Gaetano Lotti

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

Summary 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 μg/kg/min was a 9% (p < 0.05) decrease in systemic vascular resistance (SVR). At an infusion rate of 1 μg/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 < 0.001), cardiac output (CO) increased, and SVR decreased by 22% (p < 0.05). In a separate group of 12 patients, epinine infusion at rates of 0.5–1 μg/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.

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.

Effect of clomiphene citrate on plasma levels of immunoreactive luteinizing hormone-releasing hormone, gonadotropin, and testosterone in normal subjects and in patients with idiopathic oligospermia.

The effect of clomiphene citrate on plasma immunoreactive luteinizing hormone-releasing hormone (LH-RH), gonadotropin, and testosterone levels was investigated in 10 patients with idiopathic oligospermia and in 10 normal volunteers. A daily 100-mg dose of clomiphene citrate induced a marked, significant increase in plasma immunoreactive LH-RH levels, followed by significant increments in gonadotropin and testosterone values. No significant differences were detected in LH-RH, gonadotropin, and testosterone levels between controls and patients with oligospermia either under basal conditions or during clomiphene treatment.

Dynamic evaluation of prolactin secretion in patients with oligospermia: effects of treatment with metergoline.

Serum prolactin levels were measured in 50 patients with oligospermia and in 20 control subjects under fasting conditions and following the administration of levodopa, pyridoxine, metoclopramide, and synthetic thyrotropin-releasing hormone. Four patients (8%) under fasting conditions had prolactin levels slightly above the normal range. However, no significant differences in prolactin behavior were detected between patients with hyperprolactinemia, patients with normal prolactin levels, and control subjects. The four patients with hyperprolactinemia were treated with metergoline, an ergoline derivative. Metergoline administration promptly reduced the prolactin levels. Spermatogenesis was restored in three patients after 4 to 5 months of treatment.

ACETYLCHOLINE-INDUCED, CALCIUM-DEPENDENT NOREPINEPHRINE OUTFLOW FROM PERIPHERAL HUMAN LYMPHOCYTES

Catecholamines (CA) were studied in peripheral human lymphocytes, as well as in the supernatants, after incubation with L-tyrosine and L-dihydroxyphenylalanine (L-Dopa) for 1 h. The effect that the addition of acetylcholine (ACh), Veratridine, lonomycin or KCI had on the outflow of norepinephrine (NE) from lymphocytes was also studied. The effect of the addition of methoxyverapamil (D600, a Ca2+ channel blocker) and cholinergic antagonists had on the ACh-induced NE outflow was assessed. CA were determined by HPLC-ECD, both in the supernatant and in the cell lysates. L-Tyrosine and L-Dopa significantly (P < 0.01) increased intracellular NE. Neither L-tyrosine, L-Dopa, nor vehicle induced a detectable outflow of NE to the supernatants. ACh [120 microM], Veratridine [100 microM], Ionomycin [10 microM] and KCl [50 mM] (with or without the simultaneous addition of L-tyrosine or L-Dopa) all induced a detectable outflow of NE to the supernatant when added 5 min before the end of incubation. NE was not detectable in the supernatant when the chemicals were added 10 to 20 min before the end of the incubation. When the chemicals were added at lower concentrations, erratic secretion or no secretion whatsoever was observed. D600 [100 microM] was able to significantly (P < 0.01) reduce the ACh-induced NE outflow. Tetraethylammonium (nicotinic antagonist), but not atropine (muscarinic antagonist), significantly (P < 0.001) decreased the ACh-induced NE outflow. The outflow of NE from peripheral human lymphocytes was seen. NE secretion seems to be ACh- and calcium-dependent since Veratridine, Ionomycin and KCl are able to induce Ca2+ entry by means of various mechanisms. The Ca2+ channel blocker employed in this study (D600) reduced the ACh-dependent NE outflow. We can conclude that both ACh (through nicotinic receptors) and calcium are involved in the outflow of NE from peripheral human lymphocytes.

Effect of dopaminergic blockade on the secretion of growth hormone and prolactin in man

Serum growth hormone (GH) response to insulin and glucagon administration was studied in 12 male and 12 female volunteers under control conditions, and under treatment with pimozide and metoclopramide. In addition, serum prolactin levels were measured during the treatment period. Pimozide and metoclopramide administration had no effect on the GH response to insulin and glucagon. In contrast, serum prolactin levels increased markedly during the treatment period. Dopaminergic blockade is unable to affect GH secretion in response to insulin and glucagon administration in man.

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.

TSH AND PROLACTIN STIMULATION BY THE DECARBOXYLASE INHIBITOR BENSERAZIDE IN PRIMARY HYPOTHYROIDISM

200 mg of the I‐aromatic amino acid decarboxylase inhibitor benserazide were administered orally to five patients with primary hypothyroidism. Benserazide induced a significant increase in prolactin and TSH plasma concentrations in all subjects. Since the drug blocks the conversion of DOPA to dopamine, these hormonal changes may be due to a reduction in circulating and/or median eminence levels of dopamine.

LUTEINIZING HORMONE, FOLLICLE STIMULATING HORMONE AND TESTOSTERONE IN NORMAL AND IMPOTENT MEN FOLLOWING LHRH AND HCG STIMULATION

The effect of synthetic LHRH on plasma concentrations of LH, FSH, testosterone and testosterone response to i.v. HCG was studied in fifteen normal men and in fifteen men with impotence.

Effect of apomorphine and piribedil on the secretion of thyrotropin and prolactin in patients with primary hypothyroidism

The administration of apomorphine and piribedil, two dopaminergic agents, significantly reduced thyrotropin (TSH) and prolactin levels in six female patients with primary hypothyroidism. These data provide further evidence for an inhibitory role of dopaminergic stimulation on TSH secretion.