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Catheter-Based Transcoronary Myocardial Hypothermia Attenuates Arrhythmia and Myocardial Necrosis in Pigs With Acute Myocardial Infarction

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

Manuscript received February 16, 2006; revised manuscript received June 9, 2006, accepted June 19, 2006.

^_* Reprint requests and correspondence: Dr. Junya Shite, Kobe University Graduate School of Medicine, Department of Cardiology, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan. (Email: shite{at}med.kobe-u.ac.jp).

OBJECTIVES: This study evaluated the efficacy of catheter-based transcoronary myocardial hypothermia (CTMH) in pigs with acute myocardial ischemia.

BACKGROUND: Although it has been suggested that hypothermia therapy can attenuate myocardial necrosis, few applications have been accepted for clinical use.

METHODS: This study comprises 2 substudies. In both studies, pigs underwent 60 min of coronary occlusion and 180 min of reperfusion. In study 1, after 15 min of coronary occlusion with an over-the-wire-type balloon (OTWB), pigs in the hypothermia group (H) (n = 13) were directly infused with 4°C saline into the coronary artery through the OTWB wire lumen (2.5 ml/min) for 60 min. Pigs in the normothermia group (N) (n = 15) received the same amount of 36.5°C saline. In study 2, pigs in the hypothermia-reperfusion group (HR) (n = 5) were infused with 4°C saline through the infusion catheter (8 ml/min) for 30 min with a later start (60 min after coronary occlusion), whereas simple reperfusion was used for the reperfusion group (R) (n = 6).

RESULTS: Catheter-based transcoronary myocardial hypothermia was successful in both studies. In study 1, CTMH significantly decreased ventricular arrhythmia and the ratio of necrosis to ischemic risk area (H: 9 ± 2%; N: 36 ± 4%; p < 0.0001) with a significant reduction of enzyme leaks. In study 2, CTMH tended to reduce the ratio of necrosis (HR: 33 ± 2%; R: 45 ± 5%; p = 0.08). In both studies, CTMH significantly suppressed the increase of 8-iso-prostaglandin F₂ while preserving the coronary flow reserve.

CONCLUSIONS: Catheter-based transcoronary myocardial hypothermia reduced myocardial necrosis while preserving coronary flow reserve, due, in part, to attenuation of oxidative stress.

Abbreviations and Acronyms   APV = time-averaged peak velocity   CFR = coronary flow reserve   CKMB = creatinine kinase MB isozyme   cTnT = cardiac troponin T   LAD = left anterior descending coronary artery   LV = left ventricle/ventricular   LVdP/dtmax = peak positive first derivative of left ventricle   MI = myocardial infarction   OTWB = over-the-wire-type balloon   sVT = sustained ventricular tachycardia   tau = time constant of left ventricular relaxation   8-iso-PGF2 = 8-iso-prostaglandin F2

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