Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent

• Published in: Journal of the American College of Cardiology 2002-02, Vol.39 (3), p.530-537
• Main Authors: Fisher, Nicholas G, Christiansen, Jonathan P, Leong-Poi, Howard, Jayaweera, Ananda R, Lindner, Jonathan R, Kaul, Sanjiv
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bubbles; Cardiology; Cardiovascular disease; Cardiovascular system; Contrast Media - administration & dosage; Contrast Media - pharmacokinetics; Coronary Circulation - drug effects; Coronary Stenosis - complications; Coronary Stenosis - diagnostic imaging; Coronary Vessels - drug effects; Disease Models, Animal; Dogs; Echocardiography; Experiments; Heart; Heart attacks; Hyperemia - complications; Hyperemia - diagnostic imaging; Injections, Intravenous; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Laboratory animals; Medical sciences; Microcirculation - drug effects; Microscopy; Models, Cardiovascular; Myocardium - metabolism; Myocardium - ultrastructure; Ostomy; Perfluorocarbons; Retention; Ultrasonic imaging
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01759-4

This study sought to investigate the myocardial and microvascular kinetics of BR14, a novel third-generation ultrasound contrast agent. BR14 produces persistent myocardial opacification after the administration of a single intravenous bolus when the left ventricular cavity contrast has considerably diminished. The mechanism of this finding is unknown. Nine open-chest dogs with non-critical stenosis of a single coronary artery were given intravenous bolus injections of BR14 during coronary hyperemia. Time versus acoustic intensity (AI) plots were generated from the normal and stenosed beds and myocardial blood flow (MBF) was measured with radiolabeled microspheres. Intravital microscopy was performed on an exteriorized cremaster muscle in 11 wild-type mice to study the microvascular kinetics of the agent. At peak contrast enhancement, the ratio between AI in the stenosed and normal bed was 0.44 ± 0.23, which was similar to the radiolabeled microsphere-derived MBF ratio between the two beds (0.45 ± 0.20). At 400 s after injection, the AI ratio between the two beds approximated unity (0.99 ± 0.07) despite no changes in MBF, indicating redistribution of the agent. The myocardial kinetics of BR14 was best characterized by a modified lagged normal density function. Only about 3% of administered microbubbles were estimated to be retained in the myocardium. Intravital microscopy showed that most of these bubbles were retained only transiently (2 to 3 s) within capillaries. BR14 demonstrates redistribution because of transient retention within capillaries. Therefore, similar to 201Tl, it could potentially be used to detect both coronary stenosis and myocardial viability after a single injection during stress.