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(Circulation. 1998;98:2187-2194.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Albumin Microbubble Persistence During Myocardial Contrast Echocardiography Is Associated With Microvascular Endothelial Glycocalyx Damage

Presented in part at the Young Investigator Award Competition at the 8th Annual Scientific Sessions of the American Society of Echocardiography, Orlando, Fla, June 18–20, 1997, and at the 47th Annual Scientific Sessions of the American College of Cardiology, Atlanta, Ga, March 29–April 1, 1998, and published in abstract form (J Am Soc Echocardiogr. 1997;10:389 and J Am Coll Cardiol. 1998;31:439A).

Jonathan R. Lindner, MD; Suad Ismail, MD; William D. Spotnitz, MD; Danny M. Skyba, PhD; Ananda R. Jayaweera, PhD; ; Sanjiv Kaul, MD

From the Cardiovascular Division and the Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville.

Correspondence to Sanjiv Kaul, MD, Cardiovascular Division, Box 158, Medical Center, University of Virginia, Charlottesville, VA 22908. E-mail sk{at}virginia.edu

Background—We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury.

Methods and Results—The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K⁺ content, pH, PO₂, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP.

Conclusions—Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.

Key Words: microspheres • echocardiography • endothelium

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