Quantitative motor unit action potential analysis in skeletal muscles in horses and ponies.
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Biomedical subjects
Publications and source records attributed to B Ciminaghi.
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We evaluated the endothelin-1 (ET-1) and thrombin involvement in cardiovascular and respiratory dysfunction during endotoxic shock in 18 anaesthetized, mechanically ventilated pigs, divided into three groups. Group 1 was pre-treated only with lipopolysaccharide (LPS), group 2 was treated with lepirudin, a thrombin inhibitor, group 3 was pre-treated with bosentan, a dual inhibitor of ET-1 receptors. Results show that LPS caused systemic hypotension, pulmonary biphasic hypertension, increase in lung resistances (R(L)) and decrease in compliance (C(L)). Lepirudin partially reduced the LPS-dependent pulmonary hypertension, without affecting the changes in C(L) and R(L). On the contrary, bosentan completely abolished the pulmonary hypertension and the changes inC(L) and R(L), and worsened the LPS-dependent systemic hypotension. Our results show that ET-1 is largely responsible for pulmonary derangement due to endotoxic shock; at bronchial level, the ET-1 release seems due only to LPS, while, at pulmonary vascular level, it results also from LPS-dependent thrombin activation.
We evaluated the role of endothelin-1 (ET-1) and the involvement of nitric oxide in cardiovascular and respiratory dysfunction, during endotoxic shock, in 18 anaesthetised, mechanically ventilated pigs, divided into three groups. Group 1 was i.v. infused with LPS (20 microg/Kg/h for 240 min). Group 2 was pre-treated with bosentan, a dual inhibitor of ET-1 receptors, and at 180 min of endotoxic shock, L-NAME (N(G)-nitro-L-arginine methyl ester, 10 mg/Kg), a non-selective inhibitor of NO synthases, was i.v. administered. Group 3 was infused with LPS and L-NAME was administered similarly to group 2. Results show that LPS caused systemic hypotension, pulmonary biphasic hypertension, decrease in compliance (C(rs)) and increase in resistance (R(max,rs)) of respiratory system. Bosentan completely abolished the pulmonary hypertension and the changes in C(rs)and R(max,rs). L-NAME does not affect the LPS-dependent changes in respiratory mechanics, but it worsens the cardiovascular effects, causing death of pigs. Pre-treatment with bosentan prevents this deleterious effect. Our study demonstrates that the LPS-dependent respiratory effects are mediated by ET-1, which, probably causing pulmonary oedema, is responsible for the decrease in C(rs)and the increase of R(max,rs).
To evaluate the role of endothelin (ET) in respiratory homeostasis we studied the effects of the ET(A) and ET(B) receptor blocking agent bosentan on respiratory mechanics and control in seven anaesthetised spontaneously breathing pigs, for 180 min after single bolus administration (20 mg/kg i.v.). The results show that the block of ET receptors induced a significant increase in compliance and decrease in resistance of the respiratory system, entailing a significant reduction of diaphragmatic electromyographic activity, without affecting the centroid frequency of the power spectrum. Bosentan administration induced a significant increase in tidal volume (V(T)), accompanied by a significant decrease in respiratory frequency, without any significant change in pulmonary ventilation, CO(2) arterial blood gas pressure or pH. Since the relationship between V(T) and inspiratory time remained substantially constant after bosentan administration, the changes in respiratory pattern appear to be the result of an upward shift in inspiratory off-switch threshold. Both inspiratory and expiratory times during occluded breathing were increased by block of ET receptors, suggesting also a central respiratory neuromodulator effect of ET. In conclusion the present results suggest that the block of ET receptors in spontaneously breathing pigs exerts a role on mechanical properties of the respiratory system as well as on peripheral and central mechanisms of breathing control.