Reversibility of mitochondrial and contractile changes in the myocardium after cessation of prolonged ethanol intake.
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Biomedical subjects
Publications and source records attributed to S Bertuglia.
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The administration of ox-spleen homogenate, whether in rats made polycythemic by blood transfusion or in mice polycythemic by hypoxia, elicited a significant stimulatory effect on the rate of erythropoiesis. This activity remained unchanged even if the spleen, before being homogenized, was exhaustively washed with isotonic buffer pH 7.4 up to the total blood elimination.
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This study was conducted to compare separately the chronic effects of high blood levels of ethanol and acetaldehyde on the metabolism of the heart. Levels of ethanol and acetaldehyde were altered by administration of either 4-methylpyrazole (4-MP), a potent alcohol dehydrogenase inhibitor, or pargyline (PAR), a monoamine oxidase inhibitor that markedly increases acetaldehyde levels in the blood following ethanol administration. Measurements were made in rats consuming ethanol for three to four weeks. Mitochondrial respiration, in vitro contractility of glycerinated heart muscle fibers, and myocardial protein synthesis were determined. As compared to animals receiving only ethanol, administration of either-4-methyl-pyrazole or pargyline plus ethanol resulted in more severe damage to mitochondrial respiration and myocardial protein synthesis. The data illustrate that both acetaldehyde and ethanol in high concentrations can cause severe damage to myocardial metabolism.
The effects of Vaccinium myrtillus anthocyanosides (VMA) on ischaemia reperfusion injury were investigated in the hamster cheek pouch microcirculation. Ischaemia was induced by clamping the cheek pouch for 30 min followed by 30 min of reperfusion. The microvasculature was visualized by a fluorescence technique. VMA [10 mg (100 g body weight)-1] were orally administered for 2 and 4 weeks. The number of adhering leukocytes to venular vessel walls, the perfused capillary length, the increase in permeability, the arteriolar diameter changes were determined. Ischaemia and reperfusion were associated with increased number of leukocytes sticking to venules, decreased number of perfused capillaries, and increased permeability. VMA decreased the number of leukocytes sticking to the venular wall and preserved the capillary perfusion; the increase in permeability was significantly reduced after reperfusion. VMA saved the arteriolar tone and induced the appearance of rhythmic diameter changes of arterioles. These results demonstrate the ability of Vaccinium myrtillus anthocyanosides to reduce microvascular impairments due to ischaemia reperfusion injury, with preservation of endothelium, attenuation of leukocyte adhesion and improvement of capillary perfusion.
OBJECTIVE: The authors investigated the effects of ACTH-(1-24) and a high-viscosity solution in the restoration of microvascular function during resuscitation. They injected NG-monomethyl-L-arginine (L-NMMA) and superoxide dismutase (SOD) before ACTH-(1-24) in hamsters resuscitated with the hyperviscous solution to determine the role of ROS and NO in ACTH-(1-24) protective mechanism in the cheek pouch. Hemorrhagic shock (HS) was induced by withdrawing blood to reduce mean arterial pressure (MAP) to 30 mm Hg for 45 min. METHODS: Animals were injected with ACTH-(1-24) and resuscitated with dextran of low molecular weight (70 kDa) and a small amount (4%) of dextran of high molecular weight (500 kDa) plus ACTH-(1-24), or autologous (shed) blood withdrawn during HS. Microvascular effects were characterized by measuring blood flow, perfused capillary length (PCL), arteriolar diameter, and red blood cell (RBC) velocity. ROS were assayed at the beginning and after 45 min of HS and after 10 and 90 min of resuscitation. RESULTS: Resuscitation with either shed blood or dextrans 70/500 resulted in the restoration of MAP, whereas PCL, RBC velocity, and arterial diameter decreased significantly. ROS increased significantly after HS, 10 and 45 min of resuscitation. ACTH-(1-24) plus dextrans 70/500 increased MAP immediately; it increased vasodilation and PCL, and attenuated significantly ROS production and leukocyte adhesion during resuscitation. L-NMMA injected after 30 min of HS did not change the protection exerted by ACTH-(1-24) and dextrans 70/500, while SOD increased their protective effects. CONCLUSIONS: ACTH-(1-24) appears to enhance the protective effects on the endothelium exerted by increased plasma viscosity by significantly decreasing the oxidative stress and the leukocyte adhesion during resuscitation.
We investigated the effects of tyrosine kinase (TK) and nitric oxide synthase (NOS) inhibition on insulin-induced dilation of arterioles. We determined the arteriolar diameter, red blood cell velocity (VRBC) and blood flow changes in hamster cheek pouch microcirculation as affected by insulin in presence of TK and NOS inhibitors, genistein, piceatannol and NG-monomethyl-L-arginine (L-NMMA). Microvessels were visualized by a fluorescent microscopy technique. Arteriolar diameter and VRBC were measured after topical application of insulin and genistein or piceatannol or L-NMMA. Insulin (10 microU/ml) induced diameter and VRBC increase in A3 and A2 arterioles by 30 +/- 5 and 123 +/- 4%, 16 +/- 4 and 102 +/- 3%, as percent of baseline values, respectively. After genistein or piceatannol prior to insulin A3 and A2 arterioles dilated by 10 +/- 4, 5 +/- 2% and 9 +/- 4, 2 +/- 1%, respectively. After L-NMMA prior to insulin A2 and A3, arteriole diameters increased by 12 +/- 3 and 7 +/- 2%, respectively. VRBC increased significantly in all the cases. TK and NOS inhibitors applied together abolished insulin-induced dilation with a reduction in VRBC and blood flow. In conclusion, full insulin-induced dilation of hamster cheek pouch arterioles requires TK signaling pathways. Furthermore, activation of insulin receptors, as well as other TK receptors, appears to be required for vasomotor tone regulation.
Intravital microscopy and laser Doppler fluxmetry (LDF) were used to assess vasomotion and flux motion in skeletal muscle microcirculation. To clarify the relation between vessel type and LDF signals, arterioles, capillaries, and venules were sequentially studied. We used as an experimental model the hamster skin fold window preparation to record vasomotion and flux motion under control conditions and after injection of an alpha 2-adrenoceptor antagonist, yohimbine, since terminal arterioles appear to be subserved primarily by alpha 2-adrenoceptors. LDF signals were characterized by using an autoregressive modeling power spectrum technique. This analysis indicated that the flux motion fundamental frequency of terminal arterioles coincided with order 2 arteriole vasomotion fundamental frequency. The LDF fundamental frequency of order 3 arterioles was synchronous with the vasomotion frequency in the same-order vessels. The LDF fundamental frequency of order 3 venules corresponded to the frequency component coincident with the respiratory rate. The pattern of LDF oscillations was peculiar for each type of vessels, and the total power was greater in larger arterioles than in venules. Yohimbine reduced frequency and amplitude of vasomotion and flux motion in terminal arterioles, but it was possible to detect LDF oscillatory patterns due to the activity of parent vessels with a low frequency. In conclusion, the flux motion is fundamentally dependent on the type of vessel from which it originates and is directly related to the vasomotion of the arterioles.
The aim of this study was to investigate the relationships between laser Doppler perfusion monitoring (LDPM) measurements and different systemic hematocrits in microcirculation in terms of changes in oscillatory flow patterns. The hamster cheek pouch microvasculature was visualized by a fluorescent microscopy technique, and LDPM signals were derived from arterioles and venules under control conditions and after isovolemic hemodilution with saline and 6% dextran, MW 70,000 to 26.1 +/- 2.1%. Vasomotion, oscillations of microvascular blood flow (flow motion) and red blood cell (RBC) velocity were analyzed with Fourier transform and autoregressive modeling. LDPM recordings presented a significant increase in perfusion units (PU) during hemodilution-184 +/- 15 versus baseline 137 +/- 11 PU in arterioles and 40.2 +/- 3.5 versus 28.6 +/- 4.3 PU in venules-that was correlated with a significant increment in arteriolar and venular RBC velocity. There was a rise in the frequency [2.9 +/- 0.5 cycles per min (cpm) vs. 1.8 +/- 0.5 cpm] and spectral power of flow motion in arterioles whereas the increase in spectral power was related to a decrease in frequency (12.6 +/- 2.1 vs. 3.6 +/- 0.7 cpm) in venules. Oscillations in arteriolar and venular RBC velocity revealed coincident frequency components with flow motion patterns. The present data suggest that the LDPM measurements are more sensitive to velocity than hematocrit. Furthermore, hemodilution appears to affect differently arteriolar and venular flow motion patterns.