FROM HYDRALAZINE TO CGRP TO MAN
FROM HYDRALAZINE TO CGRP TO MAN
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DOI：
10.3109/02656739409010291
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发表时间：
1994-05-01
影响因子：
3.1
通讯作者：
GRIFFITHS, JR
中科院分区：
文献类型：
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作者：
FIELD, SB;BURNEY, IA;GRIFFITHS, JR
过去，有选择地减少肿瘤血流量的尝试主要集中在使用肼。然而，尽管这种血管扩张剂在实验动物中非常有效，但它只有在如此高浓度的情况下才会导致严重的、临床上不可接受的全身血压降低。在临床可接受的水平上，该药似乎能使肿瘤血流量小幅增加。我们使用磁共振波谱技术作为代谢和血流量的指标，以寻找血管活性药物，这些药物可以有效减少肿瘤血流量，而不会引起严重的低血压或其他严重的副作用。单次注射哌唑嗪或CGRP被证明比肼嗪更有效地减少肿瘤血流量，而不会大幅降低血压。连续输注CGRP更有效。在这种情况下，肿瘤血流量减少了三倍，而全身血压仅降低了15-20%。然而，所有这些研究都是在移植的动物肿瘤上进行的。使用高剂量的肼和放射或化学诱导的原发性肿瘤，我们获得的成功率只有35%左右，导致选择性减少血流量。相比之下，在来自无反应的辐射诱导原发病变的移植肿瘤系中，成功率约为95%，与大多数使用移植肿瘤的动物研究一致。这一发现的一个含义是，对移植肿瘤的血管研究结果可能不一定直接外推到自发肿瘤。CGRP是否存在这种情况需要在人类中进行研究。
Attempts to selectively reduce tumour blood flow have, in the past, concentrated on the use of hydralazine. However, although this vasodilator can be highly effective in experimental animals, it is only at such high concentration as to result in a severe and clinically unacceptable reduction in systemic blood pressure. At clinically acceptable levels, the drug appears to produce a small increase in tumour blood flow. We have used the techniques of magnetic resonance spectroscopy as indicators of metabolism and blood flow in a search for vasoactive drugs that would produce an effective reduction in tumour blood flow without causing severe hypotension or other serious side effects. Single injections of either prazosin or CGRP are shown to be substantially more effective than hydralazine in causing a reduction in tumour blood flow without massive reduction in blood pressure. Even more effective was CGRP given by continuous infusion. In this case a three-fold reduction in tumour blood flow could be obtained with a reduction of only 15-20% in systemic blood pressure. All these studies, however, have been made with transplanted animal tumours. Using high-dose hydralazine and primary tumours that were either radiation or chemically induced, we obtained a success rate of only about a 35% in causing selective reduction in blood flow. In contrast, in a transplanted tumour line derived from one of the non-responding radiation-induced primary lesions, the success rate was about 95%, consistent with the majority of animal studies using transplanted tumours. An implication of this finding is that the results of vascular studies on transplanted tumours may not necessarily be extrapolated directly to spontaneous tumours. Whether or not this is the case for CGRP needs to be investigated in man.