Biomedical subjects

M Rücker

Publications and source records attributed to M Rücker.

22 records · Page 2Linked to original sources

PubMed1997

In vitro evidence for a Donnan distribution of Mg2+ and Ca2+ by chondroitin sulphate in cartilage.

Fluoroquinolones are known for their ability to form chelate complexes with magnesium. Cartilage lesions observed in juvenile animals after quinolone treatment very probably are a consequence of the lack of functionally available magnesium. In cartilage, which contains high amounts of negatively charged proteoglycans, a Donnan distribution can be expected leading to an inhomogeneous distribution of ions (such as magnesium), which may support the toxic effects of magnesium deficiency or quinolone treatment of cartilage. We performed in vitro experiments using dialysis tubes to simulate the unequal distribution of proteoglycans in cartilage and measured the distribution of magnesium, calcium and ofloxacin. We found that the concentration of free magnesium is significantly reduced with the chondroitin sulphate-free solution due to a Donnan effect. For example, using a 3% chondroitin sulphate solution (outside the tubing) dialysed against a chondroitin sulphate-free solution (inside the tubing) the magnesium concentration decreased by 24% from 0.55 +/- 0.02 to 0.42 +/- 0.04 mmol/l inside the tubing during 48 h observation (P < 0.01). Under physiological conditions this unequal distribution of magnesium probably will be much more pronounced because chondroitin sulphate concentrations in cartilage are higher; nevertheless, magnesium concentration is sufficient for regular function of the tissue. During the sensitive phase of quinolone toxicity, magnesium in juvenile cartilage is lower than at other time points during postnatal development. Moreover, additional complexation by quinolones may further reduce the concentration of functionally available magnesium below the critical level.

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PubMed1997

Capillary dysfunction in striated muscle ischemia/reperfusion: on the mechanisms of capillary "no-reflow".

The major dysfunction of capillaries after prolonged periods of ischemia is the lack of re-establishment of nutritive blood flow upon onset of reperfusion, i.e., capillary no-reflow. Several mechanisms have been proposed to cause capillary no-reflow, including intravascular hemoconcentration and thrombosis, leukocyte plugging, endothelial cell swelling, vasomotor dysfunction, and interstitial edema formation. Electron microscopic studies suggest that thrombus formation and intravascular clotting are not significant mechanisms. Moreover, intravital microscopic studies have demonstrated that plugging of capillaries by leukocytes is not a primary cause for the manifestation of no-reflow in postischemic striated muscle. In contrast, both in vivo studies and histological examinations support the concept that ischemia/reperfusion induces the disruption of the endothelial integrity with loss of fluid to endothelial cells and the interstitial space. As a consequence, these pathological sequelae are associated with intravascular hemoconcentration, endothelial cell swelling and interstitial edema formation, which contribute to capillary lumenal narrowing, increase of hydraulic resistance, and, thus, impairment of perfusion. Whether the postischemic diameter response with dilation of reperfused capillaries and lumenal narrowing of no-reflow capillaries involves endothelin/nitric oxide-triggered capillary pericyte function remains to be determined.

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PubMed1996

A new method for the intravital microscopic quantification of hepatic sinusoidal perfusion failure using the dye bisbenzamide H33342.

In hepatic pathology, in vivo assessment of microvascular perfusion failure by intravital microscopic determination of functional sinusoidal density is a time-consuming procedure, which requires accurate identification of blood-flow conditions within each individual sinusoid. Herein we report a new method, which is easily applicable and which allows for rapid analysis of hepatic microvascular perfusion deficits by intravital fluorescence microscopy using Bisbenzamide H33342 staining of hepatocytes (excitation 330-390 nm/emission > 430 nm). To validate this method hepatic microvascular perfusion failure was induced in eight spontaneously breathing, chloralhydrate-anesthetized rats by 90-min left lobar ischemia and reperfusion. For quantitative assessment of hepatocellular bisbenzamide fluorescence intensity, gray levels were determined densitometrically, and the area of positive-stained cells was calculated automatically as percentage of the whole area of observation. Within identical acini (n = 67) area of positive hepatocellular fluorescence was correlated with functional sinusoidal density, i.e, total length of perfused sinusoids per observation area (cm/cm2), which was determined simultaneously by contrast enhancement with sodium fluorescein (450-490/ > 520 nm) using a computer-assisted image analysis system. Postischemic reperfusion was characterized by a marked heterogeneity of nutritive perfusion with a considerable number of nonperfused sinusoids. Visualization of bisbenzamide fluorescence revealed brightly stained hepatocytes in well-perfused areas, but faint hepatocellular fluorescence in areas presenting with sinusoidal perfusion failure. Linear regression analysis between area of positive hepatocellular fluorescence and functional sinusoidal density revealed a significant (P < 0.01) correlation (r2 = 0.926), indicating that automated densitometric analysis of hepatocellular bisbenzamide fluorescence represents a valid method to determine hepatic nutritive perfusion failure in vivo.

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PubMed1994

Endothelin-1 is involved in hepatic sinusoidal vasoconstriction after ischemia and reperfusion.

Endothelin-1 (ET-1), a vasoactive peptide, causes a significant rise in portal vein pressure, which is most likely a result of severe vasoconstriction in the liver. In this study, the effect of ET-1 on sinusoidal vasoconstriction in the liver after ischemia and reperfusion was directly investigated using intravital microscopy. In anesthetized female Sprague Dawley rats (200-250 g) ischemia of the median and left liver lobes was induced for 90 min by temporary ligation of the left pedicle. After declamping and a 90-min reperfusion period, the livers were exposed for intravital microscopy. Using a Nikon MM-11 fluorescence microscope (545 nm, 330x), a CCD camera (Cohu FK 6990), and a SVHS video recording unit, the hepatic microcirculation was directly investigated. Besides sham groups, two ischemia groups were studied, receiving ET-1 antiserum (anti-ET-1; 0.5 ml; Peptide Inst., Osaka, Japan) or NaCl 0.9% (0.5 ml) 5 min prior to reperfusion of the liver (n = 6/group). Following a transient drop in the mean arterial blood pressure in the anti-ET-1-treated groups, comparable systemic hemodynamic conditions among the four groups were noted during intravital microscopic assessment at the end of the 90-min reperfusion period. Reduction in the sinusoidal diameters during postischemic reperfusion (7.7 +/- 0.5 microm) was prevented by anti-ET-1 treatment (9.6 +/- 0.25 microm; P < 0.01; mean + SEM) back to control values (9.6 +/- 0.32 microm), while most of other microcirculatory parameters did not show significant differences. The results supported further the role of ET-1 in dysregulation of the sinusoidal vascular tone in the liver, e.g., after ischemia and reperfusion.

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