Marilyn J. Cipolla
tPA alone does appear to have an effect on diameter regulation of the arteries. Although it is not as pronounced as ischemia and reperfusion, the pressure at which forced dilatation occurs is significantly less. Also, the response to acetylcholine is diminished in both ischemic arteries and those perfused with tPA compared with control nonischemic arteries; arteries that were ischemic and in the presence of tPA responded significantly less than all the other groups, suggesting a combined effect of tPA in ischemic arteries. However, getting back to your original question regarding the effect of tPA on nonischemic vessels, the altered pressure-diameter curve in these arteries puts the pressure of forced dilatation in the normal myogenic range (i.e., arteries perfused with tPA lose their tone around 140mmHg, as opposed to 170mmHg in control arteries). This suggests that cerebrovascular resistance may be impaired in patients receiving tPA. As you can imagine, the consequences of this could be detrimental, especially during thrombolysis. Although we have not nailed down a mechanism, several could be involved, including those mentioned my presentation. We are currently persuing this area.