6-ketoprostaglandin-f1-alpha and Intracranial-Aneurysm

A wide literature exists about the pathogenesis of cerebral arterial spasm following subarachnoid haemorrhage: several compounds have been identified in human cerebrospinal fluid as possible vasoactive agents involved in the biochemical mechanism of vasospasm onset. Many experimental evidences exist for a major involvement of arachidonate metabolites. The present work represents a review of experimental data supporting the hypothesis of cerebral arterial spasm as a result of an imbalanced vascular regulatory mechanism involving arachidonate metabolites. The authors have also monitored, in 25 cases of aneurysmal subarachnoid haemorrhage, lumbar and cisternal CSF levels of prostacyclin and PGD2, as representative of vasodilating and, respectively, vasoconstrictor compounds. In all cases CSF arachidonate metabolite levels after SAH were significantly higher than in control cases. Ten patients presented with symptomatic vasospasm: lumbar CSF PGD2 levels show fluctuations with superimposed peaks related to the neurological deterioration due to vasospasm, while lumbar CSF prostacyclin concentration-trend suggest a decreasing synthesis. In 15 patients presenting without vasospasm, lumbar CSF concentration of arachidonate metabolites are in a 'steady-state'. These data confirm the existence of an imbalanced biochemical situation promoting vasospasm, markedly in cisterns near to the ruptured aneurysmal wall. The evaluation of cisternal CSF levels of arachidonate metabolites supports the hypothesis of the clotting phenomenon around the ruptured aneurysm as an important predictive pattern of vasospasm, as shown in CT findings.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arachidonic Acid; Arachidonic Acids; Disease Models, Animal; Epoprostenol; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Prostaglandin D2; Prostaglandins D; Subarachnoid Hemorrhage

CSF eicosanoid levels are raised following subarachnoid haemorrhage but not sufficiently to be vasoactive per se within the cerebral circulation. Rebleeding and intraventricular haemorrhage are two factors associated with a worse outcome after aneurysmal SAH. We have examined the effects of these two factors on the CSF levels of TXB2 (TXA2 metabolite), PG6-keto F1 alpha (prostacyclin metabolite), PGF2 alpha and PGE2 in 44 patients following subarachnoid haemorrhage. In 15 patients who had received no non-steroidal anti-inflammatory agent or dexamethasone, intraventricular haemorrhage increased the median levels of all four eicosanoids in ventricular CSF by 2.1-5.1-fold. In 4 patients who rebled, the CSF median levels of all four eicosanoids were raised up to 250-fold over the normal range. These concentrations are just sufficient to have cerebrovascular and neuromodulatory effects.

Topics: 6-Ketoprostaglandin F1 alpha; Aspirin; Brain Damage, Chronic; Cerebral Ventricles; Dexamethasone; Dinoprost; Dinoprostone; Drug Therapy, Combination; Eicosanoids; Humans; Infusions, Intravenous; Intracranial Aneurysm; Nimodipine; Prognosis; Recurrence; Reference Values; Subarachnoid Hemorrhage; Thromboxane B2

Authors addressed the question whether the byosynthesis and the release of specific eicosanoids may occur in human brain cortex, and if the qualitative pattern of arachidonic acid metabolism is similar to that observed in experimental SAH. Human brain samples from 18 patients operated on for anterior communicating artery aneurysm (5 unruptured aneurysms considered as control cases, 7 patients operated on between Days 1 and 4 after SAH and 6 patients operated on between Days 10 and 14) were studied for the ex vivo release of 4 selected eicosanoids (Prostaglandin D2, E2, 6-keto-PGF1a and Leukotriene C4). Levels of arachidonate metabolites were determined by radioimmunoassay technique. PGD2 release is significantly lower in cases operated on delayed phase if compared to both control cases (p less than 0.05) and patients operated on in the acute phase, while there is no significant difference between the release of PGD2 in control cases and patients operated on in the acute phase. Release of 6-keto-PGF1a is significantly higher in patients operated on in a delayed phase (p less than 0.03 vs patients operated on in the acute phase and p less than 0.05 versus control cases). The release of LTC4 is significantly enhanced (p less than 0.05) in cases operated on in the acute phase if compared with unruptured aneurysms. The release of PGE2 is significantly enhanced in patients operated on in the acute phase (p less than 0.05) if compared to patients with unruptured aneurysm.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Cerebral Cortex; Culture Techniques; Dinoprostone; Eicosanoids; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Prostaglandin D2; SRS-A; Subarachnoid Hemorrhage

Arachidonic acid (AA) metabolites may play an important role in the pathogenesis of cerebral vasospasm which complicate subarachnoid hemorrhage. Authors have studied levels of 4 major AA metabolites in lumbar CSF samples and in CSF collected from perianeurismatic cisterns of 40 patients admitted with diagnosis of subarachnoid hemorrhage. Lumbar levels of AA metabolites are significantly higher in SAH patients than in control cases; moreover, cisternal CSF levels of PGD2, TxB2 and LTC4 are significantly higher than lumbar levels. Cisternal CSF levels (expressed in pg/ml +/- SEM) are in the "spasm" group: PGD2: 1129.62 +/- 146.33; 6-keto-PGF1 alpha: 214.2 +/- 19.96; TxB2: 4350.25 +/- 656.87; LTC4: 2582.19 +/- 381.83. In the "no spasm" group: PGD2 460.1 +/- 55.89; 6-keto-PGF1 alpha: 306.37 +/- 88.74; TxB2: 5752.5 +/- 899.25; LTC4: 812.92 +/- 142.06. Statistical analysis (paired t-test) shows values significantly higher for cisternal levels of PGD2 (P less than 0.005) and LTC4 (P less than 0.005) in patients presenting vasospasm. This suggests the importance of the subarachnoidal clot as a source of vasoactive compounds. Higher levels of leukotriene C4 in patients presenting vasospasm suggest a role for the compound in the genesis of local inflammatory processes and morphological changes of the arterial wall.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Humans; Intracranial Aneurysm; Prostaglandin D2; Prostaglandins D; SRS-A; Subarachnoid Hemorrhage; Thromboxane B2

Several naturally occurring compounds have been identified in human cerebrospinal fluid (CSF) after subarachnoid haemorrhage (SAH) as possible vasoactive agents involved in the biochemical mechanism of vasospasm. The authors have measured, in 30 patients admitted for SAH, CSF concentrations of two arachidonic acid metabolites. Prostacyclin and Prostaglandin D2, as representative of vasodilator and vasoconstrictor compounds. CSF samples were made available by lumbar punctures and intraoperative cisternal punctures. Nine patients presented with symptomatic vasospasm: lumbar CSF Prostaglandin D2 levels are significantly higher than in patients without vasospasm. The Cisternal Prostaglandin D2 level is significantly higher than the lumbar CSF concentration; CSF Prostacyclin levels do not significantly differ in the two groups of patients. These data suggest the presence of an imbalanced biochemical situation responsible for promoting vasospasm. The evaluation of cisternal levels of arachidonate metabolites support the hypothesis of the clotting phenomenon around the ruptured aneurysm wall as an important predictive pattern of vasospasm onset after SAH, as shown in computed tomography.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Epoprostenol; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Prognosis; Prostaglandin D2; Prostaglandins D; Risk; Rupture, Spontaneous; Subarachnoid Hemorrhage

Experimental investigations have suggested an important role of arachidonic acid metabolites in the genesis of cerebral vasospasm following subarachnoid hemorrhage. In this clinical study the cerebrospinal fluid (CSF) and serum levels of the two main arachidonic acid metabolites prostacyclin and thromboxane A2 are evaluated by measuring their stable degradation products 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TXB2) using radioimmunoassay methods during the pre- and postoperative course in patients after aneurysm rupture. Although the serum levels of both substances do not seem to be important for the clinical course of the patients, the CSF concentrations of 6-keto-PGF1 alpha and TXB2 provide important data. A close correlation between the initial TXB2 level of the individual patient and the amount of blood in the basal cisterns as detected by computed tomography scan can be demonstrated. The predictive value of this additional information for the occurrence of cerebral angiospasm is discussed. Comparing the CSF levels of both metabolites the slight preoperative elevation of 6-keto-PGF1 alpha is significantly surmounted by an extraordinary rise in TXB2 concentration. Postoperatively, after cleavage of the basal cisterns there is a decline in the CSF levels of both substances. The pre- and postoperative clinical course in comparison to the CSF levels of 6-keto-PGF1 alpha and TXB2 is demonstrated in four patients. A nearly normal course of TXB2 and 6-keto-PGF1 alpha seems to be associated with an uneventful clinical course, whereas a high TXB2 level--whether occurring preoperatively or, even more important, as a secondary postoperative rise--seems to be associated with ischemic complications and neurological deterioration. It is suggested that pre- and postoperative monitoring of CSF levels of 6-keto-PGF1 alpha and especially TXB2 may serve as a possible indicator for the detection of patients at risk of developing cerebral vasospasm.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acids; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Risk; Rupture, Spontaneous; Subarachnoid Hemorrhage; Thromboxane B2

Imbalance between the two arachidonic acid metabolites, prostacyclin (PGI2) and thromboxane A2 (TXA2), is thought to be at least in part responsible for the development of cerebral vasospasm following aneurysm rupture. In 12 patients with subarachnoid hemorrhage the pre- and postoperative serum and CSF levels of PGI2 and TXA2 were measured as a function of their stable hydrolysis products, 6-Keto-PGF1 alpha (PGI2) and thromboxane B2 (TXA2), with a highly specific radioimmunoassay. Serum levels of both metabolites were elevated in half of the patients, but no correlation to the clinical course could be found. However, TXB2 concentration in the CSF was significantly increased preoperatively with close correlation to the amount of intracisternal blood, as detected by CT scan. Furthermore, it could be demonstrated that the postoperative course of the TXB2 concentrations in the CSF reflects the clinical course in such a way that a characteristic secondary rise of TXB2, concentration postoperatively is closely related to the occurrence of cerebral vasospasm and clinical deterioration. The conclusion is drawn that measurement of arachidonic acid metabolites in the CSF may provide important information concerning the pathophysiological events following subarachnoid hemorrhage, especially with regard to incipient cerebral vasospasm.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Arachidonic Acids; Blood-Brain Barrier; Carotid Artery Diseases; Carotid Artery, Internal; Epoprostenol; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Rupture, Spontaneous; Subarachnoid Hemorrhage; Thromboxane A2; Thromboxane B2

Experimental and clinical observations suggest the importance of arachidonate metabolites in the genesis of symptomatic cerebral vasospasm after subarachnoid hemorrhage. Prostacyclin (PG12) has a well demonstrated vasodilator action. The authors monitored CSF prostacyclin concentration in 12 consecutive cases of subarachnoid hemorrhage with the purpose of correlating the prostacyclin concentration trend with the clinical course and the risk for vasospasm. In three cases patients presented with clinical and radiological signs of vasospasm. CSF prostacyclin concentration showed a typical decreasing trend, which amounted to a minor form of protection from vasospastic agents. The nine cases which did not develop vasospasm demonstrated no significant changes in the prostacyclin CSF concentration trend. The authors also presented four cases in which cisternal CSF samples were available. In one case of developing vasospasm, the cisternal prostacyclin concentration was seven times lower than the highest lumbar CSF concentration. In three cases without evidence of vasospasm cisternal CSF demonstrated a balanced biochemical situation and a minor risk of vasospasm.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Epoprostenol; Female; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage

Two representative cases of subarachnoid hemorrhage in which prostaglandin D2 (PGD2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolite of prostacyclin (PGI2), were monitored with serial lumbar punctures and detected in cisternal CSF during operations for aneurysm, are reported. In the case with demonstrated arterial vasospasm, prostaglandin D2 has a concentration trend with characteristic peak related to vasospasm; the synthesis of prostacyclin appears inhibited after the hemorrhage. In the patient without radiologic evidence of vasospasm, arachidonate metabolite concentration trend appears in a steady-state. Cisternal prostaglandin D2 concentration in the patient with demonstrated vasospasm is two times the highest lumbar CSF concentration, while 6-keto-prostaglandin F1 alpha concentration is very low. This suggests the role of the clotting phenomenon and likely confirms the importance of arachidonate metabolites in the genesis of cerebral arterial spasm following subarachnoid hemorrhage.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Cerebral Angiography; Cisterna Magna; Humans; Intracranial Aneurysm; Ischemic Attack, Transient; Lumbosacral Region; Prostaglandin D2; Prostaglandins D; Rupture, Spontaneous; Spinal Cord; Subarachnoid Hemorrhage