Adult dogs having had 0.5 ml/kg of autogenous blood injected into the great cistern to simulate subarachnoid hemorrhage (SAH) were employed. These animals were either treated with trans-4-aminomethyl cyclohexane carboxylic acid (t-AMCHA) or left untreated, and were then investigated for changes in (1) fibrinolytic activities as measured in terms of SK-euglobulin lysis time and fibrin plate method, (2) plasma fibrinogen and FDP contents and viscosity of the blood (whole blood and plasma) and (3) cerebral blood flow (CBF), EEG and intracranial pressure (ICP) under arfonad or chlorpromazine-induced hypotension. The CBF was measured both by thermister method and by hydrogen clearance method.
1) The fibrinolytic activity in peripheral blood did not increase to a noticeable extent during the acute stage of SAH but rather showed a decline, which became particularly prominent when spasm of cerebral vessels occurred. The administration of t-AMCHA (0.2 g/kg) was followed by a significant inhibition of fibrinolytic activity.
2) The fibrinogen and FDP contents of blood showed an increasing tendency concurrently with the cerebrovascular spasm. Moreover, this tendency became even more pronounced after the administration of t-AMCHA. Administration of this antifibrinolytic agent was also attended by a significant increase in the viscosity of blood.
3) CBF values found on the 1st and 2nd days after the onset of SAH and after the 7th day ranged between 55.4 and 62.4 ml/min/100 g brain, being virtually within the normal range. However, values on the 3rd, 4th, 5th and 6th days, notably the 3rd and 4th days, were somewhat lower than the normal range. Drug-induced hypotension (40-50% of control level) was followed by an initial transient decrease in CBF with a subsequent return to normal CBF earlier than the recovery of blood pressure on the 1st, 2nd and 7th or later days after the onset of SAH. On the 3rd, 4th, 5th and 6th days of the onset of SAH, especially the 3rd to 4th days when the cerebrovascular spasm was at its height, a comparable degree of hypotension gave rise to a marked decrease in CBF (about 70% decrease being observed in arfonad treated cases) and, occasionally, associated with prolonged flattening of EEG waves which suggests irreversible changes in the brain. Chlorpromazine produced less changes in CBF than arfonad.
In conclusion, CBF decreases to a certain extent in association with vasospasm, and hypotension induced during this period may give rise to serious impairment of cerebral circulation.
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