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Biomedical subjects

N Wiernsperger

Publications and source records attributed to N Wiernsperger.

At least 73 records · Page 4Linked to original sources

Effect of indomethacin in experimental cerebral ischemia.

The effect of indomethacin treatment (4 mg/kg-1, i.v.) on the cerebrocortical post-ischemic reperfusion ischemia (rabbits) or to focal epicerebral ischemia (cats). When administered prior to global ischemia (but not after), indomethacin enhanced the cortical post-ischemic blood flow. No improvement, however, could be observed in the electrocorticogram in either case. Moreover, indomethacin pretreatment did not change the evolution of the cortical tissular pO2 following focal ischemia. It is suggested that, in spite of post-ischemic amelioration of blood flow, indomethacin is unable to improve tissular oxygenation and electrical activity of the cerebral cortex.

Animals↗

Influence of early phases of paralysis on microcirculation of rat skeletal muscle.

By combining tissue pO2 measurements with morphological visualization and counting of perfused capillaries, early microvascular changes were investigated in paralysis of skeletal muscle of the rat. The models included experimental allergic encephalomyelitis (EAE), experimental allergic neuritis (EAN), 6-aminonicotinamide intoxication, and peripheral denervation. The results showed that in all models tissue oxygenation was either normal or elevated. In most cases this was accompanied by a reduced perfusion of the capillary bed, supporting the hypothesis of a dysfunction in oxidative metabolism. The effects of paralysis on capillary perfusion were more marked in red than in white muscles, except in spastic paresis. Flaccid paralysis had more deleterious effects on muscle microcirculation than spastic paralysis. Our data suggest that: (1) microvascular changes occur very early after the onset of paralysis and (2) later developing changes in the skeletal muscle such as atrophy cannot be ascribed to a lack of oxygen supply but rather, at least in part, to a dysfunction in oxidative metabolism.

6-Aminonicotinamide↗

Dopaminergic agonists and their influence on the oxygenation and function activity of underperfused brain tissue.

The effect of two dopaminergic agonists (apomorphine and bromocriptine) on electrical activity and oxygen supply of the brain was investigated in cats submitted to hypovolemic oligemia (mean arterial blood pressure: 45 mmHg). While both drugs stimulated the brain by prolonging the oligemia-induced seizures in the caudate nucleus and in the cerebral cortex, only apomorphine improved the pO2 distribution in the cortical tissue after 120 min oligemia. Bromocriptine, in contrast, had a beneficial effect of shorter duration. These data show that under conditions of incomplete ischemia the brain can still be activated. Furthermore, these results provide additional support for the biochemically founded hypothesis of different dopamine receptors in the brain.

Animals↗

Effect of carotid ligation on cerebral tissue oxygenation in aging rat.

In order to test the ability of aged animals to compensate a cerebrovascular insufficiency, common carotid ligation was performed on young (12 months) and aged (30 months) rats. By using gold microelectrodes, the pO2 distribution in the cerebral cortex was registered for 1 h following the occlusion of the carotid arteries. It could be shown that, while the young group was able to compensate the reduction in arterial blood supply, the cortical pO2 distribution in the group of aged rats shifted towards a hypoxic profile. These results provide further evidence of the limited adaptability to functional demands with increasing age.

Aging↗

Cortical pO2 distribution during oligemic hypotension and its pharmacological modifications.

pO2 measurements in the cerebral cortex of cats have shown that the distribution of oxygen within the tissue becomes considerably affected by hypovolemic hypotension, in particular in the late period of oligemia. Pharmacological studies on this model show that the treatment of shock with a vasodilating drug such as papaverine leads to shunt-perfusion, thus impairing the oxygenation of brain tissue. In contrast, administration of the metabolically active drug dihydroergotoxine (DET, Hydergine) results in an improvement of the tissue pO2 distribution in the direction of a pre-shock state.

Animals↗

Technical note about simultaneous recording of oxygen partial pressure and neuronal activity in cat cortex.

A method is described for simultaneous measurements of pO2 and action potentials with microelectrodes using prefabricated gold wires. The construction and measuring with such gold electrodes is easier than with traditionally used platinum electrodes. Single electrodes recording is done with a specially adapted electronic circuit, allowing the separation of both signals (pO2 and action potentials. A measurement in cat brain illustrates this procedure.

Action Potentials↗

Impaired microvascular responses to acute hyperglycemia in type I diabetic rats.

Abnormal reactivity of resistance vasculature may induce long-term alterations in regional hemodynamics, contributing to the pathogenesis of diabetic microangiopathy. The purpose of this study was to examine the responses of microvessels to a hyperglycemic episode aimed at mimicking a physiological stimulus such as the postprandial state. This study is the first to report the direct, in situ, visualization of this situation by intravital microscopy in the skeletal muscle of diabetic rat and is particularly interesting as it applies to an iterative, physiological stimulus. The study was conducted in 5-month-old rats, either nondiabetic (ND) or rendered diabetic (D) for 12 weeks (streptozotocin, 60 mg/kg, i.v.). Intravital microscopy was used to examine diameter and vasomotion changes in precapillary arterioles (< 20 microm) in the spinotrapezius muscle of fasted, anesthetized rats, before and up to 60 min after infusion of glucose or isotonic saline. After intravenous glucose infusion, a precapillary arteriolar vasoconstriction associated with an increase in the number of arterioles presenting vasomotion were seen in ND rats. In contrast, no modification in either parameter was observed in D rats. Our results indicate that, microvessels react to acute changes in the metabolic environment such as induced by elevation of plasma glucose. There was a complete loss of reactivity (vasoconstriction and vasomotion) of precapillary arterioles to superimposed hyperglycemia in D rats. According to the "hemodynamic hypothesis", this impaired vasoconstriction could result in hyperperfusion of microvessels and subsequent microvascular damages which might contribute to the development of diabetic microangiopathy.

Animals↗

Vascular permeability increase as induced by histamine or bradykinin is enhanced by advanced glycation endproducts (AGEs).

Advanced glycation endproducts (AGEs) may enhance vascular permeability in diabetic subjects. To test this hypothesis, AGEs were prepared in the presence of albumin (AGE-Alb). Control albumin (Alb) and AGE-Alb were then labeled with FITC (fluoresceinisothiocyanate) and injected i.v. into anesthetized hamsters at a dose of 7 mg/100 g B.W. Normal hamsters were given FITC-Alb or FITC-AGE-Alb and FITC-dextran. Vascular permeability changes were measured by direct intravital microscopy of the hamster cheek pouch preparations in fluorescent light and recorded as number of sites (=leaks) with extravasation of FITC-labeled albumin in postcapillary venules. No changes were seen during 1 hour after i.v. injection of FITC-Alb or FITC-AGE-Alb. Repeated local application of histamine 5 x 10(6) M or bradykinin 5 x 10(7) M to the cheek pouch for 5 min with 30-min intervals induced reversible increases in vascular permeability in all hamsters. Maximal number of leaks/cm2 before and at 30 and 60 min after FITC-Alb-injection and histamine application was 257 +/- 6 (SEM), 243 +/- 6 and 231 +/- 6 leaks/cm2 in the FITC-Alb-group and 258 + 6 (SEM), 302 +/- 12 and 316 +/- 11 leaks/cm2 in the FITCAGE-Alb-group, respectively, (P < 0.05 at 30 and 60 min). Similar results were seen with bradykinin. Our conclusions showed that i.v.-injected AGEs augmented the histamine- and bradykinin-induced increase in vascular permeability by 34% and 46%.

Albumins↗

Noninvasive orthogonal polarization spectral imaging as applied to microvascular studies in mice.

In vivo observations of the mouse microcirculation can hardly be performed due to technical difficulties, limiting the knowledge that could be obtained from gene manipulated mice models. The aim of the present study was to check the applicability of a novel optical system, the orthogonal polarization spectral technology, to study the mouse microcirculation. In anaesthetized mice, the spinotrapezius muscle microcirculation was observed in situ. The diameter of precapillary arterioles was measured before and after a pharmacological or hormonal stimulation. High-contrast images of the muscle microcirculation were obtained and significant vasodilatation of arterioles was observed after topical applications of acetylcholine, sodium nitroprusside, and insulin. As compared to conventional techniques, orthogonal polarization spectral imaging makes it possible to assess and study microvascular beds in mice, which were inaccessible until now, allowing the use of gene manipulated mice to investigate, for example, the mechanisms involved in the development of diabetic microangiopathy.

Acetylcholine↗

Physiological and morphometric analysis of the microcirculation of the cerebral cortex under acute vasospasm.

Tissue PO2 measurements with microelectrodes and morphometric analysis of capillaries were combined to investigate microcirculatory changes in cat brains subjected to vasospasm (superfusion of platelet-poor plasma). It can be shown that vasospasm leads to marked tissue hypoxia as illustrated by a drastic shift in the PO2 distribution within the cortical tissue. Morphological measurements of various capillary parameters demonstrated a marked constriction in precapillary segments as well as in capillaries themselves. This decrease in perfusion of the capillary bed could not be compensated for by increasing the systemic arterial blood pressure. Our results demonstrate that, even with a platelet-poor fraction, marked changes occur on a microcirculatory level in the cerebral cortex with vasospasm, which may not be detected by macroscopic techniques.

Animals↗