[Therapy of cerebral ischemia].
The primary cause of ischaemic neuronal damage is the reduction in the regional cerebral blood flow below the threshold critical for preservation of nervous structures. The development of infarction, however, is not determined only by the severity of ischaemia but also by the duration of a blood flow disturbance below a critical level. During the ischaemic period, and also after reperfusion, secondary mechanisms are triggered (cytotoxic and vasogenic oedema, tissue lactacidosis, entry of Ca++, synthesis of prostaglandins and leukotrienes, production of free radicals and liberation of neurotransmitters), which contribute to the ischaemic cell damage. These pathophysiological mechanisms in the development of ischaemic cell damage suggest three approaches for therapeutic intervention: a. Improvement of cell tolerance against ischaemia b. Increased cerebral blood flow c. Inhibition of secondary damage. a. An improvement of the tolerance of brain cells to ischaemia can be experimentally achieved by hypothermia and barbiturate loading; due to severe side effects, these therapeutical regimens are not clinically applicable. b. An increase in cerebral blood flow, which must be induced within a short period of time, can be obtained by various drugs with different modes of action. While vasodilators are not clinically efficient, haemodilution with low molecular dextran has been shown to be a promising therapeutic concept. Other strategies to improve rheological properties of blood (venesection, other haemodiluting infusions, hydroxyethyl starch drugs acting directly on blood rheology, such as extract of ginkgo biloba) can also be applied. Anticoagulation can be performed only in a few special cases with ischaemic infarction. The increase in perfusion pressure is helpful in hypotonic patients to improve blood supply in the ischaemic region. Cerebral perfusion can also be augmented by drugs which activate function and metabolism. c. Secondary damage to cells surviving the primary ischaemic insult can be inhibited by suppression or diminution of perifocal brain oedema; under ischaemic conditions, osmotherapy is superior to corticosteroids for this purpose. Pathological biochemical mechanisms initiated during or shortly after the ischaemic episode and causing additional cell damage can be influenced by pharmacological interaction (Ca++ entry blockers, inhibitors of prostaglandin synthesis, scavengers of free radicals, e.g. flavones, opiate antagonists). However, the routine application of these drugs in clinical practice still necessitates more controlled trials. Excessive lactacidosis can be controlled by regulation of plasma glucose levels.(ABSTRACT TRUNCATED AT 400 WORDS)
Heiss
W D
WD
Max-Planck-Institut für neurologische Forschung, Universität Köln.
D000818:Animals; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology / Q000628:therapy*; D002544:Cerebral Infarction / Q000628:therapy; D002560:Cerebrovascular Circulation; D006801:Humans
Therapie der zerebralen Ischämie.