Ventricular late potentials and left ventricular function after early enalapril treatment in acute myocardial infarction.
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Aged↗
Biomedical subjects
M Møller
Publications and source records attributed to M Møller.
Electrophysiologic profile and efficacy of intravenous dofetilide (UK-68,798), a new class III antiarrhythmic drug, in patients with sustained monomorphic ventricular tachycardia. Dofetilide Arrhythmia Study Group.
There is increasing evidence that class III antiarrhythmic agents may be superior to class I agents for the long-term treatment of life-threatening ventricular tachyarrhythmias. This open study evaluated the acute electrophysiologic effects, antiarrhythmic efficacy, and safety of different doses of intravenous dofetilide, a new class III drug, in 50 patients with sustained monomorphic ventricular tachycardia inducible by programmed electrical stimulation who had previously been unsuccessfully treated with 0 to 7 (median 3) other drugs. Intravenous dofetilide was administered over 60 minutes at the following dose levels: 1.5, 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Significant class III activity was apparent at doses of 3.0 to 15.0 micrograms/kg, as evidenced by dose-related prolongation of the QTc interval by 13.4% to 14.2%, ventricular effective refractory period by 7.9% to 20.6%, and ventricular functional refractory period by 7.3% to 25.0%. The corresponding mean +/- SD plasma dofetilide concentrations ranged from 1.45 +/- 0.52 to 6.48 +/- 1.31 ng/ml. There was no evidence of reverse use-dependence. At these electrophysiologically active dose levels, intravenous dofetilide suppressed (complete response) or slowed (partial response) inducible ventricular tachycardia in 17 of 41 patients (41%) compared with 0 of 9 patients receiving only 1.5 micrograms/kg. The response rate was fairly uniform among the groups receiving 3.0, 6.0, 9.0, and 15.0 micrograms/kg. Intravenous dofetilide was hemodynamically well tolerated. Torsades de pointes (which was self-limiting) developed in only 1 patient, who was allocated to receive 15.0 micrograms/kg. There were no other proarrhythmic episodes or serious adverse effects. Further evaluation of the therapeutic potential of dofetilide in the management of life-threatening ventricular arrhythmias is justified.
Aged↗
Characteristics and prognostic importance of ST-segment elevation on Holter monitoring early after acute myocardial infarction.
The correlation between episodes of ST-segment elevation on Holter monitoring, clinical characteristics, left ventricular function, exercise testing, and long-term prognosis was determined in 123 consecutive patients 55 +/- 8 years old (mean +/- SD) with a first acute myocardial infarction (AMI). During 36 hours of Holter recording 11 +/- 5 days after AMI, 11 patients (9%) had 91 episodes of ST-segment elevation (group 1), whereas 112 patients had no such episodes (group 2). Most episodes of ST-segment elevation occurred in leads with pathologic Q waves or small, indistinct R waves. Large, anterior Q-wave AMIs were more prevalent in group 1 than in group 2, and in-hospital heart failure also occurred more frequently in group 1 patients (82% vs 23%; p < 0.0005). Regional and global left ventricular function was reduced in group 1 compared with group 2: ejection fraction 33 +/- 11% vs 50 +/- 11% (p = 0.0001). All episodes of ST-segment elevation were asymptomatic and did not correlate with different indicators of myocardial ischemia. Indeed, exercise-induced ST-segment depression was more prevalent in group 2 than in group 1: 57 vs 18% (p < 0.035). Over a mean of 5 years (range 4 to 6) of follow-up, an association between episodes of ST-segment elevation on Holter monitoring and (1) cardiac death (Kaplan-Meier analysis; p < 0.005), and (2) cardiac death and nonfatal reinfarction (Kaplan-Meier analysis; p < 0.025) was found.(ABSTRACT TRUNCATED AT 250 WORDS)
Echocardiography↗
Complex involvement of nitric oxide and cGMP at N-methyl-D-aspartic acid receptors regulating gamma-[3H]aminobutyric acid release from striatal slices.
Whilst the depolarization of postsynaptic N-methyl-D-aspartic acid (NMDA) receptors leads to an influx of Ca2+ and subsequent synthesis of nitric oxide (NO), we examined roles for NO at striatal NMDA receptors regulating transmitter release. In superfused rat striatal slices, NMDA-evoked release of gamma-[3H]aminobutyric acid ([3H]GABA) was investigated in the presence of nitrergic drugs. NMDA-induced release of [3H]GABA was attenuated by D-2-aminophosphonopentanoate, tetrodotoxin and omission of Ca2+. L-Arginine enhanced NMDA-evoked release of [3H]GABA, but exogenous NO donors were ineffective. Inhibitors of NO synthase (NG-nitro- and NG-amino-L-arginine) and guanylate cyclase (LY83583) elevated release. Since NMDA-evoked release of [3H]GABA was partially tetrodotoxin-sensitive, nitrergic-linked NMDA receptors regulating the release are both pre- and extrasynaptic. Thus not only does NO arise from multiple sites, and involve NMDA receptors with their redox site insensitive to exogenous NO donors, but the NMDA receptors are under the influence of nitrergic and cGMP-linked negative feedback mechanisms.
Aminobutyrates↗
Topographical organization of the rat suprachiasmatic-paraventricular projection.
The suprachiasmatic nucleus (SCN) is a dominant pacemaker involved in the generation of circadian rhythms in mammals. Surprisingly, the expression of the many rhythms appears to be mediated via a limited efferent projection system of the pacemaker, of which the largest pathway terminates in the subparaventricular area and in the paraventricular nucleus of the hypothalamus. In order to investigate a possible topographical organization of this major outflow pathway of the SCN, microiontophoretic injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) or the retrograde tracer cholera toxin subunit B (ChB) were centered in distinct subparts of the SCN (PHA-L) or in the subparaventricular area-paraventricular nucleus (ChB), respectively. PHA-L injections involving the entire SCN revealed not only a major projection to the subparaventricular area, but also one directed towards the medial and dorsal parvicellular subnuclei of the paraventricular nucleus. As opposed to injections involving the entire nucleus, injections of PHA-L centered in the dorsomedial subdivision of the SCN resulted in a relatively larger number of PHA-L-immunoreactive fibers in the parvicellular subdivisions of the PVN, whereas the terminal field in the subparaventricular area was less substantial. A topography of the SCN efferent output system was also revealed by the retrograde tracing with ChB. Injections of ChB in the dorsal part of the paraventricular hypothalamic nucleus, not involving the underlying subparaventricular area, gave rise to a population of retrogradely labeled cells in the dorsomedial part of the SCN. In contrast, ChB injections in the subparaventricular area resulted in labeling of neurons clustered in a more ventrolateral aspect of the SCN. The present data provide evidence for a topography in the major efferent projection system from the SCN, implying that different subparts of the rat SCN, presumably containing partly different potential neurotransmitter substances, may regulate different circadian rhythms.
Animals↗
Improved contrast in histochemical detection of cytochrome oxidase: metallic ions protocol.
The standard current technique for demonstration of cytochrome oxidase (CyOx) provides low-contrast diaminobenzidine (DAB) polymer. In order to enhance the contrast with divalent metalic ions, we have screened a number of buffers and found that Hepes, Mops and cacodylate neither precipitate these ions nor inactivate CyOx in a concentration of 0.1 M. Staining thus obtained shows a broad range of gradations between black and white. With fresh tissue the resulting image is superior to that obtained with the brown DAB product, even if a recommended blue filter or printing on very hard paper are used. The technique is as simple as the one which is currently standard. Fixed tissue, cut either in a cryostat or vibratome, can be stained well when floating but not when mounted on slides. The stained floating tissue can be used for electron microscopy, but has no advantage over the standard method.
Animals↗
Gating of retinal inputs through the suprachiasmatic nucleus: role of excitatory neurotransmission.
The mammalian circadian clock, located in the hypothalamic suprachiasmatic nucleus (SCN) is important in the regulation of many circadian rhythms, including regulation of pineal gland metabolism and melatonin secretion. Transsection of the optic nerves, disrupting the retinohypothalamic pathway, lesion of the SCN, or lesion of the hypothalamic paraventricular nucleus (PVN) abolish the regulation of pineal serotonin N-acetyltransferase activity by light. Therefore, the pathways linking the retina and the pineal gland must be channelled from the retina through the SCN and the PVN. Many lines of evidence indicate that the major neurotransmitter in the retinal afferents is glutamate. The first aim was therefore to study the retinal target neurons by localising glutamate receptors in the rodent SCN. Using in situ hybridisation, we detected NMDA-R1 and NMDA-R2C mRNA subunits in the SCN. Using immunocytochemistry, immunoreactivity for the AMPA type receptors GluR1, GluR2,3 and GluR4 was also detected in the SCN. Presentation of a short light pulse during the subjective night [i.e. circadian time (CT) 14 or 19], when light induced phase-shifting of activity-rest cycles can be accomplished, also induces expression of the immediate early-genes c-fos and junB in the rodent SCN. The second aim was to use this cellular correlate of behavioural function to determine the location of potential retinal target neurons in the SCN, and to investigate the hypothesis that glutamatergic neurotransmission mediates the effects of light on the circadian system. Thus, the ability of the NMDA receptor antagonist MK-801 to block light-induced c-fos expression in the SCN was studied. In the rat, this antagonist blocked c-fos mRNA expression in a subpopulation of cells in the ventral SCN at doses of 6, but not 2 mg/kg. In contrast, in the hamster both doses blocked light-induced c-fos expression in the ventral SCN. These data provide support for the hypothesis that glutamate mediates effects of light in the SCN, although it appers that the complexes of NMDA receptor subunits, which are involved in light-induced expression of c-fos after light, are relatively insensitive to MK-801. The diversity, heterogeneous distribution, and complexity of glutamate receptor subunits in the SCN suggest that processing of light pulses in the SCN is mediated by several cell types in the SCN. Via an integration process in the clock, the transmission of photic information takes place to other brain structures.
Animals↗
Distribution and characterization of the melatonin receptors in the hypothalamus and pituitary gland of three domestic ungulates.
With some exceptions, in most of the mammals the pituitary pars tuberalis and the hypothalamic suprachiasmatic nuclei are reportedly the main targets for the pineal hormone melatonin. However, it is not known if the conspicuous diversity in the distribution pattern of melatonin binding sites in these areas depicts differences in reproductive behavior observed in the seasonally breeding species in the temperate zones. We explored the distribution and the characteristics of melatonin binding sites in the hypothalamus and pituitary of three species (bovine, horse, and donkey) different in terms of seasonal reproductive competence. The topographical localization, investigated by in vitro autoradiography, revealed 2-[125I]iodomelatonin binding sites only in the pituitary gland in all three species, primarily in the pars tuberalis (PT), but also in the pars distalis (PD) and pars intermedia (PI). Kinetic, inhibition, and saturation studies, performed by means of in vitro binding, revealed presence of a single class high affinity binding sites. The Kd values, melatonin, and 2-iodomelatonin Ki values were in the low picomolar range. Coincubation with GTP gamma S inhibited 2-[125I]iodomelatonin binding, demonstrating that these putative receptors are linked to a G protein in their signal-transduction pathway. The hypothalamus was devoid of specific binding. In conclusion, the results suggest that in these species, the hypophysis may be a principal target for the melatonin action on the reproductive system.
Animals↗
Prognostic significance of transient myocardial ischaemia after first acute myocardial infarction: five year follow up study.
OBJECTIVE: To assess the five year prognostic significance of transient myocardial ischaemia on ambulatory monitoring after a first acute myocardial infarction, and to compare the diagnostic and long term prognostic value of ambulatory ST segment monitoring, maximal exercise testing, and echocardiography in patients with documented ischaemic heart disease. DESIGN: Prospective study. SETTING: Cardiology department of a teaching hospital. PATIENTS: 123 consecutive men aged under 70 who were able to perform predischarge maximal exercise testing. INTERVENTIONS: Echocardiography two days before discharge (left ventricular ejection fraction), maximal bicycle ergometric testing one day before discharge (ST segment depression, angina, blood pressure, heart rate), and ambulatory ST segment monitoring (transient myocardial ischaemia) started at hospital discharge a mean of 11 (SD 5) days after infarction. MAIN OUTCOME MEASURES: Relation of ambulatory ST segment depression, exercise test variables, and left ventricular ejection fraction to subsequent objective (cardiac death or myocardial infarction) or subjective (need for coronary revascularisation) events. RESULTS: 23 of the 123 patients had episodes of transient ST segment depression, of which 98% were silent. Over a mean of 5 (range 4 to 6) years of follow up, patients with ambulatory ischaemia were no more likely to have objective end points than patients without ischaemic episodes. If, however, subjective events were included an association between transient ST segment depression and an adverse long term outcome was found (Kaplan-Meier analysis; P = 0.004). The presence of exercise induced angina identified a similar proportion of patients with a poor prognosis (Kaplan-Meier analysis; P < 0.004). Both exertional angina and ambulatory ST segment depression had high specificity but poor sensitivity. The presence of exercise induced ST segment depression was of no value in predicting combined cardiac events. Indeed, patients without exertional ST segment depression were at increased risk of future objective end points (Kaplan-Meier analysis; P < 0.0045). These findings may be explained in part by a higher prevalence of left ventricular dysfunction in patients without ischaemic changes in the exercise electrocardiogram (P < 0.05). CONCLUSION: There seem to be limited reasons to perform ambulatory ST segment monitoring in survivors of a first myocardial infarction who can perform exercise tests before discharge. Patients at high risk of future myocardial infarction or death from cardiac causes are not identified. Ambulatory monitoring and exertional angina distinguish a small subset of patients who will develop severe angina pectoris demanding coronary revascularisation during follow up. Patients without exercise induced ST segment depression comprise a high risk subgroup in terms of subsequent objective end points. The role of ambulatory ST segment monitoring performed in unselected patients immediately after infarction when risk is maximal remains to be clarified.
Echocardiography↗
Effect of histamine on gene expression and release of proopiomelanocortin-derived peptides from the anterior and intermediate pituitary lobes in conscious male rats.
Via activation of H1 or H2 receptors histamine (HA) stimulates the secretion of proopiomelanocortin (POMC)-derived peptides from the anterior (AL) and intermediate (IL) pituitary lobes of male rats. During selective inhibition of the AL or IL by pretreatment with dexamethasone (Dx) or bromocriptine (Br), respectively, we studied the effect of equipotent doses of intracerebroventricularly infused HA, the H1-receptor agonist 2-thiazolylethylamine (2TEA) or the H2-receptor agonist 4-methy1HA (4MeHA) on the release of ACTH, beta-endorphin (beta-END) immunoreactivity (ir) and alpha-melanocyte-stimulating hormone (alpha-MSH) in conscious male rats. Dx blocked the ACTH responses whereas Br prevented the alpha-MSH responses. Dx and Br equally inhibited the response of beta-ENDir to HA and 4MeHA (80 and 70%, respectively). In contrast, the beta-ENDir response to 2TEA was totally blocked by Dx but only inhibited 50% by Br. The inhibitory effect of Dx on the beta-ENDir response to 2TEA was significantly stronger than the effect on the responses to HA and 4MeHA. POMC mRNA in the AL but not in the IL was increased almost 45% by HA and 2TEA and 20% by 4MeHA. Since all three histaminergic compounds in the doses used stimulated the release of beta-ENDir equipotently, the results indicate that H1-receptor activation predominantly affects the release and synthesis of beta-ENDir from the AL while H2-receptor activation affects the release of beta-ENDir equally from the two lobes and only to some extent increases the synthesis in the AL.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
[Ambulatory ST-segment monitoring after acute myocardial infarction].
Over the last decade the concept of silent myocardial ischaemia has received considerable attention. Without doubt, the increased use of ambulatory ST-segment monitoring is the most important reason for the growing interest in this field. The prevalence of ambulatory ischaemia after myocardial infarction seems to be lower than in other subgroups with coronary artery disease. In postinfarction patients, however, a greater proportion of ischaemic episodes are silent. At present there is substantial evidence that ambulatory ischaemia provides prognostic information in different subsets of patients with previous myocardial infarction, but there is considerable disagreement about how this is expressed in terms of cardiac events. Patient selection, small patient numbers, and different timing of ambulatory monitoring are proposed as important reasons for the inconsistent findings. The precise role of postinfarction ambulatory ST-segment monitoring in clinical practice has yet to be established.
Electrocardiography, Ambulatory↗
[Late potentials after acute myocardial infarction].
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Heart Conduction System↗
The adult human cerebellum is a target of the neuroendocrine system involved in the circadian timing.
In an investigation aimed at comprehensive mapping of the adult human brain with respect to receptor sites for the pineal hormone melatonin, we consistently observed specific binding in the cerebellum. Autoradiography and in vitro binding analysis with 125I-labeled melatonin were used to examine the location and the properties of these binding sites. In all cerebellar lobes, highest-density specific binding was localized to the external zone of the molecular layer. The binding was rapid, saturable, displaceable, specific and of high affinity. Physiological concentrations of NaCl decreased the affinity, while presence of calcium ions promoted it. The non-hydrolyzable GTP analog, GTP gamma S, inhibited binding in a dose-dependent manner and provoked a shift towards low affinity. The results strongly suggest that these binding sites may be functional melatonin receptors, and indicate that the adult human cerebellum is a target of melatonin, the pineal hormone involved in the control of the circadian timing.
Adult↗
[Theme: circumcision. Confusion about suturing together. Interview by Grethe Kjaergaard].
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Adolescent↗
Density of peptide histidine-isoleucine- and vasoactive intestinal peptide-immunoreactive nerve fibers in the sheep pineal gland is not affected by superior cervical ganglionectomy.
Peptide histidine-isoleucine (PHI) is a regulatory peptide, synthesized as part of the same propeptide that includes also vasoactive intestinal peptide (VIP). The present study describes the distribution of PHI-immunoreactive nerve fibers in the sheep pineal organ and compares their location with the distribution of VIP-immunoreactive fibers in both normal and superior cervical ganglionectomized sheep in order to elucidate the origin of the PHI/VIP immunoreactive nerve fibers. Several PHI-immunoreactive nerve fibers were present in the meninges and in the pineal capsule. Numerous positive nerve fibers entered the pineal gland and travelled within connective tissue spaces. Individual PHI-positive nerve fibers were either smooth, without specialization, or varicose. Generally VIP- and PHI-immunoreactive fibers were located close to connective septa and blood vessels. However, many PHIergic and VIPergic fibers possessing varicosities of variable sizes were also dispersed between pinealocytes. The distribution, density, and morphology of PHI- and VIP-immunoreactive fibers in the sheep pineal gland were similar. In superior cervical ganglionectomized animals, intrapineal VIP- and PHI-immunoreactive nerve fibers were present with the same density as in control animals. In agreement, the concentration of immunoreactive VIP and PHI did not change after ganglionectomy. No VIP- and PHI-immunoreactive cell bodies were observed in the superior cervical ganglia. Thus this study shows that the intrapineal VIP- and PHI-immunoreactive nerve fibers do not originate from the sympathetic superior cervical ganglion.
Animals↗
[Thrombolysis and acute myocardial infarction. Reduced residual ischemia in first acute myocardial infarction].
In order to assess the effect of thrombolysis on residual myocardial ischaemia, we prospectively performed maximal exercise testing and ambulatory ST-segment monitoring in a consecutive series of 123 men recovering from a first acute myocardial infarction (AMI). Seventy-four patients fulfilled our criteria for thrombolysis, but only 35 patients received thrombolytic agents, whereas 39 were conservatively treated (controls). In 49 patients thrombolytic therapy was not indicated. Thrombolysis resulted in a non-significant reduction in the prevalence of exercise-induced ST-segment depression: 43% in reperfused patients versus 62% in controls. During 36-hour ambulatory ST-segment monitoring, however, the duration of myocardial ischaemia was significantly reduced in thrombolyzed patients: 322 minutes versus 1144 minutes in controls (p < 0.05). Exercise testing revealed a higher maximal work capacity in thrombolyzed patients compared with controls: 160 +/- 41 versus 139 +/- 34 W (p < 0.02). No difference was found in left ventricular ejection fraction between the two subgroups. We conclude, that thrombolysis given for a first AMI reduces residual myocardial ischaemia. The reduced ischaemic burden is assumed to be the pathophysiologic mechanism underlying the also observed improvement in exercise tolerance.
Aged↗
The presence of opioidergic pinealocytes in the pineal gland of the European hamster (Cricetus cricetus): an immunocytochemical study.
By use of antibodies raised against leu-enkephalin and met-enkephalin immunoreactive, opioidergic bi- and multipolar cells were demonstrated in the pineal gland of the European hamster. Ultrastructural analysis of these opioidergic cells revealed them to be pinealocytes. Processes emerged from the cell bodies and terminated in club-shaped swellings containing many small clear and some larger granular vesicles. Some of the terminals made synapse-like contacts with non-immunoreactive pinealocytes. The presence of the opioidergic pinealocytes strongly indicates that the pineal gland of the European hamster, in addition to its pinealopetal nervous regulation, is regulated by intrapineal peptidergic pinealocytes via a synaptic mechanism. A possible paracrine role of the opioidergic cells must also be considered.
Animals↗
Innervation of the cat pineal gland by neuropeptide Y-immunoreactive nerve fibers: an experimental immunohistochemical study.
An immunohistochemical study of the cat pineal gland was performed using a rabbit polyclonal antibody directed against neuropeptide Y (NPY) and an antibody directed against the C-terminal flanking peptide of neuropeptide Y (CPON). Numerous NPY- and CPON-immunoreactive (IR) nerve fibers were demonstrated throughout the gland and in the pineal capsule. The number of IR nerve fibers in the capsule was high and from this location fibers were observed to penetrate into the gland proper via the pineal connective tissue septa, often following the blood vessels. From the connective tissue septa IR fibers intruded into the parenchyma between the pinealocytes. Many IR nerve fibers were observed in the pineal stalk and in the habenular as well as the posterior commissural areas. The number of NPY/CPON-IR nerve fibers in pineal glands from animals bilaterally ganglionectomized two weeks before sacrifice was low. The source of most of the extrasympathetic NPY/CPONergic nerve fibers is probably the brain from where they enter the pineal via the pineal stalk. However, an origin of some of the fibers from parasympathetic ganglia cannot be excluded due to the presence of a few IR fibers in the pineal capsule of ganglionectomized animals. It is concluded that the cat pineal is richly innervated with NPYergic nerve fibers mostly of sympathetic origin. The posttranslational processing of the NPY promolecule results in the presence of both NPY and CPON in intrapineal nerve fibers.
Animals↗