.1, n = 15). The volume of myocardium not showing contrast enhancement on 3D MCE after reperfusion also closely correlated with postmortem infarct volume (y = 1.1x - 3.9, r = 0.88, SEE = 4.8, n = 11). No changes in systemic hemodynamic variables were noted with injections of AIP201. CONCLUSIONS: When combined with AIP201, a deposit microbubble, 3D MCE can be used to accurately determine both risk and infarct volumes in vivo. This method could be used to assess the effects of interventions that attempt to alter the infarct/risk volume ratio.

Animals↗

[Ultrasound-assisted thrombolysis in acute ischemic stroke].

Numerous experimental studies,in vitro and in animal models, have demonstrated that ultrasound can accelerate clot lysis. This effect is probably related to the cavitation of microbubbles contained in the medium exposed to ultrasound. Clinical studies show that transcranial application of low-intensity, low-frequency ultrasound identical to that routinely used for diagnostic purposes can improve recanalization rates in patients with acute ischemic stroke. These promising findings should be confirmed in larger studies and using MR or CT angiography to assess recanalization independently. The optimal method of ultrasound-assisted thrombolysis has not been determined yet. Experimental data suggest that it may be enhanced by coadministration of microbubbles used as contrast agents.

Acute Disease↗

Ultrasound contrast harmonic imaging of abdominal organs.

Ultrasound contrast agents consist of microbubbles, which are the most effective acoustic backscatters. The interaction between the insonating ultrasound beam and the microbubbles is very complex and basic understanding of their behavior under various sound fields has been fundamental to the development of improved methods of visualizing and displaying the contrast agents. Although echo enhancers have been under development for a long time, their clinical applications have been limited to enhancing the Doppler signals in difficult cases. However, recent advances in harmonic imaging and the development of new tissue-specific contrast agents stand to broaden the scope of ultrasound diagnostic potential beyond simply rescuing failed Doppler examinations. This article reviews the current and potential applications of ultrasound contrast harmonic imaging in the abdomen.

Acoustics↗

Embolic occlusion of a patent foramen ovale: a cause of false negative contrast echocardiogram.

A 74-year-old man who had dyspnea and cyanosis demonstrated venous thrombosis and multiple lung ventilation-perfusion mismatches suggesting pulmonary emboli. Transthoracic echocardiography demonstrated a right atrial mass and a microbubble contrast study did not reveal right-to-left shunt. Transesophageal echocardiography revealed an embolus entrapped in the foramen ovale projecting into the left atrium that was subsequently removed. Embolic occlusion of patent foramen ovale is an important cause of false negative microbubble contrast study.

Aged↗

Albunex: a safe and effective commercially produced agent for myocardial contrast echocardiography.

Microbubble solutions of sonicated human serum albumin have been shown to be effective echocardiographic contrast agents free from adverse effects on coronary blood flow, left ventricular function, and systemic hemodynamics. Albunex is a commercially prepared solution of air-filled albumin microspheres prepared from sonicated 5% human serum albumin. The effects of Albunex on coronary blood flow, left ventricular function, and systemic hemodynamics, as well as contrast enhancement were evaluated in 10 open chest, anesthetized dogs. After an intracoronary injection, Albunex did not alter left atrial, left ventricular systolic or end-diastolic, or mean aortic pressures. It did not cause a coronary hyperemic response, alter left ventricular systolic thickening, or lower the peak positive left ventricular dp/dt. It did not alter these measurements even in the presence of a critical coronary stenosis. The contrast opacification produced by Albunex microbubbles was dose dependent (optimal dose range of 0.033 to 0.5 ml/kg), with attenuation occurring at higher doses. In conclusion, although Albunex provides adequate contrast enhancement, intracoronary injection of Albunex does not significantly alter coronary blood flow, left ventricular function, or systemic hemodynamics. Because of the standardized size and concentration of the microspheres, Albunex may be an ideal agent for myocardial contrast echocardiography.

Albumins↗

Real-time visualization of myocardial perfusion and wall thickening in human beings with intravenous ultrasonographic contrast and accelerated intermittent harmonic imaging.

Previous work has demonstrated that at higher peak negative pressures, microbubbles are destroyed by diagnostic ultrasonography. At lower pressures (lower mechanical index), less destruction occurs but enhanced contrast persists. In animals, this lower mechanical index has resulted in enhanced contrast after administration of intravenous microbubbles with intermittent imaging at faster frame rates. We tested whether this accelerated intermittent imaging technique could produce myocardial contrast and detect myocardial perfusion abnormalities in 25 patients (10 with normal wall motion, 15 after myocardial infarction). Three independent reviewers detected persistent myocardial contrast defects within the infarct zone throughout the cardiac cycle in 9 of the 15 patients after acute myocardial infarction; the presence of such defects was predictive of a persistent regional wall motion abnormality at 4-week follow-up. Interobserver agreement on regional contrast enhancement ranged from 88% to 90%. We conclude that accelerated intermittent imaging permits real-time visualization of myocardial blood flow and wall thickening.

Contrast Media↗

Differing susceptibility of echocardiographic contrast agents to adverse effects of biologic factors: multicenter, videodensitometric comparison of octafluoropropane-filled microspheres with air-filled microspheres for left ventricular opacification.

BACKGROUND: Echocardiographic contrast enhancement of the left ventricle has diagnostic value in the assessment of regional and global left ventricular (LV) function. The efficacy of both octafluoropropane-filled human albumin microbubbles (OCTA) and of air-filled human albumin microbubbles (AIR) for LV endocardial delineation and qualitative LV opacification has previously been reported. However, pulmonary disease, obesity, impaired LV function, and decreased echogenicity may diminish the efficacy of contrast agents for LV opacification. The purpose of this study was to compare the susceptibility of 2 contrast agents currently approved by the Food and Drug Administration to these biologic factors. METHODS: To compare quantitative LV opacification with OCTA (0.2, 0. 5, 3.0, 5.0 mL) versus AIR (0.08 mL/kg, 0.22 mL/kg), we performed videodensitometry in 199 patients (average age 59.2 +/- 13.3 years, 79% men) studied in 2 identical, prospective, multicenter, blinded trials, of whom 74 had impaired LV function, pulmonary disease, or both, 70 were obese (body mass index >30 kg/m(2)), and 45 were nonechogenic (>/=4 of 6 endocardial segments were not seen in the apical 4-chamber view). Changes in videodensity from noncontrast to contrast agent with the same gain settings were determined at end diastole and end systole (gray scale 0 to 255 U) for 2 regions of interest: left ventricle apex-to-mid-cavity and mid-cavity-to-base. The relative influence of clinically evident pulmonary disease, impaired LV function on echocardiography, and echogenicity on LV opacification produced by both contrast agents was determined by multivariate analysis. RESULTS: Significant videodensity increases ranging from 67% to 143% were observed with both agents. At the recommended initial doses (0.5 mL for OCTA, 0.22 mL/kg for AIR), OCTA produced greater opacification than AIR in both regions of interest and at both phases of the cardiac cycle. Poor LV function was associated with decreased LV opacification for AIR but not for OCTA. Diminished echogenicity was more strongly associated with impaired opacification for AIR than for OCTA. Obesity and clinically evident pulmonary disease were associated with diminished chamber opacification with both OCTA and AIR. CONCLUSIONS: In addition to the superiority of octafluoropropane-filled microspheres to air-filled microspheres for LV opacification, the efficacy of OCTA is relatively unaffected by impaired LV function and is less susceptible to the effects of poor echogenicity than AIR.

Albumins↗

Dynamic intrahepatic flow and cellular alterations during radiofrequency ablation of liver tissue in mice.

PURPOSE: The purpose of this study was to identify microvascular and other associated changes that occur in the liver during focal heating with monopolar radiofrequency (RF). MATERIALS AND METHODS: Intravital video microscopy was performed on exteriorized transilluminated livers of 15 live mice during RF-induced heating of liver parenchyma. Microvascular flow parameters, flow reversibility, microbubble formation, phagocytic activity, and endothelial permeability were recorded throughout a range of tip temperatures (40 degrees C-95 degrees C). RESULTS: During RF application, five discrete zones extended outward from the electrode surface: (i) tissue coagulation, (ii) cellular edema/necrosis, (iii) sinusoidal stasis, (iv) parenchymal shunting, and (v) normal liver tissue. Reversal of stasis in sinusoids and small (<25 microm) vessels occurred at tip temperatures below 50 degrees C. This zone of stasis corresponded to the hyperemic zone on histologic analysis. Although alterations in permeability and phagocytic activity were first identified at 43 degrees C, tip temperatures higher than 55 degrees C always produced local endothelial leakiness to carbon microparticles at the periphery and always inhibited phagocytic activity. At tip temperatures higher than 95 degrees C, microbubble formation occurred with bubbles ultimately tracking through necrotic tissue into patent sinusoids. Larger peripheral vessels (>30 microm) limited extension of coagulation. CONCLUSION: Although coagulation occurs at tip temperatures higher than 50 degrees C, RF heating induced reversible microvascular stasis at temperatures lower than 50 degrees C. Increased sinusoidal endothelial permeability occurs at near-coagulative temperatures. Therefore, targeted endovascular microparticle delivery through this leaky endothelium may provide an additional and complimentary adjunct for RF ablation therapy.

Animals↗

Assessment of liver and kidney enhancement with a perfluorocarbon vapor-stabilized US contrast agent.

RATIONALE AND OBJECTIVES: The authors evaluated the time-echogenicity response of liver, kidney, and implanted VX2 tumor after injection of a microbubble contrast medium and assessed use of an avascular lesion as an internal standard. MATERIALS AND METHODS: Twenty-one New Zealand White rabbits were studied. To evaluate use of an internal standard and the dose-response relationship, nine rabbits with 7-day-old avascular liver lesions created by alcohol ablation received 0.1, 0.25, 0.5, and 1.0 mL of AF0145, a microbubble contrast agent. To evaluate tumor echogenicity, 12 rabbits implanted with VX2 tumor in the liver (six also underwent alcohol ablation) received 0.5 mL of AF0145. Videodensitometry was used to analyze echogenicity changes over 10 minutes. RESULTS: Echogenicity of the alcohol-ablated liver was not affected by contrast material administration. Liver and kidney echogenicity relative to ablation increased linearly with dose, peaking 1 minute after injection and decaying to baseline over 9 minutes. Contrast material administration defined the size and margins of VX2 lesions more clearly. In the arterial phase, the tumor rim was hyperechoic relative to surrounding liver, becoming isoechoic during the portal venous phase then hypoechoic during the late phase parenchymal phase. CONCLUSIONS: Lesions created by alcohol ablation can be used as an internal standard for quantitative analysis of adjacent tissues. AF0145 enhances perfused tissues, including vascular tumors, at gray-scale, real-time ultrasonography and enhances the liver.

Animals↗

Assessment of regional myocardial hypoperfusion with myocardial contrast echocardiography using intravenous bolus application in patients with acute chest pain: a double case report.

Myocardial contrast echocardiography using power Doppler harmonic imaging is able to document myocardial hypoperfusion. Two case reports demonstrate the potential of intravenous bolus application of microbubbles in patients with acute chest pain due to myocardial ischaemia to detect regional low flow conditions. The case reports will focus on the necessity to present Doppler intensity kinetics by Doppler intensity vs time plots or coloured M-modes to present the data more objectively. In addition, the hypoperfusion detected with myocardial contrast echocardiography via bolus injection of microbubbles can only be proven by changes of regional perfusion between repetitive myocardial contrast echocardiography measurements or by additional perfusion analysis, e.g. by scintiscanning.

Acute Disease↗

Reactor Design Issues for Synthesis-Gas Fermentations.

Synthesis gas is readily obtained by gasifying coal, oil, biomass, or waste organics and represents an abundant, potentially inexpensive, feedstock for bioprocessing. The primary components of synthesis gas, carbon monoxide and hydrogen, can be converted into methane, organic acids, and alcohols via anaerobic fermentations. Bioconversion of synthesis gas is an attractive alternative to catalytic processing because the biological catalysts are highly specific and often more tolerant of sulfur contaminants than inorganic catalysts. However, because the aqueous solubilities of carbon monoxide and hydrogen are low, synthesis-gas fermentations are typically limited by the rate of gas-to-liquid mass transfer. Consequently, a major engineering challenge in commercial development of synthesis-gas fermentations is to provide sufficient gas mass transfer in an energy-efficient manner. This paper reviews recent progress in the development of synthesis-gas fermentations, with emphasis on efforts to increase the efficiency of gas mass transfer. Metabolic properties of several microbes able to ferment synthesis gas are described. Results of synthesis-gas fermentations conducted in various bioreactor configurations are summarized. Recent results showing enhancement of synthesis-gas fermentations using microbubble dispersions are presented, and studies of the mass-transfer and coalescence properties of microbubbles are described.

Journal Article↗

Irreversible unfolding of myoglobin in an aqueous solution by supercritical carbon dioxide.

The conformational changes in myoglobin, treated by microbubbling of supercritical carbon dioxide (SC-CO(2)), were investigated by measuring the circular dichroism spectra in the ultraviolet range and compared with those in other proteins (ovoalbumin, bovine serum albumin, and beta-lactoglobulin). Irreversible unfoldings were observed after the microbubbling of SC-CO(2) at 35 degrees C and 30 MPa for 30 min. The degree of unfolding depended on the number of intramolecular S-S bonds. alpha-Helix contents of myoglobin decreased with increasing density of SC-CO(2). Unfoldings of myoglobin induced by heating, pH-lowering, and the addition of a denaturant were reversible. The irreversible unfolding of myoglobin was also observed by the bubbling of gaseous CO(2) under atmospheric pressure, but heating was required.

Animals↗

Test of the Epstein-Plesset model for gas microparticle dissolution in aqueous media: effect of surface tension and gas undersaturation in solution.

The gas from a free air bubble will readily dissolve in water, driven by two main factors: the concentration (undersaturation) of dissolved gas in the aqueous solution and the surface tension of the gas bubble-water interface via a Laplace overpressure in the bubble that this creates. This paper experimentally and theoretically investigates each of these effects individually. To study the effects of surface tension, single- and double-chain surfactants were utilized to control and define interfacial conditions of the microbubble in saturated solution. To study the effect of undersaturation, solid distearoylphosphocholine lipid was utilized to coat the gas microparticle with, essentially, a wax monolayer and to achieve zero tension in the surface. The experimental work was performed using a micromanipulation technique that allows one to create and micromanipulate single air microparticles (5-50 microm radius range) in infinite dilution and to accurately record the size of the particle as it loses volume due to the dissolution process. The micropipet technique has shown to be an improvement over other previous attempts to measure dissolution time with a 3.2% average experimental error in gas microparticle dissolution time. An ability to study a gas microparticle in infinite dilution in an isotropic diffusion field is in line with the theoretical assumptions and conditions of the Epstein-Plesset model. The Epstein-Plesset model on average underpredicted the experimentally determined dissolution time by 8.6%, where the effect of surface tension was considered with a range of surface tensions from 72 down to 25 mN/m. The Epstein-Plesset model on average overpredicted the dissolution time by 8.2%, where the effect of undersaturation was considered for a microparticle with zero tension in the surface (zero Laplace pressure) and a range of gas saturations from 70% to 100%. Compared to previous attempts in the literature, this paper more appropriately and accurately tests the Epstein-Plesset model for the dissolution of a single microbubble and an air-filled microparticle in aqueous solution.

Gases↗