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J Am Coll Cardiol, 2007; 49:250-260, doi:10.1016/j.jacc.2006.06.080 (Published online 28 December 2006).
© 2007 by the American College of Cardiology Foundation
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Catheter-Based Transcoronary Myocardial Hypothermia Attenuates Arrhythmia and Myocardial Necrosis in Pigs With Acute Myocardial Infarction

Hiromasa Otake, MD, Junya Shite, MD*, Oscar Luis Paredes, MD, Toshiro Shinke, MD, Ryohei Yoshikawa, MD, Yusuke Tanino, MD, Satoshi Watanabe, MD, Toru Ozawa, MD, Daisuke Matsumoto, MD, Daisuke Ogasawara, MD and Mitsuhiro Yokoyama, MD

Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.


Figure 1
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Figure 1 Study Protocol Over Time

(A) Coronary artery was occluded for 60 min. In study 1, intracoronary saline infusion (4°C or 36.5°C, 2.5 ml/min) with balloon inflation was started 15 min after coronary occlusion, and continued for 15 min after balloon deflation. In study 2, hypothermia with reperfusion (4°C, 8 ml/min) was initiated after 60 min occlusion and compared with simple reperfusion. (B) Angiographic frame showing the location of catheters, thermister (black arrow), and over-the-wire type percutaneous transluminal coronary angioplasty balloon (white arrow). (C) Schematic representation of regional myocardial hypothermia in the study.

 

Figure 2
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Figure 2 Changes in Ischemic Myocardial Temperature

Changes in ischemic myocardial temperature relative to baseline in study 1 (A) and in study 2 (B). Data are expressed as mean ± SEM.

 

Figure 3
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Figure 3 Time Course of Hemodynamic Parameters in Study 1

The p value by 2-way analysis of variance: group difference <0.001 for peak positive first derivative of left ventricular pressure (LVdP/dtmax). *p < 0.001 versus normothermia group at the same stage by Bonferroni’s multiple-comparison t test. Data are expressed as mean ± SEM. CO = cardiac output; HR = heart rate; MAP = mean arterial pressure; Tau = time constant of left ventricular relaxation.

 

Figure 4
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Figure 4 Serial Changes in CFR by Study

Serial changes in coronary flow reserve (CFR) in study 1 (A) and in study 2 (B). The p value by 2-way analysis of variance: group <0.001, time course <0.001, group-time course interaction <0.001 for CFR from each study. Data are expressed as mean ± SEM. *p < 0.001 versus normothermia or reperfusion group at the same stage. {dagger}p < 0.001 versus baseline within the same group by Bonferroni’s multiple-comparison t test. bpm = beats/min.

 

Figure 5
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Figure 5 Enzyme Leaks and Oxidative Stress by Study

Comparisons of {Delta}CKMB, {Delta}cTnT, and {Delta}8-iso-PGF2{alpha} for the 2 groups in study 1 (A) and in study 2 (B). Data are expressed as mean ± SEM. CKMB = creatinine kinase MB isozyme; cTnT = cardiac troponin T; 8-iso-PGF2{alpha} = 8-iso-prostaglandin F2{alpha}; {Delta} = the change in values between baseline and 3 h after reperfusion.

 

Figure 6
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Figure 6 Ischemic Risk Area and Necrotic Area by Study

Ischemic risk area and necrotic area in study 1 (A) and study 2 (B). Data are expressed as mean ± SEM. LV = left ventricular.

 

Figure 7
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Figure 7 Relation Between Necrotic and Ischemic Area in Study 1

Scatter plot of necrotic area (%) to ischemic risk area (%) in study 1. LV = left ventricle.

 

Figure 8
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Figure 8 Ischemic and Necrotic Myocardium of Representative Cases

Top panels show the ischemic risk myocardium (not stained blue), and bottom panels show the necrotic myocardium (white region). The heart treated with normothermia showed a larger area of necrosis than that with hypothermia.

 

Figure 9
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Figure 9 Myocardial Water Content in Study 2

Myocardial water content of myocardium from subendocardial and epicardial sides in reperfusion and hypothermia-reperfusion groups. Data are expressed as mean ± SEM.

 




 
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