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Involvement of the central nervous system in the protective effect of melanocortins in myocardial ischaemia/reperfusion injury.
- Source :
-
Resuscitation [Resuscitation] 2002 Jan; Vol. 52 (1), pp. 109-15. - Publication Year :
- 2002
-
Abstract
- Melanocortin peptides exert, in rats, a protective effect in myocardial ischaemia followed by reperfusion, or permanent occlusion of a coronary artery. Moreover, melanocortins have an anti-shock effect. Since the mechanism of the life-saving effect of these peptides in haemorrhagic shock includes an essential brain loop, we aimed to determine whether the central nervous system (CNS) is also involved in the protective effect against the outcome of short-term myocardial ischaemia followed by reperfusion. Ischaemia was produced in anaesthetized rats by ligature of the left anterior descending coronary artery for 5 min. Reperfusion-induced ventricular tachycardia (VT), ventricular fibrillation (VF) and lethality, and the time-course of arterial blood pressure over 5 min following reperfusion were evaluated. Groups of 8-14 rats were used. Intravenous (i.v.) injection of ACTH-(1-24) (0.16-0.48 mg/kg) during the ischaemic period dose dependently reduced the incidence of VT, VF and of lethality. In saline-treated rats, coronary reperfusion caused VT in 100% animals, VF in 86%, and death in 86%. The highest dose of ACTH-(1-24) (0.48 mg/kg) completely prevented the occurrence of VT, VF and death in all rats (P<0.005). Moreover, the melanocortin peptide prevented the fall in mean arterial pressure (MAP) occurring during reperfusion. Treatment with ACTH-(1-24) by the intracerebroventricular (i.c.v.) route also reduced the incidence of VT, VF and lethality, and prevented the fall in MAP in a dose dependent manner. Complete (100%) protection occurred with an i.c.v. dose (0.048 mg/kg) 10 times less than that needed by the i.v. route. The present data show that in the protective effect of melanocortin peptides against the injury after myocardial ischaemia/reperfusion, the i.c.v. route of administration is more effective than the i.v. route. They suggest that a CNS mechanism, not yet identified, may be involved.
- Subjects :
- Animals
Disease Models, Animal
Dose-Response Relationship, Drug
Female
Injections, Intravenous
Injections, Intraventricular
Lidocaine pharmacology
Male
Myocardial Ischemia drug therapy
Myocardial Ischemia mortality
Myocardial Reperfusion Injury metabolism
Myocardial Reperfusion Injury mortality
Probability
Rats
Rats, Wistar
Reference Values
Sensitivity and Specificity
Sodium Chloride pharmacology
Survival Analysis
Adrenocorticotropic Hormone pharmacology
Central Nervous System drug effects
Myocardial Ischemia prevention & control
Myocardial Reperfusion Injury prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 0300-9572
- Volume :
- 52
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Resuscitation
- Publication Type :
- Academic Journal
- Accession number :
- 11801356
- Full Text :
- https://doi.org/10.1016/s0300-9572(01)00436-1