PubMed HealthSearch

SEARCH · PubMed Health

Results for “Microbubbles”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

Value of intraoperative left ventricular microbubbles detected by transesophageal two-dimensional echocardiography in predicting neurologic outcome after cardiac operations.

To determine whether the presence or absence of left ventricular (LV) intracavitary microbubbles during cardiac surgery predicts neurologic sequelae, 82 patients undergoing cardiac surgery were studied using transesophageal 2-dimensional (2-D) echocardiography. Cross-sectional images were recorded just before and immediately after cardiopulmonary bypass and stop frames were reviewed for the presence of microbubbles, rated as: 0 = absent, 1 = fewer than 5/frame, 2 = 10 to 25/frame, 3 = too numerous to count. Microbubbles were detected after cardiopulmonary bypass in 34 patients (41%) and found more often in valvular or other intracardiac manipulations than in coronary revascularization, 30 of 40 vs 4 of 42, respectively (p less than 0.001). When grade 2 or 3 microbubbles were identified (22 of 34 patients), mechanical attempts to eradicate them were not successful. Postoperative follow-up in all patients revealed no new focal neurologic deficits. Prolonged encephalopathy (confusional state more than 72 hours) occurred in 4 of 48 patients with no detectable microbubbles and in 3 of 34 patients with microbubbles (difference not significant). Thus, intracavitary left ventricular microbubbles are often detected during cardiac operations, particularly during valve replacement, but are not predictive of postoperative neurologic complications. This is true even if microbubbles are densely concentrated; attempts to eradicate microbubbles are unsuccessful and may be unnecessary.

Cardiac Surgical Procedures

The behavior of sonicated albumin microbubbles within the microcirculation: a basis for their use during myocardial contrast echocardiography.

The purpose of this study was to determine whether the behavior of sonicated albumin microbubbles accurately mimics red blood cell flow in the microcirculation and is thus consistent with their use as in vivo tracers of red blood cell flow during myocardial contrast echocardiography. Accordingly, microbubbles prepared from fluorescein-conjugated albumin and fluorescently labeled red blood cells were injected intravascularly in eight golden hamsters. Their intravascular distribution, velocities, arteriolar-to-venular transit and flux ratios at branch points were determined in the microcirculation of the cheek pouch. Albumin microbubbles (mean diameter, 4.9 +/- 3.6 microns) and red blood cells displayed a similar frequency of distribution across the arteriolar lumen (33% in the central 20% of the arterioles), and their arteriolar velocities were also similar (2.5 +/- 0.7 mm/sec and 2.3 +/- 0.7 mm/sec,p = NS). The mean velocities of microbubbles correlated well with those of red blood cells at baseline and after adenosine application (r = 0.97 and r = 0.89, respectively), as did the calculated maximum velocity (r = 0.98 and r = 0.80, baseline and adenosine, respectively). The velocity profiles across the lumen of the vessels for albumin microbubbles and red blood cells were similar at baseline and after adenosine-induced velocity changes. The flux ratios at branch points also correlated well (r = 0.92, p less than 0.001). Arteriolar-to-venular transit times of albumin microbubbles were similar to those of red blood cells in vessels ranging in size from 22 microns to 45 microns. We conclude that the behavior of albumin microbubbles in the microcirculation mimics that of red blood cells and supports their use as intravascular tracers of red blood cell flow during myocardial contrast echocardiography.

Animals

Microbubble-induced serotonin secretion in human platelets.

The effect of nitrogen (N2) microbubbles on platelets resembles that of common platelet agonists with respect to aggregation (Thorsen T et al., Undersea Biomed Res 1986; 13: 289-303). In the present study we examined the effect of microbubbles on platelet secretion of preloaded 14C-serotonin. We demonstrate that stirring of platelet-rich plasma with N2-microbubbles causes a loss of single platelets that is associated with secretion. However, secretion did not increase above baseline values until after 20 min of microbubble exposure, when platelet aggregation had reached 40%. After that time the secretion rate increased. There was no correlation between secreted serotonin and the degree of platelet aggregation. Although no 14C-serotonin secretion occurred in presence of acetylsalicyclic acid (ASA), microbubble-induced platelet aggregation was only marginally reduced. Epinephrine alone caused significant platelet aggregation but no 14C-serotonin secretion and it enhanced N2-microbubble-induced platelet aggregation and secretion; ASA completely prevented secretion under these circumstances but failed to abolish the enhancement of aggregation compared with microbubbles alone. Earlier studies have shown that platelets adhere to the bubble surfaces (Thorsen T et al., Undersea Biomed Res 1987; 14: 45-59). The results in the present study indicate that non-adhering platelets in the bulk phase are not activated by means of autocrine stimulation through dense granule material.

Blood Platelets

Generating precision microbubbles for use as an echocardiographic contrast agent.

To investigate whether precision microbubbles can be simply generated and used for quantitative contrast echocardiographic studies, precision microbubbles were fabricated in gelatin using a simple generator. The generator consisted of a fluid pump, a generating site containing a narrow bore tube and a bubble stream output port. Up to 5,000 microbubbles/s were generated with a controllable radius of 80 to 150 mu. No detectable interbubble size variation was observed under high power microscopy. To examine whether these bubbles could be used for quantitative contrast echocardiographic studies, they were then infused into a tube with a known flow of degassed water during ultrasonic imaging. The resulting ultrasonic contrast effect in the tube lumen at steady state was recorded and subsequently measured by videodensitometry. The precision microbubbles were visually and microscopically stable during the experimental run. Correlations between microbubble infusion rate and luminal videodensitometry on individual runs were r = 0.89, 0.83, 0.73 and 0.71. It is concluded that precision microbubbles can be generated in sufficient quantities on site to serve as an echocardiographic contrast agent for quantitative studies in vitro and at a very modest cost. These precision microbubbles are sufficiently stable to be collected and stored for short periods of time.

Air

Lipid-coated ultrastable microbubbles as a contrast agent in neurosonography.

Lipid-coated microbubbles can be synthesized from selected lipid monolayer systems for use as ultrasonic contrast. These microbubbles have the property of longevity of weeks in vitro (ultrastability) and longevity of hours in vivo. The bubbles can be manufactured with a mean diameter of approximately 2 microns in a tight diameter distribution; all are less than 6 microns and 99% are smaller than 4.5 microns. The current study compared the in vivo survival characteristics of these lipid-coated microbubbles with microbubbles produced by saline. The comparison was made in the rat brain using direct intraparenchymal injections and injections into a previously created cyst/coagulum. The echogenic enhancement by the lipid-coated microbubbles persisted in vivo for over 24 hours in both the intraparenchymal environment and in the cyst/coagulum. The saline bubble echos were not detectable by 3 hours in a cyst/coagulum, and not detectable in the parenchyma after 2 hours. The sonographic characteristics and longevity of lipid-coated microbubbles make this agent a potentially useful clinical contrast material for neurosonography.

Animals

Production of microbubbles for use as echo contrast agents.

A variety of agents have been proposed for use as contrast for ultrasound studies. Several reports suggest the use of microbubbles because of their superior sonographic resolution. We describe a method of producing calibrated microbubbles utilizing differential absorption and gas injection techniques. Gas injection methods are described using a Plexiglas microbubbler apparatus with a fine needle orifice. The bubbles originally produced by this device are in a size range of 40-100 microns and consist of nitrogen (10%) and carbon dioxide (90%). The differential absorption technique uses THAM [tris(hydroxymethyl)aminomethane hydrochloride] to absorb the carbon dioxide (diluent gas) from the bubbles selectively, leaving smaller microbubbles. The microbubbles can be calibrated using the electric gating principle of the Coulter Counter.

Bicarbonates

Air-filled proteinaceous microbubbles: synthesis of an echo-contrast agent.

Air-filled microbubbles are in clinical use as echo-contrast agents for sonographic applications. The synthesis of aqueous suspensions of air-filled proteinaceous microbubbles involves the ultrasonic irradiation of aqueous protein solutions in the presence of O2. Yields and size distributions of human and bovine serum albumin microbubbles have been determined as a function of various experimental parameters. The chemical nature of these microbubbles and the origin of their remarkably long lifetimes have been explored. The microbubbles are held together primarily by interprotein cross-linking of cysteine residues. The principal cross-linking agent is superoxide created by the extremely high temperatures produced during acoustic cavitation.

Animals

Microbubble damage to the blood-brain barrier: relevance to decompression sickness.

Decompression sickness affecting the nervous system is still a serious problem in diving, but the mechanisms involved are in dispute. Although microbubbles can be detected in the pulmonary artery on decompression using ultrasound, mammalian lungs are competent filters for microbubbles larger than 20 microns in diameter. It has been assumed that smaller bubbles released by the lungs are harmless, because there is evidence that they do not arrest in the cerebral circulation. We injected 15 +/- 5 microns diameter microbubbles in 5 ml of plasma slowly into the right carotid artery of anesthetized guinea pigs. At intervals of 1, 2, or 3 h postinjection, 2% trypan blue in 2 ml of plasma was injected into the same artery or the contralateral carotid artery. A control animal for each experiment was injected with 5 ml of plasma only, followed by the injection of dye at the same interval. After the animals were killed, the brains were examined for evidence of blood-brain barrier dysfunction. All animals at 1 h, and 9 out of 10 animals at 2 h after the injection of microbubbles, showed extravasation of the albumin-binding dye in the ipsilateral hemisphere, indicating gross blood-brain barrier dysfunction. In each of the matched controls, the barrier in the neocortex remained intact. At Hour 3 the barrier was impermeable to the trypan blue in both experimental and control animals. These experiments demonstrate that microbubbles impair the blood-brain barrier integrity to protein, causing focal edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Induction of platelet aggregation in vitro by microbubbles of nitrogen.

Microbubbles of nitrogen gas act as a platelet agonist, but the biochemical mechanisms involved in bubble-induced platelet activation are not well known. One characteristic property of a platelet agonist is to potentiate the response by another agonist in a synergistic manner at low concentrations. Possible synergism between N2 gas bubbles and the physiologic agonists ADP, epinephrine, and 5-hydroxytryptamine (5-HT) was tested. The interaction with ADP was additive; N2 microbubbles and ADP had different aggregation profiles, and the bubbles made the reversible ADP aggregation irreversible. Epinephrine caused a strong, synergistic stimulation of bubble-induced platelet aggregation. This synergism was only partially inhibited by indomethacin and acetylsalicylic acid, but abolished by yohimbine. 5-HT had an inhibitory effect on N2 microbubble-induced platelet aggregation. This effect was neutralized by the S2-serotonergic receptor blocker ketanserin. Microbubble stimulation of the platelets before stimulation with ADP, epinephrine, and 5-HT seemed to make them more sensitive to epinephrine only. The strong synergism between microbubbles and epinephrine in vitro should be evaluated for possible future use in predive selection of divers.

Adenosine Diphosphate

Myocardial contrast two-dimensional echocardiography: dose-myocardial effect relations of intracoronary microbubbles.

It is controversial whether echocardiographic contrast agents prepared by sonication cause transient myocardial depression beyond that known to occur with contrast agents alone. In nine open chest dogs, contrast injections were made into the left anterior descending coronary artery during two-dimensional echocardiography. One hundred forty-four recordings were analyzed subsequently, by an observer who was unaware of other data, for percent depression of systolic wall thickening, duration of regional wall motion abnormalities, peak contrast enhancement and contrast washout. Two microbubble sizes were obtained by sonicating Renografin-76 (meglumine sodium diatrizoate): mean diameter 12 +/- 3 (SEE) and 20 +/- 6 micron. Four doses (range 0.5 to 3 ml) of each of four agents (12 and 20 micron bubbles in Renografin, nonsonicated Renografin and saline solution) were injected in random order. Significant relations were found between percent depression of systolic wall thickening, duration of regional wall motion abnormalities and contrast washout time versus microbubble size (p less than 0.001) and microbubble dose (p less than 0.01). Little increased contrast effect was found at larger doses or with larger microbubbles compared with the smaller doses and size studied. Injections of nonsonicated Renografin caused less depression of systolic wall thickening (p less than 0.05), faster resolution of wall motion abnormalities (p less than 0.05), less contrast (p less than 0.001) and more rapid contrast washout (p less than 0.001) than did 12 micron bubbles in Renografin. A significant correlation was found between the duration of regional wall motion abnormalities and contrast washout time (r = 0.93, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Microbubbles in replicating nuclear deoxyribonucleic acid from Physarum polycephalum.

Clusters of microbubbles, represent probable sites of newly initiated DNA synthesis, were identified in nuclear DNA from Physarum polycephalum by using the electron microscope. Their presence is associated specifically with S-phase. Each microbubble corresponds in size to a replicating segment of DNA about 100-5000 nucleotide residues in length. The DNA structures containing microbubbles are metastable, and revert to native DNA in the presence of moderate concentrations of formamide used to prepare samples for electron microscopy. It is suggested that each cluster of microbubbles may correspond to a unit of replication (a replicon) in Physarum DNA.

Cell Nucleus

Precision and reliability of stable microbubble test as a predictor of respiratory distress syndrome.

The precision and reliability of the stable microbubble test as a predictor of respiratory distress syndrome (RDS) were studied. In blind experiments, the stable microbubble test was performed by three analysts in quadruplicate on six different amniotic fluid samples obtained from pregnant women whose babies developed RDS and on three samples prepared from mature controls. Three-way analysis of variance revealed that there were statistically significant differential effects of the analyst, observer, and sampling on the stable microbubble values, and also that there were statistically significant interactions between the analyst and observer as well as between the analyst and sampling. However, the magnitude of these effects was not large enough to modify the interpretation of the test results. We conclude that the rapidity, simplicity and reliability of the stable microbubble test allow for its use as a bedside procedure in identifying infants who are likely to develop RDS.

Amniocentesis

Fatty acids in human platelets and plasma. Fish oils decrease sensitivity toward N2 microbubbles.

Platelet aggregation induced by N2 microbubbles (simulating microbubbles developed during deep diving) was measured in seven volunteers before and after intake of ethyl-eicosapentaenoate (-EPA, 3.5 g/day) and ethyl-docosahexaenoate (-DHA, 2.5 g/day) for 2 wk. The relative content of arachidonic acid (AA) decreased in platelets from all individuals, whereas the content of EPA and DHA increased. The decrease of AA was almost identical with the increase of EPA plus DHA. In plasma the AA content was unchanged, while EPA and DHA increased. The N2 microbubble-induced aggregation showed a significant negative correlation with the DHA content both in platelets and in plasma. Less aggregation was also observed with high EPA content in platelets or plasma. A significant correlation between AA content in platelets and aggregation was seen. Intake of marine oils may be beneficial to divers under deep diving and to patients during extracorporeal circulation, because this may reduce the microbubble-induced aggregation.

Adult

Effects of platelet antagonists on the reduction in platelet density caused by microbubbles in vitro.

Platelet-rich plasma (PRP) was stirred and incubated at 37 degrees C with N2 microbubbles in vitro in the presence and absence of platelet antagonists. The N2 microbubbles acted as a platelet agonist, like "classical" agonists such as ADP, collagen, and thrombin, causing an agonist-induced aggregation requiring extracellular Ca2+. This aggregation is abolished by 2-ethylamineglycolether (N',N',N',N') tetraacetate (chelator of extracellular Ca2+), and 2-deoxy-D-glucose plus antimycin A (inhibitors of glycolysis and electron transport, and thereby of ATP production). Furthermore, this aggregation could be depressed pharmacologically by several antagonists of the aggregation induced by "classical" platelet agonists. The greatest inhibition of microbubble-induced aggregation was obtained by substances that increase the intracellular levels of cyclic AMP. Medications that are in common clinical use, such as theophylline, seem promising in this respect. The prostaglandin-thromboxane pathway did not seem to be involved in the N2 microbubble-induced platelet aggregation in vitro, since acetylsalicylic acid and indomethacin were without effect, nor did the 3',5'-cyclic guanosine monophosphate pathway seem to be linked to this aggregation mechanism.

3',5'-Cyclic-AMP Phosphodiesterases

[A newly developed instrument of microbubble test for evaluation of fetal lung maturity].

A new instrument for Pattle's microbubble test was devised in order to improve the diagnosis of fetal lung maturity. This instrument consists of 4 needles fixed at 8mm intervals and an air pump. Microbubbles were produced in 175 microliter of amniotic fluid placed on a slide glass by injecting 10 ml of air at 400 ml/h with an air pump through 22 gage needles. After 4 minutes, the number of stable microbubbles less than 15 um in diameter were counted in 5 microscope fields. When over 6 microbubbles were observed, fetal lung maturity was diagnosed as positive. 72 samples of amniotic fluids were tested by our method as well as the other 5 methods. The percentage of accurate diagnostic results was 97.2% with our method, 93.1% with the L/S ratio, 83.3% with the DSPC method, 86.1% with the PG method, 93.1% with the shake method, and 94.4% with the Pattle's original method. It is concluded that ours is a reliable, rapid and simple method for evaluating fetal lung maturity.

Female

Transmission and scanning electron microscopy of N2 microbubble-activated human platelets in vitro.

When N2 microbubbles are stirred in platelet-rich plasma, they cause a fall in the number of free platelets. Changes in the platelets ultrastructure during this interaction between gas bubbles and platelets have been studied by transmission and scanning electron microscopy. Platelets, and aggregates of platelets, adhere to the surface of the N2 microbubbles. This adhesion induces ultrastructural changes (shape change, pseudopod formation, granule centralization, fusion, and disappearance) that are similar to "classical" agonists like ADP, collagen, and thrombin. These ultrastructural studies further strengthen our previous contention that N2 microbubbles activate platelets in a way similar to these physiologic agonists, and show that the previously reported fall in the number of free platelets is due to platelet aggregation. Platelet aggregates are also present in the interstices between gas bubbles. Fixed N2 microbubbles have been demonstrated, and these can be broken like cracked eggs by means of the electron beam in the electron microscope. Possible mechanisms for activation of the platelets by the gas bubbles are: through ADP released from some few platelets; by diffusion of gas after bubble-platelet interaction; and through certain fractions of the plasma proteins and lipids in the bubble surface that may act as binding sites for the platelets and promote adhesion and spreading of the platelets over the surface.

Blood Platelets

Saline microbubbles monitoring sonography-assisted abscess drainage.

The objective of this study was to assess the use of saline microbubbles as a sonographic contrast medium in monitoring abscess drainage. Seven abscesses were localized and drained with sonographic guidance. Four were in the brain and three were small abscesses in the liver, the subhepatic region, and the pancreas. After aspiration of the purulent material, irrigation with saline produced a highly echogenic sonographic pattern that was free of artifacts and distinctly different from the abscess contents and capsule, and the surrounding parenchyma. In one case, previously unsuspected loculation was detected, requiring repositioning of the needle for complete drainage. All abscesses were resolved and no untoward effects, such as sepsis, were encountered. In one additional patient, microbubble sonographic evaluation was used to monitor the progress of an abscess in which a percutaneous catheter was placed. Saline microbubbles may be used as a sonographic contrast medium to monitor sonography-assisted abscess drainage.

Abdomen

Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent.

We have previously reported that ultrastable lipid-coated microbubbles make a suitable ultrasonic contrast agent in the brain, causing increased intensity of echoes that persists for many hours. We showed that intravenously administered lipid-coated microbubbles accumulate selectively in rat brain gliomas with echogenicity enhancement for up to 1 hour, allowing visualization of the growing lesions 40% (2 days) earlier than can be seen without contrast. This work is a detailed evaluation of the accumulation of the lipid-coated microbubbles in tumor and the effect of the bubbles on the echogenicity of insonified tumors. Using a lipid-specific stain, we measured and characterized the distribution of the bubbles in the brain and tumor. We showed that on the scan, the enhancement of the tumor is accompanied by a change in the signal-to-noise ratio of the echoes from the tumor. We identified characteristic textural changes associated with contrast-enhanced tumor using spectral analysis.

Animals