Katsuhisa Ide

The role of endothelin in the pathogenesis of vasospasm following subarachnoid haemorrhage

The purpose of the present study was to evaluate the vasocontractile activity of endothelin, a newly isolated endothelium-derived constrictor peptide, in canine basilar arteries in vitro and in vivo. Endothelin at concentrations of 10(-12) M approximately 3 X 10(-8) M elicited dose-dependent contractions of canine basilar arteries in vitro. The maximum tension was larger than that induced by 40 mM KCl. The EC50 value was 1.9 +/- 0.6 X 10(-9) M (mean +/- SEM). The endothelin-induced contraction was reversed by 10(-8) M nicardipine or 10(-5) M approximately 10(-4) M papaverine. An intracisternal injection of 0.6 approximately 1.2 X 10(-12) mol/kg of endothelin caused biphasic contraction of the basilar artery lasting for more than 24 h. The initial phase of the contraction accompanied remarkable changes in vital signs such as an acute rise of blood pressure, bradycardia and respiratory arrest. An intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin also induced acute contraction of the basilar artery. However, all of the dogs which received an intracisternal injection of 2.0 X 10(-12) mol/kg of endothelin died from sustained respiratory insufficiency. The present results demonstrate that endothelin induces strong and long-lasting contractions of cerebral arteries. Therefore, endothelin may play an important role in the pathogenesis of vasospasm.

The role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog.

To investigate the roles of endothelin and nitric oxide (NO) in the regulation of cerebral vascular tone under basal conditions and in cerebral vasospasm following subarachnoid hemorrhage in dogs, we used BQ-123 (cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu-) sodium salt), an endothelin ETA receptor antagonist, L-arginine, a substrate for the formation of NO, and NG-nitro-L-arginine methyl ester, an NO synthesis inhibitor, and measured the angiographic diameter of the basilar artery in vivo. In normal dogs, intracisternal (i.c.) injection of BQ-123 (0.6 mg/kg) produced a 29.4 +/- 6.11% (P < 0.01) increase in the basal diameter 24 h after injection. NG-nitro-L-arginine methyl ester (0.6 mg/kg i.c.) produced a 19.3 +/- 2.93% (P < 0.05) decrease in the basal diameter 2 h after injection. This decrease was significantly attenuated by both BQ-123 (0.06-0.6 mg/kg i.c.) and L-arginine (6 mg/kg i.c.), but not by D-arginine. In the two-hemorrhage canine model, BQ-123 significantly inhibited the development of cerebral vasospasm (36.9 +/- 4.11% decrease on day 5 and 42.0 +/- 4.54% decrease on day 6 in controls vs 21.7 +/- 4.75% decrease (P < 0.05) on day 5 and 20.8 +/- 4.14% decrease (P < 0.05) on day 6 for 0.6 mg/kg i.c.) significantly attenuated the cerebral vasospasm on day 4 from a mg/kg i.c.). Furthermore, in this model, L-arginine (6 30.9 +/- 5.78% decrease (before)) to a 12.6 +/- 5.99% decrease (after). The immunoreactive endothelin-1 levels in the endothelial layer and the adventitia of the basilar artery were much higher on days 3 and 7 after the injection of autologous blood than on day 0 before blood injection. These results suggest that endogenous endothelin and NO both participate in regulating the basal tone of cerebral arteries, and, therefore, the development of cerebral vasospasm following subarachnoid hemorrhage may be at least partially attributed to an impairment of the balanced action of endothelin and NO. Furthermore, endothelin ETA antagonists or NO products may be useful in the treatment of cerebral vasospasm following subarachnoid hemorrhage.

Cervical dural arteriovenous fistula presenting with brainstem dysfunction: case report and review.

Study Design. We present a rare case of cervical dural arteriovenous fistula (C-DAVF) presenting with brainstem dysfunction. We discuss the details of the case and review previous articles on C-DAVF. Objectives. Our case study illustrates the relation between uncommon neurologic findings and altered hemodynamics resulting from the anatomic features of the neural pathway. Based on a review of 31 cases of C-DAVFs published since 1990 (30 patients, including our own), we sought to determine which surgical treatment for C-DAVF, endovascular surgery, or direct interruption of the draining vein, is more effective. Summary of the Background Data. A combination of endovascular techniques and direct interruption procedures was successful in curing the C-DAVF in our patient. The selection between endovascular surgery and surgical interruption in the treatment of C-DAVF is controversial. Methods. We sought to identify the characteristics and surgical methods most closely associated with complete cure for C-DAVF. Results. According to the reports on 31 cases of C-DAVF treated surgically (including our own), 20 DAVFs were managed by open surgery with interruption, 8 were treated by endovascular surgery, and 3 underwent a combined open and endovascular approach. Twenty-one patients showed symptomatic improvement or stabilization without additional treatment during the postsurgical course. Surgical revisions were performed in 3 patients (10.0%) (including the present case), all of whom initially underwent endovascular surgery. None of the cases treated by surgical interruption of the draining vein showed signs of recurrence. Conclusions. Surgical interruption of the draining vein is more effective than endovascular surgery in bringing about an absolute cure for C-DAVF. In exceptional cases, however, endovascular surgery is the preferred treatment. This is particularly so for elderly or medically compromised cases with contraindications against general anesthesia, as well as for moribund cases which, like our own case, present with rapidly deteriorating neurologic status on admission.

Operative Results of Syringomyelia with Reference to Patients Who Required Multiple Treatments

We report a retrospective study of 37 patients with syringomyelia who underwent surgical treatment. The patients were classified into three groups: (1) Chiari I malformations (27 patients), (2) extramedullary compressive lesions (5 patients), and (3) arachnoiditis (5 patients). A total of 46 surgeries were performed on 37 patients. Of the 27 Chiari I patients, 14 patients were treated by our standard procedure, posterior fossa decompression (PFD) and laminectomy with duraplasty. Good results were achieved in 9 patients (64%). However, the 2 patients primarily treated by syringosubarachnoid (SS) shunt alone had a recurrence of symptoms and needed further treatment. In all 5 patients with extramedullary compressive lesions, excellent results were achieved with simple excision of the compressive lesion or SS shunt. Five patients associated with arachnoiditis were initially treated by SS shunt, syringoperitoneal (SP) shunt, or syringotomy. However, 4 of them suffered recurrences and needed further treatment. Good results were sustained in 2 of the 5 patients treated by ventriculoperitoneal (VP) shunt or lumboperitoneal (LP) shunt.

Corrigendum to ‘the role of endothelin and nitric oxide in modulation of normal and spastic cerebral vascular tone in the dog’ [Eur. J. Pharmacol. 277 (1995) 77–87]

To investigate the roles of endothelin and nitric oxide (NO) in the regulation of cerebral vascular tone under basal conditions and in cerebral vasospasm following subarachnoid hemorrhage in dogs, we used BQ-123 (cyclo(-D-Trp-D-Asp-L-Pro-D-Val-L-Leu-) sodium salt), an endothelin ETA receptor antagonist, l-arginine, a substrate for the formation of NO, and NG-nitro-l-arginine methyl ester, an NO synthesis inhibitor, and measured the angiographic diameter of the basilar artery in vivo. In normal dogs, intracisternal (i.c.) injection of BQ-123 (0.6 mg/kg) produced a 29.4 ± 6.11% (P < 0.01) increase in the basal diameter 24 h after injection. NG-nitro-l-arginine methyl ester (0.6 mg/kg i.c.) produced a 19.3 ± 2.93% (P < 0.05) decrease in the basal diameter 2 h after injection. This decrease was significantly attenuated by both BQ-123 (0.06-0.6 mg/kg i.c.) and l-arginine (6 mg/kg i.c.), but not by d-arginine. In the two-hemorrhage canine model, BQ-123 significantly inhibited the development of cerebral vasospasm (36.9 ± 4.11% decrease on day 5 and 42.0 ± 4.54% decrease on day 6 in controls vs 21.7 ± 4.75% decrease (P < 0.05) on day 5 and 20.8 ± 4.14% decrease (P < 0.05) on day 6 for 0.6 mg/kg i.c.). Furthermore, in this model, l-arginine (6 mg/kg i.c.) significantly attenuated the cerebral vasospasm on day 4 from a 30.9 ± 5.78% decrease (before) to a 12.6 ± 5.99% decrease (after). The immunoreactive endothelin-1 levels in the endothelial layer and the adventitia of the basilar artery were much higher on days 3 and 7 after the injection of autologous blood than on day 0 before blood injection. These results suggest that endogenous endothelin and NO both participate in regulating the basal tone of cerebral arteries, and, therefore, the development of cerebral vasospasm following subarachnoid hemorrhage may be at least partially attributed to an impairment of the balanced action of endothelin and NO. Furthermore, endothelin ETA antagonists or NO products may be useful in the treatment of cerebral vasospasm following subarachnoid hemorrhage.