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Brief episodes of brain ischemia define a patient population at increased risk for stroke. These brief events (TIAs) warrant urgent evaluation and treatment. It is therefore counterintuitive that transient ischemia might induce tolerance and protect the brain from subsequent ischemia. However, accumulating data from studies on both myocardium and brain support such a concept. An understanding of the mechanisms involved in ischemic tolerance may define novel therapeutic strategies for brain protection.
Ischemic tolerance in the heart.
The observation that multiple episodes of brief regional myocardial ischemia do not produce a cumulative depletion of high-energy phosphate compounds or loss of function provided the first evidence for ischemic tolerance (or ischemic preconditioning). [1,2] Such brief episodes of ischemia render the myocardium more tolerant to subsequent lethal ischemia, as evidenced by reduced infarct size, delayed ultrastructural changes, and improved recovery of regional myocardial function during reperfusion. [3,4] With ischemic preconditioning, myocardial infarct size is reduced in multiple species from 70% to 30% of the myocardium at risk. [3-5] The "dose" of ischemia adequate to produce tolerance in the heart varies from 2.5 to 10 minutes, depending on the species with some studies showing a requirement for multiple dosing. [6] The protection is substantial, doubling the duration of ischemia needed for infarction to occur. [5] The time window during which tolerance occurs in the myocardium is brief, starting between 1 and 60 minutes after preconditioning and lasting less than 3 hours in most studies. [7] A delayed secondary acquisition of tolerance, a so-called "second window of protection," also occurs in some cases 24 hours after ischemic preconditioning. [8,9] Some aspects of ischemic preconditioning are observed in the human heart as well, as evidenced by a reduction in anginal pain and ST-segment ECG alterations during the second balloon inflation (5 minutes after the first inflation) in patients undergoing percutaneous transluminal …
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