HEMODYNAMIC CHARACTERISTICS, MYOCARDIAL KINETICS AND MICROVASCULAR RHEOLOGY OF FS-069, A 2ND-GENERATION ECHOCARDIOGRAPHIC CONTRAST AGENT CAPABLE OF PRODUCING MYOCARDIAL OPACIFICATION FROM A VENOUS INJECTION

Objectives. We sought to I) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricula r wall thickening and pulmonary pas exchange when injected intravenous ly; and 2) compare the myocardial kinetics and microvascular rheology of FS-069 and Albunex when injected directly into a coronary artery. B ackground. FS-069 is a second-generation echocardiographic contrast ag ent composed of perfluoropropane-filled albumin microspheres; it is ca pable of consistent and reproducible myocardial opacification from a v enous injection. Methods. Nine dogs mere used to study the effect of F S-069 on hemodynamic function, pulmonary gas exchange, left ventricula r wall thickening and myocardial blood flow and to characterize its my ocardial kinetics when injected intravenously. These dogs were also us ed to compare the myocardial kinetics of FS-069 with those of Albunex during intracoronary injections. Nine Sprague-Dawley rats were used to compare the microvascular rheology of these two contrast agents, and in vitro modeling was performed to assess whether the microvascular fi ndings of FS-069 can explain its echocardiographic behavior during dit ect coronary injections. Results. There were no effects of 30 rapid v enous injections of FS-069 (every 20 s) on cardiac output; mean aortic , pulmonary or left atrial pressures; and peak positive and negative f irst derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured re gional myocardial blood flow, left ventricular wall thickening or pulm onary gas exchange. When injected intravenously, the myocardial transi t of this agent resembled a gamma-variate form. When diluted FS-069 wa s injected directly into the coronary artery; however, its transit res embled the integral of gamma-variate function, with persistent myocard ial opacification lasting several minutes, which was different from th at of Albunex. Intravital microscopy revealed that, unlike Albunex, wh en no bubbles are entrapped within the microcirculation after an arter ial injection, a very small fraction of the diluted, larger FS-069 mic robubbles are entrapped. in vitro modeling confirmed that this small f raction of microbubbles can result in persistent myocardial opacificat ion. Conclusions. FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary g as exchange when injected intravenously in large amounts. When diluted FS-069 is injected into the coronary artery, a very small fraction of the larger bubbles are entrapped within the microcirculation, resulti ng in a persistent contrast effect. Thus, although FS-069 is a safe in travenous echocardiographic contrast agent, it cannot provide informat ion on myocardial blood flow when injected directly into a coronary ar tery.