Therapeutic time window, acute

Around acutely infarcted brain, there is an ischemic penumbra (Astrup et al. 1981). Here the blood flow is low, function depressed and the oxygen extraction fraction high. In other words, there is viable tissue with misery perfusion where the needs of the tissue are not being met The tissue may die or recover, depending on the speed and extent of restoration of blood flow. This concept opens up the possibility of a therapeutic time window during which restoration of flow or neuronal protection from ischemic damage might prevent both immediate cell death and the recruitment of neurons for apoptosis (see Ch. 21). 

Currently, the only treatment of patients with acute ischemic stroke is thrombolysis and restoration of blood flow [3,6,7]. Only a fraction of stroke patients benefits from this therapy [3,6,7], Therapeutic recanalization of an occluded cerebral artery is a risky option that can be applied only in the case of selected patients. The main limitation of cerebral thrombolysis is the narrow, 3-hour therapeutic window during which the thrombolytic agent has to be administered to be effective. Beyond this time limit, its effectiveness is neutralized by the high risk of cerebral hemorrhage [7], In acute stroke, only a small fraction of patients benefit from intravenous administration of recombinant tissue plasminogen activator, which is the only drug with proven effectiveness in reducing the size of infarct in humans [6],... 

Based on the currently available data, three conclusions can be drawn (1) time from symptom onset remains critical in cases of IV thrombolysis, (2) better patient selection and triage criteria can be used to reduce risk, increase efficacy, and expand the therapeutic window, and (3) centers must develop an organized response to acute ischemic stroke with clinical protocols and quality of care assessment tools. 

Nitric oxide was approved by the FDA in 1999 for use as a vasodilator in the treatment of hypoxic respiratory failure in full- and near-term infants. It is a colorless and essentially odorless gas with a very narrow therapeutic window for patients. Acute exposure effects include mucous membrane irritation and drowsiness. More serious effects include delayed pulmonary toxicity and damage to the central nervous system effects. Exposed employees may seem relatively asymptomatic at the time of exposure. It can take as long as 72 hours to manifest clinical symptoms. OSHA classifies nitric oxide as a highly hazardous substance. 

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