THE USE OF HYDRALAZINE TO MANIPULATE TUMOR TEMPERATURES DURING HYPERTHERMIA
THE USE OF HYDRALAZINE TO MANIPULATE TUMOR TEMPERATURES DURING HYPERTHERMIA
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DOI：
10.3109/02656739009140980
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发表时间：
1990-11-01
影响因子：
3.1
通讯作者：
OLESON, JR
中科院分区：
文献类型：
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作者：
DEWHIRST, MW;PRESCOTT, DM;OLESON, JR
肼苯哒嗪是一种抗高血压药物，理论上可以通过减少血管“窃取”现象引起的肿瘤血流，在高热期间增加肿瘤温度。然而，在治疗上有效降低高血压患者血压的剂量可能会导致血压正常患者在高温治疗期后出现体位性低血压和其他副作用。本研究旨在评估肼苯哒嗪在正常血压患者中以安全剂量（0.125 mg/kg，i. v.）将有效地在热疗期间增加肿瘤温度。工作假设是，肼苯哒嗪在0.125毫克/公斤的剂量将有效地提高肿瘤温度在高温治疗期间，血压的变化最小。14名人类和5名犬受试者被给予肼苯哒嗪（0.125 mg/kg i. v.）在热疗过程的中间在给药前后监测体温和血压。虽然肼苯哒嗪导致血压轻微降低，但它在增加人类患者的肿瘤温度方面无效（中值温度的平均最大上升为0.26 ± 0.05 ℃）。0.32.degree. C）。在犬受试者中，相同剂量的肼苯哒嗪在所研究的五个受试者中的四个中有效降低血压（平均最大下降为22.7 ± 0.01）。4.1平均气温上升了0.8 . ±. 0.7.degree. C.在犬受试者中，血压下降越大，温度升高越大。这些结果表明肼苯哒嗪引起的肿瘤温度升高依赖于血压的下降。该实验室未来的研究将包括使用具有较短半衰期和可滴定效应的抗高血压药进行肿瘤血流操纵。使用这种方法，似乎需要提高肿瘤温度的低血压在幅度和持续时间方面将更加可控。
Hydralazine is an antihypertensive drug which theoretically could increase tumour temperatures during hyperthermia via reduction in tumour blood flow from a vascular ''steal'' phenomenon. Doses that are therapeutically effective in reducing blood pressure in hypertensive patients would probably cause postural hypotension and other side-effects in normotensive patients beyond the hyperthermia treatment session, however. This study was designed to evaluate whether hydralazine, when administered at a safe dose for normotensive patients (0.125 mg/kg, i.v.) would be effective in increasing tumour temperatures during hyperthermia. The working hypothesis was that hydralazine at a dose of 0.125 mg/kg would be effective in raising tumour temperatures during hyperthermia treatment with minimal change in blood pressure. Fourteen human and five canine subjects were given hydralazine (0.125 mg/kg i.v.) at the midpoint of a hyperthermia session. Temperatures and blood pressures were monitored before and after drug administration. Although hydralazine resulted in slight reduction in blood pressure, it was ineffective in increasing tumour temperatures in human patients (average maximum rise in median temperature was 0.26 .+-. 0.32.degree. C). In canine subjects the same dose of hydralazine was effective in reducing blood pressure in four of five subjects studied (mean maximum drop was 22.7 .+-. 4.1 mmHg) and the median temperature rose 0.8 .+-. 0.7.degree. C. In the canine subjects the greater the decrease in blood pressure, the greater the increase in temperature. These results suggest that a rise in tumour temperature induced by hydralazine is dependent on creating a drop in blood pressure. Future studies in this laboratory will include tumour blood flow manipulation with antihypertensives which have a shorter half-life and a titratable effect. Using this approach, hypotension, which seems to be required to raise tumour temperature, will be more controllable in terms of magnitude and duration.