Search PubMed⌕ Search

Biomedical subjects

H R Wagner

Publications and source records attributed to H R Wagner.

At least 55 records · Page 3Linked to original sources

Biochemical and behavioral evaluation of pergolide as a dopamine agonist in the rat brain.

The ergot derivative pergolide was evaluated as a dopamine agonist using various behavioral and biochemical analyses. Spontaneous motor activity was decreased by small doses (0.1 mg/kg) of pergolide and increased with larger doses (above 0.5 mg/kg). Hypermotility after larger doses persisted for as long as 24 hr and was succeeded by a period of hypomotility. The doses of drug, sufficient to produce hypermotility, also produced stereotypy. With repeated daily injections (2 weeks), the period of hypermotility decreased and the ensuing period of hypomotility increased. Stereotyped behavior was similarly affected. Chronic administration of pergolide did not alter the magnitude of the behavioral responses. Levels of the dopamine (DA) metabolites, dihydroxyphenylacetate (DOPAC) and homovanillic acid (HVA), in the striatum and mesolimbic regions were decreased during the periods of hypermotility but returned to control levels during subsequent hypomotility. Activation of putative inhibitory presynaptic dopamine receptors by pergolide was studied by following accumulation of DOPA in rats treated with the dopamine neuron inhibiting agent, gamma-butyrolactone (GBL) and a DOPA-decarboxylase inhibitor. Pergolide significantly inhibited both striatal and mesolimbic accumulation of DOPA. In contrast, with changes in behavioral and metabolic indices, pergolide-induced inhibition of tyrosine hydroxylase was not affected by chronic treatment with pergolide. On the basis of both behavioral and biochemical data it is proposed that pergolide acts as a dopamine agonist with particularly long-lasting effects.

3,4-Dihydroxyphenylacetic Acid↗

Origin of the left coronary artery from the right pulmonary artery.

Origin of the left coronary artery from the right pulmonary artery has rarely been documented. This is the first such case in a heart with an intact ventricular septum and paraductal coarctation of the aorta. Although an antemortem diagnosis was made and the anomalous left coronary artery was ligated, the patient, a 3 1/2 month old infant, died 1 day after surgery. Autopsy confirmed the diagnosis, but revealed that the left coronary artery was dominant. It is believed that the fatal outcome in the infant was, in part, due to the dominance of the left coronary artery and the effects of the coarctation on the already ischemic left ventricle.

Aortic Coarctation↗

Chronic levodopa or pergolide administration induces down-regulation of dopamine receptors in denervated striatum.

Refractory response to dopamine (DA) agonists is a common problem in the treatment of Parkinson's disease. In rats with unilateral lesions of the substantia nigra, denervation induced significant increases in striatal 3(H)-spiperone binding sites ipsilateral to the lesion. Chronic treatment with levodopa or with pergolide mesylate significantly decreased the number of 3(H)-spiperone striatal binding sites. Agonist-induced decreases were approximately equivalent in intact and denervated striata and did not appear to be affected by lesions. These results suggest that the poor response to DA agonist in certain parkinsonian patients with chronic drug exposure may be mediated by drug-induced DA receptor down-regulation.

Animals↗

Surgical closure of patent ductus arteriosus in 268 preterm infants.

Over a 2 year period ending in April, 1981, 268 premature infants with birth weight below 1,750 gm underwent operation for a "hemodynamically significant" patent ductus arteriosus. Operations were performed in 13 centers participating in a collaborative study, which was primarily designed to evaluate the role of indomethacin in the management of patent ductus arteriosus. No patient died during the operations, which were done at a median age of 10 days. Eight infants (3%) died within 36 hours after operation. In only one was the death directly attributable to the operative procedure. Hospital mortality (23%) and postoperative morbidity, which included bronchopulmonary dysplasia, pneumothorax, and sepsis, were unrelated to birth weight, age at operation, and degree of preexisting pulmonary disease or preoperative treatment of the infant with indomethacin. Results indicate that surgical ligation is a safe and effective procedure for treating patent ductus arteriosus with large left-to-right shunting in small premature infants.

Clinical Trials as Topic↗

Chlorpromazine methiodide-induced barrel rotation: an antimuscarinic effect.

Barrel rotation is a motor response observed in rats in which the animal twists about its long axis and rolls laterally. This response was first described following intracerebroventricular injection of somatostatin. The pharmacologic specificity of the response has been questioned, and its physiologic basis is unknown. Recently, barrel rotation following intraventricular injection of quaternary chlorpromazine, chlorpromazine methiodide (CPZMI), has been reported. We have studied the specificity and pharmacologic basis of CPZMI-induced barrel rotation. The response was not induced by 26 compounds injected as controls, and was induced by 6 anti-muscarinic compounds. Dose-response relationships for onset, duration and magnitude of CPZMI-induced barrel rotation response were studied; number of rotations increased linearly with CPZMI dose up to 20 micrograms, after which number of rotations decreased and toxic effects (sedation, seizures) occurred. CPZMI barrel rotation was inhibited by intraventricular injection of the muscarinic agonist carbachol and enhanced by intraventricular or systemic atropine. Muscarinic and dopamine receptor studies indicated that CPZMI has high affinity for the muscarinic cholinergic receptor and low affinity for the spiperone binding site. Modified Scatchard analysis of CPZMI displacement of [3H]QNB at the muscarinic receptor is consistent with muscarinic antagonist properties. We conclude that CPZMI-induced barrel rotation has a specific pharmacologic basis, that of muscarinic cholinergic antagonism.

Animals↗

The effect of chronic L-dopa administration on supersensitive pre- and postsynaptic dopaminergic receptors in rat brain.

Chronic administration of haloperidol induced supersensitivity of the pre- and postsynaptic dopaminergic receptors in rat brain. The response of the presynaptic receptors was determined by an enhanced inhibitory effect of apomorphine on dopamine synthesis after gamma-butyrolactone injection. This change in the receptor function was detected both in the nigrostriatal and mesolimbic pathways. Haloperidol also increased the 3H-spiperone binding sites in striatal membranes, indicating supersensitivity of the postsynaptic receptors. Subsequent prolonged treatment with high doses of L-DOPA/carbidopa resulted in a decrease in 3H-spiperone binding sites, but had no effect on the supersensitive presynaptic receptors. It is suggested that tardive dyskinesia may be a state of both pre- and postsynaptic dopamine receptor supersensitivity and that chronic L-DOPA treatment may have a differential effect on these sites.

Animals↗

Two novel prolactin release-inhibiting 8 alpha-amino-ergolines.

Prolactin secretion inhibition and changes in striatal dopamine metabolism in rats were compared after the administration of 8 alpha-amino-ergoline CH 29-717 and 2 derivates. CQ 32-084 was similar to but less potent than CH 29-717, while 32-085, the l-methyl derivative, showed delayed dopaminomimetic effects.

3,4-Dihydroxyphenylacetic Acid↗

beta-Adrenergic receptor regulation by agonists and membrane depolarization in rat brain slices.

Rat cerebral cortex slices exposed to (-)-isoproterenol and then washed accumulated significantly less cyclic AMP when rechallenged with isoproterenol than did control slices. The isoproterenol-induced desensitization was associated with a concurrent reduction in [3H]dihydroalprenolol membrane binding but with no change in the affinity of [3H]dihydroalprenolol or isoproterenol for the binding sites. beta-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, batrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetrodotoxin or by removing Na+ from the buffer. These data demonstrate partial participation of the membrane receptor in beta-adrenergic desensitization of rat brain slices and suggest that brain beta-adrenergic receptors, like cholinergic receptors in skeletal muscle and alpha-adrenergic receptors in rat parotid, are regulated in part by membrane voltage.

Animals↗

Deep hypothermia in infant cardiac surgery.

The value of infant cardiac surgery using deep hypothermia remains a debate. A steady number of cardiac centers have consented to this approach in spite of some filibuster. Physiologists are frightened, anesthetists may find it cumbersome, but surgeons using it enjoy the ease of correction in a bloodless and relaxed heart. The cardiologists may document acceptable results, but we also need the alert feedback from the provider of long-term health care--the pediatrician--to document possible flaws of this pristine modality. This article is intended to familiarize the pediatrician with the method of deep hypothermia: its origin, application, and appeal for consumer protection.

Cardiac Surgical Procedures↗

Q-oTc interval and blood calcium levels in newborn infants.

The interval from the beginning of the Q wave to the origin of the T wave (Q-oTc interval) and total and ionized serum calcium levels were measured in 27 full-term and 77 premature infants. The correlation between Q-oTc and total and ionized calcium levels was significant in both full-term and normal premature infants. No correlation was found in a group of critically ill premature infants, most of whom had evidence of CNS involvement. Constant infusion of calcium gluconate in a number of infants belonging to the latter group produced a significant shortening of the Q-oTc interval. It is speculated that the lack of correlation of Q-oTc interval and total or ionized calcium levels in sick premature infants could be explained on the basis of a dysfunction in cardiac sympathetics or alternatively by marked variations in serum catecholamines.

Calcium↗