rutin and Hypoxia

High-frequency pulsed electromagnetic field (PEMF) stimulation is an emerging noninvasive therapy that we have shown increases cerebral blood flow (CBF) and tissue oxygenation in the healthy rat brain. In this work, we tested the effect of PEMF on the brain at high intracranial pressure (ICP). We previously showed that high ICP in rats caused a transition from capillary (CAP) to non-nutritive microvascular shunt (MVS) flow, tissue hypoxia and increased blood brain barrier (BBB) permeability.. Using in vivo two-photon laser scanning microscopy (2PLSM) over the rat parietal cortex, and studied the effects of PEMF on microvascular blood flow velocity, tissue oxygenation (NADH autofluorescence), BBB permeability and neuronal necrosis during 4 h of elevated ICP to 30 mmHg.. PEMF significantly dilated arterioles, increased capillary blood flow velocity and reduced MVS/capillary ratio compared to sham-treated animals. These effects led to a significant decrease in tissue hypoxia, BBB degradation and neuronal necrosis.. PEMF attenuates high ICP-induced pathological microcirculatory changes, tissue hypoxia, BBB degradation and neuronal necrosis.

Topics: Animals; Blood-Brain Barrier; Cerebrovascular Circulation; Electromagnetic Fields; Hydroxyethylrutoside; Hypoxia; Intracranial Hypertension; Intravital Microscopy; Magnetic Field Therapy; Male; Microscopy, Confocal; Microvessels; Parietal Lobe; Permeability; Rats; Rats, Sprague-Dawley

A clinically available mixture of hydroxyethylrutosides (HR) was examined as a protector against endothelial cell activation by hypoxia in perfused human umbilical vein. The results showed that 500 micrograms/mL HR totally inhibited the adherence of human unstimulated neutrophils to the endothelium of umbilical vein incubated in hypoxic conditions. This inhibition was confirmed by a morphological study performed by scanning electron microscopy. In addition, neutrophils adherent to the hypoxic umbilical vein endothelium became activated, as evidence by the increased release of superoxide anions and synthesis of leukotriene B4. These processes could also be inhibited by HR. In conclusion, the results of this study suggest that the improvement in venous insufficiency observed clinically with HR could, in part, be the result of their ability to inhibit the recruitment and activation of neutrophils by endothelium activated during blood stasis.

Topics: Cell Adhesion; Endothelium, Vascular; Flavonoids; Humans; Hydroxyethylrutoside; Hypoxia; Immunoenzyme Techniques; Leukocyte Adherence Inhibition Test; Leukotriene B4; Microscopy, Electron, Scanning; Neutrophil Activation; Neutrophils; Superoxides; Umbilical Veins

1. A clinically available mixture of hydroxyethylrutosides (HR) was examined as inhibitors of endothelial cell activation by hypoxia in vitro. Thus, the effects of HR on ATP depletion, phospholipase A2 activation and neutrophil adherence were investigated in hypoxia-activated human umbilical vein endothelial cells in primary cell culture. 2. Our results show that HR inhibited two important steps of the activation of endothelial cells by hypoxia: the decrease in ATP content, which is the starting point of the process, and the activation of phospholipase A2 one enzyme responsible for the release of inflammatory mediators. This inhibition was dose-dependent with 70 to 90% inhibition at 500 micrograms ml-1 of HR. 3. In addition, hypoxia-activated endothelial cells increased their adhesiveness for neutrophils. This process could also be prevented in a dose-dependent manner if endothelial cells were incubated in the presence of HR. This inhibition was confirmed by a morphological study. 4. In conclusion, the results of this study suggest that a possible explanation for the improvement in venous insufficiency by HR observed clinically could be their ability to inhibit the activation of endothelial cells during blood stasis.

Topics: Adenosine Triphosphate; Cells, Cultured; Endothelium; Humans; Hydroxyethylrutoside; Hypoxia; In Vitro Techniques; Phospholipases A; Phospholipases A2; Umbilical Veins

Isolated rabbit hearts were perfused aerobically (45 min) and hypoxically (105 min), using a modified Langendorff technique. The mean functional diameter of capillaries (MFDC) was calculated from the perfusion rate per minute and the inflow resistance by the model of Hagen-Poiseuille. The MFDC expresses the mean lumen of all capillaries of the heart, regardless of the different behaviour of the capillaries in the different regions of the myocardium. The MFDC decreased very rapidly after the onset of a hypoxia from 3.5 +/- 0.3 micron to about 70% of the initial diameter within 5-10 min (p less than 0.01) and then in a slower range within the following 70 min to about 44% of the initial diameter. The release of lactate dehydrogenase (LDH) from the hypoxic myocardium was detectable after 45 min of hypoxia and rose drastically after 60 min of hypoxia in our model. The decrease of the MFDC as well as the release of LDH from the hypoxic myocardium can be diminished by application of O-(beta-hydroxyethyl)-rutoside or 10 mM mannitol to the hypoxic perfusion medium. Both substances have antioxidant activities. It is discussed that the injury of the microvasculature is an early process during hypoxia, which can potentiate the hypoxic changes of the myocardial cells by additional diminution of the supply with oxygen and substrates. The protecting activities of substances with antioxidant actions to hypoxic myocardium were supported.

Topics: Adenosine; Animals; Capillaries; Heart; Hydroxyethylrutoside; Hypoxia; In Vitro Techniques; L-Lactate Dehydrogenase; Mannitol; Myocardium; Perfusion; Rabbits