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Risposte vascolari e respiratorie evocate dalla somministrazione di endotelina-1 (ET-1) nel maiale
No full textEffect of endothelin-1 on respiratory neural drive and diaphragmatic activity in the pigs
No full textThe study was performed in twelve anesthetized spontaneously breathing pigs, divided into two groups. In the animals of group 1 we evaluated the effects of ET-1 administered by aerosol (200 pmol/kg in 1 ml of saline solution) on respiratory neural drive and on diaphragmatic activity. In the animals of group 2, to study the effects of ET-1 in the absence of arachidonic acid metabolites, the peptide was administered after pretreatment with indomethacin (3 mg/kg i.v.). Tracheal pressure (P0.5), obtained during the inspiratory effort was evaluated as an index of respiratory output and VT/TI ratio as an index of vagal input. Costal and crural electromyograms were recorded and avaluated as moving-average/inspiratory time ratio (DeltaEMG/TI), which is an index of neuromuscular drive, and as power spectrum quantified as centroid frequency (Cf). Our results show that in normal pigs ET-1 increases the Cf of crural diaphragm, without changing neuromuscular drive, while in pigs pretreated with indomethacin the peptide increases the Cf of the crural and costal portions of the diaphragm. These last responses are due to a modest excitatory effect on neural drive that is correlated with ET-1-dependent bronchoconstriction.These results further suggest that in the presence of prostanoids ET-1 recruits new crural fibers, while in the absence of prostanoids the recruitment involves the costal portion too. This mechanism is important to assure respiratory function in presence of bronchoconstriction through adequate diaphragmatic activity
Comparison of vascular and respiratory effects of endothelin-1 in the pig
Get PDFThe haemodynamic and respiratory responses caused by i.v. administration of endothelin-1 (ET-1) (20–100 pmol/kg) were studied in anaesthetized spontaneously breathing pigs. Intravenous bolus administration of synthetic ET-1 (40–100 pmol/kg) caused a transient decrease followed by a long-lasting increase in mean pulmonary arterial pressure and dose dependent vasoconstriction both in the systemic and pulmonary circulations. The effect on pulmonary arterial pressure was biphasic, with an initial transient fall followed by a long-lasting dose dependent increase. A biphasic response of the systemic mean arterial pressure was demonstrated only at a high dose of ET-1 (100 pmol/kg). ET-1 administration did not significantly change breathing pattern or phasic vagal input, but caused a significant decrease in passive compliance. Passive resistances or active compliance and resistances of the respiratory system were not modified. These results suggest that in the pig ET-1 is a more potent constrictor of vascular than of bronchial smooth muscle. The vasoconstrictor activity was greater in the pulmonary than the systemic circulations
Inhaled nitric oxide reverses vascular and respiratory effects of ET-1 and PAF in pigs
No full textIn anaesthetized paralysed, mechanically ventilated pigs, the vascular and respiratory effects of 80 ppm nitric oxide (NO) inhaled for 6 min were evaluated. To evoke different levels of smooth muscle contraction ET-1 or PAF, mediators involved in pulmonary disorders, were used. In control conditions, inhaled NO caused selective pulmonary vasodilatation without affecting respiratory resistances. This pulmonary vascular activity influenced the distensibility of the respiratory system and decreased inspiratory work. ET-1 administration significantly increased pulmonary arterial pressure and modestly changed mechanical properties of the respiratory system, while PAF caused potent vasoconstriction and bronchoconstriction associated with a marked change in volume-pressure relationship. In both cases, the changes in vascular and mechanical properties of the respiratory system increased inspiratory work. The vascular and respiratory activities of inhaled NO were correlated with preconstriction levels. The data show that the combination of vascular and respiratory effects improves pulmonary function, suggesting that inhalation of NO is a possible therapeutic approach for obstructive and inflammatory pulmonary diseases
Effetti della PGF2 sul diaframma nel maiale neonato
No full textThe EMG of costal and crural parts of diaphragm has been evaluated in 6 anaesthetized (Thipental-sodium mg 15/kg i.v.) and tracheostomized newborn pigs. The EMG has been evaluated in control conditons and after PGF2alpha administration (mg 0.15-0.20/kg i.v.). The experiments were performed also after bilateral vagotomy. Our results showed an inhibitory vagal mechanism regulating the diaphragmatic EMG. This mechanism may be modified by PGF2alpha that induces a postinspiratory diaphragmatic activity. PGF2alpha after vagotomy did not cause significant changes. One could conclude that a reflex vagal mechanism is present and the diaphragmatic response to PGF2alpha is vagal dependent
Effetti della PGF2alfa sul diaframma nel maiale neonato
No full textThe EMG of costal and crural parts of diaphragm has been evaluated in 6 anaesthetized (Thiopental-sodium mg 15/kg i.v.) and tracheostomized newborn pigs. The EMG has been evaluated in control conditions and after PGF2alpha administration (mg 0.15-0.20/kg i.v.) The experiments were performed also after bilateral vagotomy. Our results showed an inhibitory vagal mechanism regulating the diaphragmatic EMG. This mechanism may be modified by PGF2alpha that induces a postinspiratory diaphragmatic activity. PGF2alpha after vagotomy did not cause significant changes. One could conclude that a reflex vagal mechanism is present and the diaphragmatic response to PGF2alpha is vagal dependent
Variazioni emodinamiche indotte da endotelina (ET-1) nel maiale
No full textIn anaesthetized (Thiopental-sodium 15 mg/kg i.v.)tracheostomized, spontaneously breathing pigs, has been evaluated the circolatory activity of ET-1 (20-40-100 pM/kg) i.v. administered. Our results show a biphasic action of ET-1 on systemic (MAP) and pulmonary arterial pressure (MPAP)and on vascular resistances (SVR, PVR). The hypotensive effect appears 2 min after administration and it is followed by an increase of these parameters. The vasoconstriction is dose dependent and show a long-lasting activity of ET-1. Cardiac output and heart rate do not significantly change
Influence of the plasma ET-1 level on the vascular and respiratory systems of the pig
No full textIn this study the changes induced by the intravenous administration of ET-1 (50 ng/Kg) as a bolus injection or as an infusion to anesthetized spontaneously breathing pigs were correlated with plasma ET-1 levels. Both bolus administration and infusion of ET-1 caused statistically significant increases in arterial plasma ET-1 like immunoreactivity (ir) levels. Plasma Et-1-ir disappeared from the systemic circulation with a half-life of 1.5-1.9 min. Bolus administration of ET-1 caused a significant increase in mean pulmonary arterial pressure (MPAP) at 15 min. at which time the ET-1 plasma levels had returned to pre-injection values. This effect was not observed when the peptide was infused. ET-1 given by i.v. infusion increased total pulmonary vascualr resistances. The peptide caused a slight change in breathing pattern and passive compliance without significant changes in passive resistance. Our results suggest that in the pig ET-1 is a more potent constrictor of vascular than bronchial smooth muscle. However, changes in plasma ET-1 levels are not contemporary with altered vascular functions
Modificazioni del ritmo bulbo-pontino indotte da platelet activating factor (PAF)
No full textIn 14 anaesthetized (Thiopental-sodium mg 15/kg iv) and tracheostomized pigs were evaluated the respiratory and circulatory responses evocated by PAF (25-50 ng/kg iv). PAF caused an increase in pulmonary arterial pressure, systemic hypotension, decrease in compliance (Crs) and increase in respiratory resistances. The decrease in Crs modified the VT/TI relationship showin the vagal activity on respiratory centres. Therefore our results show the PAF, acting on vagal afferences, modifies the bulbo-pontine activity
The effects of glibenclamide, a blocker of K+ATP-sensitive potassium channels, on diaphragmatic fatigue during endotoxaemia in pigs
No full textAn in vivo porcine model of endotoxaemia was used to study the effects of glibenclamide, a K+ ATP-sensitive potassium channel blocker. Escherichia coli lipopolysaccharides (LPS, 70 micrograms/kg, i.v., as a bolus) were infused into anaesthetized, mechanically ventilated, indomethacin-treated pigs. After 120 min of endotoxaemia, glibenclamide was administered (10 mg/kg, i.v., over 5 min) to half the pigs. The strength at different frequencies of stimulation (10, 20, 30, 50 Hz, 20 V,) 1 s) and the endurance capacity (10 Hz, 20 V, 30 s) of the diaphragm were evaluated after 120 min of endotoxaemia and 5, 10, 20 and 30 min after drug infusion. Glibenclamide transiently increased the blood pressure without changing the decreased cardiac output and at the same time further impaired the diaphragmatic activity. The reduced ability of the diaphragm to generate force in response to different electrical stimulations was shown by a significant reduction in strength. The endurance index decreased 5 min after glibenclamide infusion, returning to the pre-glibenclamide values by 150 min. These results indicate that glibenclamide modifies the activity of vascular smooth muscle and of the diaphragm
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