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Biomedical subjects

T Peters

Publications and source records attributed to T Peters.

At least 181 records · Page 10Linked to original sources
PubMed1991

Restenosis 1 to 24 months after clinically successful coronary balloon angioplasty: a necropsy study of 20 patients.

This report describes clinical, morphologic and histologic findings at necropsy late (range 1.6 to 24.1 months [average 8.2 months]) after clinically successful coronary balloon angioplasty in 20 patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 patients (70%), including 6 patients with sudden coronary death. Of the 20 patients, 14 (70%) had a cardiac cause of death and 6 (30%) had a noncardiac cause of death. Two major subgroups of histologic findings were observed: 1) intimal proliferation (60%), and 2) atherosclerotic plaque only (40%). Of the eight sites with atherosclerotic plaque only, six were eccentric lesions and two were concentric lesions. No morphologic evidence of previous angioplasty injury (cracks, breaks, tears) was observed in the eight patients with atherosclerotic plaque only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphologic findings at angioplasty restenosis sites, specific treatment strategies for restenosis after coronary artery balloon angioplasty are proposed.

Angioplasty, Balloon, Coronary↗
PubMed1991

Baroreflex and atrial natriuretic factor concentration correlate with myocardial infarct size and predict early death in rabbits: implications for drug studies.

The severity of myocardial infarction (MI) and its functional consequences are difficult to assess in small animals. We searched for criteria to achieve such an assessment in rabbits 1 week after MI. Thirteen large mongrel rabbits (3-4 kg) were anesthetized with pentobarbitone for ligating a branch of the circumflex coronary artery and 7 rabbits were subject to a sham operation without ligation. All sham-operated rabbits and 12 MI animals survived for 1 week, when blood was obtained for biochemical analyses and the baroreflex was tested. Six animals survived to the third week (survivors) and six died earlier (nonsurvivors). The MI size, measured immediately after death, was 42 +/- 3% of the left ventricular mass in nonsurvivors and 20 +/- 7% in survivors. The plasma atrial natriuretic factor (ANF) concentration was correlated linearly with MI size (r = 0.77) over the whole range of infarct sizes and, like the MI size itself, was associated with the risk of early death (critical limit: 80 pM). Plasma renin activity and catecholamines yielded less prognostic information. The baroreflex control of the heart rate (tested using phenylephrine and nitroprusside) of nonsurvivors was severely impaired and the slopes correlated with MI size (r = 0.90 for phenylephrine and r = 0.67 for nitroprusside). The plasma ANF concentration and the baroreflex both accurately reflected MI size and also correctly classified 11/12 rabbits into survivors and nonsurvivors. An ANF- and baroreflex-based stratification of animals for future studies on therapeutic interventions after MI will reduce the number of animals required by at least 65%, making such studies far more feasible than in the past.

Animals↗
PubMed1991

Differential effect of R 56865 on ouabain binding to isolated sarcolemma and intact atrial tissue of guinea-pig.

1. R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl- 2-benzothiazolamine) is a compound known to antagonize cardiac glycoside intoxication. Therefore, the effect of the compound on ouabain binding to intact cardiac tissue as well as cardiac membrane preparations was investigated. 2. The binding of ouabain to highly purified sarcolemmal membranes was not influenced by R 56865 1 x 10(-6) mol l-1 (ouabain: KD = 1.3 x 10(-7) mol l-1, Bmax = 160 pmol mg-1; ouabain + R 56865: KD = 1.4 x 10(-7) mol l-1, Bmax = 168 pmol mg-1). 3. In contrast to the results in purified membranes, the binding of ouabain (10(-8) mol l-1 to 5 x 10(-7) mol l-1) to intact atria was significantly reduced. 4. Ouabain, 5 x 10(-7) mol l-1, led to a transient positive inotropic effect of about 220% followed by a developing negative inotropic effect after 3 h. R 56865, 10(-7) mol l-1, led to a maximal positive inotropic effect of about 290% also followed by a delayed decline of contractile force. A tenfold higher concentration of R 56865 led to sustained positive inotropic effect of about 250% in the same time interval. 5. The different effects of R 56865 on ouabain binding in subcellular preparations and intact tissue do not support the view that R 56865 interferes directly with the action of ouabain on Na/K-ATPase. An indirect effect, which may be mediated by a lowered intracellular sodium load is discussed.

Animals↗
PubMed1991

Characterization of the interaction of R 56865 with cardiac Na- and L-type Ca channels.

1. In isolated cardiac muscle, submicromolar concentrations of R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl]-N-methyl-2- benzothiazolamine) have been shown to attenuate the toxicity of cardiac glycosides. 2. We studied the influence of R 56865 on calcium and sodium currents in single isolated ventricular cardiomyocytes. The effect of R 56865 on action potential and contractile force in the presence of increased sodium load was also tested by exposing papillary muscles to veratridine or Anemonia sulcata toxin ATX II. 3. The calcium current was not affected by R 56865 as assessed in slow action potentials of papillary muscles and current measurements in ventricular cardiomyocytes. 4. In papillary muscles, R 56865 (1 mumol l-1) abolished veratridine-induced aftercontractions and afterdepolarizations without affecting the profound prolongation of the action potential. When pretreated with R 56865, the occurrence of afterdepolarizations was prevented and the decline of the resting membrane potential was attenuated. 5. Pretreatment with R 56865 (1 mumol l-1) did not counteract the ATX II-induced prolongation of the action potential. 6. The sodium current (Nao 30 mmol l-1) was concentration-dependently decreased by R 56865 (0.1-10 mumol l-1). The blocking effect was more pronounced at less negative holding potentials. 7. Our results demonstrate that the protective effect of R 56865 against veratridine-induced electrical and mechanical oscillations is not due to a direct effect on the calcium current. A potential-dependent inhibition of the sodium current may contribute. Additional sites of action, like interference with intracellular calcium release and inhibition of potassium currents, remain to be investigated.

Action Potentials↗
PubMed1991

Synaptosomal respiration: a potent indicator of veratridine-induced Na influx.

Inhibition of the voltage-dependent Na channel by tetrodotoxin (5 mumol/l) decreased by about 86% the stimulation of the respiration of rat brain synaptosomes induced by veratridine (10 mumol/l). A similar effect was achieved by blocking Na(+)-K(+)-ATPase with ouabain (1 mmol/l). Pharmacological manipulations of Ca homeostasis suggested that the veratridine-induced stimulation of respiration did not depend upon Ca entry. These data suggest that the veratridine-induced stimulation of synaptosomal respiration may result primarily from an increase in intracellular Na+. They provide the basis for an indirect method, which only requires recording of synaptosomal respiration, to test drugs for their possible interaction with excessive Na influxes.

Amiloride↗
PubMed1991

Increased iron absorption in uroporphyrin-treated rats.

Rats were given 59Fe (28 micrograms) together with doses of 0, 2 and 200 micrograms of uroporphyrin III in paired observations. Absorption of 59Fe was determined by comparing whole body counts of the rats 30 min and 7 days after dosing. Prior treatment with 200 micrograms of uroporphyrin twice daily for 3 days was associated with significantly increased 59Fe absorption of 6.2% compared to the absorption of 4.6% without uroporphyrin (control) and 4.6% with a 2-micrograms dose (p less than 0.05).

Animals↗
PubMed1991

Calcium channels in the brain as targets for the calcium-channel modulators used in the treatment of neurological disorders.

Recent investigations of calcium channels in brain cells by voltage-clamp techniques have revealed that, in spite of electrophysiological similarities, the pharmacological properties of these channels differ considerably from channels in peripheral tissues, e.g., heart and smooth muscle. Therefore, instead of extrapolation from results obtained on cardiac or smooth muscle cells, a reclassification of calcium-channel modulators applied in disorders of the brain appears necessary. The present article reviews some pertinent observations from groups involved in neuronal calcium-channel characterization and draws the attention to major pharmacological differences on neurons in comparison to those in the heart and in smooth muscle. For certain therapeutic applications in neurology particularly, the low-voltage activated types of calcium channels deserve considerable attention.

Animals↗
PubMed1991

[The role of pancreatic polypeptide in the pathogenesis of malabsorption in ulcerative colitis].

Pancreatic function was evaluated in 16 22-56-year-olds with ulcerative colitis. The diagnosis was verified by coprogram, glycemic curves, blood and urine amylase, ultrasound and endoscopic findings. A basal level of pancreatic polypeptide (PP) was measured in blood serum under glucose tolerance test (50 g) using radioimmunoassay. Intracavitary pH-metry provided data on pH in the upper gastrointestinal tract. The results were processed according to Student's t-criterion. The evidence demonstrated pancreatic involvement with secretory and endocrine insufficiency leading to homeostatic derangement of enteral medium and malabsorption in ulcerative colitis. The addition of pancreatic enzymes and antacids is advisable as pathogenetically valid.

Adult↗
PubMed1991

Low dose methotrexate therapy for rheumatoid arthritis complicated by pancytopenia and Pneumocystis carinii pneumonia.

In a patient with rheumatoid arthritis pancytopenia and Pneumocystis carinii pneumonia occurred during low dose methotrexate therapy. This case emphasizes the potential development of opportunistic infections even with low dose methotrexate. Pneumocystis carinii pneumonia resembles methotrexate induced pneumonitis. Therefore opportunistic infections should be considered before a definite diagnosis of methotrexate induced pneumonitis is made.

Adolescent↗
PubMed1991

Morphological observations late (greater than 30 days) after clinically successful coronary balloon angioplasty.

This report describes clinical, morphological, and histological findings late (1.6-24.1 months [average, 8.2 months]) after clinically successful coronary balloon angioplasty in 20 necropsied patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 (70%) of patients, including six patients with sudden coronary death. Of the 20 patients, 14 (70%) had cardiac causes of death and six (30%) had noncardiac causes of death. Two major subgroups of histological findings were observed: 1) intimal proliferation (60%) and 2) atherosclerotic plaques only. Of the eight sites with atherosclerotic plaques only, six were eccentric lesions and two were concentric lesions. No morphological evidence of previous angioplasty injury (cracks, breaks, or tears) was observed in the eight patients with atherosclerotic plaques only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphological findings at angioplasty restenosis sites, specific treatment strategies for coronary artery balloon angioplasty restenosis are proposed.

Angioplasty, Balloon, Coronary↗
PubMed1991

[Pharmacokinetics and pharmacodynamics of flunarizine in multimorbid, geriatric patients with vertigo].

Ten multimorbid, geriatric, hospitalised patients, mean age 76 years, were treated for vertigo and received 10 mg flunarizine (CAS 52468-60-7; Sibelium) daily for 3 weeks. The study of the pharmacokinetics and pharmacodynamics of this dosage scheme revealed that the kinetics did not change during the three weeks of therapy. The terminal half-life is 7.3 +/- 3.3 days. Since a steady state concentration is only to be expected after about 5 half-lives, this condition was not fully met yet in most patients after three weeks. The data obtained from the patients examined are essentially identical with those in young and old healthy subjects. The unchanged kinetics during long-term treatment prevent side-effects due to cumulation on the one hand or the decrease of plasma levels to inactive concentrations resulting from enzyme induction. There was not measurable anti-aggregator effect on thrombocytes or erythrocytes. The effectiveness in connection with vertigo seems to be due to a direct labyrinth depressor activity and/or to a selective vasospecific action. No side-effects were observed during the three weeks of therapy.

Aged↗
PubMed1990

Interdependence of tumor necrosis factor, prostaglandin E2, and protein synthesis in lipopolysaccharide-exposed rat Kupffer cells.

Kupffer cells are the main producers of tumor necrosis factor-alpha (TNF; cachectin) and eicosanoids in the liver exposed to lipopolysaccharide (endotoxin; LPS). A very rapid but transient release of TNF is followed by a slow, steady synthesis of prostaglandin E2 (PGE2). TNF itself is able to provoke eicosanoid synthesis in Kupffer cells; the rate and pattern of prostaglandin production are similar to those observed after treatment with LPS. Anti-TNF antibodies completely neutralize TNF action on Kupffer cells, thus ruling out any participation of contaminating LPS. LPS stimulation of PGE2 production in Kupffer cells is reduced by the antiserum to 50%, indicating an involvement of TNF in the stimulatory action of LPS. On the other hand, PGE2, a potent inhibitor of LPS-elicited TNF release, is able to suppress LPS- but not TNF-stimulated eicosanoid synthesis in rat Kupffer cells. In addition to this autocrine circuit, extrahepatic factors participate in the regulation of Kupffer cell activation: glucocorticoids not only inhibit TNF or prostaglandin production, they also reverse the LPS-specific changes in the prostaglandin pattern of Kupffer cells. LPS, TNF or cycloheximide when given alone in the concentration range applied in this study do not affect the viability of rat Kupffer cells. However, the combinations of cycloheximide and either LPS or TNF cause rapid death of the cultured cells. The cytolytic potential of either combination cannot be alleviated by treatment with glucocorticoids.

Animals↗
PubMed1990

An approach to differentiate between noradrenaline-elicited contractile processes in the rat isolated aorta.

The aim of the present study was to assess the different processes contributing to the contraction induced by noradrenaline (NA, 1 mumol/l) in the rat isolated aorta. Pretreatment with maximally effective concentrations of nifedipine or cromakalim reduced the NA-induced contraction to 80 +/- 3.5% or 63 +/- 2.0%, respectively, without alteration of the shape of the response. After pretreatment with Mn2+, NA caused a transient phasic contraction followed by a sustained tonic component, comparable to the response obtained in "Ca2(+)-free" medium. Ryanodine--in the presence of extracellular Ca2(+)-caused a slight increase in resting tension, but did not modify the NA-induced contraction. In "Ca2(+)-free" medium the contraction elicited by NA consisted of a transient phasic and a sustained tonic component. The amplitude of the phasic contraction decreased exponentially with the time of exposure to "Ca2(+)-free" medium. The phasic component was identified as elicited by Ca2+ released from the sarcoplasmic reticulum (SR) by means of ryanodine. If Ca2+ depleted tissues (80 min in "Ca2(+)-free" solution) were exposed to Ca2+ in the presence of Mn2+ or cromakalim, the NA-induced phasic response was inhibited, suggesting that Mn2+ and cromakalim blocked the refilling of the store. It can be concluded that activation of alpha 1-adrenoceptors in the rat aorta by NA elicits Ca2(+)-entry processes which have a different sensitivity to nifedipine, cromakalim and Mn2+. The Ca2+ released from SR contributes about 20% to the overall contractile response. Our data suggest that the depleted SR can be refilled from the extracellular space via a direct cromakalim- and Mn2(+)-sensitive pathway.

Animals↗
PubMed1990

Effects of the selective beta 1-adrenoceptor antagonist, nebivolol, on cardiovascular parameters in the pithed normotensive rat.

In the pithed rat we investigated the cardiovascular properties of d,l-nebivolol and its enantiomers. We used the increase in heart rate elicited by (-)-adrenaline and (-)-noradrenaline as a model for studying beta 1-adrenoceptors. A leftward shift of the logarithmic dose-pressor response curve of (-)-adrenaline reflects beta 2-adrenoceptor-blocking properties. The blood pressure responses of methoxamine, B-HT 920 and serotonin (5-HT) were studied in order to test whether d,l-nebivolol has alpha 1-, alpha 2- and 5-HT2-receptor-blocking properties. Furthermore, the interaction of d,l-nebivolol with the peripheral sympathetic neurotransmission was investigated in pithed rats by electrical stimulation of the spinal cord. d,l-Nebivolol and d-nebivolol (threshold concentration 10(-8) mol/kg) were demonstrated to be selective beta 1-adrenoceptor antagonists. l-Nebivolol was a factor of 1,000 less potent as beta 1-adrenoceptor blocker. Up to a dose of 10(-5) mol/kg, d,l-nebivolol appeared to have neither alpha 1-, alpha 2-, beta 2-, 5-HT2-, angiotensin II-receptor antagonistic, calcium entry blocking, converting enzyme inhibiting nor direct vasodilating properties and did not interact with the sympathetic neurotransmission in the vascular wall. An explanation for an antihypertensive effect independent of beta-adrenoceptor blockade as found in spontaneously hypertensive rats and man could not be found in this model, therefore we suggest that this blood-pressure-lowering effect does not originate from conventional peripheral mechanisms.

Adrenergic alpha-Agonists↗
PubMed1990

Differential influence of various calcium-modulating compounds on ouabain intoxication in isolated rat left atria.

Various calcium-modulating compounds were tested with respect to their protective action against cardiac glycoside toxicity. At the concentrations applied, control force of contraction was reduced by nifedipine and verapamil and slightly attenuated by flunarizine, R 56865, and cimetidine, while it was strongly enhanced by Bay K 8644. The positive inotropic response to ouabain (stimulation rate: 1 Hz) was impaired by nifedipine and verapamil. The increment in contractile force induced by Bay K 8644 was not enhanced by ouabain. The increase in diastolic tension during toxic conditions of ouabain (stimulation rate: 3 Hz) was attenuated by nifedipine, verapamil, bepridil, flunarizine, cimetidine, phenytoin, and R 56865 but not by diltiazem, amiodarone, and amiloride. K loss was prevented by nifedipine, verapamil, diltiazem, bepridil, flunarizine, cimetidine, phenytoin, and R 56865. The increase in cellular Na content was inhibited by R 56865 only. Ca gain was prevented by verapamil, bepridil, flunarizine, R 56865, and cimetidine but not by nifedipine, diltiazem, phenytoin, amiodarone, and amiloride. Ionic deterioration was enhanced by Bay K 8644. These results suggest that pretreatment with various calcium-modulating compounds protects against mechanical and ionic changes during ouabain intoxication induced by Na-Ca overload through different mechanisms.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗