Optimization of the size distribution and myocardial contrast effect of perfluorocarbon-filled albumin microbubbles by lyophilization under continuous negative pressure.
This study was undertaken to evaluate the effect of lyophilization under continuous negative pressure on perfluoropropane-filled albumin microbubble size distribution and myocardial contrast effect. Three different microbubble preparations were studied: (1) 1% albumin solution without a sugar (Optison), (2) 1% albumin and 5% dextrose (PESDA), and (3) 1% albumin and 5% fructose (PESFA). The 2 preparations containing sugar were also subjected to lyophilization under continuous negative pressure. Microbubble size distribution was measured with a Coulter Multisizer II (Beckman Coulter, Inc, Fullerton, Calif). The microbubbles were injected intravenously into a rat during intravital microscopy of the mesenteric microcirculation. Finally, the different albumin microbubbles were injected intravenously into 10 dogs, and myocardial contrast effect was assessed by videodensitometry. Results of the Coulter counter studies showed lyophilized PESFA to have a smaller size distribution with 99.9% + or - 0.1% of microbubbles <10 microm in diameter and 88.5% + or - 1.4% <4 microm in diameter (P <.05 compared with Optison or PESDA). On intravital microscopy, PESFA microbubbles behaved as intravascular tracers without microvascular plugging or coalescence. Finally, myocardial peak gray scale and area under the curve were significantly higher for PESFA than for PESDA or Optison, respectively. In conclusion, lyophilization of perfluoropropane-filled albumin microbubbles results in smaller microbubbles with a more uniform size distribution and brighter myocardial contrast. In addition, the substitution of fructose for dextrose improves size distribution and contrast effect. These findings have important implications regarding the use of novel imaging technologies that take advantage of microbubble destruction to image myocardial perfusion.
Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern, Dallas, Texas, USA.
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Chen
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Wang
Y T
YT
Zhou
P A
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Grayburn
D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000187:drug effects; D004285:Dogs; D004452:Echocardiography / Q000379:methods*; D005466:Fluorocarbons / Q000008:administration & dosage*; D005612:Freeze Drying; D006352:Heart Ventricles / Q000000981:diagnostic imaging*; D007262:Infusions, Intravenous; D008863:Microspheres; D010316:Particle Size; D011312:Pressure; D051381:Rats; D013152:Splanchnic Circulation / Q000187:drug effects; D014741:Video Recording
D000418:Albumins; D005466:Fluorocarbons; C042852:perflutren