alpha-Methylnorepinephrine, a selective alpha2-adrenergic agonist for cardiac resuscitation.

OBJECTIVES: The purpose of this study was to investigate the effects of a selective alpha2-adrenergic agonist, alpha-methylnorepinephrine (alphaMNE) as an alternative vasopressor agent during cardiopulmonary resuscitation (CPR). BACKGROUND: For more than 40 years, epinephrine has been the vasopressor agent of choice for CPR. Its beta- and alpha1-adrenergic effects increase myocardial oxygen consumption, magnify global myocardial ischemia and increase the severity of postresuscitation myocardial dysfunction. METHODS: Ventricular fibrillation (VF) was induced in 20 Sprague-Dawley rats. After 8 min of untreated VF, mechanical ventilation and precordial compression began. AlphaMNE, epinephrine or saline placebo was injected into the right atrium 2 min after the start of precordial compression. As an additional control, one group of animals was pretreated with alpha2-receptor blocker, yohimbine, before injection of alphaMNE. Defibrillation was attempted 4 min later. Left ventricular pressure, dP/dt40, negative dP/dt and cardiac index were measured for an interval of 240 min after resuscitation. RESULTS: Except for saline placebo and yohimbine-treated animals, comparable increases in coronary perfusion pressure were observed after each drug intervention. All animals were successfully resuscitated. Left ventricular diastolic pressure, cardiac index, dP/dt40 and negative dP/dt were more optimal after alphaMNE; this was associated with significantly better postresuscitation survival. Pretreatment with vohimbine abolished the beneficial effects of alphaMNE. CONCLUSIONS: The selective alpha2-adrenergic agonist, alphaMNE, was as effective as epinephrine for initial cardiac resuscitation but provided strikingly better postresuscitation myocardial function and survival.

Modification of local anesthetic toxicity by vasoconstrictors.

We studied the effects of epinephrine or levonordefrin on the toxicity (convulsions) and lethality of four local anesthetics in mice. Appropriate doses of procaine, lidocaine, tetracaine or bupivacaine--either alone or in combination with 15 mcg/kg epinephrine or levonordefrin--were injected intravenously into the tail vein of male mice. Dose-response curves were constructed from the data obtained, and the CD50 and LD50 values for each local anesthetic alone and in combination with each of the vasoconstrictors were calculated by probit analysis. Both epinephrine and levonordefrin decreased the toxicity and lethality of procaine with respect to dose. Epinephrine, but not levonordefrin, increased the toxicity and lethality of bupivacaine as well as the lethality of tetracaine. Neither vasoconstrictor significantly affected the toxicity of lidocaine in mice but in rats epinephrine markedly increased lidocaine's lethality under identical conditions. Tight physical restraint decreased the LD50 values of all four local anesthetics and eliminated any modifying effect of the vasoconstrictor.

Desensitization of vascular and platelet alpha 2-adrenoceptors in rabbits with perinephritis hypertension.

The effects of infusion of alpha-adrenoceptor agonists on blood pressure, pressor responses to bolus doses of agonists and to platelet aggregation were examined in rabbits with perinephritis hypertension and in sham-operated controls. Pressor responses to bolus doses and infusions of phenylephrine, an alpha 1-selective agonist, were greater in hypertensive rabbits. In contrast, responses to boluses but not infusions of alpha-methylnoradrenaline, a selective alpha 2-agonist, were increased in hypertensives. During alpha-methylnoradrenaline infusions pressor responses to bolus doses of alpha-methylnoradrenaline and the aggregatory response of platelets to adrenaline were attenuated in all rabbits, consistent with alpha 2-adrenoceptor desensitization. Attenuation and recovery were observed within minutes of commencing and ceasing infusion. The extent of attenuation and rate of change were generally increased in hypertensive animals. This could explain the apparent increase in pressor responses to bolus doses but not infusions of alpha-methylnoradrenaline in the hypertensive rabbits. It might also contribute to the lability in blood pressure observed in these animals.

[Result and treatment of tinnitus in our clinic]. / Bilan et traitement des acouphènes dans notre clinique.

The authors propose a test consisting in performing injections of Renovaine, a very strong anaesthetic drug, in the external ear duct in order to reduce momentarily severe and decompensated tinnitus. They discuss the usefulness of this test and develop two concepts to explain its action. They make a pragmatic approach of the tinnitus etiopathogeny.

Effects of alpha-methylnoradrenaline and alpha-methyldopamine in reserpine-induced ulcers in rats.

alpha-Methyldopamine and alpha-methylnoradrenaline administered intraperitoneally afforded significant protection in reserpine-induced ulcers in rats. The optimal doses were 2 and 4 mg/kg. Lower and higher doses were less effective. alpha-Methyldopamine and alpha-methyl-noradrenaline probably act by reestablishing the normal adrenergic tone which is diminished in reserpine-induced ulcers.