Ralf G. Hempelmann

Therapeutical considerations in patients with intracranial venous angiomas.

The clinical presentation of intracranial venous angiomas are usually headache, seizures or dizziness. Very often these anomalies are found incidentally on magnetic resonance imaging (MRI). We reviewed 35 patients, which were examined in our department between 1994 and 2000. Only one patient became symptomatic with an intracranial haematoma, which was removed surgically. In three patients an associated cavernous angioma was found, which was removed successfully with preservation of the coexisting venous angioma. There is no indication in operating a venous angioma because the risk of postoperative deterioration caused by venous infarction is high. When removing cavernous angiomas the associated venous angioma has to be preserved.

Granular-cell tumour: a rare suprasellar mass.

Abstract Granular-cell tumour is a rare suprasellar space occupying lesion, which usually presents with visual deterioration, endocrine deficits or headache. We present two women with extraordinarily large tumours, measuring 3.8 and 4.0 cm in diameter. In both cases the tough, vascular tumour could be removed only subtotally.

Endothelium‐dependent noradrenaline‐induced relaxation of rat isolated cerebral arteries: pharmacological characterization of receptor subtypes involved

1 The endothelium‐dependence of catecholamine‐induced relaxation of rat cerebral arteries was investigated in vitro. 2 In the basilar artery (BA), the maximal relaxant response was most pronounced with noradrenaline (NA), less with isoprenaline (Iso), and only very little with terbutaline. Methoxamine and the α2‐adrenoceptor selective agonists BHT 933 and clonidine, had no relaxant effect. 3 In BA, the relaxation by NA or Iso was markedly attenuated by Nω‐nitro‐l‐arginine (l‐NOARG) 10−4 m. Short term perfusion of the vessels by Triton X 100 (1:1000) suppressed the NA‐induced relaxation. 4 The relaxation induced by NA or Iso was markedly reduced in presence of l‐NOARG in the posterior, medial and anterior cerebral artery. 5 In BA, NA‐induced relaxation was non‐competitively inhibited by propranolol, atenolol, and the β1‐ and β2‐adrenoceptor selective antagonists, CGP 20712 A and ICI 118551. 6 The relaxant NA‐effect was not affected by prazosin but was non‐competitively blocked by phentolamine. 7 The Iso‐induced relaxation was competitively blocked by propranolol, whereas atenolol, CGP 20712 A and ICI 118551 caused a non‐competitive inhibition. 8 The experiments indicate that the catecholamine‐induced relaxation in rat isolated cerebral arteries depends upon the endothelium. They suggest that the NA‐induced relaxation of BA is mediated by different α‐ and β‐adrenoceptors and that the Iso‐induced relaxation is mediated by different β‐receptors. The findings would also be compatible with the idea of a receptor type which cannot be characterized by the pharmacological tools that we have used.

The vasorelaxant effect of pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide in isolated rat basilar arteries is partially mediated by activation of nitrergic neurons

The structurally related neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are recognised by two G protein-coupled receptors, termed VPAC(1)-R and VPAC(2)-R, with equal affinity. PACAP and VIP have previously been shown to relax cerebral arteries in an endothelium-independent manner. The aim of the present study was to test if intramural neurons are involved in the mediation of PACAP/VIP-induced vasodilatory responses. Therefore, the vascular tone of isolated rat basilar arteries was measured by means of a myograph. The vasorelaxing effect of PACAP was assessed in arteries precontracted by serotonin in the absence or presence of different test compounds known to selectively inhibit certain signaling proteins. The vasorelaxant effect of PACAP could be significantly reduced by the inhibitor of neuronal N-type calcium channels omega-conotoxin GVIA (omega-CgTx), as well as by 3-bromo-7-nitroindazole (3Br-7-Ni), an inhibitor of the neuronal nitric oxide-synthase (nNOS). The localization of N-type calcium channels and VPAC-Rs within the rat basilar artery was investigated by confocal laser scanning microscopy using omega-CgTx- and VIP-analogs labelled with fluorescent dyes. These findings suggest that activation of intramural neurons may represent an important effector mechanism for mediation of the vasorelaxant PACAP-response.

Non-synergistic relaxant effects of vasoactive intestinal polypeptide and SIN-1 in human isolated cavernous artery and corpus cavernosum

Since vasoactive intestinal peptide (VIP) and nitric oxide (NO) are considered to be non-adrenergic, non-cholinergic (NANC) inhibitory mediators in human penile erectile tissue, the goal of this study was to discover possible synergistic effects of exogeneous VIP and the NO donor 3-morpholino-sydnonimine (SIN-1) in human isolated cavernous arteries and cavernosal smooth muscle. In contrast to VIP, SIN-1 elicited complete and reproducible relaxant actions. Combined administration of VIP and SIN-1 revealed non-synergistic, independent relaxant effects in both investigated tissues. The results do not favour a combined administration of VIP and SIN-1 as a new therapeutic approach in the treatment of erectile dysfunction.

Interactions between vasoconstrictors in isolated human cerebral arteries

SummaryThis study investigates whether different endogeneous vasoconstrictors exert synergistic effects in isolated human cerebral arteries, because potentiation of contractile effects may play a role in the pathogenesis of cerebral vasospasm.Isolated human pial arteries obtained from macroscopically intact tissue during brain tumour operations were mounted onto a wire myograph. Concentration-response curves of 5-hydroxytryptamine (5-HT) were constructed in the absence and presence of threshold concentrations of the thromboxane A2 (TXA)-analog U46619, and endothelin-1 (ET-1).Threshold concentrations of U46619 markedly enhanced the maximum contractile effect of 5-HT. The response to 5-HT Threshold concentrations of ET-1 increased the maximum response to 5-HT, and markedly shifted the dose-response curve to the left. Even after washout of ET-1, the dose-response curve of 5-HT remained shifted to the left. The increase of the contractile effect of 5-HT in the presence of U46619 did not correlate with the relaxant action of the endothelium-dependent vasodilator carbachol.Thus, synergism between contractile substances such as 5-HT, U46619, or ET-1 is seen in human cerebral arteries, and responses to 5-HT are potentiated even after washout of ET-1 and U46619. The potentiation does not depend on the endothelial function. We conclude that synergistic responses between endogeneous vasoconstrictors such as 5-HT, TXA and ET-1 may be involved in the pathogenesis of cerebral vasospasm after subarachnoid haemorrhage.

Role of potassium channels in the relaxation induced by the nitric oxide (NO) donor DEA/NO in the isolated rat basilar artery

This study investigates whether potassium ion (K+) channels are involved in the nitric oxide (NO)-induced relaxation in segments of the isolated rat basilar artery, mounted onto a wire myograph. A high extracellular K+ concentration partly inhibited the relaxant effects of the NO donors DEA/NO and SIN-1 (3-morpholino-sydnonimine). Whereas single applications of the K+ channel inhibitors tetraethyl-ammonium (10(-3) M), glibenclamide (10(-6) M), 4-aminopyridine (10(-3) M), or BaCl(2) (5 x 10(-5) M) did not affect the responses to DEA/NO, a combination of these inhibitors reduced the effects of DEA/NO. These data suggest, that the relaxant effects of NO donors are partly mediated via activation of K+channels. Different K+ channel types seem to be involved that function in a redundant manner and compensate for each other.

Effects of Potassium Channel Openers in Isolated Human Cerebral Arteries

The objective of this study was to compare the relaxant effects of the K+ channel openers pinacidil and lemakalim in isolated human pial arteries with the effects of the dihydropyridines nifedipine and nimodipine and the prostacyclin analog iloprost. Relaxation was measured in vessels contracted by 40 mmol/L K+. In contrast to the potent and consistent relaxant effects of nifedipine, nimodipine, and iloprost, the potency of pinacidil and lemakalim proved to be highly variable and inversely correlated with the onset velocity of the preceding contractions of K+ as well as with the endothelium-dependent relaxation of carbachol. Thus, in contrast to dihydropyridines and iloprost, pinacidil and lemakalim selectively elicited potent relaxations in those arteries that exhibited signs of altered vascular wall functions.

Quinidine-induced potentiation of cardiovascular effects of nitrendipine: functional aspects and possible molecular mechanisms

The functional interaction between the dihydropyridine calcium channel blocker nitrendipine and quinidine was studied in isolated preparations from guinea-pig cardiac ventricle and in mesenteric arterial segments under a variety of experimental conditions. The negative inotropic potency of nitrendipine is clearly enhanced by quinidine (3·10−6-10−4 mol/l) by up to two orders of magnitude, i.e. cardiac nitrendipine effects are potentiated. Vasorelaxant effects, however, remain largely unaffected (nitrendipine potency is increased by half an order of magnitude maximally).To elucidate the mechanism of this interaction, the ability of quinidine to potentiate the negative inotropic effect of a series of 12 dihydropyridines was compared with their voltage-dependence of action in guinea-pig left atria. No significant correlation is found (r = 0.18). Furthermore, quinidine inhibits rather than stimulates binding of tritiated nitrendipine, nimodipine or (S)-isradipine to isolated cardiac membranes. Therefore, the mechanism of the quinidine-nitrendipine interaction differs from those previously proposed for modulation of dihydropyridine binding by other drugs.We hypothesize that quinidine-occupied calcium channels adopt an intermediate affinity for nitrendipine, higher than in resting channels, but lower than the high affinity present with inactivated channels. Model calculations which are based on this assumption are able to reproduce all experimental findings of this study.

Clinical Outcome after Surgery of Intracranial Unruptured Aneurysms: Results of a Series Between 1991 and 2001

The clinical results of surgery for unruptured aneurysms in the Neurosurgical Department of Kiel were analyzed to further discuss whether an operative treatment can be advised. Between 1991 and 2001, 54 unruptured aneurysms in 45 patients were operated in our department. No complications occurred in 38 patients; transient complications (slight aphasia, hemiparesis, psychiatric disorders) in 4 patients; postoperative seizures in one, epidural haematoma with the need of re-operation in one, and infection in another patient. At the time of discharge, GOS was 5 in 33 patients, 4 in 12 patients. But the slight disabilities were due to the aneurysm operation only in two patients, in the other 10 patients they were caused by pre-existing concomitant diseases. The Rankin-Scale after at least 6 months was 1 (no disability) in 31 patients (37 patients investigated); 2 (slight disability) in 5, and 3 (moderate disability) in one patient. In only one of these patients, the slight disability was caused by the aneurysm operation. During a telephone interview performed between 6 months and 7 years after the operation, all patients except two (31 patients investigated) gave a positive answer to the question, whether, in case of diagnosis of an aneurysm, they would undergo an operation again. Regarding our results, we still advocate treatment of unruptured aneurysms in patients who are in stable clinical conditions, especially in young patients and in patients with unique aneurysm configurations and aneurysm sizes approaching 10 mm.