Fitchett D H, Coltart D J, Littler W A, Leyland M J, Trueman T, Gozzard D I, Peters T J
Cardiovasc Res. 1980 Dec;14(12):719-24. doi: 10.1093/cvr/14.12.719.
Although high blood transfusion regimens have improved the life expectancy of the patient with Thalassemia Major, cardiac failure and arrhythmias remain a cause of early death. It is not certain whether the massive myocardial iron deposition found in such patients is preventable by intensive chelation therapy. This study evaluates endomyocardial biopsy as a method of assessing myocardial iron deposition. Of four patients with clinical and biochemical evidence of severe haemochromatosis, only one had a myocardial iron content comparable to that found in severe haemochromatotic myocardium. The one patient with cardiac failure had an endomyocardial iron content within the normal range. Studies of the iron distribution in haemochromatotic myocardium demonstrate that the subendocardial myocardium contains only half the iron content of the subepicardial layer, and there is a large sampling variation. It is concluded that catheter endomyocardial biopsy is an insensitive method of determining early myocardial deposition because of the location of iron and the variability of the sampling. Studies of the nature of the myocardial iron protein with CM32 cation exchange resin chromatography show that there is a large increase in the haemosiderin: ferritin ratio (5:1) in iron overload myocardium as compared with the normal heart (2:1). Similar results have been observed in the liver with iron overload, where the increase in hepatic haemosiderin was associated with greater lysosomal fragility. It is possible that myocardial cell damage may also occur by the rupture of iron engorged lysosomes.
尽管高输血方案提高了重型地中海贫血患者的预期寿命，但心力衰竭和心律失常仍是早期死亡的原因。目前尚不确定通过强化螯合疗法能否预防这类患者出现的大量心肌铁沉积。本研究评估心内膜活检作为评估心肌铁沉积的一种方法。在4例有严重血色素沉着症临床和生化证据的患者中，只有1例的心肌铁含量与严重血色素沉着性心肌病患者的心肌铁含量相当。1例心力衰竭患者的心内膜铁含量在正常范围内。对血色素沉着性心肌病中铁分布的研究表明，心内膜下心肌的铁含量仅为心外膜下层的一半，且存在较大的取样差异。结论是，由于铁的位置和取样的变异性，导管心内膜活检是一种确定早期心肌沉积的不敏感方法。用CM32阳离子交换树脂色谱法对心肌铁蛋白的性质进行研究表明，与正常心脏（2:1）相比，铁过载心肌中的含铁血黄素：铁蛋白比值大幅增加（5:1）。在铁过载的肝脏中也观察到了类似结果，肝脏中含铁血黄素的增加与更大的溶酶体脆性有关。铁过载的溶酶体破裂也可能导致心肌细胞损伤。
