Author + information
- Received April 15, 1996
- Revision received June 20, 1996
- Accepted July 1, 1996
- Published online November 1, 1996.
- Danny M. Skyba, PhD,
- Gustavo Camarano, MD1,
- Norman C. Goodman, BS,
- Richard J. Price, PhD2,
- Thomas C. Skalak, PhD and
- Sanjiv Kaul, MD, FACC**,3
- ↵**Address for correspondence: Dr. Sanjiv Kaul, Cardiovascular Division, Box 158, Medical Center, University of Virginia, Charlottesville, Virginia 22908.
Objectives. We sought to 1) study the effects of FS-069 on cardiac and systemic hemodynamic function, myocardial blood flow, left ventricular wall thickening and pulmonary gas exchange when injected intravenously; and 2) compare the myocardial kinetics and microvascular theology of FS-069 and Albunex when injected directly into a coronary artery.
Background. FS-069 is a second-generation echocardiographic contrast agent composed of perfluoropropane-filled albumin microspheres; it is capable of consistent and reproducible myocardial opacification from a venous injection.
Methods. Nine dogs were used to study the effects of FS-069 on hemodynamic function, pulmonary gas exchange, left ventricular wall thickening and myocardial blood flow and to characterize its myocardial kinetics when injected intravenously. These dogs were also used 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 findings of FS-069 can explain its echocardiographic behavior during direct coronary injections.
Results. There were no effects of 30 rapid venous injections of FS-069 (every 20 s) on cardiac output; mean aortic, pulmonary or left atrial pressures; and peak positive and negative first derivative of left ventricular pressure (dP/dt). Similarly, there were no effects of this agent on radiolabeled microsphere-measured regional myocardial blood flow, left ventricular wall thickening or pulmonary gas exchange. When injected intravenously, the myocardial transit of this agent resembled a gamma-variate form. When diluted FS-069 was injected directly into the coronary artery; however, its transit resembled the integral of gammavariate function, with persistent myocardial opacification lasting several minutes, which was different from that of Albunex. Intravital microscopy revealed that, unlike Albunex, when no bubbles are entrapped within the microcirculation after an arterial injection, a very small fraction of the diluted, larger FS-069 microbubbles are entrapped. In vitro modeling confirmed that this small fraction of microbubbles can result in persistent myocardial opacification.
Conclusions. FS-069 produces no changes in hemodynamic function, myocardial blood flow, left ventricular wall thickening or pulmonary gas 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, resulting in a persistent contrast effect. Thus, although FS-069 is a safe intravenous echocardiographic contrast agent, it cannot provide information on myocardial blood flow when injected directly into a coronary artery.
↵1 Dr. Camarano was the recipient of a Fellowship Training Grant from Mallinckrodt Medical, Inc., Saint Louis, Missouri.
↵2 Dr. Price is the recipient of a Postdoctoral Training Grant from the Virginia Affiliate of the American Heart Association, Glen Allen, Virginia.
↵3 Dr. Kaul is an Established Investigator of the National Center of the American Heart Association, Dallas, Texas.
This study was supported in part by Grants R01-HL48890, R01-HL-39680 and R01-HL-49146 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; a grant from Molecular Biosystems, Inc., San Diego, California; and an equipment grant from General Electric Medical Systems, Milwaukee, Wisconsin.
This study was presented in part at the 5th and 7th Annual Scientific Sessions of the American Society of Echocardiography, San Francisco, California, June 1994 and Chicago, Illinois, June 1996, respectively.
- Received April 15, 1996.
- Revision received June 20, 1996.
- Accepted July 1, 1996.
- American College of Cardiology