The effect of FMRFa-like peptides on rats reanimated after clinical death

Abstract

The effects of the endogenous paraopioid FMRFa and FMRFa-like peptides are compared upon reanimation of rats after clinical death caused by acute hemorrhage. It is found that FMRFa restores cardiohemodynamics and respiratory function more effectively than RFa and RFx2HC1. The nonpeptide opioid antagonist naloxone does not alleviate the effects of acute hemorrhage. It is assumed that the reanimating effect of the studied peptides is realized via mechanisms that are not associated with opiates. Key Words: reanimation; paraopioid peptides; naloxoneWhen used in shock of various etiologies, opiate receptor blockers (specifically, naloxone) normalize the autonomous functions, particularly in the early stages of shock [2,3,6,8]. In rats exposed to hypoxic shock, the paraopioid tetrapeptide Phe-Met-ArgPhe-NH 2 (FMRF-amide or FMRFa), which is probably an endogenous opiate antagonist, produces an effect similar to that of naloxone but much more potent [1]. This effect may be due to the pronounced hypertensive and cardiostimulating activity of FMRFa-like peptides [5].Our objective was to compare the effects of FMRFa-like peptides and naloxone in a model of clinical death brought about by acute hemorrhage. MATERIALS AND METHODSExperiments were performed on 33 outbred female albino rats (180-220 g) under Nembutal anesthesia (40 mg/kg intraperitoneally). A tracheotomy tube was inserted in the trachea and hooked up to an assisted ventilation apparatus. Acute hemorrhage was modeled by draining the blood via a catheter in the common carotid artery 2 min after intraarterial inNizhny Novgorod State University; M. V. Lomonosov Moscow State University jection of 500 U/kg heparin. Blood was collected in a graduated cylinder. FMRFa, RFa, RFx2HC1, or naloxone were added in a dose of 0.5 mg/kg to the collected blood of experimental rats; an equivalent volume of normal saline (0.5 ml) was added to the blood of control rats. Clinical death from acute blood loss lasted 10 min from the cessation of respiration, after which the rats were reanimated. For this purpose blood was delivered via an intraarterial catheter, artificial ventilation was begun, and, if necessary, direct heart massage was performed. The autonomous functions were assessed from the heart rate (HR), respiration rate (RR), and mean blood pressure (MBP) recorded by standard methods throughout the experiment. The survival rate was also taken into account. The results were analyzed using the standard nonparametric tests. RESULTSBy the 10th min of reanimation, HR and MBP in half of the control rats were 22.5 and 24.5% of the baseline values, respectively (Fig. 1, Table 1). The other rats developed uncontrolled fibrillation in response to reinfusion of heparinized blood with normal saline. Spontaneous respiration was not restored. All control rats died by the 40th min of re-

Antiarrhythmic activity of the antiopioid peptide nociceptin and its effect on the fast Na+ channels in cardiomyocytes

“…were found in humans and animals. They do not directly affect the opiate receptors, but produce effects that are opposite to those of opioids on the cardiovascular system [4]. The family of "antiopioids" was recently enlarged by another peptide, nociceptin (NC or orphanin FQ) [8,10].…”