Biomedical subjects
Publications and source records attributed to A Riedel.
Cloprostenol, a synthetic derivative of prostaglandin F2 alpha, exhibits antiarrhythmic properties against reperfusion induced fibrillation in guinea-pig hearts in vitro. It decreases the incidence of fibrillation from 75.0% to 0%. This antifibrillatory effect of cloprostenol could be confirmed also by in vivo experiments.
Platelet-activating factor (PAF) induced arrhythmogenic effects in ouabain-induced arrhythmias and in untreated guinea pigs. The ischemic induced arrhythmias are aggravated by PAF in open-chest dogs. TX receptor antagonizing substances such as BM 13177 and specific PAF antagonists for example BN 52021 and WEB 2086, completely inhibited the PAF induced cardiac arrhythmias. An inhibitor of lipoxygenase such as esculetin inhibited the PAF effect to a small extent, too. Non-specific PAF antagonists such as diltiazem, diazepam, buphenin and trapidil have no or only a slight influence on PAF induced arrhythmias, although the antiarrhythmic effect of diltiazem and trapidil was shown on ouabain induced arrhythmias without PAF. The present study supports the hypothesis that PAF aggravates cardiac arrhythmias under pathophysiological conditions in which PAF is involved. Specific PAF antagonists and TX receptor antagonists induce antiarrhythmic effects under these conditions.
Platelet-activating factor (PAF) in a concentration of 10(-11) mole per animal decreased the threshold doses for onsets of arrhythmia, ventricular flutters and fibrillation in ouabain induced arrhythmia in guinea-pigs in a statistically significant manner. The specific PAF antagonist BN 52021 (20 mg/kg, orally) completely inhibited the PAF effect for all types of arrhythmia, while the Ca2+ antagonistic drug diltiazem (0.1 mg/kg, i.v.) failed to counteract the PAF action. BN 52021 (20 mg/kg, per os) alone did not exert any effect on ouabain induced arrhythmia, but as expected, diltiazem (0.1 mg/kg, i.v.) showed antiarrhythmic effects. These results confirm the specific PAF antagonistic activity of BN 52021, its usefulness for PAF related cardiac rhythm disturbances and indicate that the method used could be a further useful tool to screen PAF antagonistic substances.
Platelet-activating factor (PAF), 10(-11) mol decreased the threshold of ouabain induced arrhythmia in guinea-pigs. The thresholds inducing premature ventricular beats and ventricular flutter were statistically significantly decreased by 27.4% and 15.6%, respectively. BM 13.177 (30 mg/kg), a thromboxane receptor antagonizing substance, and esculetin (1.2 mg/kg), a lipoxygenase inhibitor, abolished this arrhythmogenic effect of PAF. Acetylsalicylic acid (10 mg/kg) showed only a tendency to inhibit the PAF effect. These results suggest that PAF could play a role in cardiac arrhythmias under special conditions and it supports the hypothesis that PAF action is mediated by the release of leukotrienes and thromboxane.
The present study suggests that a diminished level of HDL is connected with an enhanced susceptibility to arrhythmogenic stimuli only in rats pretreated with a diet deficient in polyunsaturated fatty acids (PUFA), but not after a PUFA-rich or pellet diet. The endogenous level of total cholesterol did not influence the thresholds for ventricular flutter or ventricular fibrillation in aconitine-induced arrhythmia in rats or in ouabain-induced arrhythmia in guinea pigs.
Plasma levels of ANF were determined and chromatographically analysed in normotensive controls, cirrhotic patients with and without ascites, hypertensive patients, patients with congestive heart failure and heart transplant recipients. A comparison of baseline plasma levels allowed for the conclusion that cirrhotic patients do not differ in this regard from control subjects (9.0 +/- 1.3, n = 41 vs. 9.6 +/- 1,0 fmol/ml, n = 51). Cirrhotic patients with ascites do not have lower plasma levels than cirrhotic patients without ascites (8.8 +/- 1.4, n = 8 vs 8.6 +/- 1.5 fmol/ml, n = 10). Stimulation of the ANF-system by head-out water immersion, however, revealed an impaired increase in ANF release in cirrhotic patients with ascites (146 +/- 18% vs 204 +/- 16%). Patients with cardiovascular disease display tonically-elevated ANF plasma levels. Heart failure patients displayed the highest plasma concentration (81.5 +/- 32.7 fmol/ml, n = 17), whereas plasma levels in hypertensive patients ranged from normal to greatly elevated (61.7 +/- 13.2 fmol/ml, n = 36). Heart transplant recipients also had significantly elevated plasma levels as compared to control subjects (31.2 +/- 7.9 fmol/ml, n = 14) but levels were lower than in hypertensive patients in spite of a comparable arterial pressure. Short term ventricular pacing (f = 150/min for 5 min) revealed an impaired phasic activity of the ANF system in heart failure patients and heart transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of a single dose (50 mg) of thymopentin, administered subcutaneously, on antigen-induced proliferation of peripheral blood mononuclear cells (PBMCs) was investigated in 25 volunteers (all over 50 years of age) and in nine patients undergoing major surgery. Blood samples from another nine patients having the same type of surgery were used as control in the second trial. A statistically significant increase in the proliferative response was observed in the group of volunteers two hours after thymopentin administration. This increment was not demonstrable as significant 24 h later. In contrast to this observation, the surgical procedure-induced significant decrement in the proliferation of PBMCs observed on the first and third postoperative days did not occur in the thymopentin-treated patients on the first postoperative day. This preventive effect of the single dose of thymopentin administered two hours before surgery was no longer demonstrable on the third postoperative day. Further studies are ongoing in order to establish a treatment regimen with thymopentin for the therapy of trauma-induced immune deficiencies.
The balance between the eicosanoids seems to be involved in the biochemical regulation of cardiac rhythm. Under several pathophysiological conditions thromboxane (TX) could be an important factor for the genesis of cardiac arrhythmias. Shifting the balance between the arrhythmogenic TX and the antiarrhythmic prostacyclin (PGI2) in favour of PGI2 by substances influencing the arachidonic acid cascade might by useful for the treatment of arrhythmias. PAF induced toxic arrhythmogenicity seems to be mediated by TX. Therefore the suppression of TX influence can antagonize these arrhythmias, too.
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Cortical morphology of the brains of eight Western Australian Aboriginals was documented. Sulcal patterns permitted classification of the brains into separate groups. Characteristic patterns were found for the shape of the prosencephalon and for the insular, parietooccipital, and frontal cortex in the aboriginal group. The length of the frontal, parietal, and occipital lobes and the width of the temporal lobes was measured. Length, width, and height of the Aboriginal prosencephalons were compared to measurements of eleven Caucasian brains. Postmortem changes, genetic differences, and factors influencing brain development were discussed.
The brain volumes of 8 male Australian Aborigines and 11 male Caucasians were determined. Total brain volume was significantly smaller for Aborigines (1199 +/- 84 ml) compared to Caucasians (1386 +/- 98 ml). Significantly smaller volumes were also found for cerebellum, prosencephalon-mesencephalon unit, cerebral cortex, frontal cortex, parieto-occipitotemporal cortex, and hippocampus. Volumes of ponsmedulla oblongata unit (21 +/- 3 ml for Aborigines and 22 +/- 3 ml for Caucasians) and visual cortex (14.9 ml +/- 2.6 ml and 14.6 +/- 2.2 ml, respectively) did not differ significantly. The striate cortex extended further onto the lateral surface of the occipital lobe in Aboriginal brains. The frontal portion of cerebral cortex was larger in Aboriginal than in Caucasian brains. According to the specific growth periods for the areas studied, these differences could be explained by the higher incidence of malnutrition and infectious diseases for Aboriginals during the development of the brain in early childhood, especially after the 6th postnatal month. However, genetic influences cannot be excluded. The results for the visual cortex of Aborigines might represent an adaptation to living conditions in the bush and desert regions of Australia.
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Trapidil and some selected derivatives of trapidil were investigated in ouabain induced arrhythmia in guinea-pigs and in aconitine induced arrhythmia in rats. In both models trapidil exerted a marked antiarrhythmic effect. Investigations on ouabain induced arrhythmia showed that three derivatives were more effective than trapidil concerning the threshold for premature ventricular beats and flutter. One derivative only was able to decrease the sensitivity for fibrillation in the same order of magnitude as trapidil. On aconitine induced arrhythmia all derivatives of trapidil were less effective in elevating the threshold of arrhythmia than trapidil itself, but three derivatives showed antiarrhythmic properties.
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The macrovibratome is a newly developed sectioning apparatus designed especially for the preparation of human brain material subject to macroscopic and morphometric examinations. The brain is embedded in an aqueous agar solution and cut into slices with a minimum thickness of 2 mm. Using a 20% or 40% gelatin solution as the embedding material results in an average shrinkage of the tissue blocks of 9.8 or 31.7% in volume, respectively. With a 3% agar solution the volume shrinkage lies on the average at 1.0% for smaller brain pieces and 4.5% for cerebra.
In a prospective study (n = 50) the clinical usefulness of a fine-needle-catheter-jejunostomy based on the method of Delany et al. [1] was studied. In all cases the jejunostomy was inserted intraoperatively without difficulty and without complication. The set used (Intestofix) consisted of one polyurethan-catheter (75 cm length), 2.1 mm inner diameter) and of two hollow needles constructed as split-cannulas. This system has been proved in our study to be simple, rapid and safe. Patient's tolerance of the feeding was, however, unsatisfactory; diarrhea occurred on the 5th postoperative day in 35% of all patients, in addition we observed inconvenient belching (42.5%) and sensation of repletion (25%). There may be different causes for these uncomfortable symptoms; for example application schedule or the composition of food. We think that the operation itself exerts an important influence upon patient's tolerance because patients without operation but under the same conditions tolerate the nutrition via jejunostomy better than those in our study (with concomitant operation).
The influence of intracellular pH (pHi) on intracellular Ca2+ activity ([Ca2+]i) in HT29 cells was examined microspectrofluorometrically. pHi was changed by replacing phosphate buffer by the diffusible buffers CO2/HCO3- or NH3/NH4+ (pH 7.4). CO2/HCO3- buffers at 2,5 or 10% acidified pHi by 0.1, 0.32 and 0.38 pH units, respectively, and increased [Ca2+]i by 8-15 nmol/l. This effect was independent of the extracellular Ca2+ activity and the filling state of thapsigargin-sensitive Ca2+ stores. Removing the CO2/HCO3- buffer alkalinized pHi by 0.14 (2%), 0.27 (5%), and 0.38 (10%) units and enhanced [Ca2+]i to a peak value of 20, 65, and 143 nmol/l, respectively. Experiments carried out with Ca2+-free solution and with thapsigargin showed that the [Ca2+]i transient was due to release from intracellular pools and stimulated Ca2+ entry. NH3/NH4+ (20 mmol/l) induced a transient intracellular alkalinization by 0.6 pHunits and increased [Ca2+]i to a peak (Delta [Ca2+]i = 164 nmol/l). The peak [Ca2+]i increase was not influenced by removal of external Ca2+, but the decline to basal [Ca2+]i was faster. Neither the phospholipase C inhibitor U73122 nor the inositol 1,4,5-trisphosphate (InsP3) antagonist theophylline had any influence on the NH3/NH4+-stimulated [Ca2+]i increase, whereas carbachol-induced [Ca2+]i transients were reduced by more than 80% and 30%, respectively. InsP3 measurements showed no change of InsP3 during exposure to NH3/NH4+, whereas carbachol enhanced the InsP3 concentration, and this effect was abolished by U73122. The pHi influence on "capacitative" Ca2+ influx was also examined. An acid pHi attenuated, and an alkaline pHi enhanced, carbachol- and thapsigargin-induced [Ca2+]i influx. We conclude that: (1) an alkaline pHi releases Ca2+ from InsP3-dependent intracellular stores; (2) the store release is InsP3 independent and occurs via an as yet unknown mechanism; (3) the store release stimulates capacitative Ca2+ influx; (4) the capacitative Ca2+ influx activated by InsP3 agonists is decreased by acidic and enhanced by alkaline pHi. The effects of pHi on [Ca2+]i should be of relevance under many physiological conditions.
The hetrazepine derivative WEB 2086 (0.5-2 mg/kg, i.v.), a well known PAF receptor antagonist, was found to reduce the arrhythmogenic effect of PAF in a dose dependent manner on ouabain induced arrhythmias in guinea-pigs. There was no detectable substance-specific influence of WEB 2086 on the threshold doses of ouabain, since in a dose of 2 mg/kg given i.v. it was able to inhibit cardiac rhythm disturbances induced by PAF as well. Guinea-pigs actively sensitized with ovalbumin responded to antigenic challenge with an increased susceptibility to ouabain induced arrhythmias. This arrhythmogenic effect could also be inhibited by WEB 2086. In conclusion, WEB 2086 was found to exert marked protective effects against PAF related cardiac arrhythmias, indicating its potential usefulness for the treatment of cardiac anaphylaxis.