Noninvasive transthoracic low frequency ultrasound augments thrombolysis in a canine model of acute myocardial infarction--evaluation of the extent of ST-segment resolution.
BACKGROUND
Recently it has been demonstrated that transcutaneous delivery of ultrasound combined with tissue plasminogen activator (tPA) is more effective than tPA alone in recanalizing acutely thrombosed canine coronary arteries. In the present study, we investigated the incidence of partial (> or =50%) and complete (> or =70%) ST-segment elevation resolution in the precordial leads of dogs with experimental acute myocardial infarction that were treated with tissue plasminogen activator (tPA) alone or in combination with noninvasive transcutaneous delivery of high-intensity low frequency (27[emsp3 ]kHz) ultrasound.


METHODS
Thrombotic coronary occlusions were induced in the midportion of left anterior descending (LAD) coronary artery by electrical injury in 24 dogs. All dogs were given intravenous heparin and tPA. Dogs were randomized to tPA alone (n=12) or combined tPA and adjunctive transcutaneous ultrasound (US) delivery (n=12). Electrocardiograms were recorded at 1) baseline, 2) after coronary occlusion just before initiation of therapy, 3) when coronary angiography showed recanalization of the coronary artery (or at 90 minutes after initiation of therapy if reperfusion did not occur before then) and 4) 90 minutes later. ST amplitude was measured in all 6 precordial leads.


RESULTS
ST-segment amplitude at baseline was comparable between the tPA and the US group. Before initiation of therapy, sum of ST-segment elevation tended to be higher in the US group. At reperfusion and 90 minutes thereafter, sum of ST-segment amplitude tended to be smaller for the US group than in the tPA group (p<0.001 for the time effect; p=0.118 for the time x group interaction). Up to 90 minutes after initiation of therapy >/=50% resolution of the sum of precordial ST elevation was detected in 7 out of 11 dogs (63.6%) in the tPA group versus 10 out of 11 dogs (90.9%) in the US group. Ninety minutes thereafter, 3 out of 7 dogs in the tPA group (42.9%) versus 9 of 11 dogs in the US group (81.8%) had >/=50% resolution of the sum of precordial ST elevation.


CONCLUSIONS
The combination of tPA with noninvasive transcutaneous delivery of low frequency high-intensity ultrasound resulted in greater resolution of ST-segment elevation when reperfusion occurs and 90 minutes thereafter, as well as a higher rate of epicardial coronary artery reperfusion.
Birnbaum
Y
Y
Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Luo
H
H
Atar
S
S
Fishbein
M C
MC
Brasch
A V
AV
Nagai
T
T
Pal
D
D
Nishioka
T
T
Chae
J S
JS
Zanelli
C
C
Peterson
T M
TM
Siegel
R J
RJ
D000818:Animals; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion / Q000379:methods; D015912:Thrombolytic Therapy / Q000379:methods* / Q000592:standards; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D014464:Ultrasonic Therapy / Q000379:methods*; D018084:Ultrasonography, Interventional / Q000379:methods* / Q000592:standards
D010959:Tissue Plasminogen Activator