Crawford Marguerite, Ford Sara, Henry Michele, Matherne G Paul, Lankford Amy
Department of Pediatrics, Division of Cardiology, Cardiovascular Research Center, University of Virginia, Charlottesville, Virginia 22908, USA.
Can J Physiol Pharmacol. 2005 Jun;83(6):493-8. doi: 10.1139/y05-038.
Cold ischemic storage of hearts for transplantation is limited to 4-6 h, and therefore the development of strategies to extend preservation time may increase the donor pool of hearts. Overexpression of A1-adenosine receptors (A1AR) can protect hearts from acute ischemic injury, and the purpose of this study was to test the hypothesis that overexpression of A1AR will improve tolerance to longer periods of cold ischemic preservation. Hearts from 18 wild type and 16 transgenic mice with overexpression of A1AR (A1AR Trans) were isolated and perfused, and then subjected to 18 h of preservation in 5 degrees C University of Wisconsin solution followed by 2 h of reperfusion. Left ventricular end diastolic pressure and left ventricular developed pressure were measured as indices of ventricular function. Cell viability was assessed by determination of infarct size and myocardial cell apoptosis. A1AR Trans hearts showed improved function following 18 h of ischemia, as shown by lower end diastolic pressure (p < 0.05) and higher recovery of left ventricular developed pressure (p < 0.05) during reperfusion. A1AR Trans hearts had markedly reduced infarct size (p < 0.05) and decreased apoptosis (p < 0.05). Overexpression of cardiac A1AR imparts cardioprotection during long-term cold ischemic preservation.
用于移植的心脏冷缺血保存时间限制在4 - 6小时，因此，开发延长保存时间的策略可能会增加心脏供体库。A1 - 腺苷受体（A1AR）的过表达可以保护心脏免受急性缺血损伤，本研究的目的是验证A1AR过表达将提高对更长时间冷缺血保存耐受性的假设。分离并灌注来自18只野生型小鼠和16只A1AR过表达转基因小鼠（A1AR Trans）的心脏，然后在5℃威斯康星大学溶液中保存18小时，随后再灌注2小时。测量左心室舒张末期压力和左心室发展压力作为心室功能指标。通过测定梗死面积和心肌细胞凋亡来评估细胞活力。A1AR Trans心脏在缺血18小时后功能得到改善，表现为再灌注期间较低的舒张末期压力（p < 0.05）和较高的左心室发展压力恢复（p < 0.05）。A1AR Trans心脏的梗死面积明显减小（p < 0.05），凋亡减少（p < 0.05）。心脏A1AR的过表达在长期冷缺血保存期间具有心脏保护作用。
