Pathological Laboratory of the University of North Carolina, Chapel Hill, N. C.
J Exp Med. 1912 Jun 1;15(6):579-97. doi: 10.1084/jem.15.6.579.
The paroxysm of hematin intoxication in the rabbit undoubtedly presents many features of striking similarity to the paroxysm of human malaria; still one must hesitate to apply such results unreservedly in an attempt to identify the causative agent of the malarial paroxysm. When, in addition to the character of the paroxysm, we consider the sequence of events in the two instances, the analogy becomes so close that it seems impossible to regard the matter as a mere coincidence. The injection of hematin, especially in fractional doses, is in a measure comparable to the liberation of hematin into the human circulation by the malarial parasite. In these experiments, See PDF for Structure both solution and finely divided suspensions of hematin have been found equally effective in eliciting the phenomena of the paroxysm, and while it seems possible that a portion of the malarial pigment might be dissolved in the alkaline human serum, such an assumption is probably not essential. It might be objected that the toxic action of foreign hematin thus injected into the circulation would probably be greater than that of hematin derived from an animal's own blood, but as far as I have been able to determine, this objection does not seem valid, as rabbit hematin, dog hematin, and ox hematin produce in the rabbit effects that are alike in both character and degree. The dose of hematin remains as the one factor to which it is possible to attach some degree of uncertainty, but even here the author feels that the range of experimental conditions has been kept within the bounds of legitimate analogy with conditions existing in the human subject of malarial infection. Finally, the most conservative estimate of the value of such experiments points strongly to the fact that we have at least a potentially toxic substance in the pigment hematin as liberated by the malarial parasite into the circulation of the human host. There is also abundant evidence to show that the action of hematin is not confined to the paroxysmal phenomena of malaria, but that other features of the disease may find their explanation in the action of this pigment. For the present, however, it seems advisable to confine the discussion to this one phase of the question.
兔血卟啉中毒的发作无疑呈现出许多与人类疟疾发作惊人相似的特征；但在试图确定疟疾发作的病原体时，人们必须对这些结果持保留态度。除了发作的特征外，如果我们考虑这两种情况的事件顺序，那么这种相似性就变得如此之近，以至于似乎不可能将其视为纯粹的巧合。血红素的注射，特别是分次剂量，在某种程度上类似于疟原虫将血红素释放到人体循环中。在这些实验中，无论是血红素溶液还是血红素的细分散悬浮液，都被发现同样有效地引起了发作现象，虽然可能有一部分疟色素会溶解在碱性的人血清中，但这种假设可能不是必需的。有人可能会反对，因此注入循环系统的外来血红素的毒性作用可能比来自动物自身血液的血红素更大，但就我所能确定的而言，这种反对似乎没有根据，因为兔血红素、狗血红素和牛血红素在兔体内产生的作用在性质和程度上是相似的。血红素的剂量仍然是一个可能存在一定不确定性的因素，但即使在这里，作者也认为实验条件的范围已经保持在与疟原虫感染的人类宿主中存在的条件具有合理类比的范围内。最后，对这些实验价值的最保守估计强烈表明，我们至少有一种潜在的毒性物质，即疟原虫释放到人体循环中的色素血红素。也有充分的证据表明，血红素的作用不仅限于疟疾的发作现象，而且这种色素的作用可能解释了其他疾病的特征。然而，目前看来，将讨论仅限于这个问题的一个方面是明智的。
