Initially neurons in the penumbra can maintain their integrity by keeping ATP levels near normal. If perfusion does not return to normal levels, these neurons eventually loose their ability to preserve ATP generation. The duration of time during which the penumbra remains viable depends on the degree of blood flow reduction. Animal models suggest that the penumbra can remain viable for only a few hours if normal blood flow is not restored. Since brain tissue within the penumbra is salvageable, the potential exists for altering the final outcome from focal brain ischemia.
Most brain infarctions are due to an arterial occlusion.
For nearly forty years there has been experimental interest in using thrombolytic drugs to open symptomatic cerebrovascular arterial occlusions. The first randomized trial to investigate the efficacy of a thrombolytic drug for treatment of stroke was published in 1963. 3 Six other randomized trials were conducted between 1963 and 1992. Although these trials did not demonstrate efficacy, three of the trials that were conducted in the early 1990s 7-9 demonstrated that it was feasible to conduct a large, randomized study of early thrombolysis. TPA's thrombolytic effects are mediated by plasminogen.