Alternative treatment strategies: augmentation of flow and oxygen supply
Prof. Wolf-Dieter Heiss
47 slide(s) – 00:22:49– English –2010-09-27
In about 80% stroke is caused by ischemia, i. e. critical reduction of cerebral blood flow (CBF) to the brain mostly as a result of thrombotic or embolic occlusion of supplying arteries leading to lack of oxygen and metabolic substrates in the tissue. The sudden decrease of CBF is responsible for immediate functional deficits and triggers a cascade of pathophysiological mechanisms leading to tissue damage. If tissue with some residual flow is reperfused within a limited time period, neuronal function can recover.With more severe perfusional disturbance lasting for longer periods irreversible morphological damage develops. This concept of a “penumbra”, i. e. of functionally impaired butmorphologically intact critically perfused tissue - characterised by critical flow and increased oxygen extraction as visualised by positron emission tomography - is the basis of therapy in acute ischemic stroke. However, up to now only thrombolytic treatment up to 4.5 hours after onset of symptoms was efficient in large controlled trials, whereas other interventions aimed at neuroprotection or other mechanisms to prevent ischemic infarction so far have failed in controlled clinical studies. As available therapy, i. e. thrombolysis, has limited efficacy and is only applied in a low portion of stroke victims (up to 15% in some centres) additional strategies are necessarywhich can be applied to larger patients' populations. One method is the augmentation of collateral flowto brain tissue surrounding the ischemic territory therefore limiting the development of persistent damage. This concept is realised by the NeuroFlow catheter, by which the aorta is obstructed by 80% at the level of the renal arteries and thereby the perfusion is augmented to the upper part of the body. The resulting increase in brain perfusion was documented in animal experiments, where also the infarct volume due to occlusion of the middle cerebral artery was reduced. Pilot studies in stroke patients indicated improved collateral flow and suggested some clinical benefit. Therefore a large controlled study was performed, the results of which will be presented in the near future.Another concept uses hyperbaric oxygenation to improve oxygen supply to ischemic tissue. This procedure - breathing 100% oxygen pressurised at 1.5 to 3 atmospheres for 60 to 120 min repeatedly - is thought to increase oxygen availability in ischemic tissue and limit brain swelling as well as secondary neurotoxic mechanisms and therefore should reduce the volume of final infarcts. Several controlled randomised trials were performed, but up to now consistent evidence of the efficacy of HBOT was not presented. Further studies are required in acute stroke (within 6 hours of symptom onset). Overall, the efficacy and applicability of treatment of acute ischemic stroke is still disappointing. Further innovative attempts are needed, as well as an improvement of restorative and rehabilitative measures supporting neuroplasticity and neurorepair by which the functional outcome can be ameliorated.