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Microbubble elimination during priming improves biocompatibility of membrane oxygenators.

We tested the hypothesis that platelet loss following blood contact with foreign materials is partly related to the presence of microbubbles of gas (gas nuclei) trapped in surface defects on the membrane material. Extracorporeal membrane oxygenator perfusions were conducted in two groups of sheep, with use of standard priming techniques for the oxygenator in one group and a new vacuum priming technique in the other group. The vacuum priming technique was developed to eliminate gas nuclei from the oxygenator surface. With denucleation priming, platelet loss during perfusion was markedly reduced, as was thrombus formation on the membrane surface. The platelet particle-size distribution curve showed a shift consistent with platelet aggregation with the standard priming technique but not with the vacuum priming technique. We conclude that the elimination of trapped gas nuclei from the membrane surface during priming reduces the initial interaction between blood elements and the foreign surface.

Animals

Sonography with intraarterial infusion of carbon dioxide microbubbles (sonographic angiography): value in differential diagnosis of hepatic tumors.

Differential diagnosis of small liver tumors is important, but is not always possible, even with angiography. To solve this problem, we introduced sonographic angiography, which combines sonography and angiography. The vascular pattern of a variety of hepatic nodules was evaluated with sonographic angiography, and the results were compared with those of conventional angiography. Sonographic angiography (sonography performed during intraarterial infusion of carbon dioxide microbubbles) was performed in 184 patients with a total of 222 hepatic nodules: 139 hepatocellular carcinomas, nine adenomatous hyperplasias, seven regenerative nodules, 21 hemangiomas, 33 metastases, seven lymphomas, one granuloma, and five focal nodular hyperplasias. Sonographic angiography detected a hypervascular pattern with peripheral blood supply in cases of hepatocellular carcinoma (sensitivity, 90%; specificity, 89%). Typical vascular patterns of adenomatous hyperplasia, hemangioma, metastasis, and focal nodular hyperplasia on sonographic angiography were hypovascularity (sensitivity, 100%; specificity, 91%), spotty pooling (sensitivity, 100%; specificity, 100%), peripheral hypervascularity (sensitivity, 64%; specificity, 100%), respectively. The detectability of hypervascularity was greater with sonographic angiography than with conventional angiography in hepatocellular carcinoma, metastasis, and hemangioma. Our experience indicates that sonographic angiography depicts characteristic vascular features that reflect the vascular anatomy of specific types of hepatic tumors, and thus is useful in the differential diagnosis of these lesions.

Carbon Dioxide

[Prenatal assessment of fetal lung maturity by the stable microbubble method--fundamental and clinical study].

Diagnostic value of RDS was investigated by the Stable Microbubble Method. When this method was applied to the tracheal fluid of fetuses in rabbit (28 days of gestation), the PV curve and lung-thoracic compliance showed mature patterns in the test results for weak, medium, and strong as compared with those for zero and very weak in which they showed an immature pattern. Results by this method correlated with the DSPC level in human amniotic fluid, and were little affected by the contamination of meconium or fresh plasma. Amounts of DSPC were 0.69 +/- 0.05 (mg/dl, Mean +/- SE) in zero, 1.19 +/- 0.15 in very weak, 3.99 +/- 5.06 in weak, 6.58 +/- 2.01 in medium, and 7.70 +/- 1.15 in strong test results. The coefficient of correlation was 0.56 (p less than 0.01). In the clinical study, when the mature level was arbitrarily defined as weak, the diagnostic accuracy was 76.8%, false negative rate was 0%, and false positive rate was 27.5%. If the mature level was defined as very weak, the diagnostic accuracy was 94.2% and the false positive rate was 3.4%. But the false negative rate increased to 18.8%. The diagnostic accuracy of this method was higher than the double shake test (72.2%), and was as high as the measurement of the DSPC level (92.0%).

Amniotic Fluid

A new method for assessing right-sided heart pressures using encapsulated microbubbles--a preliminary report.

A new noncatheter method for measuring pressures of the right side of the heart uses specially manufactured microbubbles of carbon dioxide injected into the peripheral venous system. Sudden expansion of these bubbles in the cardiac chambers causes bubble oscillations at a frequency that is primarily a function of surrounding pressure. The oscillations are recordable by a microphone on the chest wall. The preliminary experience has been in dogs and further development is needed before we can begin clinical testing of the method. In its current form, the potential for measuring higher systolic pressures seems better than that for lower diastolic pressures.

Animals

Effect of intracoronary injections of sonicated microbubbles on left ventricular contractility.

Despite the recent interest in contrast-enhanced echocardiography as a means of defining myocardial perfusion, the effects of echo contrast agents on left ventricular (LV) contractility in humans remains poorly defined. This is particularly relevant because intracoronary injection of contrast agents used for angiographic visualization of coronary arteries produces significant alterations in LV hemodynamics. The relation of LV end-systolic wall stress (sigma es) to rate-corrected velocity of fiber shortening (Vcfc), a load-independent index of contractility, was studied in 7 patients undergoing elective coronary arteriography. Two-dimensional and targeted M-mode echocardiographic and central aortic pressure tracings were recorded during injections of standard volumes of angiographic (7 to 9 ml of nonsonicated Renografin-76) and echocardiographic (1.5 to 2.0 ml of sonicated Renografin-76) contrast agents into the left main coronary artery. The order in which agents were injected was randomly determined. Myocardial contractility was assessed under control conditions and 5 and 15 seconds after injection. Alterations in contractility relative to control were measured as the change in Vcfc after elimination of afterload (sigma es) as a confounding variable. An injection of Renografin-76 adequate for angiographic imaging of coronary artery anatomy resulted in a significant depression of LV contractility (p less than 0.001) in conjunction with a tendency toward increased afterload (p = 0.12); recovery occurred by 15 seconds after injection. The smaller amounts of sonicated Renografin-76 required to give adequate contrast enhancement of the myocardium did not alter LV contractile state or afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Evaluation of ultrasonic bubble detectors in vitro using calibrated microbubbles at selected velocities.

Two standard Doppler ultrasonic devices, currently used for detecting bubbles in vivo, have been evaluated and compared in vitro using carefully calibrated uniform micro-bubbles rising at terminal velocity through a static aqueous medium. Two unexpected findings were observed: (a) the focal length of the transducer apparently decreases for smaller bubble sizes, and (b) a significant horizontal convection current was produced by one of the instruments. When the medium was in motion, it was found that the sensitivity varied markedly with bubble velocity, varying from a minimum detectable diameter of 40 mum at 55 cm/sec to 170 mum at 20 cm/sec. These findings are discussed with regard to the limitations of the Doppler technique for monitoring gas emboli in vivo and as an early warning for decompression sickness in divers.

Decompression Sickness

Measurements of frequency spectra of transmission coefficients to ultrasound through trapped microbubbles.

Techniques which use hydrophobic polycarbonate thin sheets containing randomly spaced, fairly uniform small pores immersed in water to trap air bubbles have been found to be useful in biophysical experiments. The utilization of broadband polyvinylidene fluoride transducers in this work made it possible to measure a continuous frequency spectrum of the transmission coefficient of the trapped bubbles. The results of the measurements show: (1) the frequency response curve of the bubble ensemble is much broader than that of a single bubble predicted by theory; and (2) as the incident sound pressure at a micropore membrane increases from 110 to 660 Pa the resonance frequency of bubbles shifts to lower values by as much as 7%.

Air

Imaging microbubbles and tissues using a linear focussed scanner operating at 20 MHz: possible implications for the detection of cavitation thresholds.

B-Scan images have been used as a means of detecting the onset of cavitation in tissues. New echoes appearing during simultaneous sonication with therapeutic ultrasound have often been attributed to bubble formation. In this study temperature rises up to 15 degrees C W-1 cm2 in guinea pig leg (post-mortem) were found, which would itself increase the rate of growth of gas bubbles. It is also hypothesized that a temperature dependent attenuation coefficient predicted by Bamber and Hill may, at least in part, account for new echoes appearing in tissues. Possible artefactual echoes in the B-scan images arising from acoustically induced gas bubbles in the coupling medium are also discussed.

Animals

Contrast agents for diagnostic ultrasound: development and evaluation of polymer-coated microbubbles.

Although the concept of an ultrasound contrast agent dates from Gramiak's work in 1968 in which indocyanine green was injected into the ascending aorta and heart, no universally accepted contrast agent for ultrasound now exists. This is primarily due to problems with stability, size and/or toxicity of the agents which have been investigated. Development of an effective ultrasound contrast agent would be highly significant for the health care industry, since it would greatly expand the scope of ultrasound (a noninvasive and safe procedure) as a diagnostic technique. While encapsulated gas bubbles offer particular advantages in stability over hand-agitated systems, they frequently present problems with size. Capsules larger than 10 microns in diameter become entrapped in the capillary bed of the lung. This paper describes the use of ionotropic gelation of the naturally occurring polysaccharide, alginate, for microencapsulation of air. Two procedures have been investigated. A novel jet head has been developed which allows co-extrusion of a solution of sodium alginate and air to produce nascent microencapsulated air bubbles which fall into a hardening solution of calcium ions. A second method employs ultrasound to introduce cavitation-induced bubbles into the alginate before capsule formation by spraying. Power spectra of these preparations demonstrate echogenicity (that is strong scatter of the incident ultrasound wave back to the emitting transducer, which also acts as a receiver), with resonant peaks that are a function of capsule size and wall characteristics.

Alginates

Echocardiographic contrast agents: effect of microbubbles and carrier solutions on left ventricular contractility.

Recently, there has been a resurgence of interest in the use of contrast-enhanced echocardiography as a means of noninvasively assessing myocardial perfusion. However, if injections of echocardiographic contrast agents are to be used for this purpose it is essential that they are not intrinsically toxic to the heart. In this study, the left ventricular end-systolic wall stress-rate-corrected velocity of fiber shortening relation, a load independent index of contractility, was studied in nine dogs. Two-dimensional and targeted M-mode echocardiographic as well as central aortic pressure tracings were made during echocardiographically gated, pressure- and volume-controlled aortic root injections of nonsonicated and sonicated Renografin-76, saline and dextrose 70% (n = 6), and sonicated and hand-agitated Renografin-76/saline mixture (n = 5). Two of nine dogs received all agents. Off-line computer videodensitometric analysis documented myocardial perfusion. In all cases, data were obtained at control and 5 and 15 seconds after injection. Additional data were collected at 25 seconds after injection for the Renografin-76/saline mixture. Alterations in contractility were measured relative to control as changes in rate-corrected velocity of fiber shortening after afterload (measured as end-systolic wall stress) was eliminated as a confounding variable. Under no condition did saline or Renografin-76 cause alterations in left ventricular contractility. Nonsonicated and sonicated dextrose 70% increased left ventricular contractility at 15 seconds but not at 5 seconds after injection. Hand-agitated Renografin-76/saline mixture induced a negative inotropic effect at 5 and 15 seconds after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals