Biomedical subjects

S Herzig

Publications and source records attributed to S Herzig.

65 records · Page 4Linked to original sources

PubMed1990

Differentiation between negative inotropic drugs by means of potentiated post-rest contractions in guinea-pig heart.

1. It was tested using isolated guinea-pig atria whether negative inotropic drugs could be differentiated by measuring force under both equilibrium conditions and after a rest period leading to potentiated beats. 2. A drug believed to interfere with sarcoplasmic reticular function, ryanodine, preferentially suppressed potentiated beats, whereas the calcium antagonists gallopamil and felodipine selectively depressed force under continuous stimulation. 3. Gentamicin and doxorubicin also exerted characteristic effects on the two force parameters, the former resembling calcium antagonists, the latter ryanodine. 4. The method used is suitable for a descriptive classification of negative inotropic drugs, possibly according to their cellular mode of action.

Animals↗

PubMed1990

Beta-adrenergic stimulation of calcium channels occurs by potentiation of high-activity gating modes.

cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca channels, but the molecular manifestation of this effect remains controversial. Previous work implicates either an increase in the number of functional channels or graded changes in the gating of individual channels. We now find that single cardiac Ca channels display three patterns of activity ("modes") and that isoproterenol or 8-bromoadenosine 3',5'-cyclic monophosphate redistributes the relative proportions of modes such that the two most active (mode 1, bursts of brief openings; mode 2, very long-lasting openings) are favored (P less than 0.05; n = 7). Conversely, a pattern of sparse brief openings (mode 0a) is selectively inhibited (P less than 0.01). Despite differences in the relative frequencies of the various modes before and during drug exposure, the gating within each mode is not detectably changed. We conclude that potentiation of highly active modes of Ca channel gating underlies the enhancement of calcium influx by beta-adrenergic stimulation.

1-Methyl-3-isobutylxanthine↗

PubMed1989

On the ocular distribution of cardiac glycosides in guinea pigs following acute administration.

Tritiated ouabain, digitoxin, and digoxin were given IV to anesthetized guinea pigs. The tritium content of the ocular tissues (cornea, iris, lens, vitreous body, retina, choroid, sclera, and optic nerve) was measured after 1 and 3 h and compared with the amount of tritium found in the brain and some peripheral organs. High levels of digitoxin were found in the brain and retina. Digoxin was detected in large quantities in the retina, but only small levels were found in brain tissue. Ouabain was nearly absent in the retina and cerebrum, whereas in most other ocular and peripheral tissues the three cardiac glycosides were present in comparable quantities. The IP injection of tritiated digoxin resulted in lower absolute tissue levels, but a pattern of distribution similar to that observed in anesthetized guinea pigs was found in conscious animals.

Animals↗

PubMed1989

The binding of (+)-isradipine by guinea-pig intact atria.

1. The accumulation of [3H]-(+)-isradipine (PN 200-110) was measured in quiescent guinea-pig left atria with normal (K+ 2.7 mM) or lowered (K+ 40 mM) membrane potential. 2. Under control conditions (2.7 mM K+) a high affinity binding of (+)-isradipine could not be detected. If, however, the atria were partially depolarized to about -30 mV by 40 mM K+, high affinity binding became evident displaying a dissociation constant of 4.2 x 10(-11) M and a capacity of 9.7 nmol kg-1 wet wt. 3. The depolarization-induced binding was reversible upon repolarization of the atria although isradipine was still present in the medium. This indicates that the high affinity binding sites disappear as soon as the cell membranes become polarized. 4. Isradipine belongs to the less hydrophobic dihydropyridines, but nevertheless the unsaturable binding led to an accumulation of about 84 fold. At a concentration of 2 x 10(-8) M (+)-isradipine, which reduces the contractile force by 50%, the cellular concentration will rise to more than 10(-6) M.

Animals↗

PubMed1988

Interpretation of [3H]ouabain binding in guinea-pig ventricular myocardium in relation to sodium pump activity.

1. The attempt was made to analyse the complex [3H]ouabain binding curves obtained in intact cardiac ventricular preparations electrically stimulated at different frequencies. The result of this analysis was used to draw conclusions from the binding curves on the frequency dependence of sodium pump activity. 2. [3H]Ouabain binding to isolated, electrically stimulated (1.5 Hz) ventricular strips of guinea-pig hearts was investigated. The positive inotropic effects were studied in separate experiments. Specific [3H]ouabain binding barely reached an equilibrium within 3 h of incubation. A binding curve was constructed using the equilibrium values of specific [3H]ouabain binding obtained at different ouabain concentrations. This binding curve revealed a concentration-proportional component at positive inotropic concentrations and a saturating component at high, toxic concentrations. At very low, inotropically ineffective ouabain concentrations, however, binding values were higher than expected from a linear relationship between ouabain concentration and binding. 3. The peculiar shape of the binding curve could be largely accounted for by a mathematical model, which takes into consideration biochemical properties and physiological regulation of the sodium pump. The model predicts a concentration-proportional pattern of binding which takes place in the non-toxic ouabain concentration range. The slope of the concentration-proportional component of the binding curve should represent a measure of sodium pump activity. 4. Investigation of binding curves at various stimulation frequencies revealed that, as predicted by the model, the slope of the concentration-proportional component of the binding curves was increased and the maximum non-toxic equilibrium binding was decreased with increasing beat frequencies. 5. Quantitative evaluation of the binding curves led to the conclusion that sodium pump activity is a linear function of stimulation frequency in guinea-pig ventricular preparations, the activity in resting preparations amounting to about 15% of the maximum activity. Comparison of the present results with former studies on sodium pump function suggests that [3H]ouabain binding reflects steady-state sodium pump activity. If the complex pattern of binding curves is taken into consideration, [3H]ouabain binding measurements may serve as a means of studying sodium pump function.

Animals↗

PubMed1987

Acrihellin, a cardioactive steroid escaping from the organ-bath.

The concentration of acrihellin rapidly declines in oxygenated Tyrode-solution, because the compound escapes from the organ-bath being enriched in droplets sprayed from the surface of the bubbled solution. As checked by radiochromatography, acrihellin remains chemically unaltered during this process. Hellebrin and hellebrigenin persist in gassed Tyrode-solution, suggesting that the 3 beta-substituent dimethylacrylic acid endows acrihellin with amphiphilic properties, thus promoting its enrichment at gas-water interphases. Measurements of the inotropic effects in guinea pig left atria performed at concentrations of acrihellin kept constant yielded a dose-response curve, which closely resembles that of the conventional cardioactive steroid ouabain.

Animals↗

PubMed1987

[The acute physiology score as a stratification and prognostic criterion in patients in a surgical intensive care ward].

In order to compare different groups of intensive-care patients and therapeutic interventions a measuring system is needed reflecting the patient's pathophysiologic status with great accuracy. The APACHE-system designed by Knaus et al. (APS) meets the requirements when comparing groups of patients. This prospective study was undertaken to determine whether APS is useful to forecast survival and death of 764 individual patients of a surgical ICU. The results were compared to daily statements obtained from the head surgeon of the intensive-care department. Both the physician and APS gave true judgements in 95% of the cases. Overestimation of the operative procedures by the physician was revealed to be a major source of error in wrong statements. When a combination of APS and physician's judgement was used the forecasts were found true in 99% of the patients. The authors conclude that APS by itself is not able to give a sufficient prognosis in an individual ICU patient but is an excellent tool to assure or modify the physician's opinion.

Humans↗

PubMed1985

On the cooperativity of ouabain-binding to intact myocardium.

A theoretical concept is presented which proposes that binding of ouabain to intact myocardium should be positive cooperative. It is based on the assumption that the myocardial Na/K-ATPases expose the ouabain-binding site only at a particular conformation adopted during a turnover cycle. The turnover rate and thus the ouabain-binding properties are regulated by the cytosolic Na-ion-concentration Nai. Any occupation of cellular Na/K-ATPases should affect the ouabain-binding properties of the unoccupied Na/K-ATPases, because their turnover rate is increased via an elevated Nai. A computer model which takes into account the interrelationships of the Na/K-ATPases both with Nai and with the ouabain-concentration predicts that ouabain-binding should proceed in a concentration-proportional fashion as long as the Na-load can be counterbalanced by non-occupied Na/K-ATPase molecules. The concentration-proportional binding reflects a positive cooperativity. Experimental results reveal that (3H)ouabain-binding to Na/K-ATPase of electrically stimulated guinea-pig left atria was in fact concentration-proportional under certain experimental conditions. The biological significance of the proposed concept remains to be elucidated.

Animals↗

PubMed1985

Sodium load and high affinity ouabain binding in rat and guinea-pig cardiac tissue.

An estimation of the actual Na/K-ATPase transport activity in intact cardiac cells was made by measuring the binding of [3H]-ouabain to rat and guinea-pig ventricular strips. At the low [3H]-ouabain concentration of 1 nM equilibrium binding was hardly obtained after an incubation time of five hours. Different procedures known to alter the sodium load of the cardiac preparations influenced [3H]-ouabain binding: the sodium ionophore monensin enhanced [3H]-ouabain binding, the local anaesthetic dibucaine and a reduction of external sodium ion concentration diminished [3H]-ouabain binding; [3H]-ouabain binding was similarly affected by these procedures in the rat and guinea-pig. Since [3H]-ouabain binding occurred predominantly at the high-affinity binding sites of rat myocardium under the applied experimental conditions, it was concluded that these binding sites represent Na/K-ATPase molecules involved in sodium ion transport.

Animals↗

PubMed1984

Action of ouabain on rat heart: comparison with its effect on guinea-pig heart.

The inotropic dose-response curve of ouabain in rat cardiac ventricular strips exceeded a concentration range of two decades (1 X 10(-7) M to 3 X 10(-5) M) displaying an intermediate plateau phase. In guinea-pig ventricular strips the inotropic ouabain concentrations spanned only one decade (1 X 10(-7) M-1 X 10(-6) M). Ouabain-intoxication in guinea-pig ventricular strips occurring at 3 X 10(-6) M consisted of arrhythmia and contracture, while in rat ventricular strips at the toxic concentration of 1 X 10(-4) M only a progressive increase in diastolic tension was observed. By means of atomic absorption spectroscopy the ouabain-induced loss of cellular potassium and gain of sodium in rat ventricular strips was detected only at concentrations of ouabain higher than 10(-4) M. Ouabain reduced the activity of Na/K-ATPase prepared from rat and guinea-pig cardiac ventricles to half of its maximum at 6.5 X 10(-5) M in rat and 1.0 X 10(-6) M in guinea-pig, rat heart Na/K-ATPase thus being about 60 fold less sensitive towards ouabain. Specific [3H]-ouabain binding to membrane suspensions prepared from rat and guinea-pig ventricles was characterized by a similar affinity in rat (KD = 4 X 10(-8) M) and guinea-pig (KD = 13 X 10(-8) M). The number of ouabain binding sites in rat membranes was only about 10% of the number found in guinea-pig membranes. In rat the presence of additional ouabain-binding with low affinity and high capacity seemed possible, but could not be verified for methodological reasons. In the light of the biochemical results and binding data, the wider range of ouabain concentration exerting a positive inotropic effect in the rat may be attributed to the existence in the latter of two populations of receptors with different affinities for ouabain and different capacities. In contrast, in the guinea-pig, there is a single population. Nevertheless it is probable that all the receptors in both species are part of the Na/K-ATPase complex and mediate a positive inotropic effect after ouabain-binding in an identical manner.

Animals↗

PubMed1979

Lacrimal sac calculi.

Analysis of dacryoliths removed at operation showed that most consisted of calcium. One consisted of ammonium and could be directly related to the presence of bacteria. Tear samples obtained from 14 patients with dacryoliths were compared with seven normal patients with regard to calcium, phosphorus, and uric acid concentrations, tear to serum calcium ratios, and calcium-phosphate products. There was no significant difference between the two groups and thus no evidence that dacryoliths from because of abnormal tear electrolytes. We believe that dacryolith formation results from chronic obstruction and inflammation of the sac causing a build up of various electrolytes, particularly calcium. The preoperative dacryocystograms showed either a filling defect or apparent displacement of the lacrimal sac.

Calcium↗