naloxone and Heart-Failure

In a canine model of congestive heart failure beta endorphin concentrations were high and opioid receptor antagonists exerted beneficial haemodynamic effects. In humans previous studies have suggested that opioid peptides may modify the perception of breathlessness and fatigue in heart failure.. Plasma concentrations of beta endorphin were measured in patients with acute and chronic heart failure and cardiogenic shock. A subgroup of eight patients with New York Heart Association (NYHA) class III-IV heart failure was assessed for acute haemodynamic effects of naloxone, an opioid receptor antagonist. A separate group of 10 patients with class II-III heart failure, was randomised to a double blind placebo controlled study of the effects of intravenous naloxone on cardiopulmonary exercise performance.. Plasma concentrations of beta endorphin were usually normal in patients with chronic heart failure and did not correlate with severity as assessed by NYHA class. In 29% of patients with acute heart failure and 71% of those with cardiogenic shock beta endorphin concentrations were high. The median concentration in the cardiogenic shock group was significantly higher than in either of the two heart failure groups and there was some evidence of a relation between beta endorphin concentrations and survival. At the doses tested, naloxone was unable to modify systemic haemodynamics, exercise performance, or symptoms in patients with chronic congestive heart failure.. Circulating concentrations of beta endorphin are usually normal in patients with chronic congestive heart failure. Inhibition of the endogenous opioid system is unlikely to have therapeutic potential in heart failure.

Topics: Acute Disease; Adult; Aged; beta-Endorphin; Chronic Disease; Double-Blind Method; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Shock, Cardiogenic; Stroke Volume; Ventricular Function, Left

Two groups of patients with acute congestive heart failure (CHF), New York Heart Association class III, presenting elevated plasma values of beta-endorphin, norepinephrine, atrial natriuretic factor (ANF) and endothelin-1, underwent the Mental Arithmetic Test (MAT) during placebo (n = 10) and naloxone hydrochloride (n = 10) infusion. The MAT during placebo significantly (p < 0.01) increased blood pressure, heart rate, plasma levels of Met-enkephalin, dynorphin B, beta-endorphin, norepinephrine, ANF and endothelin-1. The increases in norepinephrine, ANF and hemodynamics after the MAT during naloxone infusion were higher (p < 0.01) than those during placebo; thus, the transient upregulation of the endogenous opioid system during stress in CHF patients attenuates the hemodynamic response by reducing norepinephrine release.

Topics: Atrial Natriuretic Factor; beta-Endorphin; Blood Pressure; Endothelin-1; Enkephalin, Methionine; Female; Heart Failure; Heart Rate; Hemodynamics; Humans; Intelligence Tests; Male; Middle Aged; Naloxone; Narcotic Antagonists; Norepinephrine; Opioid Peptides; Stress, Physiological

The aim of our study was to evaluate the effects of endogenous opioids on the secretion of atrial natriuretic factor (ANF) in moderate chronic heart failure (HF).. We evaluated the effects of i.v. volume load (NaCl 0.9% at 0.25 ml/Kg/min for 60 minutes) on heart rate (HR), on mean arterial pressure (MAP) and on the plasma levels of beta-endorphin (beta-end), met-enkephalin (Met-enk), dynorphin (Dyn), atrial natriuretic factor (ANF) and noradrenaline (NA) in 10 patients (age 58 +/- 9) with HF in NYHA class II (group I) and in 8 healthy control subjects (age 54 +/- 10) group II). The volume load was repeated after at least three days during infusion of naloxone (2 micrograms/Kg/min), evaluating the above mentioned hemodynamic and hormonal parameters.. The acute volume expansion caused an increase in ANF concentration (from 51.7 +/- 19.7 to 67.4 +/- 36.9 pg/ml; p < 0.05) and in beta-end (from 11.9 +/- 5.3 to 16.6 +/- 7.5 fmol/ml; p < 0.05), In group I. In group II an isolated increase in ANF was observed (from 14.1 +/- 7.8 to 21.9 +/- 7.9 pg/ml; p < 0.02). No significant changes were detected for HR, MAP, Dyn, Met-enk and NA. In group I the percent increase of ANF is less than in group II (30 vs 55%; p < 0.05). The volume load infused during naloxone infusion caused a significant increase in HR (from 73 +/- 6 to 78 +/- 9 bpm; p < 0.05) and in NA (from 311 +/- 123 to 415 +/- 142 pg/ml; p < 0.05) In group I. In group II, an increase in ANF was detected (from 13.8 +/- 6.0 to 23.6 +/- 5.0 pg/ml; p < 0.01).. Our data suggest that in moderate HF beta-end stimulates the secretion of ANF and inhibits the activity of the sympatho-adrenergic system during acute volume expansion.

Topics: Adult; Aged; Analysis of Variance; Atrial Natriuretic Factor; beta-Endorphin; Chronic Disease; Data Interpretation, Statistical; Dynorphins; Enkephalin, Methionine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Narcotic Antagonists; Norepinephrine; Plasma Volume; Receptors, Adrenergic; Sodium Chloride; Sympathetic Nervous System

The aim was to test the therapeutic efficacy of naloxone, an opiate receptor antagonist, upon murine coxsackievirus B3 myocarditis with the analysis of neurohumoral kinetics.. Two week old C3H/He mice were inoculated with 10(3) plaque forming units of coxsackie B3 virus. Naloxone, 1 mg.kg-1.d-1, was given intraperitoneally daily on days 0-14 in experiment I, and on days 14-28 in experiment II. The treated groups were compared to infected controls in each experiment. For the analysis of the endogenous opiate and neurohumoral system, plasma beta endorphin and catecholamines were measured.. In experiment I, survival rate did not differ significantly between naloxone treated and untreated groups (11/15 v 8/15, p = NS). Pathological scores (infiltration and necrosis), myocardial virus titres, and plasma beta endorphin and catecholamine concentrations did not differ significantly between the two groups. In experiment II, survival rate (13/16 v 6/14, P < 0.05) was higher and cardiac pathology was less severe, with a lower incidence of congestive heart failure, in naloxone than in controls groups. In addition, beta endorphin and noradrenaline were significantly increased in the naloxone group compared to the control.. The endogenous opiate system is activated in congestive heart failure caused by severe myocardial damage in murine coxsackie B3 myocarditis, where an associated limitation of the sympathetic system may be present. Naloxone is beneficial in congestive heart failure caused by coxsackie B3 myocarditis because of its neurohumoral modulating effect.

Topics: Animals; beta-Endorphin; Coxsackievirus Infections; Heart Failure; Male; Mice; Mice, Inbred C3H; Myocarditis; Myocardium; Naloxone; Norepinephrine; Survival Rate

We have shown previously that right heart failure (RHF) in dogs is associated with activated endogenous opiate systems, and that administration of the opioid receptor antagonist, naloxone, increases arterial pressure, cardiac contractile function and organ blood flows. To study whether the cardiovascular effects of naloxone are mediated via the mu- or delta-opioid receptors, we administered ICI-154,129, a delta-receptor antagonist, and naloxonazine, a mu-receptor antagonist, to 10 conscious dogs with RHF on 2 separate days. Like naloxone, ICI-154,129 increased mean aortic pressure, cardiac output, peak positive first derivative of left ventricular pressure, and blood flows to the myocardium, kidneys, splanchnic beds, and skeletal muscle. These changes were associated with increases in plasma epinephrine and norepinephrine. In contrast, naloxonazine had no effects on systemic hemodynamics, regional blood flow distribution, and plasma catecholamines in RHF. These findings suggest that the increased endogenous opioids during heart failure act on the delta-opioid receptors to decrease myocardial mechanical performance and alter regional blood flow distribution. Opioid receptor-blocking agents may exert beneficial cardiovascular effects in heart failure.

Topics: Animals; Blood Circulation; Cardiovascular System; Dogs; Enkephalin, Leucine; Heart Failure; Hemodynamics; Naloxone; Narcotic Antagonists; Receptors, Opioid, delta; Receptors, Opioid, mu; Regional Blood Flow; Ventricular Function, Right

The purpose of this study was to determine the effects of naloxone on systemic hemodynamics and reflex function in dogs with congestive heart failure induced by rapid pacing.. We have shown previously that naloxone, an opiate receptor antagonist, improves cardiac output, aortic blood pressure, systolic performance and the baroreflex function in conscious dogs with chronic right-sided congestive heart failure. However, whether endogenous opioids also play a role n mediating the reduction of myocardial and baroreflex function in animals with left heart failure remains controversial.. We administered naloxone (1 mg/kg body weight) and normal saline solution to 15 dogs with pacing-induced congestive heart failure (225 beats/min for 8 weeks) and 11 control dogs. In addition to systemic hemodynamic measurements, the slope of pressure-area relation obtained from echocardiography with intravenous bolus injection of phenylephrine was taken as a load-independent index of myocardial contractility. Baroreflex function was estimated by the slope of the regression line relating systolic aortic pressure and RR interval.. Plasma beta-endorphin levels were elevated in dogs with congestive heart failure. Naloxone administration increased heart rate, mean aortic pressure, first derivative of left ventricular pressure, cardiac output and myocardial contractility in pacing-induced congestive heart failure. These changes correlated significantly with basal plasma beta-endorphin levels and were accompanied by increases in plasma beta-endorphin and catecholamines after naloxone administration. However, unlike the hemodynamic and cardiac effects of naloxone, baroreflex function did not change after naloxone in dogs with congestive heart failure.. The increase in basal plasma beta-endorphin suggests that the endogenous opiate system is activated in left-sided congestive heart failure. Because naloxone improves the systemic hemodynamics and myocardial contractile function under this condition, the endogenous opioids appear to play an important role in mediating the myocardial depression that occurs in heart failure. However, the endogenous opiate system has no apparent effect on the regulation of baroreflex control in heart failure induced by rapid pacing.

Topics: Animals; Baroreflex; beta-Endorphin; Disease Models, Animal; Dogs; Epinephrine; Heart Failure; Hemodynamics; Myocardial Contraction; Naloxone; Narcotic Antagonists; Norepinephrine; Ventricular Function, Left

We evaluated plasma atrial natriuretic factor (ANF), beta-endorphin, met-enkephalin, dynorphin and noradrenaline levels in 20 healthy subjects and 20 acute congestive heart failure (CHF) patients. In all acute CHF patients plasma values of these hormones were higher than in healthy subjects. The hormonal pattern differed in patients with the more severe acute CHF (group 1) from patients with less severe acute CHF (group 2) (ANF 53.8 +/- 1.0 vs 34.6 +/- 1.5 pg.ml-1, noradrenaline 563.8 +/- 13.4 vs 202.4 +/- 10.6 pg.ml-1, met-enkephalin 41.0 +/- 3.2 vs 17.0 +/- 1.6 fmol.ml-1, dynorphin 46.8 +/- 3.7 vs 25.2 +/- 2.0 fmol.ml-1, P < 0.01; beta-endorphin 50.6 +/- 5.2 vs 41.8 +/- 4.1 fmol.ml-1,ns). Administration of an opioid antagonist (naloxone, 8 mg i.v.) did not modify ANF or noradrenaline concentration in healthy subjects. In group 1 naloxone administration significantly raised ANF (68.0 +/- 1.4 pg.ml-1), noradrenaline (776.6 +/- 18.7 pg.ml-1), blood pressure and heart rate, whereas in group 2 it significantly decreased ANF values (21.9 +/- 0.5 pg.ml-1) and did not modify the other parameters. Our findings suggest that the opioid system affects ANF release in acute CHF. In patients with severe CHF opioid peptides may attenuate ANF secretion reducing noradrenergic stimulation. On the other hand, when CHF is less severe and the sympathetic activity is moderate, opioid peptides may directly stimulate ANF secretion.

Topics: Acute Disease; Aged; Atrial Natriuretic Factor; beta-Endorphin; Case-Control Studies; Dynorphins; Enkephalin, Methionine; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Norepinephrine

Opiate receptor inhibition causes adrenergic receptor-mediated increases in aortic pressure, cardiac output, and left ventricular contractile function in right heart failure. To study whether the effects of opiate receptor inhibition are mediated by means of an action on the central opiate system, we administered equimolar doses of naloxone hydrochloride and naloxone methobromide (MeBr) and normal saline to heart failure dogs. Chronic stable right heart failure was produced by progressive pulmonary artery constriction and tricuspid valve avulsion. Naloxone hydrochloride caused an increase in mean aortic pressure, cardiac output, left ventricular dP/dt and dP/dt/P, plasma catecholamines, and regional blood flows to the myocardium, quadriceps muscle, kidneys, and splanchnic beds. Plasma beta-endorphin and adrenocorticotropin also increased. In contrast, neither normal saline nor naloxone MeBr (which does not cross the blood-brain barrier) affected the systemic or regional hemodynamics or neurohormones. Naloxone hydrochloride was also administered to anesthetized heart failure dogs. Pentobarbital anesthesia removed cortical perception of nociceptive stimulation, reduced the increase in plasma epinephrine, and abolished vasodilation in skeletal muscle that occurred in conscious dogs after naloxone hydrochloride administration but had no major effects on responses of plasma norepinephrine, systemic hemodynamics, or other regional blood flows to opiate receptor inhibition. Naloxone hydrochloride had no effect in sham-operated dogs. The results indicate that the hemodynamic effects of naloxone are mediated by an action within the central nervous system. Furthermore, since pentobarbital anesthesia did not markedly alter the hemodynamic responses to naloxone hydrochloride, the acute salutary effects of opiate receptor inhibition probably are not caused by removal of the antinociceptive effect of endogenous opioids in heart failure.

Topics: Anesthesia; Animals; Catecholamines; Central Nervous System; Consciousness; Dogs; Heart Failure; Hemodynamics; Naloxone; Receptors, Opioid; Regional Blood Flow; Sodium Chloride

The endogenous opiate system is activated in congestive heart failure. because endogenous opioids are known to depress the baroreflex function, we conducted studies to determine whether the increased endogenous opioids play a role in causing the reduced baroreflex function that occurs in heart failure. Right-sided congestive heart failure was produced in 16 dogs by tricuspid avulsion and progressive pulmonary artery constriction. Seven sham-operated dogs were included for comparison. Baroreflex function was measured in the conscious dogs after pretreatment with either normal saline or an opiate-receptor antagonist by bolus administration of phenylephrine. The slope of the regression line relating systolic blood pressure to cardiac cycle (R-R) interval was taken as an index of baroreflex sensitivity. Plasma beta-endorphin was elevated in the dogs with heart failure (15.3 +/- 2.5 pmol/l) compared with the sham-operated dogs (4.2 +/- 0.4 pmol/l, p less than 0.001). The dogs with heart failure also exhibited a reduced baroreflex sensitivity (3.84 +/- 0.19 msec/mm Hg) after saline pretreatment when compared with the sham-operated dogs (10.86 +/- 1.20 msec/mm Hg, p less than 0.001). Administration of naloxone hydrochloride increased the baroreflex sensitivity of dogs with heart failure to 5.16 +/- 0.26 msec/mm Hg (p less than 0.01) but produced no significant effects in sham-operated dogs (11.36 +/- 1.42 msec/mm Hg). To further study the site of action for the effect of naloxone, we measured baroreflex sensitivity in the dogs with heart failure after pretreatment with naloxonazine, a selective mu-receptor antagonist, with ICI 154,129, a selective delta-receptor antagonist, or with naloxone methobromide, a quaternary analogue of naloxone that does not penetrate the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Pressure; Consciousness; Dogs; Electrocardiography; Enkephalin, Leucine; Heart Failure; Naloxone; Narcotic Antagonists; Oxymorphone; Phenylephrine; Pressoreceptors; Receptors, Opioid; Reflex

Topics: Adult; Blood Vessels; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Naloxone; Pulmonary Circulation; Rest

Topics: Aged; Heart Failure; Humans; Hypotension; Infusions, Parenteral; Male; Naloxone; Respiration, Artificial; Respiratory Insufficiency

Topics: Adolescent; Adult; Coma; Female; First Aid; Heart Failure; Humans; Male; Naloxone; Respiratory Insufficiency; Shock; Wounds and Injuries