The discovery of the cardiac conduction system: the testimony of the authors.
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Europe↗
Biomedical subjects
W Ehrlich
Publications and source records attributed to W Ehrlich.
In vitro studies on genotoxicity and cytotoxicity of the anticancer drugs cisplatin and cofplaton, a caffeine-8-ether plus cisplatinum compound.
The cytotoxic and genotoxic properties of the newly designed anticancer drug 'cofplaton' were investigated. Since cofplaton is a cisplatin (CDDP) plus caffeine compound, the widely applied anticancer drug CDDP alone or in combination with caffeine was studied in parallel. As measured by the MTT test the cytotoxicity of the two drugs was comparable, but cofplaton exhibited significantly fewer genotoxic side effects than CDDP in the chromosome aberration test as well as in the SCE assay. First results from animal studies indicate that cofplaton exerts antitumor activity comparable to CDDP. Because of its relatively low genotoxicity, cofplaton seems to be a promising drug in human anticancer therapy.
Animals↗
The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on cell growth and the induction of DNA damage in Chinese hamster ovary cells.
It is shown that p-tetrachlorohydroquinone (TCH), the metabolite of the environmental chemical pentachlorophenol (PCP), is more toxic to cultured CHO cells than PCP, and that it causes DNA single-strand breaks and/or alkali-labile sites at concentrations of 2-10 microgram/ml as demonstrated by the alkaline elution technique.
Animals↗
Efficiency of work of inspiratory muscles in standing and in exercising dogs.
The objective of this study was to elucidate the resistive, elastic, and total inspiratory muscle work and mainly the efficiency of the inspiratory muscle work in still standing and in exercising dogs. In 180 experiments with nine mongrel dogs, respiratory and circulatory functions were recorded at rest and during a 1.5-mph walk on a treadmill belt which was inclined by 9 degrees. Each dog had been trained and surgically prepared before the series of experiments started. An electronic pressure transducer together with a fluid-filled catheter was attached to the ribs at the midthoracic level. Airflow was monitored with a pneumotachygraph attached to a face mask. Aortic flow was monitored with an electromagnetic flow transducer. Catheters in the atria, the ventricles, and the pulmonary and systemic vessels were used to determine hemodynamic parameters and blood gas levels. All recorded and all derived functions were evaluated by a dedicated computer. At rest, resistive inspiratory work (0.98 kg cm) was smaller than elastic work (1.36 kg cm). Elastic work did not change with exercise but resistive work increased to 1.46 kg.cm. The increase of total work from 2.33 kg.cm at rest to 2.79 kg.cm during exercise did not reach significance. Inspiratory power increased with exercise. Estimated diaphragmatic oxygen consumption increased from 2.23 ml/min at rest to 3.64 ml/min during exercise. It was 1.6 percent of the total oxygen consumption at rest and 1.7 percent of the total oxygen consumption during exercise. The estimated efficiency of the work of inspiratory muscles was 15.8 percent at rest and 25.8 percent during exercise. These values did not vary substantially between different animals.
Animals↗
[Studies of the in vitro toxicity of D-penicillamine in the Chinese hamster ovary system].
The amino-thiol-containing compound D-penicillamine is used as a disease-modifying drug in the treatment of rheumatoid arthritis. In the present study the effects of D-penicillamine on Chinese hamster ovary cells (CHO) were evaluated. It could be shown that only high doses, i.e. doses exceeding the therapeutically occurring plasma concentration many times, were toxic to the cells, leading to an early death of the cells. High doses (1,500 micrograms/ml) of D-penicillamine caused an inhibition of the endogenous pyrimidine synthesis of the CHO and lead to a drastic reduction of the cellular protein biosynthesis. The observations made are discussed with respect to formerly published data about mutagenicity and carcinogenicity of D-penicillamine.
Animals↗
Changes of phasic pleural pressure in awake dogs during exercise: potential effects on cardiac output.
Eighty experiments were performed with nine awake dogs to study the changes of phasic-pleural pressure with exercise. The increased minute volume with exercise was obtained by more frequent pleural pressure swings and by a substantial extension of the pressure swings in both directions. The cyclic changes of stroke volume following the pressure swings support the hypothesis that alterations of pleural pressure affect the stroke volume and can act, if necessary, as a secondary pump for the circulation. Mean pleural pressure during exercise fell by 2.5 cm H2O from the rest value of 12.1 cm H2O. The absolute right atrial pressure during exercise (-2.69 mm Hg) was not different from that at rest (-2.39 mm Hg). However, the transmural right atrial pressure of 7.6 mm Hg during exercise was higher than the pressure of 6.2 mm Hg at rest because during exercise the right atrium was perfused by 38% higher blood flow than that at rest. The phasic pattern of right atrial pressure shows that there is good reason to assume that during inspiration the extrathoracic veins are collapsed at their entrance into the chest, but this collapse is removed during expiration. There is no reason to assume an effective, sustained collapse of extrathoracic veins. Rather we can visualize a rhythmical change of flow in extrathoracic veins from transient limitation to transient acceleration.
Animals↗
Interaction between high frequency jet ventilation and cardiovascular function.
We have studied the interaction of high frequency jet ventilation with cardiovascular pressures and flows. Results in dogs show that the amplitude of all intrathoracic pressures and flows fluctuate with a frequency equal to the difference between the heart rate and ventilator rate. The magnitude of this amplitude variation may be sufficient to obliterate periodically the pulsations in pulmonary artery and right atrial pressures. It is also shown that these cardiovascular beats can occur when the ventilator rate is close to integral multiples of the heart rate. Direct measurement of pleural pressure and the observation that the beats are markedly reduced when the chest is open support the hypothesis that the primary mechanism responsible for these beats is the interaction of the respiratory fluctuations in pleural pressure with the cardiac-generated pressure pulsations.
Animals↗
The effect of pentachlorophenol and its metabolite tetrachlorohydroquinone on RNA, protein, and ribosome synthesis in Saccharomyces cells.
The effect of pentachlorophenol (PCP) and its metabolite tetrachlorohydroquinone (TCH) were tested on growth, RNA, protein and ribosome syntheses, and ribosome content in yeast cells. Cells exposed to increasing concentrations of PCP show increasing inhibition to RNA and ribosome synthesis, and to cell growth. TCH causes a delay of the growth of the cell culture (prolongation of the lag phase) but does not cause inhibition. After treatment with TCH the maximum of the RNA synthesis was retarded, but subsequently reached nearly the same level as the untreated control cells. On ribosome synthesis and ribosome content, treatment with increasing concentrations of PCP, as well as of TCH, leads to a substantial decrease in ribosomal synthesis and, finally, total inhibition. Parallel to this, the content of free and membrane-bound ribosomes is diminished. PCP exhibits a stronger effect than TCH. The protein synthesis is only slightly reduced after treatment with PCP or TCH (with concentrations up to 20 micrograms/ml).
Chlorophenols↗
Thiopyronine-sensitized photodynamic effect on cell growth, RNA and DNA synthesis of Chinese hamster ovary cells.
After treatment of Chinese hamster ovary (CHO) cells with very low concentrations of thiopyronine (TP; 1 microgram/ml) and visible light, a delay in growth of cell cultures (prolongation of the lag phase] was observed. The lengthened lag phase, however, was followed by normal growth of the cells. The length of the lag period is dependent on the irradiation dose applied. A similar effect on DNA and RNA synthesis could be seen after photodynamic treatment with TP in CHO cells: the maxima of RNA and DNA synthesis occur later but are not significantly reduced after treatment with low concentrations of TP and irradiation with visible light. This result is further evidence that the photodynamic effect with TP does not involve attack on nuclear DNA in eukaryotic cells.
Animals↗
Classical article: Cheiralgia paresthetica (entrapment of the radial nerve). A translation in condensed form of Robert Wartenberg's original article published in 1932.
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History, 20th Century↗
Investigation of a test system for the rapid differentiation of nuclear and cytoplasmic damage in eucaryotes.
The effect of various agents which cause cell inactivation on the growth curves and RNA synthesis rates of yeast cells has been studied. On the basis of these investigations it was concluded that such studies can be used as a rapid test system for drawing preliminary conclusions as to whether a particular agent primarily damages the DNA of the cell nucleus or cytoplasmic structures.
Acrylonitrile↗
The effect of trichloroethylene and acrylonitrile on RNA and ribosome synthesis and ribosome content in Saccharomyces cells.
The effects of trichloroethylene (TCE) and acrylonitrile (ACN) on growth, RNA synthesis, ribosome synthesis, and ribosome content were tested in yeast cells. TCE causes a delay of the growth of a cell culture (prolongation of the lag phase), but does not cause inhibition. Cells exposed to increasing concentrations of ACN show increasing damage, so that, at a certain point of the growth curve, cell division stops altogether. Similar results were obtained when RNA synthesis was investigated: After treatment with TCE, the maximum RNA synthesis of the cell culture was retarded, but subsequently reached the same level as the untreated control cells. In the presence of ACN, however, the rate of RNA synthesis was lowered with increasing ACN concentrations. The same effect was observed upon investigation of ribosome synthesis: Whereas TCE produces only a slight effect, treatment with increasing concentrations of ACN leads to a substantial decrease in ribosome synthesis, and finally to total inhibition. Parallel to this, the content of free and membrane-bound ribosomes is diminished. Obviously, the decrease in ribosome content is caused not only by an inhibition of ribosome synthesis, but also by a degradation of existing ribosomes, as well as by induction of a ribosome-associated RNase.
Acrylonitrile↗
Instantaneous renal arterial pressure-flow relations in anesthetized dogs.
Instantaneous renal arterial pressure-flow (P/ Qra ) relations were investigated in 11 anesthetized dogs using the nonpulsatile fall in aortic pressure and renal arterial flow ( Qra ) during cardiac arrest caused by vagal stimulation. We found that P/ Qra relations were linear with an extrapolated zero flow intercept (Ped, effective downstream pressure) of 20.8 +/- 1.9 mmHg and the reciprocal of the slope (Ra, arterial resistance) of 0.6 +/- 0.04 mm Hg X ml-1 X min. These values are markedly lower than the values found in similar experiments in coronary and femoral arteries. Raising renal venous pressure (5 dogs) decreased Qra and elevated Ra and Ped in the ipsilateral renal artery while decreasing Qra and elevating Ra but not Ped in the contralateral renal artery. Carotid artery occlusion (6 dogs) decreased Qra and elevated Ra and Ped. Alpha-Adrenergic blockade (4 dogs) lowered Ped and Ra. Arterial resistance seems to be more important for change in P/Q relations in the renal arterial bed than it is in other arterial beds investigated so far. We suggest that the effective downstream pressure to renal arterial flow is downstream from the glomerular capillaries. The location of the "vascular waterfall " phenomenon appears to be between the intrarenal veins and the veins outside the capsule.
Anesthesia, General↗
Effect of coronary sinus occlusion on coronary pressure-flow relations.
We studied the effect of transient occlusion of the coronary sinus on the relationship between aortic pressure and circumflex coronary blood flow in open-chest anesthetized dog preparations during artificially prolonged diastoles. The coronary pressure-flow relation was linear, and flow stopped at an arterial pressure (Pf = 0) that always exceeded coronary venous pressure (Pcv). During reactive hyperemia, Pf = 0 was 31 mmHg when Pcv was 5 mmHg and increased to 52 mmHg when the coronary sinus was occluded (Pcv, 38 mmHg). Elevation of Pcv translated the coronary pressure-flow relation to a higher Pf = 0 without altering the slope of the relation. Pf = 0 increased by about two-thirds of the increase in Pcv. We found no evidence that there existed a level of Pcv below which changes in Pcv had no effect on the coronary pressure-flow relation. These data are not compatible with the existence of a vascular waterfall mechanism in the coronary circulation unless it is assumed that Pcv is one of the determinants of Pf = 0.
Animals↗
Hemodynamic responses to aortic occlusion.
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Animals↗
Instantaneous femoral artery pressure-flow relations in supine anesthetized dogs and the effect of unilateral elevation of femoral venous pressure.
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Anesthesia↗
Cardiovascular changes in awake dogs caused by suddenly induced aortic hypertension.
Cardiovascular adaptation to the sudden inflation of a balloon in the descending aorta was investigated in intact awake, standing dogs. The balloon inflation raised pressure in the arterial bed proximal from the balloon. Initially, it lowered heart rate and cardiac output. After 4 sec, heart rate and cardiac output began increasing again and within the next 14 sec, these functions returned almost to the control values. The restoration of cardiac output was associated with a further rise in aortic pressure. These findings are consistent with the hypothesis that the prime circulatory adaptation to a hindrance to arterial flow is restoration of blood flow even though this requires a further elevation of arterial pressure. The demands of the tissues for an adequate supply of blood appear to override the inhibitory baroreceptor reflexes. The circulatory changes observed under conditions of attenuated parasympathetic inhibition and under conditions of attenuated beta-adrenergic stimulation were consistent with this interpretation. The findings suggest that arterial hyertension may involve a comparable adaptation of cardiac output in patients whose blood flow is hindered by pathologically narrowed arterioles.
Animals↗
Cardiovascular changes in conscious dogs during spontaneous deep breaths.
Cardiovascular functions were evaluated beat by beat during 29 spontaneous deep breaths in three conscious dogs. When pleural pressure was significantly lower than during quiet breathing, stroke volume was reduced, heart rate elevated, as well as transmural pressure in the pulmonary artery (PPA-Ppl) and in the thoracic aorta (PAO-Ppl); the left ventricular filling pressure (LVEDP-Ppl) did not decrease. The authors suggest that these findings are not consistent with the classical hypothesis which explains the decrease in left ventricular output primarily by a reduction in the venous return to the left heart. The results indicate that the decrease in pleural pressure is responsible for an increase in the afterload on the left heart and suggest that this is the predominate factor in the reduction of the stroke volume without decrease in left ventricular filling pressure.
Animals↗