The Study Of Experiment And Clinical Application By Left Heart Contrast Echocardiography With Perfluoropropane-albumin Microsphere Injection

BACKGROUND AND PURPOSE Contrast echocardiography was applied in clinical diagnosis in 1968. The application of this technique to clinic was not popularized, because it was invasive. 1970s the contrast cehocardiography was performed by intravenous injection of echo-contrast agents. The method is noninvasive, right heart contrast echocardiography was employed widely in clinic. However, echo-contrast agents was invasively injected into the heart during operation or by the cardiac catheter in the left heart contrast echocardiography. 1980s the technique of sonicated microbubble was devised, contrast echocardiography came into left heart contrast echocardiography age from right heart contrast echocardiography age. 1990s the manufacture technology of echo-contrast agents was improved stepwise. The novel echo-contrast agents can go into left heart through pulmonary circulation and myocardial tissue via coronary artery by intravenous injection. Simultaneously, the resolution power of the instrument was enhanced step by step and the novel imaging technique was exploited, the technique of myocardial contrast echocardiography (MCE) is tending towards ripe. Now, the MCE has been popularized in clinical application and is the very important research field.At present, because of the expensive price of the echo-contrast agents, the application of the echo-contrast agents is restricted in China. Which blocks the advance of the domestic contrast echocardiography study. The perfluoropropane-albumin microsphere injection is the first venous left heart cho-contrast agents, which is made in China. The gas is perfluoropropane(C₃F₈) in the microbubbles. There is great progress in the facture technology. The finished product is preserved as a freeze-dried solid shape. The time of preservation of the hermetic perfluoropropane-albumin microsphere injection is longer under low temperature. The results of multiple center stage I and II clinical trial showed that the agent could enhance the resolution of LV endocardial borders , had little side effect and would be appropriate for clinical use.In this study, wo performed left heart contrast echocardiography by intravenous injection of perfluoropropane-albumin microsphere.Using real-time three-dimensional echocardiography (RE-3DE) to evaluate the coronary collateral circulation after acute coronary artery occlusion. To estimate the feasibility of clinical application by two-dimensinal imaging (2D) and real-time tri-plane imaging (RT-3PI) with perfluoropropane-albumin microsphere injection. The study was divided into three parts as follows:Part 1 Experimental Study on the Coronary Collateral Circulation after Acute Coronary Artery Occlusion with Contrast Real-Time Three-dimensional EchocardiographyThe purpose of this part was to quantitatively evaluate the coronary collateral circulation after acute coronary artery occlusion by contrast RT-3DE and to find the relation between coronary collateral circulation and no-reflow. The model of canine's acute coronary artery occlusion was made successfully. The MCE was performed before coronary occlusion, shortly, 30 minutes, 180 minutes after coronary occlusion, and 180 minutes after reperfusion. Results: The left ventricular mass by contrast RT-3DE (LVM_RT-3DE) was 61.78±6.20g, the true left ventricular mass (LVM_Ture) was 62.42±6.78g. LVM_RT-3DE was strongly correlated with LVM_Ture (r=0.98). The coronary collateral circulation growed to different extent after ligating left anterior descending (LAD) coronary artery in all canine. The LVM supplied with coronary collateral circulation is 9.65±2.90g at the time of 30 minutes after LAD ligation (LVM_30min). The LVM supplied with coronary collateral circulation is 12.58±3.98g at the time of 180 minutes after LAD ligation (LVM_180min). There is the significant difference between LVM_30min and LVM_180min (P=0.004, P<0.01). The left ventricular mass supplied with LAD was 24.03±3.21g (LVM_LAD). The ratio of LVM_180min to LVM_LAD was 53.25±19.47%. The absence of myocardial contrast perfusion was observesd by MCE after reperfusion in 2 canines. That is no-reflow phenomena. The results indicated the coronary collateral circulation could be observed clear by contrast RT-3DE and the LVM supplied with coronary collateral circulation could be assessed quantificationally. The coronary collateral circulation growth could ruduce the area of myocardial infarction and occurrence of no-reflow phenomena after reperfusion.Part 2 The Clinical Study on Enhanced Resolution of Left Ventricular Endocardium and Myocardial Perfusion Imaging by Perfluoropropane-albumin Microsphere InjectionThis part was designed to evaluate the left ventricular (LV) echo enhancement effect, myocardial contrast agent perfusion effect and safety of perfluoropropane-albumin microsphere injection. Diluted perfluoropropane-albumin microsphere injection was given intravenously to permitted objects at a dose of 0.01ml/kg. Observers A and observers B evaluated the contrast effect respectively by self-comparison between pre-injection and post-injection. Results: Both observers considered the number of clearly recognized endocardial border segments increased significantly. The interobserver difference is not of significance (P>0.05). Oberver A had a result that in 2% patients the LV endocardial border enhancemen reached Grade 2 and in 98% patients reached grade 3, while obervers B had a result that in 4% patients reached grade 2 and in 96% patients reached grade 3. The results between two observers had no significant difference (P>0.05). The number evaluated by observer A increased from 3.06 ± 0.67 to 5.99 ± 0.10 while from 3.10 ± 0.68 to 5.99 ± 0.11 by observers B (P<0.01). The results between two observers had no significant difference (P>0.05). The average contrast enhancement rate of LV endocardial border was 99.7%. The left ventricular walls of apical four-chamber view were divided into 6 segments. The myocardial contrast agent perfusions of 300 segments were clearly visualized in 50 patients.The perfluoropropane-albumin microsphere injection had no significant effection on vital signs such as blood prssure, heart rate and respiration. Electrocardiogram didn't change markedly and the variance of the laboratory findings like blood and urine routine examination, hepatic and renal function was in normal range.The perfluoropropane-albumin microsphere injection could enhance the resolution of left ventricular endocardium, make the judgement of regional myocardial movement easier. The myocardial opacification was observed. It has little side effect and will be appropriate for clinical application.Part 3 Study of Clinical Application of the Left Heart Contrast Echocardiography by Real-time Tri-plane ImagingTo evaluate the feasibility of clinical application of the left heart contrast echocardiography by real-time tri-plane imaging (RT-3PI). The left heart contrast echocardiography by RT-3PI, using intravenous pill injection of fluorocarbon contrast agent, was performed in the 20 patients. It were observed that Left ventricular opacification grades and myocardial contrast agent perfusions. Results: The left ventricular opacification grade of 20 patients is 3 grade. Contrast agent enhances visualization of the left ventricular border. The myocardial contrast agent perfusion of left ventricular walls were clearly visualized in 20 patients. Electrocardiogram didn't change markedly and the variance of the laboratory findings like blood and urine routine examination, hepatic and renal function was in normal range. The effect of left heart contrast echocardiography was observed simultaneity from multi-plane and multi-angle.Conclusions1, Contrast RT-3DE can be applied to display the coronary collateral circulation and provide more accurate and comprehensive data.2, Quantitative assessment of the coronary collateral circulation after acute coronary artery occlusion can be executed by contrast RT-3DE. The LVM supplied with coronary collateral circulation is 9.65±2.90g at the time of 30 minutes after LAD ligation (LVM_30min). The LVM supplied with coronary collateral circulation is 12.58±3.98g at the time of 180 minutes after LAD ligation (LVM_180min).3, The coronary collateral circulation growth was observed dynamically by contrast RT-3DE. There is the significant difference between LVM_30min and LVM_180min (P=0.004, P<0.01). The results showed that the coronary collateral circulation growth is a course of advancing gradually.4, A well developed coronary collateral circulation can reduce the occurrence of no-reflow phenomena.5, The perfluoropropane-albumin microsphere injection could enhance the resolution of left ventricular endocardium, make the judgement of regional myocardial movement easier. The myocardial opacification was observed. It has little side effect and will be appropriate for clinical application.6, The effect of left heart contrast echocardiography was observed simultaneity from multi-plane and multi-angle.