Original Article 5’- Adenosine monophosphate induced hypothermia reduces early stage myocardial ischemia/reperfusion injury in a mouse model
Zhenyin Tao, Zhaoyang Zhao, Cheng Chi Lee
Department of Biochemistry & Molecular Biology, Medical School of The University of Texas Health Science Center at Houston, Houston TX 77225, USA.
Received June 15, 2011; Accepted July 12, 2011; Epub July 18, 2011; Published August 15, 2011
Abstract: Early intervention using hypothermia treatment has been shown to reduce early inflammation, apoptosis and infarct size in an animal model of cardiac ischemia/reperfusion. We have shown that 5’-adenosine monophosphate (5’-AMP) can induce a reversible deep hypothermia in mammals. We hypothesize that 5’-AMP- induced hypothermia (AIH) may reduce ischemic/reperfusion damage following myocardial infarct. C57BL/6J male mice were subjected to myocardial ischemia by ligating the left anterior descending coronary artery (LAD) followed by reperfusion. Compared to euthermic controls, mice given AIH treatment exhibited significant inhibition of neutrophil infiltration and a reduction in matrix metallopeptidase 9 (MMP-9) expression in the infarcted myocardium. A decrease in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive nuclei in the left ventricle myocardium were also observed. The overall infarct size of the heart was significantly smaller in AIH treated mice. Myocardial ischemia in mice given 5’-AMP without hypothermia had similar ischemia/reperfusion injuries as the euthermic control. Thus, the AIH cardio-protective effects were primarily hypothermia based. (AJTR1106003).
Address all correspondence to: Cheng Chi Lee, MD Department of Biochemistry & Molecular Biology Medical School of The University of Texas Health Science Center at Houston 6431 Fannin Street, MSB 6.200, Houston, TX 77225, USA. Tel: 713 500 6832; Fax: 713 500 0652 E-mail: cheng.c.lee@uth.tmc.edu