Loncar R, Flesche C W, Deussen A
Institut für Hämostaseologie und Transfusionsmedizin, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Acta Physiol Scand. 2004 Jan;180(1):21-8. doi: 10.1046/j.0001-6772.2003.01213.x.
Ferritin acts as an iron scavenger and thereby may reduce iron catalysed oxygen radical production during reperfusion injury. We tested the hypothesis that the myocardial ferritin concentration is enhanced during ischaemia in proportion to the blood flow reduction.
In 10 anaesthetized, open chest Beagle dogs (six controls and four with 60 min coronary occlusion) regional myocardial blood flow (RMBF) was measured with the tracer microsphere technique and ferritin was determined in samples with an average mass of 125 mg (124-256 samples per heart).
Under physiological conditions heart rate was 88 +/- 12 bpm, mean aortic pressure 98 +/- 8 mmHg, and RMBF 0.99 +/- 0.33 mL min-1 g-1. Data did not differ between experimental groups, P > 0.05. In the control group regional myocardial ferritin concentration averaged 11.76 +/- 3.54 ng mg-1 protein and exhibited a significant blood flow independent heterogeneity (CV(biol) = 0.27). However, between low and high flow areas (relative flow <0.5 and >1.5 times the average RMBF, respectively) no significant difference in ferritin was found, P > 0.05. In four experiments, in which regional blood flow was reduced by 40% to 0.60 +/- 0.23 mL min-1 g-1, regional ferritin content was significantly higher as compared with the control group 27.95 +/- 6.16 vs. 11.76 +/- 3.54 ng mg-1 protein, respectively. An inverse relationship was observed between ferritin and RMBF, r = -0.61, P < 0.001. Thus, a reduction of RMBF of >80% was associated with a 2.75-fold increase of the average ferritin content. Between subepicardium and subendocardium no significant difference in ferritin content was observed, neither in the control group nor in the group with induced ischaemia. Regions with control low and high flow responded similarly to the coronary constriction with regard to the local ferritin concentration: 27.88 +/- 15.22 vs. 30.10 +/- 14.91 ng mg-1, P > 0.05, respectively. A data analysis using Baye's theorem indicated that sensitivities were 0.28 and 0.94 for average flow reductions of 5 and 93%. In additional in vitro measurements (ischaemic incubation at 37 degrees C) myocardial ferritin content increased almost linearly within the first 60 min of incubation and thereafter remained unchanged.
(1). Local physiological ferritin content in myocardium is heterogeneous and unrelated to control myocardial blood flow. (2). Ischaemia results in an enhanced ferritin content in relation to the degree of ischaemia. (3). The increase of myocardial ferritin requires a severe degree of ischaemia.
铁蛋白作为一种铁清除剂,因此可能会减少再灌注损伤期间铁催化的氧自由基生成。我们检验了这样一个假设,即心肌缺血期间心肌铁蛋白浓度会随着血流量减少而成比例增加。
在10只麻醉开胸的比格犬(6只为对照组,4只进行60分钟冠状动脉闭塞)中,采用示踪微球技术测量局部心肌血流量(RMBF),并在平均质量为125毫克的样本中测定铁蛋白(每只心脏124 - 256个样本)。
在生理条件下,心率为88±12次/分钟,平均主动脉压为98±8毫米汞柱,RMBF为0.99±0.33毫升·分钟⁻¹·克⁻¹。实验组之间的数据无差异,P>0.05。对照组局部心肌铁蛋白浓度平均为11.76±3.54纳克·毫克⁻¹蛋白质,且呈现出显著的与血流量无关的异质性(生物学变异系数(CV(biol))=0.27)。然而,在低流量和高流量区域(相对流量分别<0.5倍和>1.5倍平均RMBF)之间,铁蛋白未发现显著差异,P>0.05。在4个实验中,局部血流量减少40%至0.60±0.23毫升·分钟⁻¹·克⁻¹,与对照组相比,局部铁蛋白含量显著更高,分别为27.95±6.16与11.76±3.54纳克·毫克⁻¹蛋白质。观察到铁蛋白与RMBF之间呈负相关,r = -0.61,P<0.001。因此,RMBF降低>80%与平均铁蛋白含量增加2.75倍相关。在对照组和缺血诱导组中,心外膜下和心内膜下铁蛋白含量均未观察到显著差异。对照组低流量和高流量区域对冠状动脉收缩时局部铁蛋白浓度的反应相似:分别为27.88±15.22与30.10±14.91纳克·毫克⁻¹,P>0.05。使用贝叶斯定理的数据分析表明,对于平均流量减少5%和93%,敏感性分别为0.28和0.94。在另外的体外测量(37℃缺血孵育)中,心肌铁蛋白含量在孵育的前60分钟内几乎呈线性增加,此后保持不变。
(1). 心肌局部生理铁蛋白含量是异质性的,且与对照心肌血流量无关。(2). 缺血导致铁蛋白含量相对于缺血程度增加。(3). 心肌铁蛋白的增加需要严重程度的缺血。