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EXPERIMENTAL STUDIES

Flow dynamics of QW7437, a new dodecafluoropentane ultrasound contrast agent, in the microcirculation

Microvascular mechanisms for persistent tissue echo enhancement

Takanori Yasu, MD, PhD^*, Geert W. Schmid-Schönbein, PhD, Bruno Cotter, MD^* and Anthony N. DeMaria, MD, FACC^*

^* Cardiology Division, Department of Medicine, University of California at San Diego, La Jolla, California, USA
Department of Bioengineering, University of California at San Diego, La Jolla, California, USA

Manuscript received December 11, 1997; revised manuscript received March 6, 1999, accepted April 14, 1999.

Reprint requests and correspondence: Dr. Geert W. Schmid-Schönbein, Institute for Biomedical Engineering and Department of Bioengineering, University of California, at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0412.
gwss{at}bioeng.ucsd.edu

OBJECTIVES

The purpose of this study was to test the hypothesis that a subgroup of QW7437 microbubbles, dodecafluoropentane-based ultrasound contrast microspheres, resides for prolonged periods in the microvasculature.

BACKGROUND

QW7437 produces echo enhancement in myocardium which may persist relatively longer than opacification in the left ventricular cavity. The mechanism for this persistent enhancement remains unknown.

METHODS

The transit of fluorescently labeled erythrocytes was examined by fluorescence intravital microscopy in the microvessels in five rat mesenteries. Ten rats were used to observe the behavior of fluorescently labeled QW7437 microbubbles in the mesenteric microcirculation.

RESULTS

There was no significant change in erythrocyte velocity in the arterioles and venules after the administration of QW7437 microbubbles (0.05 ml/kg) preactivated by negative hydrodynamic pressure. Of 552 microbubbles observed in four arterioles and five capillaries, 549 (99.5%) passed without stoppage (0.1 s stoppage); only one stopped transiently in arteriole and two in capillaries, each for <0.5 s. Sixty-five of 478 microbubbles (13.6%) observed in six postcapillary venules 11 to 30 µm in diameter and 24 of 408 microbubbles (5.9%) in four venules 31 to 50 µm in diameter stopped transiently (0.1 to 180 s) with an attachment to venular endothelium; the remaining microbubbles passed through the venules without stoppage.

CONCLUSIONS

Prolonged survival as microbubbles in the circulation and transient stoppage of a subgroup of microbubbles in the microvasculature, particularly in venules, are potential mechanisms for the persistent tissue echo enhancement by QW7437 microbubbles during contrast echocardiography.

Abbreviations and Acronyms   DDFP = dodecafluoropentane   EC = endothelial cells   MCE = myocardial contrast echocardiography

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