Why do all drugs work in animals but none in stroke patients? 1. Drugs promoting cerebral blood flow.

Medical treatments which presumably alter cerebral blood flow (CBF) have been quite unimpressive in their effect on stroke outcome. In considering experimental and clinical data from the use of haemodilution and of the antiplatelet agent prostacyclin in focal cerebral ischaemia, and the current work with fibrinolytic agents in acute stroke, several lessons are apparent. Often agents hypothesized to affect CBF receive an underserved reputation based on sparse experimental evidence. Significant even unsuspected differences between species limit application to the clinical setting. Limitations of CBF measurements in experimental models and in humans raise questions about apparent responses to those agents. The failure to confirm a relationship between CBF enhancement and reduction in infarct development experimentally has plagued these approaches. The need for early application of agents which may modulate CBF during cerebral ischaemia is critical. Attention to these general issues and careful application of appropriate models are necessary so that a potentially useful therapeutic intervention is not overlooked.