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Detection of bleeding in injured femoral arteries with contrast-enhanced sonography.

OBJECTIVE: The purpose of this study was to investigate the feasibility of detecting acute arterial bleeding by means of contrast-enhanced sonography. METHODS: Puncture injury was produced transcutaneously with an 18-gauge needle in 26 femoral arteries (13 in the control group and 13 in the contrast-enhanced group) of rabbits. A sonographic contrast agent (Optison; Mallinckrodt Inc, St Louis, MO) was administered intravenously at a dose of 0.06 to 0.07 mL/kg. Sonography of the femoral arteries was performed before and after injury, both before and after injection of Optison, with B-mode imaging, color Doppler imaging, and pulse inversion harmonic imaging (PIHI). RESULTS: The specific location of active bleeding could not be visualized in B-mode and PIHI scans in the control group (no Optison injection). After administration of Optison, the bleeding site was visualized because of the increased echogenicity of the extravasated blood at the puncture site in both B-mode imaging and PIHI. In color Doppler images, bleeding sites were localized successfully in 84.6% of the cases in the presence of Optison and in 30.8% of the cases without Optison. Histologic examination (light microscopy) of the hematoma confirmed the presence of contrast agent microbubbles in the extravascular space surrounding the artery. CONCLUSIONS: Contrast-enhanced sonography may provide an effective method for detecting arterial bleeding.

Albumins↗

Significant safety advantages gained with an improved pressure-regulated blood pump.

A prototype of a non-occlusive pressure-regulated blood pump (M-pump) was evaluated in-vitro for safety in a comparative study with the roller and centrifugal pumps. The M-pump consists of collapsible tubing of unique design wrapped under tension around a rotor without a stator. The prototype M-pumps were tested in vitro to evaluate performance with respect to flow/ pressure characteristics, hemolysis, bubble generation (cavitation) and durability. The M-pump and centrifugal pump did not overpressurize at any RPM when the pump outlet was occluded, but the roller pump reached pressures in excess of 1000 mmHg. The M-pump did not generate negative pressures upon occlusion of the inlet, whereas the roller and centrifugal pumps produced near-vacuum pressures. Furthermore, the M-pump was unable to empty a blood reservoir when the height of the pump inlet was placed slightly above the reservoir outlet. The levels of microbubbles in the M-pump were significantly lower than the roller and centrifugal pumps upon sudden restriction of the pump inlet as determined with an ultrasonic bubble detector. The results of our in-vitro evaluation of the M-pump have shown it to have lower hemolysis than the centrifugal pump and lower or comparable hemolysis to roller pumps at flowrates of 0.1, 0.5, 4.0 and 6 L/min. We determined that the M-pump design possesses important safety advantages over roller and centrifugal pumps for cardiopulmonary bypass applications.

Air↗

Transcranial Doppler: preventing stroke during carotid endarterectomy.

Carotid endarterectomy (CEA) is more effective at preventing strokes than medical therapy alone in those patients with severe symptomatic stenosis of the internal carotid artery and this benefit persists despite a perioperative stroke/death rate of approximately 5%. Thromboembolism has been established as the underlying cause of the majority of perioperative strokes, but this could not be detected using the existing methods of monitoring or quality control. Early studies demonstrated that transcranial Doppler monitoring (TCD) could detect intraoperative embolism, but the clinical significance of this finding was questioned as the incidence of these emboli far exceeded the incidence of perioperative strokes. This study aimed to establish the clinical relevance of TCD-detected emboli during CEA by differentiating emboli into two broad categories; air and particulate, and comparing the quantity of each with a variety of clinical outcomes including neurological and cognitive function, retinal fundoscopy, automated visual fields and CT/MRI brain scans. This prospective study was performed on 100 consecutive patients undergoing CEA with all assessments performed pre- and postoperatively by independent specialists in the relevant fields. Embolisation was detected in 92% of successfully monitored operations. Most emboli were characteristic of air microbubbles and not associated with the development of adverse clinical events. However, emboli characteristic of particulate material were detected during the initial dissection phase and in the recovery phase after final restoration of flow. These particulate emboli were associated with the development of both neurological and cognitive deficits. In particular, persistent embolisation after final restoration of flow heralded incipient carotid artery thrombosis and the development of stroke. Early intervention based on the TCD evidence of continuing embolisation can prevent the stroke from occurring.

Aged↗

Hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS) is a rare complication of liver cirrhosis and is characterised by the typical triad of liver cirrhosis, arterial hypoxemia, and intrapulmonary vascular dilatation. Except for pleural effusions associated with liver cirrhosis no other disease of the lungs or the heart is detectable. The structural hallmark of HPS is dilatation of pulmonary precapillary vessels which impairs diffusion-perfusion and causes unequal ventilation-perfusion. The diagnosis of HPS is based on PaO2 measurements when breathing room air and 100% oxygen. The increased intrapulmonary vascular diameter allows microbubbles to traverse the lung capillaries when agitated saline is administered intravenously. Only on rare occasions is a patient limited by his pulmonary impairment, the leading morbidity is that of liver disease and its classical complications. Drug therapy is of no proven benefit, oxygen supplementation might improve dyspnea. Vascular embolisation of discrete arteriovenous shunts, if present, or liver transplantation may dramatically improve pulmonary function in selected patients.

Arteriovenous Fistula↗

Extension of logarithmic growth of Thiobacillus ferrooxidans by potential controlled electrochemical reduction of Fe(III).

In this study, we demonstrated that the period of logarithmic growth for Thiobacillus ferrooxidans could be extended when optimal conditions for cell growth were maintained using potential controlled electrochemical cultivation with sufficient aeration. The optimal pH and Fe(II) concentration for the electrolytic cultivation were determined to be 2.0 and 150 mM, respectively. When the potential was set to 0.0V vs Ag/AgCl, the Pt electrode reduced Fe(III) to Fe(II) with an efficiency of 95%. A porous glass microbubble generator was used to maintain adequate levels of dissolved oxygen, which was the electron acceptor for T. ferrooxidans when the cell density in the medium was high. Under these conditions, cells at an initial density of 10(7) cells/mL grew logarithmically for 4days until the cell density was 4 x 10(9) cells/mL. This corresponded to a period of logarithmic growth that was 3 times longer than was observed in batch cultures without electrolysis. In addition, the final cell density reached 10(10) cells/mL after 6 days of electrochemical cultivation, which was a 50-fold increase over conventional batch culture. Under conditions of increasing cell density, potentiostatic electrolysis made it possible to remove Fe(III), which causes product inhibition, at an increasing rate and to correspondingly increase the production rate of Fe(II), which is the electron donor for T. ferrooxidans. Thus, our cultivation system provides a sufficient supply of electron donor and acceptor for T. ferrooxidans, thereby elongating the period of logarithmic growth and producing very high cell densities.

Culture Media↗

[Newly developed technology for intravenous contrast echocardiography].

Until now we have not been able to employ a contrast enhancer for ultrasonic echocardiography at the everyday clinical level because the agent itself, composed of microbubbles, was too easily dispersed or even destroyed by several factors. However, contrast echocardiography has made a great leap forward with major developments on two fronts; the application of some new intravenous contrast enhancers, and newly developed machine technology permitting second harmonic imaging, intermittent or triggered imaging, pulse inversion harmonic imaging, and so on. New contrast enhancing agents are proving durability enough to permit greatly enhanced imaging for more than several minutes after injection. Recent new echocontrast specific imaging allows real-time visualizing of myocardial perfusion and assessment of myocardial function.

Contrast Media↗

The effect of air and nitrox divings on platelet activation tested by flow cytometry.

BACKGROUND: Nitrogen (N2) microbubbles activate the blood platelets and coagulaltion system. HYPOTHESIS: Breathing nitrox rather than air may reduce the level of platelet activation associated with decompression. METHODS: We tested platelet counts and the expression of functional membrane molecules on platelets in 10 divers subjected to saturated compression in nitrox at 4 ATA and in 9 divers subjected to compression in air at 2.8 ATA. Blood samples were taken before and immediately after the test. We measured the percentages of microplatelets, platelet aggregates and platelets bearing the activation marker C-D62P, and bearing molecules forming receptors for fibrinogen (CD61) and for von Willebrand factor (CD42b) using flow cytometry and specific monoclonal antibodies. Symptoms for DCS were also evaluated. RESULTS: DCS symptoms were not noted in either the nitrox or air group. In both groups we observed a marked increase in the percentage of activated platelets bearing CD62P molecules and an enhanced number of microplatelets and a marked drop in the platelets count in the blood of (divers in the air group. CONCLUSION: In all divers we observed certain changes in the platelet system, nevertheless decompression in nitrox resulted in a lesser degree of platelet activation. Though this study cannot exclude platelet activation as an etiological factor in DCS, the findings suggest platelet activation can occur in the absence of observable sign of DCS. Thus, platelet activation may be too sensitive a marker to serve as a predictor of DCS.

Adult↗

Coronary Ultrasound Thrombolysis: From Acute Myocardial Infarction to Saphenous Vein Grafts and Beyond.

During high-power ultrasound irradiation in fluids, microbubbles are formed and collapse to generate shock waves and induce fibrinolysis. In vivo, intracoronary injection of ultrasound-lysed clots increased myocardial perfusion. The experience with the ultrasound thrombolysis catheter in the ACUTE (Analysis of Coronary Ultrasound Thrombolysis Endpoints) trial showed that primary percutaneous coronary ultrasound thrombolysis (PCUT) in patients with anterior acute myocardial infarction and occluded left anterior descending artery was very successful in inducing safe and effective reperfusion and excellent myocardial salvage. The left ventricular ejection fraction at 6-month follow-up increased by 29% (P = 0.0005). The Acolysis Registry investigated prospectively PCUT in patients with acute coronary syndromes (n = 160) in a multicenter (n = 32) registry. Procedural success was achieved in 124 (98%) patients. In the saphenous vein graft (SVG) subset (n = 34), (78% of the vessels occluded at baseline) PCUT led to successful recanalization (TIMI 2-3) in 75% of the patients (P = 0.0003). Currently, PCUT is being evaluated in a randomized trial (ATLAS ) for the treatment of thrombus-containing coronary SVGs. These data suggest that thrombus debulking prior to percutaneous transluminal coronary intervention by therapeutic ultrasound is a very safe and effective percutaneous coronary intervention strategy. Ultrasound can be used to treat thrombi of a side spectrum of age and size.

Journal Article↗

[Assessment of the effects of dipyridamole and dobutamine on coronary microcirculation using myocardial contrast echocardiography].

OBJECTIVES: To evaluate the effects of dipyridamole and dobutamine on myocardial blood flow (MBF) and myocardial blood volume (MBV), and their ability to detect non-flow-limiting coronary stenoses with myocardial contrast echocardiography (MCE). METHODS: Thirteen closed-chest dogs were studied at 7-10 days after placement of ameroid constrictors around proximal coronary arteries and their branches. MBF was measured with radiolabeled microspheres and myocardial plateau video intensity (VI, which indicates relative MBV) and microbubble velocity (beta) were measured with MCE at rest, after dipyridamole (0.56 mg/kg), and during peak dobutamine dose (30-40 micrograms.kg-1.min-1). RESULTS: The effects of both agents on MBF were similar in abnormal and normal segments. Plateau VI increased more and beta increased less with dobutamine than dipyridamole (P < 0.05), but the plateau VI ratios and beta ratios between abnormal and normal segments were almost identical during both drugs (P < NS), resulting in similar perfusion defects. Excellent linear relations were found between the plateau VI ratio or beta ratio and MBF (derived from radiolabeled microspheres) ratio from abnormal and normal beds during dipyridamole and dobutamine. CONCLUSION: Although the effect of dipyridamole and dobutamine on MBV is different, they unmask MBF reserve to a similar extent. Thus, the quantification of stenosis severity is identical using both agents with MCE.

Animals↗

Topical role and future perspectives of sonographic contrast agents in the differential diagnosis of solid thyroid lesions.

Gray scale sonography and US-guided biopsy are cost-effective and reliable procedures in the differential diagnosis of focal thyroid lesions. The frequent presence of multiple foci can make multiple biopsies intolerable to the patient. The use of a sonographic contrast agent (Levovist) composed of microbubbles was evaluated in the differential diagnosis of focal solid lesions of the thyroid. Time/intensity curves after bolus injection of contrast were studied with samplings at the level of focal lesions, extranodular parenchyma and common carotid in 29 lesions of 25 patients (16 females and 9 males) ranging in age 21 to 68 years. The evaluated parameters were: the curve morphology, the time to peak value, the mean enhancement time and the wash-in/out variate gamma curve. All focal lesions underwent biopsy. No significant differences were observed as for mean enhancement time while for time to peak values only two malignant lesions seemed to show values different from those of other solid lesions. Wash-in/out variate gamma curves seemed more interesting; they presented a dual morphology: 1) parenchymal for hyperplastic areas, pseudonodular neoformations during thyroiditis and healthy thyroid parenchyma, 2) vascular for malignant lesions and carotid lumen. Autonomous nodules showed an intermediate morphology. In spite of major limitations, the results seem to pave the way for additional possibilities of noninvasive differential diagnosis in the evaluation of focal solid thyroid lesions.

Adult↗

Contrast-enhanced transcranial Doppler sonography in patients with acute cerebrovascular diseases.

The aim of the study was to evaluate the diagnostic potential of galactose-based microbubble suspension (Levovist) in patients with acute cerebrovascular disease and inadequate transtemporal acoustic window, when examined by transcranial Doppler (TCD). We studied 10 patients with either transient ischemic attack (no. = 3) or stroke (no. = 7). Inadequate transtemporal acoustic window was unilateral in 3 patients and bilateral in the remaining 7 patients. Signals from middle, anterior, and posterior cerebral arteries (MCA, ACA, PCA) were recorded after injecting Levovist 300 mg/ml. Six patients needed 3 injections of Levovist, 1 patient two, and 3 patients one. Mean +/- SD duration of optimal signal enhancement was 175.2 +/- 53.2 s, range 70-290 s. Doppler waveform analysis was possible in 14 (82.3%) MCA, 11 (65%) ACA, and 9 (53%) PCA. Levovist improved the reliability of TCD in patients with acute cerebrovascular disease and insufficient transtemporal insonation.

Aged↗

[Utility of echo enhancers in the study of pulmonary circulation time].

UNLABELLED: Pulmonary circulation time (PCT) varies under different clinical conditions. To evaluate the PCT, the persistence of contrast in both ventricles and the digital arterial saturation of oxygen with peripheral intravenous injection of microbubbles, were examined 14 patients. Groups: I normals, II left ventricular hypertrophy (EF > 50%), III with mitral stenosis and IV in congestive heart failure. In seven patients, isosorbide S/L was administered after the first injection. The transpulmonary transit in beats was 7.3 in normals, and larger in the others. The persistence of echo contrast in right chambers was 31 beats in group I, and larger in the other groups. In left chambers it was 20.6 beats in group I, and larger in others. There were no alterations with regards to peripheral arterial saturation of oxygen. AII patients with isosorbide presented shorter PCT and persistence of contrast in right chambers. CONCLUSIONS: There are differences in PCT among normals, patients with mitral stenosis and those with congestive heart failure. Prolonged persistence contrast in right chambers indicates abnormally slow transpulmonary transit. Patients with congestive heart failure and ventricular damage, have longer persistence of echo contrast. PCT studied with contrast is an easy means of evaluating some aspects of pulmonary circulation.

Contrast Media↗

[Effect of oxygen inhalation on myocardial opacification using levovist: an animal experimental study].

OBJECTIVES: Levovist can opacify the myocardium via venous injection, and is widely used in the clinical field. However, left ventricular opacification deteriorates during oxygen inhalation using Albunex, one of the first generation of contrast agents. This study examines the effect of blood oxygen pressure on the myocardial opacification by Levovist. METHODS: Myocardial contrast echocardiography (Toshiba Power Vision 6000) was performed using second harmonic imaging, intermittent exposure of ultrasound (every 4 cardiac beats) and acoustic power of 1.4 mechanical index. The video intensity of the ventricular septum after venous injection of Levovist (0.5 ml of 300 mg/ml) was measured under various respiratory conditions by manipulating the respirator and oxygen inhalation. Arterial blood gas was measured and correlated with the myocardial video intensity. RESULTS: The video intensity of myocardial opacification was lower with higher oxygen pressure in the arterial blood. Visual recognition of myocardial opacification was only 14% under high oxygen pressure over 200 mmHg. Microbubbles of Levovist form from normal air, and are easily affected by the gas concentration of the surrounding blood. CONCLUSIONS: Myocardial opacification using Levovist is deteriorated under high oxygen pressure at examination.

Administration, Inhalation↗

Myocardial contrast echocardiography: a new tool in the noninvasive assessment of perfusion.

Although the ability to visualize the microvascular circulation by injection of microbubbles has been recognized for over 30 years, only recently the considerable progress in both ultrasound techniques and new contrast media has made myocardial contrast echocardiography a reliable, noninvasive method for the assessment of regional myocardial perfusion. Several clinical studies have validated this technique for the identification of resting myocardial perfusion defects after myocardial infarction and the detection of no-reflow in ischemia-reperfusion model. In addition, preliminary studies have shown the ability of this method to recognize regional myocardial ischemia during pharmacological stress tests in known or suspected coronary artery disease. Finally, in the experimental setting, the estimation of different degrees of severity of coronary artery stenosis has been proposed using the quantitative assessment of myocardial perfusion by time-intensity curves. Although to date some unresolved questions hinder the routine clinical application of this novel noninvasive technique, myocardial contrast echocardiography is close to providing significant advances in the ultimate goal of any cardiac imaging technique, i.e. the simultaneous assessment of both perfusion and function.

Contrast Media↗

The effect of exercise and rest duration on the generation of venous gas bubbles at altitude.

BACKGROUND: Decompression, as occurs with aviators and astronauts undergoing high altitude operations or with deep-sea divers returning to surface, can cause gas bubbles to form within the organism. Pressure changes to evoke bubble formation in vivo during depressurization are several orders of magnitude less than those required for gas phase formation in vitro in quiescent liquids. Preformed micronuclei acting as "seeds" have been proposed, dating back to the 1940's. These tissue gas micronuclei have been attributed to a minute gas phase located in hydrophobic cavities, surfactant-stabilized microbubbles, or arising from musculoskeletal activity. The lifetimes of these micronuclei have been presumed to be from a few minutes to several weeks. HYPOTHESIS: The greatest incidence of venous gas emboli (VGE) will be detected by precordial Doppler ultrasound with depressurization immediately following lower extremity exercise, with progressively reduced levels of VGE observed as the interval from exercise to depressurization lengthens. METHODS: In a blinded cross-over design, 20 individuals (15 men, 5 women) at sea level exercised by performing knee-bend squats (150 knee flexes over 10 min, 235-kcal x h(-1)) either at the beginning, middle, or end of a 2-h chair-rest period without an oxygen prebreathe. Seated subjects were then depressurized to 6.2 psia (6,706 m or 22,000 ft altitude equivalent) for 120 min with no exercise performed at altitude. RESULTS: Of the 20 subjects with VGE in the pulmonary artery, 10 demonstrated a greater incidence of bubbles with exercise performed just prior to depressurization, compared with decreasing bubble grades and incidence as the interval of rest increased prior to depressurization. No decompression illness was reported. CONCLUSIONS: There is a significant increase in decompression-induced bubble formation at 6.2 psia when lower extremity exercise is performed just prior to depressurization as compared with longer rest intervals. Analysis indicated that micronuclei half-life is on the order of an hour under these hypobaric conditions.

Adult↗

Contrast enhanced reflux sonography in children: a comparison to standard radiological imaging.

PURPOSE: The diagnosis of vesicoureteral reflux is routinely performed by voiding cystourethrography. Especially in the course of conservative treatment, the radiation dose might increase during the years. With the development of ultrasound echo enhancing agents we assessed their diagnostic efficacy for evaluation of vesicoureteral reflux to replace voiding cystourethrography with radiation-free ultrasound. MATERIALS AND METHODS: A total of 104 children with a mean age of 5.4 years were examined using echo enhancing ultrasound after informed consent was obtained. For control purposes, all children underwent standard voiding cystourethrography as well. The diagnosis of vesicoureteral reflux was positive when microbubbles appeared in the ureter or renal pelvis. The sonographic findings were correlated with those obtained by standard voiding cystourethrography. RESULTS: Of the 208 ureter and renal units investigated vesicoureteral reflux was detected in 76 (37%) by both technologies. Diagnosis was made sonographically in 5 units and by voiding cystourethrography in 3. All reflux grades (I to V) could be identified. The specificity and sensitivity of the contrast reflux ultrasound were significantly high. The long contrast time of up to 30 minutes combined with the high contrast effect resulted in convincing images with high levels of diagnostic confidence. CONCLUSIONS: Our results clearly demonstrate that the diagnostic accuracy of vesicoureteral reflux by contrast enhanced ultrasound is statistically significant compared to standard radiological voiding cystourethrography. Therefore, this methodology represents an exceptional approach to reduce the number of children being exposed to ionizing radiation especially during conservative followup.

Adolescent↗

Hematology and blood chemistry in saturation diving: I. Antiplatelet drugs, aspirin, and VK744.

Blood chemistry and cellular parameters were studied before, during, and after saturation (2.4 ATA) dives in the HYDRO-LAB habitat on two separate occasions. In both, platelet count fell greater than 20% 12-24 hours after surfacing and moderate (5%) reductions in hemoglobin, red-cell count, and packed-cell volume were observed. Plasma cholesterol and triglyceride levels were depressed postdive as were most plasma enzymes (GOT, GPT, CPK, LDH, ALP). The latter changes were very slight. In the first study, the incidental ingestion of aspirin by some divers did not prevent the loss of platelets even though the platelet-release reaction in response to ADP was inhibited. In the second study the platelet-suppressive drug VK744 was administered, on a double-blind randomized basis, to six divers, six others taking a placebo capsule. Dosage of VK744 was 300 mg TID for 2 days before, 5 days during, 3 days after saturation dive. The drug inhibited the postdive loss of circulatory platelets and in fact the treated group showed a rebound in platelet count above control values, 48-72 hours postdive. Megathrombocyte counts indicated the production of new platelets in both groups at this point. The treated group also showed a marked and significant reduction in plasma cholesterol and triglycerides, suggesting an antilipidemic effect of the drug. Theses results confirm previous observations and indicate that postdecompression loss of platelets may be related to sequestering of reactive platelets, possibly by microbubbles, and that the phenomenon can be inhibited by some antiplatelet drugs.

Adult↗

Usefulness of ultrasound contrast for image enhancement during stress echocardiography.

Although stress echocardiography has been established as a diagnostic technique for the detection and assessment of ischemia, there are still a number of limitations to the technique. These are related to suboptimal image quality with poor visualization of endocardial borders. Because assessment of wall motion is fundamental to the diagnostic value of stress echocardiography (both pharmacologic and exercise), endocardial border visualization is of utmost importance. Furthermore, interinstitutional observer agreement of 100% in highest image quality patients to a cumbersome 43% in low image quality patients is present. Therefore, improvements of image quality during stress are essential. One of the recent improvements is harmonic imaging, which improves visualization of endocardial borders at rest and during dobutamine stress. However, there is room for improvement. Since the introduction of ultrasound contrast agents, contrast has been increasingly used for better endocardial border visualization. Data from centers with a large number of stress echocardiography tests have shown that the addition of contrast agents decreases the number of more redundant diagnostic testing. Data obtained in our center in a subset of patients administered with SonoVue, a new generation contrast agent made of stabilized microbubbles containing sulfur hexafluoride, an inert gas, showed an improvement in the number of evaluable segments with fundamental and harmonic imaging and in the endocardial border detection during dobutamine stress echocardiography. Contrast also enables future quantitative analysis using acoustic quantification (AQ), and color kinesis. These studies should be carried out now that contrast has been approved for introduction to the market.

Echocardiography↗