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Biomedical subjects

N R Musso

Publications and source records attributed to N R Musso.

12 recordsLinked to original sources

Effects of intravenous epinine administration on left ventricular systolic performance, coronary hemodynamics, and circulating catecholamines in patients with heart failure.

Twenty-six patients with mild to moderate heart failure were studied to determine the effects of epinine infusion (at a rate producing plasma levels similar to those measured after oral administration of 100 mg of the prodrug ibopamine) on left ventricular (LV) function (14 patients), and coronary flow and circulating catecholamines (12 patients). The only significant hemodynamic change at an infusion rate of 0.5 microgram/kg/min was a 9% (p less than 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 microgram/kg/min (mean free epinine plasma levels 14.3 +/- 3.7 ng/ml), heart rate (HR), dP/dtmax (1,405 +/- 255 to 1,490 +/- 320 mm Hg, NS), (dP/dt)/DP40, and the relaxation rate remained unchanged, but the ejection fraction (EF) increased from 32 to 38% (p less than 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p less than 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5-1 microgram/kg/min produced no significant changes in coronary blood flow or myocardial oxygen uptake. At these infusion rates, arterial norepinephrine (NE) and dopamine (DA) levels decreased slightly and arterial and coronary sinus epinephrine increased. In conclusion, epinine, at concentrations similar to those achieved during therapeutic use of ibopamine, had negligible effect on myocardial contractility and relaxation rate in heart failure patients. Cardiac pump function was improved by a decrease in SVR rather than by inotropic stimulation. The data also suggest that these low concentrations of epinine may modulate the sympathetic nervous system, but further studies are needed to determine whether this effect could have clinical significance.

Adult

Norepinephrine-induced plasma dopamine decrease in man: pharmacological evidence of the involvement of alpha 2-adrenoceptors.

OBJECTIVE: The purposes of this study were: (1) to test whether intravenous infusion of norepinephrine can affect plasma dopamine levels; and (2) to explore to what extent dopamine-2 or alpha 2-receptors play a role in this response. DESIGN: Norepinephrine infusion in man was performed to test whether the increase in norepinephrine during sympathetic stimulation can affect dopamine release. Specific antagonists of presynaptic dopamine-2 and alpha 2-receptors were administered to test the receptor(s) involved in this possible regulatory phenomenon. METHODS: Plasma catecholamine levels were investigated in seven normal subjects before and after administration of domperidone (dopamine-2 antagonist), yohimbine (alpha 2-antagonist) and norepinephrine. RESULTS: Both oral domperidone and yohimbine induced a significant increase in both plasma norepinephrine and plasma dopamine. Norepinephrine infusion induced a significant decrease in plasma dopamine. Pretreatment with domperidone only partially counteracted this inhibitory effect of norepinephrine infusion, whereas yohimbine fully counteracted it. CONCLUSIONS: Our data show that norepinephrine may act as a hormone at plasma concentrations as low as 450 pg/ml. The norepinephrine-induced plasma dopamine decrease seems to be alpha 2-adrenoceptor-mediated. This norepinephrine effect may be involved in the physiologic decrease in plasma dopamine that we demonstrated in the upright position in normal subjects.

Administration, Oral

Absence of correlations between plasma catecholamine levels and mononuclear leukocyte beta 2-adrenergic receptors in the elderly.

To assess the effects of aging on catecholamine plasma levels and mononuclear leukocyte (NML) beta 2-adrenergic receptors and on the possible relationships between these two parameters, we evaluated two groups of human subjects: 18 elderly volunteers (age 65-70 years) and 13 young volunteers (age 21-35 years). Norepinephrine plasma levels were significantly higher in the elderly subjects compared to the younger ones (P less than 0.05), whereas plasma epinephrine levels were not different. Also MNL beta 2-adrenoceptor density was significantly higher in elderly subjects (P less than 0.05). The binding dissociation constants were not significantly different. In young subjects there was a significant (P less than 0.02), inverse relationship between receptor densities and plasma norepinephrine levels; this relationship was not present in elderly persons. Our data suggest that the increase in beta 2-adrenoceptors may be due to a compensatory phenomenon, owing to the reduced beta-adrenergic sensitivity observed in the elderly subjects; moreover, the regulation of beta-adrenoceptors by plasma catecholamines seems to be altered by aging.

Adult

Intraindividual variation of beta 2-adrenergic receptors on mononuclear leukocytes and their relationships with endogenous plasma catecholamines in man.

The interindividual and intraindividual variations of both MNL beta 2-adrenergic receptor density and dissociation constant of binding were evaluated in 19 healthy volunteers. In addition the possible relationships between catecholamine plasma levels and MNL beta 2-adrenergic receptor density were studied in 8 of these subjects. The volunteers were studied three times with ten days' interval. There was a significant inverse relationship between receptor density and norepinephrine plasma levels, only. Neither epinephrine nor dopamine were correlated with receptor density. Interindividual coefficient of variation was 29.57%. The mean value of the intraindividual coefficients of variation was 14.1%, while the mean value of the analytical coefficients of variation was 10%. Our results are at some variance with data in the literature and may contribute to elucidate the role of MNL beta 2-adrenergic receptors as an index of sympathetic function in man.

Adult

Plasma dopamine response to sympathetic activation in man: a biphasic pattern.

We studied the plasma catecholamine response to standing and bicycle ergometric tests in 16 normal male subjects. During the standing test (performed in 10 subjects), we observed an early increase in plasma dopamine together with the fast increase in norepinephrine values; in the second half of this test (i.e. from 5 to 10 min of standing), we observed an increase in plasma dopamine levels. During the ergometric test (performed in 6 subjects), we observed a plasma dopamine increase at the maximal exercise; this persisted during the early recumbent recovery phase (6 min), despite the clear-cut decrease of both norepinephrine and epinephrine plasma levels. Our data are not in agreement with previous papers describing a simple increase in plasma dopamine after stimulation. This paper provides no informations regarding the mechanisms of this response of plasma dopamine. Other approaches must be used to study this aspect more directly.

Adult

Free and sulfoconjugated catecholamines in normotensive uremic patients: effects of hemodialysis.

In 9 normotensive uremic patients undergoing chronic hemodialysis, the baseline plasma catecholamines varied widely from low-normal to very high; sulfoconjugated plasma catecholamines were constantly high. A dialysis-induced fall of all sulfated catecholamines and epinephrine was observed. Norepinephrine decreased in 5 patients and increased in 4, with a strong inverse correlation between predialysis norepinephrine and delta norepinephrine (p less than 0.0001). No correlation was evident between clinical parameters (mean arterial pressure, heart rate) and catecholamines (both predialysis and postdialysis). Significant (p less than 0.0001 and p less than 0.0002) inverse correlations between epinephrine and norepinephrine and their sulfoconjugation degree were demonstrated only in predialysis. Our data may support the presence of a uremic autonomic neuropathy and adrenoceptor damage.

Adult

Reversed-phase HPLC separation of plasma norepinephrine, epinephrine, and dopamine, with three-electrode coulometric detection.

We present a method involving minor modifications of previous techniques, in which we use an ion-pair reversed-phase HPLC separation with three-electrode coulometry. Isocratic baseline separations can be obtained in 5 min. The sample preparation procedure, involving extraction with alumina at low temperature, allows good reproducibility (within-run and between-run CVs less than 10%) and improved sensitivity (less than 5 pg of each catecholamine per extract). This method allows approximately 70 low-cost plasma catecholamine analyses to be done in a working day.

Catecholamines

Interaction between morphine, an opioid agonist, and clonidine, an alpha-adrenergic agonist, on the regulation of anterior pituitary hormone secretion in normal male subjects.

In order to investigate the possible interaction between opioid system and noradrenergic system in the regulation of pituitary hormone secretion, the effects of morphine (an opioid agonist, 10 mg i. v.), clonidine (an alpha-adrenergic agonist, infusion of 0.3 mg in 15 minutes) and clonidine + morphine (infusion of the same dose of clonidine beginning 30 minutes before morphine 10 mg i.v.) on anterior pituitary hormone secretion were studied in six normal male volunteers. Morphine alone induced both an increase in TSH and PRL serum levels and a decrease in cortisol serum levels with no changes in GH serum levels. On the contrary clonidine was able to increase GH and TSH levels and to decrease cortisol levels; PRL secretion was not affected. As regards interaction between morphine and clonidine we observed that morphine-induced increase in PRL release was potentiated by clonidine pretreatment; as regards TSH secretion its increase was greater after the administration of the two drugs with respect to the effect of the single drugs. This study, in agreement with our previous data concerning LH secretion, confirms the important link between clonidine and opioid system in neuroendocrine function, too; the possible explanations of our data are discussed.

Adult

Evaluation of the effects induced by four opiate drugs, with different affinities to opioid receptor subtypes, on anterior pituitary LH, TSH, PRL and GH secretion and on cortisol secretion in normal men.

In order to ascertain the subtype(s) of opioid receptors involved in the control of pituitary function the effects of four different opiate drugs (morphine, pentazocine, nalorphine and buprenorphine) were studied in four groups of six normal male volunteers. Each of the drugs tested induced, with varying degrees, both a significant increase in PRL and a significant decrease in LH and cortisol. On the contrary TSH secretion was stimulated by buprenorphine and morphine only and GH by nalorphine only. FSH did not change significantly after administration of any drug. Taking into account the different affinities of the drugs used by us for the different opioid receptors, our data do not allow to demonstrate a well-defined correlation between subtypes of opioid receptors and the control of pituitary hormone secretion. The possible explanations of this fact are discussed.

Adult

Morphine-induced TSH release in normal and hypothyroid subjects.

The effects of morphine (10 mg i.v.), an opioid agonist, and of naloxone (10 mg i.v.), an opioid antagonist, on serum levels of TSH and PRL were studied in 7 hypothyroid patients and in 5 normal volunteers. Morphine administration induced a prompt, significant increase in serum TSH and PRL in all subjects. The degree of PRL release after morphine was similar in the two groups, while, as regards TSH, the increase was more evident in hypothyroid subjects. Pretreatment with naloxone (4 mg i.v. 5 min before morphine administration) blocked these effects in all subjects. In contrast, naloxone alone was not able to affect significantly TSH and PRL secretion. Moreover, in 5 other euthyroid volunteers, morphine significantly enhanced the response of TSH and PRL to TRH stimulation (200 micrograms i.v.). These data demonstrate that morphine exerts a stimulatory action on TSH and PRL secretion: the possible mode of action of this drug and the physiologic significance of these findings are discussed.

Adult

Neuroendocrine effects of interferon alpha 2-a in healthy human subjects.

The acute effects of interferon alpha-2a (3 x 10 IU im) on catecholamine and immunoreactive beta endorphin plasma levels, cortisol serum levels and lymphocyte beta 2-adrenoceptor density were evaluated in ten healthy volunteers. Interferon induced a significant increase in plasma norepinephrine; there was an increased norepinephrine standing response, too. On the contrary, epinephrine standing response was reduced by interferon. Lymphocyte beta 2-adrenoceptors decreased significantly after interferon administration; dissociation constant of binding was unchanged. Cortisol serum levels increased significantly with respect to control test, whereas immunoreactive beta endorphin did not change. These results support the hypothesis of functional relationships between neuroendocrine and immune systems; moreover they may be useful in clinical trials given the administration of interferon alpha in an increasing number of diseases.

Adult