Haemorrhagic shock in cardiac surgery. Pharmacological treatment with ACTH (1–24)

Noera, Giorgio; Angiello, Luisa; Biagi, Bruno; Pensa, P.

doi:10.1016/0300-9572(91)90002-g

Cited by 22 publications

(5 citation statements)

References 10 publications

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“…So far accumulated experimental data suggest that, in conditions of haemorrhagic shock, melanocortin peptides, which have negligible cardiovascular effects under normal conditions, except for γ‐MSHs (Van Bergen et al , 1995) activate, or restore, a complex vasomotor reflex that eventually leads to the mobilization of the peripherally‐pooled residual blood; a reflex which is seemingly obtunded, in conditions of failure of the circulatory homeostasis, by the massive release of endogenous opioids (Bertolini et al , 1986a,b,c; Bertolini, 1995). This effect of melanocortins has been confirmed in dogs (Bertolini et al , 1986b) and in another model of hypovolaemic shock in rabbits (Ludbrook & Ventura, 1995), as well as in human conditions of haemorrhagic or cardiogenic shock (Bertolini et al , 1987; Pinelli et al , 1989; Noera et al , 1989, 1991).…”

Section: Introductionmentioning

confidence: 62%

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

Guarini

Bazzani

Bertolini

1997

British J Pharmacology

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1 The resuscitating activity of melanocortin peptides (MSH-ACTH peptides) was tested in an experimental model of prolonged respiratory arrest. 2 Anaesthetized, endotracheally intubated rats subjected to a 5 min period of ventilation interruption, invariably died from cardiac arrest within 6 ± 9 min of resumption of ventilation. 3 When resumption of ventilation was associated with the simultaneous intravenous (i.v.) injection of a melanocortin peptide (a-MSH or ACTH-(1 ± 24)) (160 mg kg 71) there was an almost immediate (within 1 min), impressive increase in cardiac output, heart rate, mean arterial pressure (+560% of the beforetreatment value) and pulse pressure (+356% of the before-treatment value), with full recovery of electroencephalogram after 30 ± 45 min. Blood gases and pH were normalized within 15 ± 60 min after treatment, and all treated animals eventually recovered completely and survived inde®nitely (= more than 15 days). 4 The same response was observed in adrenalectomized animals, as well as in animals pretreated with a b 1 -adrenoceptor blocking agent (atenolol, 3 mg kg 71 , i.v.), or with an a 1 -adrenoceptor blocking agent (prazosin, 0.1 mg kg 71 , i.v.), or with an adrenergic neurone blocking agent (guanethidine, 10 mg kg 71 , intraperitoneally). 5 An eect quite similar to that produced by melanocortins was obtained with ouabain (0.1 mg kg 71 , i.v.); the antioxidant drug, glutathione (75 mg kg 71 , i.v.) also produced 100% resuscitation, but the eect was slower in onset. On the other hand, adrenaline (0.005 mg kg 71 , i.v.) was able to resuscitate only 1 out of 8 rats and dobutamine (0.02 mg kg 71 , i.v.) resuscitated 4 out of 8 rats; moreover, the eect of both catecholamines was much slower in onset than that of melanocortins and the initial, impressive stimulation of cardiovascular function was absent. 6 These results show that melanocortin peptides have a resuscitating eect in a pre-terminal condition produced in rats by prolonged asphyxia. This eect seems primarily due to the restoration of cardiac function, not mediated by catecholamines. These data also suggest that these peptides may have potential therapeutic value in conditions of transient cardiac hypoxia and re-oxygenation such as occur in coronary artery disease.

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Section: Introductionmentioning

confidence: 62%

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

Guarini

Bazzani

Bertolini

1997

British J Pharmacology

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“…35 ACTH-(1-24) has then been successfully used in human conditions of hemorrhagic and cardiogenic shock (intravenous bolus of 5-10 mg), both in anecdotal cases and randomized controlled studies. 33,[89][90][91][92] Clinical studies on the effectiveness of melanocortins in circulatory shock are in progress. From a practical point of view, availability of drugs able to retard shock progression toward an irreversible state, extending the time-limit for a successful first aid of civilian and military victims of traumatic accidents, is of great importance.…”

Section: Antishock Effects Of Melanocortinsmentioning

confidence: 99%

Melanocortins and the Cholinergic Anti-Inflammatory Pathway

Giuliani

Ottani

Altavilla

et al. 2010

Advances in Experimental Medicine and Biology

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Experimental evidence indicates that small concentrations of inflammatory molecules produced by damaged tissues activate afferent signals through ascending vagus nerve fibers, that act as the sensory arm of an "inflammatory reflex". The subsequent activation of vagal efferent fibers, which represent the motor arm of the inflammatory reflex, rapidly leads to acetylcholine release in organs of the reticuloendothelial system. Acetylcholine interacts with α7 subunit-containing nicotinic receptors in tissue macrophages and other immune cells and rapidly inhibits the synthesis/release of tumor necrosis factor-α and other inflammatory cytokines. This neural anti-inflammatory response called "cholinergic anti-inflammatory pathway" is fast and integrated through the central nervous system. Preclinical studies are in progress, with the aim to develop therapeutic agents able to activate the cholinergic anti-inflammatory pathway. Melanocortin peptides bearing the adrenocorticotropin/α-melanocyte-stimulating hormone sequences exert a protective and life-saving effect in animals and humans in conditions of circulatory shock. These neuropeptides are likewise protective in other severe hypoxic conditions, such as prolonged respiratory arrest, myocardial ischemia, renal ischemia and ischemic stroke, as well as in experimental heart transplantation. Moreover, experimental evidence indicates that melanocortins reverse circulatory shock, prevent myocardial ischemia/reperfusion damage and exert neuroprotection against ischemic stroke through activation of the cholinergic anti-inflammatory pathway. This action occurs via stimulation of brain melanocortin MC3/MC4 receptors. Investigations that determine the molecular mechanisms of the cholinergic anti-inflammatory pathway activation could help design of superselective activators of this pathway.

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“…The opposite central and peripheral actions of ACTH(1–24) suggest that it may be useful as an adjunct to blood volume replacement in clinical hypovolaemia. The virtual lack of acute toxicity and other favourable clinical data 67–69,72 make the idea of first‐aid use of ACTH(1–24) even more attractive, but prospective clinical trials are necessary.…”

Section: Adrenocorticotropic Hormonementioning

confidence: 99%

John Ludbrook APPS Symposium Neural Mechanisms In The Cardiovascular Responses To Acute Central Hypovolaemia

Evans

Ventura

Dampney

et al. 2001

Clin Exp Pharma Physio

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1. The haemodynamic response to acute central hypovolaemia consists of two phases. During phase I, arterial pressure is well maintained in the face of falling cardiac output (CO) by baroreceptor-mediated reflex vasoconstriction and cardio-acceleration. Phase II commences once CO has fallen to a critical level of 50-60% of its resting value, equivalent to loss of approximately 30% of blood volume. 2. During phase II, sympathetic vasoconstrictor and cardiac drive fall abruptly and cardiac vagal drive increases. In humans, this response is invariably associated with fainting and has been termed vasovagal syncope. 3. In both experimental animals and in humans, the responses to acute central hypovolaemia are greatly affected by anaesthetic agents, in that the compensatory responses during phase I (e.g. halothane) or their failure during phase II (e.g. alfentanil) are blunted or abolished. 4. Therefore, our present knowledge of the neurochemical basis of the response to hypovolaemia depends chiefly on the results of experiments in conscious animals. Use of techniques for simulating haemorrhage has greatly enhanced this research effort, by allowing the effects of multiple treatments on the response to acute central hypovolaemia to be tested in the same animal. 5. The results of such experiments indicate that phase II of the response to hypovolaemia is triggered, at least in part, by a signal from cardiac vagal afferents. There is also strong evidence that phase II depends on brainstem delta-opioid receptor and nitrergic mechanisms and can potentially be modulated by circulating or neuronally released adrenocorticotropic hormone, brainstem serotonergic pathways operating through 5-HT1A receptors and opioids acting through mu- and kappa-opioid receptors in the brainstem. 6. Phase II also appears to require input from supramedullary brain centres. Future studies should determine how these neurotransmitter systems interact and their precise neuroanatomical arrangements.

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Haemorrhagic shock in cardiac surgery. Pharmacological treatment with ACTH (1–24)

Cited by 22 publications

References 10 publications

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

Resuscitating effect of melanocortin peptides after prolonged respiratory arrest

Melanocortins and the Cholinergic Anti-Inflammatory Pathway

John Ludbrook APPS Symposium Neural Mechanisms In The Cardiovascular Responses To Acute Central Hypovolaemia

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