In vivo X-ray digital subtraction and CT angiography of the murine cerebrovasculature using an intra-arterial route of contrast injection.

BACKGROUND AND PURPOSE: Investigation of the anatomy, patency, and blood flow of arterial and venous vessels in small animal models of cerebral ischemia, venous thrombosis, or vasospasm is of major interest. However, due to their small caliber, in vivo examination of these vessels is technically challenging. Using micro-CT, we compared the feasibility of in vivo DSA and CTA of the murine cerebrovasculature using an intra-arterial route of contrast administration. MATERIALS AND METHODS: The ECA was catheterized in 5 C57BL/6J mice. During intra-arterial injection of an iodized contrast agent (30 µL/1 sec), DSA of the intra- and extracranial vessels was performed in mice breathing room air and repeated in hypoxic/hypercapnic mice. Micro-CTA was performed within 20 seconds of intra-arterial contrast injection (220 µL/20 sec). Image quality of both methods was compared. Radiation dose measurements were performed with thermoluminescence dosimeters. RESULTS: Both methods provided high-resolution images of the murine cerebrovasculature, with the smallest identifiable vessel calibers of ≤ 50 µm. Due to its high temporal resolution of 30 fps, DSA allowed identification of anastomoses between the ICA and ECA by detection of retrograde flow within the superficial temporal artery. Micro-CTA during intra-arterial contrast injection resulted in a reduced injection volume and a higher contrast-to-noise ratio (19.0 ± 1.0) compared with DSA (10.0 ± 1.8) or micro-CTA when using an intravenous injection route (1.3 ± 0.4). CONCLUSIONS: DSA of the murine cerebrovasculature is feasible using micro-CT and allows precise and repeated measurements of the vessel caliber, and changes of the vessel caliber, while providing relevant information on blood flow in vivo.

Maintained functionality of an implantable radiotelemetric blood pressure and heart rate sensor after magnetic resonance imaging in rats.

Radiotelemetric sensors for in vivo assessment of blood pressure and heart rate are widely used in animal research. MRI with implanted sensors is regarded as contraindicated as transmitter malfunction and injury of the animal may be caused. Moreover, artefacts are expected to compromise image evaluation. In vitro, the function of a radiotelemetric sensor (TA11PA-C10, Data Sciences International) after exposure to MRI up to 9.4 T was assessed. The magnetic force of the electromagnetic field on the sensor as well as radiofrequency (RF)-induced sensor heating was analysed. Finally, MRI with an implanted sensor was performed in a rat. Imaging artefacts were analysed at 3.0 and 9.4 T ex vivo and in vivo. Transmitted 24 h blood pressure and heart rate were compared before and after MRI to verify the integrity of the telemetric sensor. The function of the sensor was not altered by MRI up to 9.4 T. The maximum force exerted on the sensor was 273 ± 50 mN. RF-induced heating was ruled out. Artefacts impeded the assessment of the abdomen and thorax in a dead rat, but not of the head and neck. MRI with implanted radiotelemetric sensors is feasible in principal. The tested sensor maintains functionality up to 9.4 T. Artefacts hampered abdominal and throacic imaging in rats, while assessment of the head and neck is possible.

[Current concepts for experimental micro-CT in small animals]. / Aktueller Stand der Mikro-CT in der experimentellen Kleintierbildgebung.

The number of publications describing the use of micro-computed tomography (microCT) for preclinical in vivo imaging of small animals has risen considerably within the last few years. The purpose of this review is to familiarize the reader with the basic principles of microCT, to present successful experimental approaches in order of the evaluated organ system, and to highlight limitations that need to be considered when planning microCT-based studies.

Tapetoretinal degeneration in brothers with apparent Cohen syndrome: nosology with Mirhosseini-Holmes-Walton syndrome.

We report on 2 brothers with marked eye anomalies, documented with histopathological studies, and several other findings fitting the diagnosis of both the Cohen and the Mirhosseini-Holmes-Walton syndromes. In accordance with Norio and Raitta (Norio R, Raitta C (1986): Am J Med Genet 25:397-398) we come to the conclusion that these 2 syndromes constitute one clinical but possibly heterogeneous entity.

Evaluation of autonomic neuropathy in diabetes mellitus. Comparison of clinical, functional and biochemical parameters.

Quantitative assessment of signs or symptoms of neuropathy, and the beat-to-beat variation, valsalva, orthostasis, handgrip and cold pressor tests, and measurements of plasma renin and catecholamine excretion rate were performed in 23 diabetic patients and 10 age-matched normal subjects. Significant inverse correlations were found between the clinical score and the beat-to-beat variation (a test of efferent vagus function) (r=-0.55, -0.72, P less than 0.0005) or the pressor response to handgrip (possible test of efferent sympathetic integrity (r=p less than 0.005) or the values of both tests combined (r=-0.79, P less than 0.0005); but not with the other measured parameters. Beat-to-beat variation was abnormal in all 9 diabetics with increased and in 9 of 14 with normal clinical score, whereas only seven and one patient from these subgroups, respectively, had an abnormal Valsalva ratio. The pressor response to handgrip was only slightly reduced in the diabetic patients, with greater tendency in those with abnormal clinical score. Additional possible indices of adrenergic dysfunction such as the pressor response to cold stimulus, plasma renin levels and noradrenaline or adrenaline excretion rates did not differ significantly between normal subjects and diabetics. These finding demonstrate a greater prevalence of parasympathetic as compared to sympathetic impairment in diabetic autonomic neuropathy; the beat-to-beat variation was the most sensitive among the tests used. An assessment of clinical evidence combined with non-invasive functional procedures such as the beat-to-beat variation and handgrip tests provide a valuable and easy to perform tool in the evaluation of diabetic neuropathy.

alpha-Adrenoceptor-mediated inhibitory effect of the sympathetic nervous system on the isoprenaline-induced increase in plasma renin concentration.

The importance of the sympatho-adrenal system for the isoprenaline-induced increase in plasma renin concentration was investigated in conscious rats Ganglionic blockade by trimethidinium (10 mg kg-1) increased the dose-dependent elevation of plasma renin concentration induced by isoprenaline (0.03-0.48 microgram kg-1 min-1). Also treatment of the rats with guanethidine (6 mg kg-1) or reserpine (2.5 mg kg-1, given 16 and 7 h prior to the experiments) further increased the effect of isoprenaline (0.5 microgram kg-1 min-1) on plasma renin concentration. Unilateral renal denervation combined with contralateral nephrectomy doubled the effect of the beta-sympathomimetic amine on renin release. The alpha-adrenoceptor antagonist phenoxy-benzamine (3 mg kg-1) also enhanced the effect of isoprenaline on this parameter. It is concluded that apart from a stimulation of renin release via beta-adrenoceptors the sympathetic nervous system may inhibit renin release via stimulation of alpha-adrenoceptors.

Inhibition of the adrenalectomy-induced increase in plasma renin concentration by vasoconstrictor agents in rats.

Plasma renin concentrations in rats increase after bilateral adrenalectomy without sodium substitution. The effects of i.v. infused (asp1-beta-amid, val5)-angiotensin II (1 mug/kg min), felypressin (phen2, lys8-vasopressin) (40 mU/kg min) and phenylephrine (30 mug/kg min) were investigated on the increase in plasma renin concentration. These effects of the agents were compared with their actions on blood pressure, heart rate and renal hemodynamics. In rats with destroyed macula densa cells the effect of bilateral adrenalectomy without sodium substitution was also studied. Adrenalectomy still increased the plasma renin concentration. Angiotensin II and felypressin, also depressed under these conditions the elevation of plasma renin concentration caused by adrenalectomy. The mechanism of the adrenalectomy-induced renin release and its suppression by vasoconstrictor agents is discussed.

Inhibition of furosemide-induced renin release by vasoconstrictors.

The effect of i.v. infused (asp1-beta-amid, val5)-angiotensin II (1.0 mug/kg min), octapressin (phe2, lys8-vasopressin) (10.0 mU/kg min) and of the alpha-sympathomimetic amine phenylephrine (40.0 mug/kg min) on the stimulation of renin secretion by furosemide (10.0 mg/kg i.v.) was investigated. The vasoconstrictors abolished the renin release induced by forosemide. Studies on the clearance of p-aminohippuric acid (PAH) (i.e. renal plasma flow) showed that the action of the vasoconstrictors cannot be explained by a decrease in access of furosemide to its intrarenal sites of action. The mechanism of the suppressive action of the vasoconstrictors on renin release is discussed.

Inhibition of isoprenaline-induced increase in plasma renin concentration by vasoconstrictors.

The vasoconstrictors angiotensin II, vasopressin and the alpha-sympathomimetic phenylephrine significantly inhibit the renin release caused by the beta-sympathomimetic isoprenaline. The mechanism of the inhibition is discussed.

Studies on the juxtaglomerular apparatus. IV. Freeze-fracturing of membrane surfaces.

The juxtaglomerular apparatus of the rat was studied after freeze-fracturing with special respect to intercellular junctions. It was found that juxtaglomerular granulated cells of the vas afferens are interconnected by gap junctions to adjacent cells (granulated cells, possibly also smooth muscle cells). Gap junctions have also been found on the surface of lacis cells and mesangial cells. It is therefore concluded that these cells of the juxtaglomerular apparatus and the glomerulus--granulated cells (possibly also smooth muscle cells) of the vas afferens, lacis cells and mesangium cells--form a functional system reacting in a coordinated manner to physiological stimuli.