Horsman Michael R
Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus C, Denmark.
Int J Hyperthermia. 2006 May;22(3):197-203. doi: 10.1080/02656730600689066.
The most important physiological parameter influencing tissue response to heat is blood flow. At mild hyperthermia temperatures blood perfusion increases in many tumours and this effect is heating time-, temperature- and tumour-dependent. These flow increases can improve tumour oxygenation. When heating is terminated, perfusion and oxygenation commonly recover, although how quickly this occurs appears to be tumour-specific. While these effects are unlikely to have any anti-tumour activity they can be exploited to improve the combination of heat with other therapies. However, since similar physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity by changing the tumour micro-environmental parameters, primarily an increase in tumour acidity. Such changes are generally not seen in normal tissues, thus resulting in a therapeutic benefit.
影响组织对热反应的最重要生理参数是血流量。在轻度热疗温度下，许多肿瘤的血液灌注会增加，这种效应与加热时间、温度和肿瘤类型有关。这些血流量的增加可以改善肿瘤的氧合作用。当加热终止时，灌注和氧合作用通常会恢复，尽管其恢复速度似乎因肿瘤而异。虽然这些效应不太可能具有任何抗肿瘤活性，但可以利用它们来改善热疗与其他疗法的联合应用。然而，由于正常组织中也会出现类似的生理效应，因此必须谨慎应用这种联合疗法。将肿瘤加热到更高温度通常会在加热过程中导致灌注短暂增加，随后血管塌陷，如果塌陷足够严重，将增加肿瘤坏死。血管塌陷的速度和程度取决于加热时间、温度和所使用的肿瘤模型。这种血管塌陷通常发生在某些正常组织中导致血流量大幅增加的温度下，因此可以实现优先的抗肿瘤效应。肿瘤血管供应也可用于改善对热的反应。在开始加热之前，使用短暂的生理调节剂或作用时间更长的血管破坏剂来减少血流量，既可以增加肿瘤内物理热的积累，也可以通过改变肿瘤微环境参数（主要是肿瘤酸度增加）来提高热敏感性。这种变化在正常组织中通常不会出现，从而带来治疗益处。
