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Cardiovascular disease is associated with the aging of the population, obesity, metabolic syndrome, and diabetes. Therefore, it is important to develop non-invasive imaging systems to detect "at-risk" populations. New data suggest that contrast-enhanced ultrasound (CU) imaging of the carotid arteries enhances luminal irregularities (i.e., ulcers and plaques), improves near-wall, carotid intima-media thickness, and uniquely permits direct, real-time visualization of neovasculature of the atherosclerotic plaque and associated adventitial vasa vasorum. With continued clinical investigation, CU imaging of the carotid artery may afford an effective means to non-invasively identify atherosclerosis in "at-risk" populations while providing new standard for therapeutic monitoring.

Objectives: This study sought to compare the impact of primary coronary angioplasty and thrombolytic therapy for acute myocardial infarction (AMI) on 1-month infarct size and microvascular perfusion., Background: The effect of the reperfusion strategies of primary coronary angioplasty and thrombolytic therapy on microvascular integrity still remains to be determined., Methods: Sixty-two consecutive patients with a first AMI, undergoing intravenous tissue-type plasminogen activator (t-PA) therapy (32 patients, Group I) or primary angioplasty (30 patients, Group II), were studied. Only patients with 1-month Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 were selected for the study. Patients in whom primary angioplasty was unsuccessful or those with clinical evidence of failed reperfusion were excluded. Microvascular perfusion was assessed at 1 month by intracoronary injection of sonicated microbubbles. Contrast score index (CSI) and wall motion score index (WMSI) were derived using qualitative methods., Results: At baseline there were no significant differences between groups for age, risk factors, time to hospital presentation, Killip class on admission, prevalence of multivessel disease or anterior infarct site, infarct area extension before reperfusion, peak creatine kinase levels and postinfarction treatment. Conversely, significant differences between groups were found at follow-up for percent residual infarct related-artery (IRA) stenosis (70 +/- 12 vs 36 +/- 14 [mean +/- SD], p = 0.0001), CSI (1.02 +/- 0.4 vs. 1.49 +/- 0.5, p = 0.0003) and WMSI (1.67 +/- 0.3 vs. 1.45 +/- 0.3, p = 0.015). In particular, in the subset of patients with TIMI grade 3 flow, a perfusion defect occurred in one or more segments subtended by the IRA in 72% of Group I versus 31% of Group II patients (p < 0.00001) and in 27% of Group I versus 8% of Group II segments (p < 0.00001)., Conclusions: The present study shows, in a highly selected cohort with successful IRA recanalization, that primary angioplasty is more effective than thrombolysis in preserving microvascular flow and preventing extension of myocardial damage at 1-month after AMI.

Myocardial contrast echocardiography has been found to be a safe and useful technique for evaluating relative changes in myocardial perfusion and delineating areas at risk. Although earlier contrast agents required direct delivery into the coronary arteries or aortic root, a new echocardiographic contrast agent, sonicated albumin microspheres (Albunex), has been found to cross the pulmonary circulation in experimental models. To determine the safety and preliminary efficacy of intravenous injections of Albunex in humans, 71 patients at three independent medical institutions underwent two-dimensional echocardiographic examination before, during and after the administration of three intravenous doses of Albunex, ranging from 0.01 to 0.12 ml/kg body weight. All patients provided a complete history and underwent physical and neurologic examination and laboratory and electrocardiographic evaluation before the injections; all evaluations (except for the history) were repeated at 2 h and 3 days after the injections of Albunex. The efficacy of the injections was qualitatively assessed by two independent blinded observers using a grading system of 0 to +3, with 0 indicating an absence of contrast effect and +3 indicating full opacification of the cavities examined. All injections were well tolerated and no serious side effects were noted in any of the patients. Irrespective of dose group, a cavity opacification greater than or equal to +2 was seen in the right ventricle in 212 (88%) of 240 injections and in the left ventricle in 151 (63%) of 240 injections as judged by the independent observers. The degree of ventricular cavity opacification appeared to be dose and concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

To facilitate the passage of echo contrast agents through the microcirculation and the echocardiographic study of myocardial perfusion, ultrasonic energy (sonication) was employed to produce contrast agents consisting of relatively uniform, stable and small (less than 10 mu diameter) gaseous microbubbles suspended in liquid solutions. The size and persistence of the microbubbles was verified by light microscopy and an in vitro system were employed for comparative assessment of peak echo amplitude and echo persistence characteristics of various contrast agents. The study indicated that although a variety of hand-agitated and sonicated contrast agents provided satisfactory echo intensities, sonication was clearly superior to the hand-agitation method, because sonication produced smaller, more uniform and more stable microbubbles that may be suitable for myocardial contrast echocardiography. It is concluded that of the contrast agents examined, sonicated solutions of sorbitol (70%) and dextrose (70%) appeared to have particular potential because of the small sizes of the microbubbles (6 +/- 2 and 8 +/- 3 mu, respectively) and their prolonged in vitro persistence. The use of sonication to produce standardized, small and stable microbubbles should facilitate physiologic passage of the contrast agent through the capillary beds and allow two-dimensional imaging of the left heart myocardium during right-sided, aortic root, coronary sinus or intracoronary contrast injections.

The potential for the use of contrast echocardiography to study myocardial perfusion has generated efforts to develop standardized echo contrast agents. The two methods used in this laboratory to generate microbubbles in solutions serving as contrast agents included the widely used hand-agitation method and the newer ultrasonic microcavitation (sonication) method. The latter has been demonstrated to generate smaller and more uniform microbubbles in an in vitro system. The present study was designed to observe, by direct microscopic examination of a cat mesentery preparation, the behavior and fate of the microbubbles in an in vivo system. The in vivo mesentery observations confirm the critical role of microbubble size in its unhindered passage through the capillary vasculature. The smaller and more uniform sonicated microbubbles passed rapidly through the microcirculation along with the red blood cells, whereas the larger microbubbles were observed to coalesce and interrupt the flow of blood and subsequently collapse or shrink.

Assessment of viable myocardium before and after interventional therapy has become a critical issue in modern cardiology. This report describes a new contrast echocardiographic technique using conventional two-dimensional imaging during direct intracoronary injections of small volumes (1.5 to 2.0 cc) of sonicated Renografin-76. Contrast echocardiography was performed before and after coronary angioplasty in seven patients with single vessel coronary artery disease. Before angioplasty a contrast (that is, perfusion) defect was noted in all seven patients. This defect correlated with the anatomic distribution of the epicardial coronary stenosis. After angioplasty the mean gradient across the stenotic lesion decreased from 52 +/- 11 to 13 +/- 14 mm Hg (p less than 0.01) in association with a fall in the mean diameter of the lesion from 84 +/- 8 to 29 +/- 13% (p less than 0.001). Increased myocardial perfusion to the area of "contrast defect" was demonstrated in only five of the seven patients, despite hemodynamically and angiographically successful angioplasty. Thus, contrast echocardiographic techniques performed during interventional therapy and used in conjunction with standard coronary angiographic procedures may provide additional physiologic information regarding regional myocardial perfusion after attempts at revascularization.

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)

In humans, the physiologic relation between myocardial blood flow and epicardial coronary artery anatomy remains poorly defined. With the recent development of sonicated microbubble contrast agents, it is now possible to use contrast echocardiography to assess myocardial perfusion and to correlate blood flow with angiographically identified coronary artery anatomy. The purpose of the current study was to determine myocardial perfusion patterns in patients without significant coronary artery disease. The results may be used as a reference to analyze myocardial blood flow in patients with coronary artery disease. Sonicated meglumine sodium diatrizoate solution (Renografin-76), which contains microbubbles measuring 4.5 +/- 2.8 micrograms in diameter by laser analysis, was used as the echocardiographic contrast agent during elective coronary arterriography in 14 patients without significant coronary artery disease. Patients received intracoronary injections of 1.5 to 2 ml of sonicated Renografin-76 without complications. Perfusion characteristics were studied by visual assessment of the two-dimensional echocardiographic images obtained after individual injections. In patients found to be free of significant coronary artery disease by arteriography, the left coronary system always supplied the anteroseptal, anterior, anterolateral and posterior regions of the left ventricle at the mid-papillary, cross-sectional level. The right coronary artery system perfused the inferior and inferoseptal regions in 89% of the patients identified with a right dominant system. The anterolateral papillary muscle was perfused from the left coronary system in all cases. The posteromedial papillary muscle was perfused from the left coronary system in 58% of the patients and from the right system in 42% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)