Contrast enhanced pulsed Doppler and colour-coded duplex studies of the cranial vasculature.

INTRODUCTION: The aim of this study was to assess the effect of Albunex, a vascular contrast agent based on albumin-coated air microbubbles, on pulsed Doppler and colour-coded duplex sonography of the cranial vasculature. METHODS: Twenty healthy male volunteers received intravenous injections of contrast in single doses ranging from 0.08 to 0.30 ml/kg. Pulsed wave Doppler sonography examination and colour-coded duplex sonography were carried out in the right internal carotid artery (ICA) and middle cerebral artery (MCA) before and after i.v. contrast. The relative intensity increase of the Doppler signal was measured in decibels. RESULTS: Transpulmonary passage of contrast occurred in sufficient amounts to enhance the intensity of the Doppler signal significantly, but the duration of this effect was short. Contrast enhancement also improved visualization of both the ICA and MCA in all subjects. For the transcranial examinations, this resulted in visualization of a greater length of the middle cerebral arteries and additional vessels in the Circle of Willis. CONCLUSIONS: These results confirm that contrast enhancement can significantly improve the quality of Doppler examination and colour-coded duplex sonography of both the intracranial and extracranial vessels. However, the use of Albunex in neurosonology will be of limited value due to its relatively short duration.

Assessment of left ventricular wall motion and delineation of the endocardial border after intravenous injection of Infoson during dobutamine stress echocardiography.

OBJECTIVES: To investigate whether intravenous injection of Infoson facilitates the assessment of left ventricular wall motion and definition of endocardial border and thereby reduces inter- and intra-observer variability during dobutamine stress echocardiography. BACKGROUND: Clear detection of the endocardial border is essential during dobutamine stress echocardiography. Although several contrast agents have been tested for their efficacy in enhancing definition of left ventricular endocardium, their usefulness during dobutamine stress echocardiography has not been evaluated. METHODS: Thirty coronary artery disease patients underwent dobutamine stress echocardiography. Infoson was injected at 0.2 ml/kg in both apical four- and two-chamber views. Detection of the left ventricular endocardial borders was scored from 0 (undetectable) to 10 (best) and expressed as a percentage of image quality at rest and peak stress by two independent observers. Regional wall motion was also evaluated and the total wall motion score index calculated each time. RESULTS: Delineation of the left ventricular endocardium improved from 76 +/- 4% to 84 +/- 2% at rest (P < 0.01) and from 75 +/- 4% to 89 +/- 1% at peak stress (P < 0.01) after administration of Infoson. The greatest improvement was seen in the basal and middle regions of the lateral and anterior walls. Inter- and intra-observer variability was reduced after administration of Infoson. At rest, the probability of concordance between two observers increased from 0.86 (0.82-0.89) to 0.91 (0.88-0.94) (P < 0.05) and at peak stress from 0.86 (0.82-0.9) to 0.90 (0.86-0.92) after administration of Infoson (P < 0.05). The probability of concordance between on- and off-line assessment by one observer also increased from 0.84 (0.8-0.88) to 0.90 (0.86-0.93) (P < 0.01) at rest and from 0.90 to 0.92 (NS) at peak stress. Overall, a change in wall motion score index occurred in 16 of 30 (53%) patients after administration of Infoson, thus improving the accuracy of the stress test compared with coronary angiography. The wall motion score index was overestimated in 11 of 16 (37%) patients without Infoson while the detection of new wall motion abnormalities increased in 5 of 16 (17%) (P < 0.01). CONCLUSIONS: Intravenous administration of Infoson facilitates the assessment of wall motion, particularly of the basal lateral and anterior walls where endocardial border drop-out frequently occurs during dobutamine stress echocardiography; it thus reduces the inter- and intra-observer variability.

Assessment of left ventricular systolic function in low-echogenic patients by intravenous Infoson injection during dopamine echocardiography. An open, phase III trial.

This trial evaluated whether the intravenous injection of an ultrasound contrast agent (Infoson) facilitates the assessment of systolic function in 40 low-echogenic patients undergoing low-dose (4 mcg/kg/min) dopamine echocardiography. Interobserver difference in calculated ejection fraction at entry was > 10%. Echocardiographic monitoring was performed in the apical 4-chamber view at four intervals: baseline, no contrast; first Infoson injection; dopamine infusion, no contrast; dopamine infusion+second Infoson injection. The left ventricle was divided into 5 segments and analysis was performed by two blinded observers. Wall motion abnormalities, ejection fraction and the confidence in detecting the endocardial border, were assessed. Infoson provided adequate left ventricular opacification in 90% of the injections, with a significant improvement in endocardial border detection. The interobserver variability of ejection fraction measurements was significantly reduced. The probability of attaining concordance between the investigators on wall motion assessment improved significantly. These results suggest potential applications in stress echocardiography.

Contrast echocardiography in coronary artery diseased patients: effect of systemic and pulmonary artery pressures on left heart opacification after intravenous injection of Albunex.

BACKGROUND: Contrast echocardiography is a useful tool for assessing repeatedly patients with coronary artery disease. Nevertheless, elevated pulmonary artery and systemic blood pressures likely to be associated with cardiac ischemia may limit the left ventricular opacification (LVO) because of the microspheres' sensitivity to pressure. OBJECTIVE: To determine the effects of systemic and pulmonary artery blood pressures on LVO. METHODS: We performed 55 intravenous injections (0.08 and 0.22 ml/kg) of a new transpulmonary contrast agent (Albunex), during two separated exposures, into 20 cardiac ischemic patients while monitoring invasively their cardiac indexes, and intracardiac, systemic, and pulmonary artery blood pressures. LVO was graded qualitatively from faint to full. RESULTS: A logistic model with the grade of LVO as the dependent variable and a selection from among the dose, exposure, right and left atrial blood pressures, systolic systemic and pulmonary artery blood pressures (ranges 94-208 and 14-45 mmHg, respectively), cardiac index, stroke index, and pulmonary and systemic vascular resistances as the explanatory variables demonstrated that increasing the dose gives an increasing probability of LVO (P = 0.02) and that increasing the pulmonary artery pressure reduces that probability (P = 0.006). A decreased cardiac index tended also to be associated with decreased LVO. The systemic blood pressure and the pulmonary and systemic vascular resistances had no statistically significant effect on the grade of LVO. CONCLUSIONS: LVO after intravenous administration of Albunex is dose-dependent and limited by an elevated pulmonary artery pressure. These data suggest that one should use higher doses for cardiac ischemic patients with elevated pulmonary artery pressures and that use of Albunex has the potential to detect pulmonary hypertension in patients.

Safety of a new transpulmonary echocontrast agent (Albunex) in repeated echocardiographic studies in patients.

BACKGROUND AND HYPOTHESIS: Multiple contrast-enhanced echocardiographic studies are to be expected in patients with cardiac ischemic disease, but the sonication process used to produce the echocontrast agent Albunex may result in new epitopes that could cause an immunogenic response. METHODS: Repeated exposures to intravenous Albunex over a period of time long enough to allow development of an eventual immune reaction were performed in 12 patients while monitoring for lymphocyte transformation, microsphere specific IgE and IgG antibodies, and systemic, pulmonary artery, capillary wedge, and right atrial pressures, as well as cardiac output, left ventricular fractional shortening, and blood gases. RESULTS: No significant 3H-thymidine incorporation and thus no specific blastic transformation of the patients' lymphocytes were observed either for high or low Albunex concentrations, corresponding to the expected hepatic and plasma concentrations of microspheres. No formation of microsphere-specific IgE and IgG antibodies was observed after the first or second Albunex exposure. Furthermore, no clinically significant hemodynamic or respiratory adverse reactions were observed in any patient. CONCLUSION: These results suggest that repeated exposures to intravenous Albunex induce no adverse effect on the cellular and humoral immune systems and on left and right heart hemodynamics in patients.

Left ventricular opacification after intravenous injection of Albunex. The effect of different administration procedures.

A clinical study has been performed to investigate the influence of different administration procedures on the degree of contrast enhancement of the left ventricle. The administration variables assessed included Albunex injection rate, arm position, flushing rate and flushing fluid. Twenty-four healthy male volunteers were included. Compared to an injection rate of 1 ml/sec an injection rate of Albunex of 2 ml/sec caused an earlier appearance of contrast in the right ventricle (1 heart beat), whereas transpulmonary passage was not influenced. Horizontal arm position caused a delay in time to peak intensity of 2 to 3 heart beats in both systole and diastole as compared to elevated arm position. Injection rate of 1 ml/sec compared to 2 ml/sec caused a higher peak intensity and mean area under the curve and a longer mean time to peak intensity and transit time. Differences varied from 6 to 230 grey level units out of mean values of 2500. All the observed differences were small and thus probably of no clinical importance. The present study indicates that improvements in the pressure stability characteristics of the albumin microspheres in Albunex have been achieved. This implies that a simple administration procedure can be used. It is recommended that the contrast agent, after resuspension, is injected through a three-way stop cock cannula, followed by 10 ml of saline for flushing. The cannulas or syringes used should be no smaller than 20 G. The injection rate should be 1-2 ml/sec, depending on the diameter of the cannula. By using this procedure, a reliable transpulmonary passage and left ventricular opacification may be obtained.

Lack of an immune response to Albunex, a new ultrasound contrast agent based on air-filled albumin microspheres.

Albunex is a new ultrasound contrast agent consisting of air-filled microspheres of heat-aggregated human albumin suspended in a 5% (w/v) solution of human albumin for infusion. The structural alterations induced in the albumin molecules during heat aggregation may cause the formation of new epitopes that may provoke an immunological response in recipients. To assess the possible immunogenicity of the contrast agent, 34 healthy volunteers were randomized to receive four injections of either Albunex or 5% human serum albumin (0.01 ml/kg) at 4-week intervals. Analysis of blood samples taken 3 weeks after each injection did not reveal any formation of IgE or IgG antibodies directed against the Albunex microsphere protein or albumin in any of the recipients. The evaluation of novel enzyme immunosorbent assays developed to detect the presence of these specific IgE and IgG antibodies is described. It was also investigated whether the heat-aggregated microsphere albumin was structurally altered in such a way that it could be recognized by cat albumin specific IgE, present in the sera of individuals allergic to cat albumin. 187 serum samples shown to contain elevated levels of cat albumin specific IgE were used in the study. No cross-reactive binding of the heat-aggregated human albumin to anticat albumin IgE could be detected. There is no evidence from the present studies that the heat-aggregated albumin of the Albunex microspheres will provoke an immunological reaction upon repeated injections or cause an adverse reaction when administered to allergic individuals having cat albumin as one of their allergens.

Safety and efficacy of a new transpulmonary echo contrast agent in echocardiographic studies in patients.

OBJECTIVES: This study was designed to investigate in patients the effect of a new transpulmonary echo contrast agent, made from 5% human serum albumin (Albunex), on systemic and pulmonary hemodynamics and the influence of the contrast doses on left ventricular opacification. BACKGROUND: New intravenous transpulmonary echo contrast agents are promising, allowing contrast stress echocardiography and myocardial contrast echocardiography. Nevertheless, some shortcomings still remain. Thus, the pulmonary hypertension observed in pigs after Albunex injection should be investigated in humans, and the optimal dose of contrast agent remains to be determined because previous experiments indicated that the left ventricular opacification and attenuation are dose dependent. METHODS: Albunex in doses of 0.08 and 0.22 ml/kg was successively injected intravenously in 20 catheterized patients; in 11 of them, anti-inflammatory drugs were withdrawn to avoid the blocking of an eventual thromboxane-mediated pulmonary artery hypertension. Systemic blood pressure and pulmonary artery, capillary wedge and right atrial pressures were continuously monitored. Cardiac output, left ventricular fractional shortening and blood gases were determined 5 min before and 5 and 10 min after each injection. The left ventricular opacification was qualitatively assessed by three independent observers using a grading scale from 0 to 3, with 0 indicating an absence of contrast effect and 3 indicating full opacification. RESULTS: No clinical, hemodynamic or respiratory adverse reactions were observed in any patient. Irrespective of doses, a left ventricular opacification grade > or = 2 was observed in 74% of the 35 injections that could be evaluated. This percentage increased to 94% when the higher dose group was considered alone. CONCLUSIONS: This first report of the effect of Albunex injected intravenously on pulmonary artery pressures in humans demonstrates that this contrast agent appears to be safe. The significant left ventricular opacification obtained in a majority of patients without an important increase in attenuation supports the use of the higher dose of the contrast agent.