Enhanced visualization of intravascular and left atrial appendage thrombus with the use of a thrombus-targeting ultrasonographic contrast agent (MRX-408A1): In vivo experimental echocardiographic studies.

Echocardiographic evaluation for the recognition of intravascular and left atrial appendage thrombus remains a difficult problem. A thrombus-specific ultrasonographic contrast agent has the potential for an alternative approach for their delineation. The aim of this study was to investigate the usefulness of thrombus-specific contrast agent MRX-408A1 for the detection of acute experimentally created intravascular and intracardiac thrombus. In the first study, we created inferior vena cava thrombus in 9 dogs. With the use of fundamental 2-dimensional echocardiography imaging, we recorded images of the inferior vena cava thrombus at baseline (n = 9), with the thrombus-specific contrast agent MRX-408A1 (n = 9), and with nonspecific contrast agent MRX-113 (n = 6). In the second study, we created a left atrial appendage thrombus in 8 dogs. We imaged left atrial appendage thrombus at baseline and during MRX-113 and MRX-408A1 infusion. Thrombus was successfully created in all dogs in study 1 and in 6 of 8 dogs in study 2. MRX-408A1 produced a visually apparent increase in ultrasonographic contrast enhancement of the thrombus in all cases in which thrombus was found on autopsy. In both studies, MRX-408A1 increased the videointensity of the thrombus significantly compared with baseline images and images obtained during MRX-113 infusion. The size of the visually detectable thrombus on the image was also significantly larger during MRX-408A1 infusion than at baseline and during MRX-113 infusion. These data provide in vivo demonstration of the efficacy of a thrombus-specific contrast agent, MRX-408A1, in the detection of acute intravascular and intracardiac thrombus. It has the potential to improve the diagnostic accuracy of ultrasonography for the detection of acute thrombi at various cardiovascular sites in the clinical setting.

Mortality reduction by antiadrenergic modulation of arrhythmogenic substrate: significance of combining beta blockers and amiodarone.

Over the last 3 decades, there have been numerous experimental and clinical studies that utilized beta blockers for acute as well as chronic myocardial syndromes, especially in the setting of myocardial infarction in which the focus has been on mortality reduction. The results of these studies demonstrated the benefits of these agents at all stages of coronary artery disease. Although these data have always indicated that beta blockade per se is an antiarrhythmic as well as an antifibrillatory mechanism, the recognition of this phenomenon has been slow in finding universal appreciation. More recent studies have evaluated the additive role of beta blockers to newer therapies. A number of investigations have now established that this class of drugs does exert antifibrillatory action in preventing the occurrence of ventricular tachycardia (VT) and ventricular fibrillation (VF), thereby reducing sudden arrhythmic death and prolonging survival. It is of interest that 2 of the leading antiarrhythmic drugs, amiodarone and sotalol, also have antiadrenergic properties. This article reviews the expanding role of beta-blocking drugs in the control and prevention of life-threatening ventricular tachyarrhythmias with a particular focus on the evidence for synergistic benefits when they are combined with other interventions, especially amiodarone.

Does magnesium modify left ventricular remodeling after experimental myocardial infarction?

BACKGROUND: Magnesium therapy has been shown to improve survival and decrease the incidence of left ventricular failure when given to patients shortly after a myocardial infarction, but the mechanisms are unknown. We tested the hypothesis that the benefits of magnesium therapy are due to a favorable effect on early left ventricular remodeling, particularly on infarct shape changes. METHODS: Rats were infarcted and randomly allocated to two groups: group 1 (n = 8) received intravenous magnesium sulfate (200 mumol/kg) over 10 min started 30 min after coronary ligation, then an intraperitoneal dose (800 mumol/kg), which was repeated 6 h later. Group 2 (n = 10) served as a control group, and received normal saline. Using this regimen, the trough level of ionized magnesium 12 h after the intravenous dose was 33% above the control level. Three weeks after infarction, the hearts of the rats were arrested with saturated potassium chloride and fixed in formalin at 7.5 mmHg. The hearts were cut transversely into four slices. Photographs of both sides of each slice were taken and projected for morphometric analysis. RESULTS: Infarct size was similar in the magnesium and control groups (35 +/- 4 versus 30 +/- 2%). Infarct thickness, expansion index, and cavity area were also similar in both groups. CONCLUSIONS: Magnesium has no effect on early left ventricular remodeling or infarct expansion. The mechanism of its clinical benefits remains unexplained.