Asgeri Mehrdad, Pourafkari Leili, Kundra Amita, Javadzadegan Hassan, Negargar Sohrab, Nader Nader D
Department of Medicine, University Hospitals , Cleveland, Ohio , USA .
Immunol Invest. 2015;44(1):23-35. doi: 10.3109/08820139.2014.921689. Epub 2014 Jun 20.
To examine the dose response of TNFα in an ex vivo rat model of myocardial ischemia reperfusion.
Seventy-two rat hearts were mounted on Langendorff apparatus and perfused with oxygenated Krebs-Henseleit solutions. Ischemia was induced by reducing the perfusate flow rate. During reperfusion, incremental doses of recombinant TNFα were infused as a part of perfusate. TNFα was blocked with monoclonal TNFα antibody. Myocardial function was measured by dP/dT and relaxation time (IVRT). Cellular injury was assessed by released myoglobin and tissue concentration of malondialdehyde activity of the heart homogenates. Baseline +dP/dT was 1645 ± 125 mmHg/sec, -dP/dT was 945 ± 73 mmHg/sec and IVRT was 65 ± 5 msec. At the conclusion of reperfusion period, lower doses of TNFα increased +dP/dT and lowered IVRT. In contrast, the higher doses of TNFα decreased +dP/dT and prolonged IVRT. Pretreating the hearts with monoclonal TNFα antibody completely abolished the effects of TNFα on myocardial contractility and relaxation comparable to ischemia controls.
Low dose TNFα improved myocardial function and decreased resultant cellular injury while high dose TNFα decreased myocardial function and increased myocardial injury following ischemia and reperfusion.
在离体大鼠心肌缺血再灌注模型中研究肿瘤坏死因子α（TNFα）的剂量反应。
将72只大鼠心脏安装在Langendorff装置上，用含氧的Krebs-Henseleit溶液灌注。通过降低灌注液流速诱导缺血。在再灌注期间，作为灌注液的一部分注入递增剂量的重组TNFα。用单克隆TNFα抗体阻断TNFα。通过dp/dT和舒张时间（IVRT）测量心肌功能。通过释放的肌红蛋白和心脏匀浆中丙二醛活性的组织浓度评估细胞损伤。基线+dp/dT为1645±125mmHg/秒，-dp/dT为945±73mmHg/秒，IVRT为65±5毫秒。在再灌注期结束时，较低剂量的TNFα增加+dp/dT并降低IVRT。相反，较高剂量的TNFα降低+dp/dT并延长IVRT。用单克隆TNFα抗体预处理心脏完全消除了TNFα对心肌收缩性和舒张的影响，与缺血对照组相当。
低剂量TNFα改善心肌功能并减少由此产生的细胞损伤，而高剂量TNFα在缺血再灌注后降低心肌功能并增加心肌损伤。
