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Biomedical subjects

W Ferrari

Publications and source records attributed to W Ferrari.

At least 19 recordsLinked to original sources
PubMed1992

Capsaicin prevents the adrenocorticotropin-induced improvement of cardiovascular function and survival in hemorrhage-shocked rats.

A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock.

Adrenocorticotropic Hormone↗
PubMed1992

Reversal of experimental hemorrhagic shock by dimethylphenylpiperazinium (DMPP).

In a rat model of hemorrhagic shock which caused the death of all control rats within 30 min, i.v. injection of the ganglion-stimulating drug dimethylphenylpiperazinium (DMPP) caused a dose-dependent reversal of the shock condition--without the need for reinfusion of the shed blood--starting from the dose of 4 ng/kg i.v. Shock reversal was associated with the mobilization of residual blood and improvement in blood flow, particularly at the carotid level. These results could influence our thinking on pathophysiology and first-aid management of shock.

Animals↗
PubMed1991

Nicotine reverses hemorrhagic shock in rats.

Cholinergic mechanisms are currently thought to play an essential role in blood pressure homeostasis. Here we show that, in urethane-anaesthetized rats bled to severe hemorrhagic shock, the i.v. administration of nicotine 0.2-50 micrograms/kg causes a prompt, sustained and dose-dependent improvement in cardiovascular and respiratory functions, the animals' survival rate being significantly higher than that of animals treated with saline. These effects are prevented by bilateral cervical vagotomy and by concurrent local anaesthesia of the carotid bodies, which suggests that stimulation of visceral afferents is the main mechanism of action of nicotine in hemorrhagic shock.

Animals↗
PubMed1990

Circulatory and respiratory consequences of massive hemorrhage are reversed by protoveratrines.

In a rat model of severe hypotension and respiratory depression induced by step-wise bleeding, protoveratrines cause a prompt and sustained improvement of cardiovascular and respiratory functions, both in anesthetized and in conscious animals, seemingly through a magnification of the reflex response originated by the chemoreceptors of aortic and carotid bodies. The restoration of cardiovascular function is attributable to an increase both in total peripheral resistance and cardiac output. The finding could provide the basis for a new approach to the first-aid management of massive blood losses.

Animals↗
PubMed1990

Early treatment with ACTH-(1-24) in a rat model of hemorrhagic shock prolongs survival and extends the time-limit for blood reinfusion to be effective.

The ability of ACTH-(1-24) to prolong survival and to extend the deadline for effective blood reinfusion has been studied in a model of lethal hypovolemic shock in the rat. Anesthetized rats were bled to a mean arterial pressure of 18 to 25 mm Hg and then subjected to one of the following iv treatments: a) saline; b) ACTH-(1-24), 160 micrograms/kg; c) blood reinfusion; d) ACTH-(1-24), 160 micrograms/kg; c) blood reinfusion; d) ACTH-(1-24), with saline 5 min after bleeding died within 0.05 h. On the other hand, the treatment with ACTH-(1-24) induced an almost complete and sustained recovery of cardiovascular and respiratory functions associated with a survival time of 44 +/- 18 h, while four of six rats reinfused with the withdrawn blood were still alive 15 days later. The time-lapse between bleeding and treatment was of crucial importance, and neither ACTH-(1-24) injection nor blood reinfusion had any effect if performed 25 min after bleeding. However, treatment with ACTH-(1-24) shortly after bleeding (5 min) greatly improved the effect of a later blood reinfusion. These data indicate that ACTH-(1-24) can prolong survival and permit the time-lapse between blood loss and blood reinfusion to be extended.

Animals↗
PubMed1989

The adrenocorticotropic hormone (ACTH)-induced reversal of hemorrhagic shock.

Adrenocorticotropic hormone (ACTH), while having negligible effects on cardiovascular function in the intact animal, induces a potent and sustained reversal of an otherwise invariably, rapidly fatal condition of hemorrhage-induced hypovolemic shock, in rats and dogs. The main site(s) of action are at the peripheral level; however, subsidiary site(s) of action in the CNS cannot be excluded. The studies on the mechanism of action indicate that the ACTH-induced reversal of hemorrhagic shock (a) is an extra-hormonal, adrenal-independent effect, because it is not affected by adrenalectomy and is shared by many ACTH-fragments practically devoid of corticotropic activity; (b) is antagonized by morphine in a surmontable way; (c) needs the functional integrity of the sympathetic nervous system (it is prevented by guanethidine, reserpine, and clonidine) and the availability of peripheral alpha-adrenoceptors (it is antagonized by dibenamine, prazosin and yohimbine, but not by practolol); (d) requires the integrity of afferent vagal fibers (it is almost completely abolished by vagotomy); (e) involves central cholinergic networks (it is antagonized by atropine sulphate, but not by atropine methyl bromide; and it is prevented by the intracerebroventricular injection of hemicholinium-3); (f) is associated with a massive increase in the volume of circulating blood, likely due to a mobilization from peripheral pooling sites (it is largely prevented by splenectomy or by suprahepatic veins ligature, and is associated with a restoration of the venous blood flow in peripheral vascular beds and with a normalization of venous PO2); (g) is associated with a restoration of heart and spleen adrenoceptors, whose number is significantly decreased during hemorrhagic shock. The survival time of hemorrhage-shocked animals, which is 26 +/- 3 min in controls, is greatly prolonged (44 +/- 18 h) by ACTH, provided that the treatment is made within 5-10 min after bleeding. Finally, in animals treated with ACTH within 5-10 min after bleeding, blood reinfusion retains its effectiveness and reverse shock even if performed 2-5 h later.

Adrenocorticotropic Hormone↗
PubMed1989

Adrenocorticotropic hormone (ACTH) and centrally-acting cholinomimetic drugs improve survival of rats with severe hemorrhagic shock through distinct central cholinergic mechanisms.

Pharmacological doses (40-160 micrograms/kg) of adrenocorticotropic hormone (ACTH) intravenously injected to urethane-anesthetized rats subjected to otherwise lethal hemorrhagic shock (mean arterial pressure stabilized at 20-25 mmHg) promptly restore blood pressure to about the pre-bleeding values, and prevent death (anti-shock effect). Hemicholinium-3 (i.c.v. injected) and atropine sulphate, but not atropine methylbromide, antagonize these ACTH effects. Moreover, since pirenzepine, injected i.v. or i.c.v., does not affect the anti-shock activity of ACTH, the central cholinergic mechanism participating in this ACTH action must involve M2, but not M1 brain muscarinic receptors. Intravenous physostigmine, too (but not neostigmine) and oxotremorine have an ACTH-like anti-shock effect, which however is neither affected by hemicholinium-3, nor by atropine methylbromide, nor by atropine sulphate, but only by high i.c.v. doses of gallamine or pancuronium. On the other hand, reserpine, guanethidine, and alpha-adrenoceptor blocking drugs inhibit the anti-shock effect of ACTH as well as that of oxotremorine and physostigmine. It is suggested that, in rats, both ACTH and cholinergic drugs must activate a central cholinergic mechanism(s) in order to exert a sympathetic nerve-mediated anti-shock effect. However, receptors involved are of the muscarinic M2 subtype in the case of ACTH, and probably nicotinic in the case of cholinergic drugs. That ACTH and cholinergic drugs activate different central cholinergic mechanisms is also suggested by the fact that cholinergic drugs have a centrally-mediated hypertensive action in normal animals, which is not shared by ACTH.

Adrenocorticotropic Hormone↗
PubMed1989

Reversal of haemorrhagic shock in rats by cholinomimetic drugs.

1. In an experimental model of haemorrhagic shock resulting in the death of all rats within 20-30 min, the intravenous (i.v.) injection of the tertiary amine cholinesterase inhibitor physostigmine (17-70 micrograms kg-1) induced a prompt, sustained and dose-dependent improvement of cardiovascular and respiratory function, with marked increase in the volume of circulating blood and survival of all treated animals, at least for the 2 h of observation. 2. Similar results were obtained with the i.v. injection of the cholinoceptor agonist oxotremorine (5-25 micrograms kg-1), while neostigmine (54 or 70 micrograms kg-1), a quaternary cholinesterase inhibitor which cannot cross the blood-brain barrier, had negligible effects. 3. The anti-shock activities of oxotremorine and physostigmine were blocked by the intracerebroventricular injection of either of the combined nicotinic and M2-muscarinic receptor antagonists gallamine and pancuronium, or of the nicotinic antagonist mecamylamine. They were also blocked by intraperitoneal injection of the adrenergic neurone blocking agent guanethidine, but they were not antagonized by either the combined M1- and M2-muscarinic receptor antagonist atropine, the M1-muscarinic receptor antagonist pirenzepine, or the M2-muscarinic receptor 4-diphenylacetoxy-N-methylpiperidine methobromide. 4. It is concluded that cholinomimetic drugs can reverse hypovolaemic shock through central activation (seemingly mediated by nicotinic receptors) of sympathetic tone, with mobilization and redistribution of the residual blood.

Animals↗
PubMed1988

Involvement of the sympathetic nervous system in the cardiovascular effects of ACTH-(1-24) during hemorrhagic shock in rats.

In urethane-anesthetized rats, removal of about 50% of the total blood volume over a period of 25-30 min caused hypovolemic shock, with extreme hypotension (MAP = 18-25 mm Hg and death of all animals within 22 +/- 5 min. The i.v. injection of ACTH-(1-24) in the dose range of 40-160 micrograms/kg induced a sustained, dose-dependent, and, at the highest dose used, an almost complete recovery of blood pressure, and 100% survival, at least for 2 h after treatment. The effect of ACTH-(1-24) was completely prevented by reserpine (5 mg/kg) and clonidine (0.1 mg/kg), significantly reduced by prazosin (0.1 mg/kg), dibenamine (15 mg/kg) and i.v. yohimbine (1 mg/kg) and unaffected by i.c.v. yohimbine (0.2 mg/kg) and i.v. practolol (15 mg/kg). These data suggest that the effect of ACTH-(1-24) in hypovolemic shock depends on the functional integrity of the sympathetic nervous system and is mediated through an activation of peripheral alpha-adrenoceptors.

Animals↗
PubMed1988

Anti-shock effect of ACTH-(1-24): influence of subtotal hepatectomy.

Subtotally hepatectomized or sham-operated rats were bled to hypovolemic shock (mean arterial pressure = 18-25 mmHg) and then treated with an intravenous bolus injection of ACTH-(1-24), 160 ug/kg. The treatment caused a prompt and sustained reversal of hypotension, with survival of all sham-operated animals, at least for the first 2 h, while in hepatectomized rats the arterial pressure increase was negligible and there was a 50% mortality within 2 h after treatment. Moreover, the blood volume which could be drained from an arterial catheter prior to death, measured 15-20 min after ACTH injection, was 1.51 +/- 0.12 and 0.64 +/- 0.11 ml/100 g b.w. in sham-operated and hepatectomized rats, respectively. These results further support the idea that the effect of ACTH in haemorrhagic shock is due to the mobilization of blood pooled in peripheral reserve organs.

Animals↗
PubMed1987

Different cholinergic pathways are involved in the improvement induced by CCK-8 and by ACTH-(1-24) in massive acute hemorrhage, in rats.

Cholecystokinin octapeptide (CCK-8) (20 micrograms/kg i.v.) and tetracosactide [ACTH-(1-24)] (160 micrograms/kg i.v.) restore blood pressure and allow rats subjected to otherwise invariably fatal acute hemorrhage to survive. Atropine sulphate (2-8 mg/kg i.p.), which crosses the blood-brain barrier, dose-dependently prevents this effect both in the case of ACTH-(1-24) and in that of CCK-8. On the other hand, atropine methyl bromide (2-8 mg/kg i.p.), which does not cross the blood-brain barrier, prevents the effect in the case of CCK-8, but not in that of ACTH-(1-24). These data suggest that a cholinergic mechanism is involved in the anti-shock effect of both ACTH-(1-24) and CCK-8, though the sites of action appear to be in the CNS, in the case of ACTH-(1-24), and outside the CNS, in that of CCK-8.

Animals↗
PubMed1987

Anti-shock effect of ACTH: haematological changes and influence of splenectomy.

ACTH-(1-24), injected i.v. into rats subjected to otherwise invariably fatal bleeding, at the dose of 160 micrograms/kg, causes a prompt and sustained increase in mean arterial and pulse pressure, with survival of all treated animals, at least for the first 2 hr. This is associated with a 100% increase in the volume of circulating blood, which is of normal composition, so that also the number of circulating red cells is doubled as compared to controls. Splenectomy greatly impairs the beneficial effect of ACTH on blood pressure, blood volume and survival. It is concluded that, in cases of acute hypovolemia, ACTH-(1-24) induces a recall of blood from storage sites and its redistribution, though the precise mechanism is as yet unknown.

Animals↗
PubMed1986

Alpha-MSH and other ACTH fragments improve cardiovascular function and survival in experimental hemorrhagic shock.

Hypovolemic shock was produced in rats by withdrawing about 50% of the estimated total blood volume. Following mean arterial pressure stabilization in the range of 15-25 mm Hg, with a pulse pressure of 7-12 mm Hg, the rats were given intravenous bolus injections either of ACTH fragments or of saline. The following ACTH fragments or analogs were used: ACTH-(4-10), alpha-MSH, ACTH-(1-16), ACTH-(1-17), ACTH-(1-18), [Nle4,D-Phe7]alpha-MSH, [beta-Ala1,Lys17]ACTH-(1-17)-4-amino-n-butilamide (alsactide). ACTH-(1-24) and human synthetic ACTH-(1-39) were used for comparison. All animals treated with saline died in 22.51 +/- 3.62 min. Treatment with ACTH fragments (160 micrograms/kg i.v.) increased blood pressure and pulse amplitude, the effect starting within a few minutes, gradually increasing, and reaching a maximum in 15-30 min. The blood and pulse pressure increases were sustained, remaining almost stable until the end of the 2 h recording. Two out of nine rats treated with alsactide, which was the least active, died within 2 h after treatment, while all rats treated with the other ACTH fragments or analogs were still surviving at that time. Both on a weight and on a molar basis, the most active was ACTH-(1-24), followed by ACTH-(1-16), by the alpha-MSH analog [Nle4,D-Phe7]ACTH-(1-13), by ACTH-(1-18) and by ACTH-(1-17). The present results show that melanocortins reverse otherwise fatal hypovolemic shock, and suggest a new therapeutic approach for shock treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1986

Adrenocorticotropin reversal of experimental hemorrhagic shock is antagonized by morphine.

ACTH-(1-24) dose-dependently improved cardiovascular function in rats and dogs subjected to experimental hemorrhagic shock, and intravenous dose of 160 and 100/microgram/kg, respectively, completely restoring arterial blood pressure and pulse amplitude. All saline-treated animals died within 30 min of bleeding, while all ACTH-treated animals were still alive at the end of the observation period (2 hr). The injection of ACTH-(1-24) also dramatically improved the respiratory function. Morphine, i.v. injected into rats at the dose of 2.5 mg/kg, antagonised the effect of ACTH-(1-24) to a greater or lesser degree, depending on the dose of peptide employed: at 160/microgram/kg, antagonism was complete, at 320/microgram/kg antagonism was only partial, while at 480/microgram/kg antagonism was almost completely overcome. These data further support the idea that melanocortins are physiological antagonists of opioids, and suggest that melanocortin peptides may prove to be rational and effective drugs in the treatment of hypovolemic shock.

Adrenocorticotropic Hormone↗
PubMed1986

Influence of vagotomy and of atropine on the anti-shock effect of adrenocorticotropin.

ACTH-(1-24), intravenously injected at the dose of 160 micrograms/kg to rats bled to the point of otherwise irreversible hypovolemic shock, causes a prompt and sustained increase in blood pressure and pulse amplitude, all treated rats surviving at the end of the experiment (2 hr). Bilateral vagotomy, as well as atropine sulphate (2 mg/kg i.p. immediately before bleeding), almost completely abolishes the anti-shock activity of ACTH. These data indicate that a central cholinergic pathway and vagal afferent (but not efferent) fibers play an important role in the anti-shock effect of ACTH.

Adrenocorticotropic Hormone↗