[Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic disorders]. / Vinpocetin infúizió hatásának retrospektív vizsgálata szemészeti megbetegedésekben.

Retrospective analysis of the effect of vinpocetine infusion in ophthalmologic disorders. The authors retrospectively examined the effect of vinpocetine infusion on various ophthalmological disorders. Based on the data of 280 patients they concluded that vinpocetine infusion has beneficial effects in numerous ophthalmologic disorders of vision and visual field. There was a clear difference regarding the response to treatment. Best results were achieved in diseases characterized by sclerosis, hypertonia and macular degeneration. The improvement was modest or progression was slowed in patients with nervus opticus ischaemia, glaucoma and myopia. These results are in accordance with the literature data. The beneficial effect of vinpocetine can be explained by the fact that the vessels of the eye are in direct connection with the cerebral circulation and hereby the circulation improving effect of vinpocetine could be effective. The neuronal effects of vinpocetine could also play a role at least in two ways. On the one hand by the direct effect exerted on the cells of retina (these cells are related to the neurons), and on the other hand by the improvement of the circulation and metabolism of the secondary visual cortex found in the occipital lobe (this effect is proved by PET studies).

Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.

The pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism in chronic ischemic stroke patients (n=13) were studied with positron emission tomography in a double-blind design. The regional and global cerebral metabolic rates of glucose (CMRglc) and cerebral blood flow (CBF) as well as vital physiological parameters, clinical performance scales, and transcranial Doppler parameters were measured before and after the treatment period in patient groups treated with daily intravenous infusion with or without vinpocetine. While the global CMRglc values did not change markedly as a result of the infusion treatment with (n=6) or without (n=7) vinpocetine, the global CBF increased and regional CMRglc and CBF values showed marked changes in several brain structures in both cases, with more accentuated changes when the infusion contained vinpocetine. In the latter case the highest rCBF changes were observed in those structures in which the highest regional uptake of labelled vinpocetine was measured in other PET studies (thalamus and caudate nucleus: increases amounting to 36% and 37%, respectively). The findings indicate that a 2-week long intravenous vinpocetine treatment can contribute effectively to the redistribution of rCBF in chronic ischemic stroke patients. The effects are most pronounced in those brain regions with the highest uptake of the drug.

Clinical and non-clinical investigations using positron emission tomography, near infrared spectroscopy and transcranial Doppler methods on the neuroprotective drug vinpocetine: a summary of evidences.

Vinpocetine (Cavinton, Gedeon Richter, Budapest) is widely used as a neuroprotective drug in the prevention and treatment of cerebrovascular diseases. Vinpocetine is a potent inhibitor of the voltage-dependent Na(+) channels and a selective inhibitor of the Ca(2+)/caldmoduline-dependent phosphodiesterase 1. The clinical efficacy has been supported by several previous studies. Positron emission tomography (PET) is a powerful method to evaluate the fate, the site of action, the pharmacological and physiological effects of a drug in the brain and other organs. We have demonstrated in monkey that the [11C]-labelled vinpocetine rapidly enters the brain after intravenous (i.v.) injection, the maximal uptake being approximately 5% of the total injected radioactivity. The distribution pattern of vinpocetine in the brain was heterogenous, with the highest uptake in the thalamus, basal ganglia and visual cortex. These findings were confirmed in healthy humans, where the i.v. administered [11C]-labelled vinpocetine had a similar distribution pattern. The highest uptake in the brain was 3.71% of the total administered radioactivity. Quite recently, we have shown that [11C]-labelled vinpocetine administered orally to healthy human volunteers also rapidly appears in the brain and shows a similar distribution pattern, the highest uptake being 0.71% of the total administered radioactivity. In two separate sets of clinical studies where chronic ischaemic post-stroke patients were either treated with a single infusion (Study 1) or with daily vinpocetine infusion for 2 weeks (Study 2), we have shown that vinpocetine increases the regional cerebral glucose uptake and to a certain extent glucose metabolism in the so-called peri-stroke region as well as in the relatively intact brain tissue. The 2-week-long treatment also increased the regional cerebral blood flow (CBF) especially in the thalamus, basal ganglia and visual cortex of the nonsymptomatic hemisphere. We have demonstrated the cerebral perfusion-enhancing and parenchymal oxygen extraction-increasing effects of vinpocetine in subacute ischaemic stroke patients by near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) methods.

[Impairment of vasoreactivity in brainstem and hemispheral small vessel disease: comparative study]. / A vazoreaktivitás zavara agytörzsi és hemisphaerialis kisérbetegségben: összehasonlító vizsgálat.

AIMS: Cerebrovascular small vessel disease may lead to an impairment of vasoreactivity (VR). Vasoregulatory impairment in internal carotid artery distribution area has been established. In this study the authors sought the answer to the question if VR of vertebrobasilar (VB) territory was impaired in brainstem small vessel diseases and if vasoregulatory impairment differed between the two distribution territories. METHODS: VR of carotid and VB territory was compared applying different functional tests (ventilation, tilting, acetazolamide) in 25 patients with brainstem lacunar infarcts, 20 patients with periventricular leukoaraiosis and in 35 control subjects. Cerebral blood flow velocity (CBFV) of basilar artery (BA) and middle cerebral artery (MCA) was monitored with transcranial Doppler (TCD), systemic blood pressure and CO2 partial pressure of expired air were also registered. RESULTS: In the BA territory the VR was significantly smaller in the patient than in the control group (3.1 +/- 4.6 cm/sec/kPa vs. 8.2 +/- 6.2 cm/sec/kPa, p = 0.01) during hypercapnia. In a subgroup of patients with mean baseline CBFV < 25 cm/sec, the VR was significantly smaller and Pl non-significantly higher than in patients with baseline CBFV > 25 cm/s (VRCO2 1.5 +/- 2.0 cm/sec/kPa vs. 6.5 +/- 6.5 cm/sec/kPa, p = 0.007; Pl 1.11 +/- 0.30 vs. 1.0 +/- 0.26, p = 0.4) indicating higher vascular resistance in the former group. Results of tilting tests showed similar but nonsignificant changes while acetazolamide tests revealed no differences between the two groups. In the MCA territory the VR was significantly lower in patients than in the controls during hypercapnia (4.7 +/- 3.7 cm/sec/kPa vs. 18.4 +/- 6.8 cm/sec/kPa, p < 0.001) and showed a nonsignificant tendency to be lower in patients than in controls during hypocapnia (14.6 +/- 13.8 cm/sec/kPa vs. 24.7 +/- 21.2 cm/sec/kPa, p = 0.1). Although CBFV measurements during acetazolamide test tended to support these findings, they showed no significant differences between patients and controls. During head-up tilt the CBFV did not differ significantly between the two groups. The VRCO2 is significantly higher in the MCA than in the BA territory (18.4 CI95 2.98 vs. 10.1 CI95 3.01; p < 0.001). The impairment of VRCO2 was more severe in the MCA territory (VR decreased to 26% of baseline in the MCA and to 34% in the BA territory). CONCLUSION: The capacity of carotid territory VR exceeds that of VB territory. The impairment of VR is present in both the carotid and VB territories and is more severe in the former region. The most feasible test to reveal this impairment is the hypercapnic test. There is a strong correlation between the extent of vasoregulatory impairment and baseline CBFV in brainstem small vessel diseases.

Vinpocetine increases cerebral blood flow and oxygenation in stroke patients: a near infrared spectroscopy and transcranial Doppler study.

OBJECTIVE: To investigate the effect of vinpocetine on cerebral blood flow (CBF) in the compromised circulation of a stroke affected hemisphere using transcranial Doppler (TCD) and near infrared spectroscopy (NIRS) methods. METHODS: 43 patients with ischemic stroke were randomized into vinpocetine (VP) and placebo group in a double blind, placebo-controlled study of the effect of a single-dose i.v. infusion of vinpocetine on cerebral blood perfusion and oxygenation. In the VP group 20 mg VP in 500 ml saline, in the placebo group 500 ml saline alone were administered. The concentrations of oxy-, reduced- and total hemoglobin were measured by NIRS frontolaterally on the side of lesion while the mean cerebral blood flow velocity (CBFV), the pulsatility index (PI) and Doppler spectral intensity (DSI) were monitored by TCD in the middle cerebral artery on the same side. Values were averaged for the first 5 min prior to the infusion and for the last 5 min of infusion and they were compared between groups. RESULTS: The concentration of all three chromophores increased during infusion in the VP group (mean dHbT = 1.03, CI(95) = 0.84, P = 0.058; mean dHbO = 0.92, CI(95) = 0.91, P = 0.071; mean dHb = 0.10, CI(95) = 0.21, P = 0.297). The HbT and HbO showed a substantially smaller increase in the placebo group (mean dHbT = 0.31, CI(95) = 0.74, P = 0.22; mean dHbO = 0.57, CI(95) = 0.80, P = 0.094) while the Hb decreased (mean dHb = -0.26, CI(95) = 0.29, P = 0.05). Comparing to the placebo group Hb increased significantly in the VP group (P = 0.027) while the increase of HbO and HbT did not reach the level of significance (P = 0.29 and 0.11). DSI showed a significantly larger increase in the VP than in placebo group (dDSI=25.8 CI(95)=8.8 [VP]; dDSI =3.3, CI(95) = 3.7 [Placebo], P < 0.005). The CBFV and PI did not differ significantly between groups. (dVm = 5.0+/-2.98 cm/s [VP], dVm = 4.1+/-2.57 cm/s [Placebo], P = 0.28; dPI = 0.08 [VP], dPI = 0.09 [Placebo]; P = 0.47). CONCLUSION: VP increases cerebral perfusion and parenchymal oxygen extraction as well. The increased perfusion was indicated by NIRS and by TCD measurement of DSI while conventional velocity and pulsatility measurements failed to detect theses effects. NIRS is a sensitive, feasible method of measuring changes in regional blood flow and tissue oxygenation in the superficial cortex.