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Biomedical subjects

A Villringer

Publications and source records attributed to A Villringer.

At least 109 records · Page 6Linked to original sources
PubMed1993

Blockade of nitric oxide synthesis in rats strongly attenuates the CBF response to extracellular acidosis.

We tested the hypothesis that the CBF response to extracellular acidosis is mediated by nitric oxide (NO). A closed cranial window, superfused with artificial CSF (aCSF), was implanted over the parietal cortex in anesthetized and ventilated Wistar rats. Regional cerebral blood flow (rCBF) was measured continuously with laser-Doppler flowmetry (LDF). The reaction of rCBF to hypercapnia (PaCO2 from 30.5 +/- 1.8 to 61.3 +/- 5.8 mm Hg by adding CO2 to the inspiratory gas) was 2.9 +/- 1.4%/mm Hg, and the reaction of rCBF to H+ (superfusion of acidic aCSF, pH 7.07 +/- 0.05) was 101.7 +/- 24.7%/pH unit. The regional NO synthase (NOS) activity was blocked by superfusing aCSF containing 10(-3) M N omega-nitro-L-arginine (L-NA, n = 10). After 30 min of L-NA superfusion, rCBF was reduced to 80.1 +/- 6.5% of baseline, and the rCBF responses to hypercapnia (PaCO2 from 30.9 +/- 2.9 to 58.8 +/- 7.7 mm Hg) and extracellular acidosis (aCSF pH 7.08 +/- 0.06) were reduced to 0.8 +/- 1.1%/mm Hg and 10.1 +/- 23.0%/pH unit, respectively (both p < 0.001). This effect was stereospecific since aCSF containing 10(-3) M N omega-nitro-D-arginine affected neither baseline rCBF nor the response to H+ (n = 5). The NOS blockade did not affect the vasodilatation by the NO donor sodium nitroprusside (n = 5, 114.3 +/- 25.1% before vs. 130.2 +/- 24.7% after NOS blockade). The results confirm the involvement of NO in the CBF reaction to hypercapnia and demonstrate for the first time that NOS blockade also strongly attenuates the H+ response of the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1993

[Venous MR angiography for the primary diagnosis and follow-up of sinus venous thrombosis. The correlation with the clinical picture and DSA].

30 patients clinically suspected of suffering from venous sinus thrombosis were examined by MRT with venous MR angiography (FLASH 2-D). In 8 patients selective arterial angiography was also performed and 5 patients were followed up by MR angiography after an interval of three months. The MRT images and individual MR angiography images were analysed and 3-D reconstruction performed. In 11 patients MR angiography correctly demonstrated venous sinus thrombosis; the most frequently affected were the superior sagittal sinus, the ascending cerebral veins and the transverse sinus. Compared with DSA, magnetic resonance angiography achieved a high degree of accuracy in our patients. It was significantly better in evaluating the basal sinus system whereas thrombosis of individual ascending veins was better shown by DSA. In summary, primary use of MRT and MR angiography is recommended for the diagnosis of venous sinus thrombosis.

Adult↗
PubMed1993

Global forebrain ischaemia in the rat: controlled reduction of cerebral blood flow by hypobaric hypotension and two-vessel occlusion.

We developed and characterized a model of global forebrain ischaemia in rats, permitting control of CBF at any desired ischaemic level with minimum surgery and without anticoagulation. Both common carotid arteries are occluded temporarily and systemic arterial pressure is lowered by pooling venous blood by lower body negative pressure with a cheap suction device. By measuring rCBF continuously (laser-Doppler-flowmetry) and regulating systemic arterial pressure, the model was used to automatically control cortical rCBF at predetermined ischaemic levels at 50, 30, 15, and 5% of normal rCBF (n = 5). When both common carotid arteries were occluded and systemic arterial pressure was lowered to 55 mmHg with hypobaric hypotension (n = 5), cortical CBF always fell to less than 5% of normal rCBF (n = 5). Prompt recirculation was achieved after reopening of the carotid arteries and return to normobaric body pressure. Hypobaric hypotension with bilateral common carotid occlusion requires only carotid surgery and measurement of systemic arterial pressure; it produces global forebrain ischaemia without anticoagulation as a true step function type insult. If rCBF is measured continuously, the model can be used to control ischaemic CBF to predetermined values.

Animals↗
PubMed1993

Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics.

We investigated the cerebral blood flow (CBF) response to somatosensory stimulation. Stimulation of neuronal activity was performed by deflection (2-3/s) of the mystacial vibrissae in rats over a period of 60 s, and regional cortical CBF was measured continuously in the contralateral somatosensory cortex with laser-Doppler flowmetry. CBF within the somatosensory cortex was studied through the parietal bone thinned to translucency (n = 7) or through a closed cranial window with the dura mater removed (n = 7). In addition, the differential effect of anesthetics (halothane-N2O, n = 5; thiobutabarbiturate, n = 5; and alpha-chloralose, n = 7) on the CBF response to stimulation was investigated. After a rapid increase after stimulation onset (maximum reached within 2-3 s), CBF remained above baseline with a slight tendency to decrease despite continued stimulation. On termination of stimulation, CBF fell to near prestimulation values within 2-3 s. The following mean CBF responses above baseline during the 60-s stimulation period were obtained: halothane-N2O anesthesia, 25.4 +/- 5.9%; thiobutabarbiturate anesthesia, 10.6 +/- 2.4%; and alpha-chloralose anesthesia, 16.9 +/- 2.3 (through the translucent bone) and 16.2 +/- 2.9% (closed cranial window, dura removed). We conclude that coupling of CBF to neuronal function has a very high temporal resolution (< 3 s) and that whisker deflection in rats provides a physiological stimulus to study coupling with laser-Doppler flowmetry.

Anesthetics↗
PubMed1992

In-vivo confocal scanning laser microscopy of the cerebral microcirculation.

Confocal scanning laser microscopy (CSLM) was used to study the microcirculation of the brain neocortex in anaesthetized rats. After removal of the dura mater, implantation of a closed cranial window, and intravenous injection of fluorescein, three-dimensional reconstructions of cortical capillaries were performed down to a depth of 250 microns below the pial surface. Using a one-dimensional approach (single line scanning), erythrocyte (negative contrast in fluorescently labelled plasma) and leucocyte (labelled with rhodamine 6 G) velocity and supply rate in cortical capillaries were measured. The effect of CO2-inhalation on capillary blood flow dynamics was studied. Capillaries were imaged continuously for up to 1 h without changes in flow or fluorescence pattern. However, by increasing the laser power 10-100-fold, aggregate formation was induced and capillaries were occluded, possibly due to damage to vascular endothelium. We conclude that CSLM can be used to study morphological and dynamic aspects of fluorescently labelled subsurface structures in organs of experimental animals.

Angiography↗
PubMed1991

Heparin treatment in sinus venous thrombosis.

Treatment of sinus venous thrombosis (SVT) is controversial. Although heparin has been used for this condition, many investigators have opposed its use because of the frequent occurrence of intracranial haemorrhage (ICH) and SVT. Therefore we have evaluated anticoagulation with adjusted-dose intravenous heparin for treatment of aseptic SVT in a randomised, blinded (patient and observer), placebo-controlled study in 20 patients (10 heparin, 10 placebo). The clinical course of the two groups, as judged by a newly designed SVT-severity scale, started to differ in favour of the heparin group after 3 days of treatment (p less than 0.05, Mann-Whitney U-test) and the difference remained significant (p less than 0.01) after 8 days of treatment. After 3 months, 8 of the heparin-treated patients had a complete clinical recovery and 2 had slight residual neurological deficits. In the placebo group, only 1 patient had a complete recovery, 6 patients had neurological deficits, and 3 patients died (p less than 0.01, modified Fisher's exact test). An additional retrospective study on the relation between heparin treatment and ICH in SVT patients was based on 102 patients, 43 of whom had an ICH. 27 of these patients were treated with dose-adjusted, intravenous heparin after the ICH. Of these 27 patients, 4 died (mortality 15%), and 14 patients completely recovered. Of the 13 patients that did not receive heparin after ICH, 9 died (mortality 69%) and only 3 patients completely recovered. We conclude that anticoagulation with dose-adjusted intravenous heparin is an effective treatment in patients with SVT and that ICH is not a contraindication to heparin treatment in these patients.

Adult↗
PubMed1991

Imaging of leukocytes within the rat brain cortex in vivo.

Confocal laser scanning microscopy was used in a rat closed cranial window preparation in order to study rhodamin 6G-labeled leukocytes within the brain cortex in vivo. Leukocytes were visualized up to 150 microns beneath the rat brain surface in noninvasive optical sections. In pial venules, leukocytes were seen flowing with the blood stream, rolling along or sticking to the endothelium, and migrating through the vessel wall. Within cerebral capillaries, leukocyte flux, velocities, and leukocyte plugging were measured. After additional intravenous administration of fluorescein, the plasma, leukocytes, and erythrocytes were visualized simultaneously. Based on stacks of optical sections of fluorescein-labeled capillaries, the individual capillaries were localized within the three-dimensional microvascular network. The usefulness of this technique was illustrated in a feasibility study in which leukocyte sticking to the vascular walls of venules, leukocyte extravasation, and intracapillary leukocyte plugging were monitored in a model of global cerebral ischemia.

Animals↗
PubMed1991

Three-dimensional reconstruction of the rat brain cortical microcirculation in vivo.

We used confocal laser scanning microscopy (CLSM) to investigate the morphology and three-dimensional relationships of the microcirculation of the superficial layers of the rat brain cortex in vivo. In anesthetized rats equipped with a closed cranial window (dura mater removed), after i.v. injection of 3 mg/100 g of body weight of fluorescein in 0.5 ml of saline, serial optical sections of the brain cortex intraparenchymal microcirculation were taken. Excitation was at a wavelength of 488 nm (argon laser), and emission was collected above 515 nm. CLSM provided images of brain vessels with sufficient signal-to-noise ratio for three-dimensional reconstructions down to a depth of 250 microns beneath the surface of the brain. Compared to conventional fluorescence microscopy, CLSM has a much higher axial resolution and higher depth of penetration. Laser light-induced intravascular aggregates, irregularities of erythrocyte flow, or microvascular occlusions ("light and dye injury") were not apparent in the current experimental paradigm. CLSM is a promising new tool for in vivo visualization of the cerebral microcirculation. Future studies have to characterize the potential damage to the tissue dye mechanisms.

Animals↗
PubMed1990

[3D-MR-angiography using Gd-DTPA].

Projection angiograms similar to DSA can be obtained via 3D-gradient echo techniques by subtraction of data sets acquired before and after the intravenous administration of Gd-DTPA (0.1-0.2 mmol/kg body weight). As Gd-DTPA does not penetrate the blood-brain barrier, image subtraction results in complete cancellation of non vascular tissue. In organs without blood-brain barrier Gd-DTPA induced signal enhancement results in modest background superposition of vascular anatomy. With Gd-DTPA angiography vessels are imaged favouring the venous system because of the more constant flow velocity and the lack of ECG synchronization. Gd-DTPA angiography results in high signal-to-noise angiograms and can even be performed with MR imagers which do not meet the hardware requirements for angiography based on flow compensated gradients.

Blood Vessels↗
PubMed1990

Angiotensin II induces endothelium-dependent vasodilation of rat cerebral arterioles.

We evaluated the response of cerebral arterioles to angiotensin II (ANG II) in anesthetized rats equipped with a closed cranial window. Topical application of 10(-10)-10(-5) M ANG II induced dose-dependent arteriolar vasodilation. Maximum vasodilation of 24 +/- 2.2% (+/- SE) was attained at a concentration of 10(-6) M ANG II. The dilation in response to ANG II was blocked by 3 micrograms/ml indomethacin, a cyclooxygenase inhibitor, and was reversed to minimal vasoconstriction by 10(-5) M methylene blue, a substance that has been reported to eliminate endothelium-dependent vasodilation. Coapplication of indomethacin with methylene blue reduced the arteriolar response to ANG II to a similar extent as the application of indomethacin alone. Indomethacin or methylene blue did not inhibit the vasodilation induced by 10(-5) M adenosine, which is not endothelium and cyclooxygenase dependent. Mercury light illumination of the pial vessels after intravenous injection of fluorescein dye, a technique that has been used by others to functionally damage endothelial cells, reversed ANG II (10(-6) M)-induced vasodilation into a -14.2 +/- 2.3% constriction while not affecting the response to adenosine. Our data suggest that ANG II produces vasodilator responses of rat cerebral arterioles by the release of a factor that is derived from the endothelium and may be generated through a cyclooxygenase-dependent mechanism.

Angiotensin II↗
PubMed1989

Confocal laser microscopy to study microcirculation on the rat brain surface in vivo.

We demonstrate the feasibility of using confocal laser microscopy (CLM) to study the microcirculation on the rat brain surface. Using a closed cranial window model in vivo, microvessels in the size range of capillaries (8 microns) and dynamic events were observed through an intact dura. This study is the first step in the development of a system which simultaneously monitors vascular and metabolic processes using CLM.

Animals↗
PubMed1989

B-waves in healthy persons.

The objective of this study was to determine, whether 0.5-2/min oscillations in intracranial pressure ('B-waves') are a physiological phenomenon. In a group of 5 patients 0.5-2/min oscillations of ventricular pressure simultaneous with oscillations in the middle cerebral artery (MCA) flow velocity, as assessed by transcranial Doppler sonography, were observed. Similar oscillations in MCA blood flow velocity were demonstrated in 8 out of 10 healthy subjects with an amplitude of about 10% of the mean flow velocity. We speculate that oscillations both in ventricular pressure and middle cerebral artery blood flow velocity are caused by rhythmic diameter changes of cerebral vessels with concomitant cerebral blood volume oscillations. Our data support the suggestion that B-waves may be physiological.

Adult↗
PubMed1988

Dynamic imaging with lanthanide chelates in normal brain: contrast due to magnetic susceptibility effects.

Using a one-dimensional rapid imaging technique, we have found that injection of lanthanide chelates such as Gd(DTPA)2- leads to a significant decrease (50%) in rat brain signal intensity at 1.45 T using T2-weighted pulse sequences; however, no effect of comparable size is observed with T1-weighted pulse sequences. The transient effect and its kinetics were followed with a temporal resolution of between 1 and 8 s. Experiments with different lanthanide chelates show that the observed decrease in signal intensity correlates with the magnetic moment of each agent but not with their longitudinal relaxivity. Three-dimensional chemical-shift resolved experiments demonstrate significant line broadening in brain during infusion with Dy(DTPA)2-. Our results show that the cause of this effect is the difference in susceptibility between the capillaries, containing the contrast agent, and the surrounding tissue. As a result of these susceptibility differences, field gradients are produced in the tissue and diffusion of water through these gradients leads to a loss of spin phase coherence and thus a decrease in signal intensity. We propose this as a new type of contrast agent mechanism in NMR. The effect and its kinetics are likely to be related to important physiological parameters such as cerebral blood volume and cerebral blood flow, and do not depend on a breakdown of the blood-brain barrier as do conventional contrast agent techniques.

Animals↗