RESUSCITATING EFFECT OF MELANOCORTIN PEPTIDES AFTER PROLONGED RESPIRATORY ARREST

1 The resuscitating activity of melanocortin peptides (MSH-ACTH peptid es) was tested in an experimental model of prolonged respiratory arres t. 2 Anaesthetized, endotracheally intubated rats subjected to a 5 min period of ventilation interruption, invariably died from cardiac arre st within 6-9 min of resumption of ventilation. 3 When resumption of v entilation was associated with the simultaneous intravenous (i.v.) inj ection of a melanocortin peptide (alpha-MSH or ACTH-(1-24)) (160 mu g kg(-1)) there was an almost immediate (within 1 min), impressive incre ase in cardiac output, heart rate, mean arterial pressure (+560% of th e before treatment value) and pulse pressure (+356% of the before-trea tment value), with full recovery of electroencephalogram after 30-45 m in. Blood gases and pH were normalized within 15-60 min after treatmen t, and all treated animals eventually recovered completely and survive d indefinitely (= more than 15 days). 4 The same response was observed in adrenalectomized animals, as well as in animals pretreated with a beta 1-adrenoceptor blocking agent (atenolol, 3 mg kg(-1), i.v.), or w ith an al;adrenoceptor blocking agent (prazosin, 0.1 mg kg(-1), i.v.), or with an adrenergic neurone blocking agent (guanethidine, 10 mg kg( -1), intraperitoneally). 5 An effect quite similar to that produced by melanocortins was obtained with ouabain (0.1 mg kg(-1) i.v.); the ant ioxidant drug, glutathione (75 mg kg(-1), i.v.) also produced 100% res uscitation, but the effect was slower in onset. On the other hand, adr enaline (0.005 mg kg(-1), i.v.) was able to resuscitate only 1 out of 8 rats and dobutamine (0.02 mg kg(-1), i.v.) resuscitated 4 out of 8 r ats; moreover, the effect of both catecholamines was much slower in on set than that of melanocortins and the initial, impressive stimulation of cardiovascular function was absent. 6 These results show that mela nocortin peptides have a resuscitating effect in a pre-terminal condit ion produced in rats by prolonged asphyxia. This effect seems primaril y due to the restoration of cardiac function, not mediated by catechol amines. These data also suggest that these peptides may have potential therapeutic value in conditions of transient cardiac hypoxia and re-o xygenation such as occur in coronary artery disease.