Microvascular permeabilization and cardiomyocyte injury provoked by myocardial contrast echocardiography in a canine model.
OBJECTIVE
The aim of this research was to evaluate the potential for myocardial contrast echocardiography (MCE) to provoke microscale bioeffects in a canine model.


BACKGROUND
Myocardial contrast echocardiography induces bioeffects in rat hearts, but translation of such results to larger animal models is uncertain.


METHODS
Dogs were anesthetized and prepared for open- (n = 22) or closed- (n = 6) chest MCE. Evans blue dye was injected intravenously as an indicator of microvascular leakage, and propidium iodide was used to stain for irreversibly injured myocytes in frozen sections. The contrast agent (Definity, Bristol-Myers Squibb Medical Imaging Inc., North Billerica, Massachusetts) was diluted in saline and infused intravenously at 2 microl/kg/min. Myocardial contrast echocardiography in a short-axis (open-chest) or modified four-chamber view (closed-chest) with 1:4 end systolic electrocardiogram triggering was performed at 1.5 MHz for 10 min in a single imaging plane.


RESULTS
Petechiae and leakage of Evans blue were observed in the ultrasound scan plane within the anterior left ventricle. For 1.2 MPa and 2.2 MPa, open- or closed-chest MCE, Evans blue content in tissue within the scan plane was significantly greater than in tissue outside this plane. Counts of propidium-iodide-stained nuclei for 2.2 MPa open-chest MCE were also significantly greater inside than outside the scan plane.


CONCLUSIONS
In a canine model, MCE induces myocardial injury comparable to that seen in the rodent model.
Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA. douglm@umich.edu
Douglas L
DL
Miller
Edward M
EM
Driscoll
Chunyan
C
Dou
William F
WF
Armstrong
Benedict R
BR
Lucchesi
D000818:Animals; D002199:Capillary Permeability; D002467:Cell Nucleus / Q000378:metabolism; D004396:Coloring Agents / Q000493:pharmacokinetics; D004285:Dogs; D004452:Echocardiography / Q000009:adverse effects*; D005070:Evans Blue / Q000493:pharmacokinetics; D005260:Female; D006352:Heart Ventricles; D008297:Male; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000473:pathology*; D011419:Propidium / Q000493:pharmacokinetics; D011693:Purpura / Q000209:etiology
D004396:Coloring Agents; D011419:Propidium; D005070:Evans Blue