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"OBJECTIVES: We sought to determine which ion current predominantly affects defibrillation outcomes by using specific pharmacologic probes (lidocaine [a sodium channel blocking agent] and cesium [an outward potassium channel blocking agent]) in 26 swine. BACKGROUND: The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion channel predominates. METHODS: Each pig was randomly assigned to one of four treatment groups with two treatment phases: group 1 = placebo (D5W) in treatment phase I followed by placebo plus cesium in treatment phase II (n = 6); group 2 = lidocaine followed by lidocaine plus placebo (n = 7); group 3 = lidocaine followed by lidocaine plus cesium (n = 7); group 4 = placebo followed by placebo plus placebo (n = 6). Defibrillation threshold values and electrocardiographic measurements were obtained at baseline and at treatment phases I and II. RESULTS: Lidocaine increased defibrillation threshold values from baseline by 71% in group 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no changes in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean +/- SD) returned to baseline values (from 15.7 +/- 3.46 to 7.55 +/- 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold values from 7.10 +/- 1.27 to 4.14 +/- 1.75 J (p < 0.01). The effect of cesium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 +/- 14% and 51 +/- 18%, respectively (p = 0.28). CONCLUSIONS: Cesium, through potassium blockade, reverses lidocaine-induced elevation in defibrillation threshold values. The magnitude of defibrillation threshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade." cesium.defibrillation.K and Na channel blockade.doc

"Our primary novel finding concerning cesium is that relatively large concentrations of this ion are able to block a small, but statistically significant fraction of outward potassium current for potentials less than approximately 50 mV positive to reversal potential. This effect is relieved at more positive potentials. We have also found that external rubidium blocks outward current with a qualitatively similar voltage dependence. This effect is more readily apparent than the cesium blockade, occurring even for concentrations less than that of external potassium. Rubidium also has a blocking effect on inward current, which is relieved for potentials more than 20-40 mV negative to reversal, thereby allowing both potassium and rubidium ions to cross the membrane. We have described these results with a single-file diffusion model of ion permeation through potassium channels. The model analysis suggests that both rubidium and cesium ions exert their blocking effects at the innermost site of a two-site channel, and that rubidium competes with potassium ions for entry into the channel more effectively than does cesium under comparable conditions." cesium and rubidium effects on potassium currents.doc

Lithium, cesium: "Using inductively coupled plasma source mass spectrometry, we have studied the red cell element concentrations of alcoholic subjects with different periods of abstinence before testing. We found consistently elevated red cell caesium concentrations and also reduced red cell selenium concentrations. These may represent persistent abnormalities in oxidation/anti-oxidation mechanisms, and red cell caesium in particular may be a long-term marker of alcohol dependence. Erythrocyte lithium, cerium and boron concentrations were also reduced in the abstinent alcoholic groups." cesium high.selenium low in rbc of alcoholics.doc

"Cesium ions block potassium channels in biological membranes in a voltage dependent manner." cesium blocks inward potassium current.doc

The effects of cesium were tested by a researcher on himself: "There was an initial general feeling of well-being and heightened sense perception. A gradual decrease in appetite was noted initially before it was stabilized at a later date. Discontinuation of rich bread meals resulted in pre-nausea sensation which was followed by diarrhea 48 hr later. The institution of high potassium nutrition decreased the feeling of nausea and abolished diarrhea. A "tingling sensation in the lip and cheek regions was experienced 15 min subsequent the cesium chloride dosage compared to same sensation occurring at moderate intensity in hands and feet at end of the experiment. No adverse effects of CsCl were noted in performance of mathematical analyses or in driving skill. It is concluded that CsCl is devoid from toxicity provided adequate diet and supplements are administered."cesium effects on a human.single case.doc

"Cesium attenuates conditioned avoidance response in rats and mice."

"Two months after the nuclear accident of Chernobyl, postmortem measurement of radiocaesium (137 Cs and 134 Cs) were started in different organs to study incorporation, organ distribution, and kinetics. 250 corpses were examined between July 1986 to August 1987 in the Department of pathology, St. P¨olten. Highest concentrations were found in skeletal muscles, with a median value of 2.3 pCi/g wet weight (80-90% of the total incorporated dose), followed by liver, lung, spleen, kidneys, thyroid gland, heart, blood and brain, with values between 0.8 and 1.3 pCi/g. No caesium was detectable in fatty tissue. During the observation period an increase in caesium concentration was observed in almost all organs. The concentration almost doubled within 10 months in skeletal muscles. Only the lung demonstrated a decrease in the radiocaesium concentration within the first months, which can be explained only by inhalation of radiocaesium. A statistically significantly higher caesium concentration in most organs was found in females as compared with males. A possible explanation is the known lower urinary caesium concentration in women. Statistically significant correlations were found between caesium concentration and nutritional status, presence of malignancy, and the most recent intravital serum creatinine value." cesium.postmortem levels in Chernobyl victims.doc

"The model analysis suggests that both rubidium and cesium ions exert their blocking effects at the innermost site of a two-site channel, and that rubidium competes with potassium ions for entry into the channel more effectively than does cesium under comparable conditions." cesium and rubidium effects on potassium currents.doc

"From the 137Cs/40K ratios it was found that cesium rather than potassium was selectively taken up from the soils by fungi such as Suillus granulatus and Lactarius hatsudake. cesium and potassium in mushrooms.doc

Cesium-137 was detected in most samples of dried and raw shiitake (Lentinus edodes (Berk.) Sing.). cesium and shiitake mushroom.doc

The authors' result show that new types of dietary cellulose and composite food additives based on alfalfa polymers have rather pronounced antiradioactive properties against Cs-137 and Sr-85. This makes it necessary to organize the manufacture of these food additives whose daily dose of 12-20 should be supplemented into human diet every day. cesium.alfalfa may block absorption.doc

The levels of radiocesium in meat were reduced by a combination of countermeasures such as special feeding, use of cesium binders (bentonite and Prussian blue), cesium is bound by bentonite.doc

Practical experience gained after the Chernobyl accident has shown that both clay minerals and hexacyanoferrates are effective in preventing high radiocaesium levels in animal products. Chemicals such as bentonite clays and CaCO3, cesium binders.doc

The depressive patients had reduced blood levels of caesium which increased towards normal on recovery. This finding is discussed in relation to pertinent neurochemical and behavioural effects of caesium. cesium low in depression.doc

These results indicate a specific neurosuppressant action of CsCl on mouse CNS and suggest exploration of this alkali earth metal for antipsychotic-like activity. cesium.antidepressant antipsychotic effect.doc

We explored the clearance of cesium in man and found that an oral dose of 50 mg maintains elevated blood cesium levels for 80 days. Cesium is accumulated mainly in the red blood cell fraction. Larger doses (6-9 grams) produce no observed harmful effects and maintain elevated blood levels of cesium for more than a year. cesium clearance by braverman.doc

The biological half-life of 137Cs and its organ distribution were investigated in mice fed various potassium-deficient diets. The biological half-life, which was 6.1 days in mice receiving the normal level of potassium, became longer as the dietary potassium content decreased, and 137Cs was hardly excreted from the body when dietary potassium content was restricted to 200 mg/kg or less. The muscle showed the highest concentration of 137Cs in both mice that had sufficient amounts of potassium and those that were potassium-deficient. Clearance of 137Cs from tissues was generally suppressed when mice were fed a potassium-deficient diet, but the relative distribution pattern of 137Cs was not affected by dietary potassium content. These results suggest that dietary potassium intake, which may vary with eating habits, affects the biological half-life of 137Cs in humans. cesium half-life decreased by potassium intake.doc

Cesium chloride administration causes ventricular tachyarrhythmias in dogs, with many of the features of the clinical long QT syndrome. cesium-induced arrhythmias.doc

Cesium-accumulating bacteria, strains CS98 and CS402, were isolated from soil by a radioactive autoradiographic method using 137Cs. These strains displayed the rod-coccus growth cycle and contained mesodiaminopimelic acid, mycolic acids, and tuberculostearic acids. cesium accumulating bacteria.doc

Intracellular calcium plays an essential role in regulation of many cellular processes, but increases in internal calcium levels can also exacerbate pathophysiologic or pharmacologic responses, in particular myocardial arrhythmias. Pharmacologic increases in intracellular calcium may be obtained by opening calcium channels, either directly or indirectly, or by increasing calcium release from intracellular stores. In this study, cesium chloride administered intracoronarily (i.c.) through the left anterior descending coronary artery (LAD) dose-dependently elicited ventricular arrhythmias. Glyburide (3 micrograms/kg/min i.c.), clofilium (1 micrograms/kg/min i.c.) or ryanodine (0.03 micrograms/kg/min i.c.) exacerbated arrhythmias. cesium induced arrythmias and calcium.doc

The chloride salts of lithium (Li+) and cesium (Cs+) were evaluated for their ability to influence the growth of Sarcoma I implants in A/J mice. The administration of daily doses of either 1 or 3 mEq/kg CsCl to these mice reduced the incidence and size of tumor implants. This effect was not apparent in animals receiving a smaller dose (0.5 mEq/kg) of the same drug. At the time of sacrifice the serum level of Cs+ in this latter group was approximately half that recorded in animals receiving the higher doses of CsCl. No effect on tumor incidence or rate of growth was observed in animals receiving different doses of LiCl. Because of the similarities that existed between cesium and potassium, it was postulated that the effect of cesium was due to alterations in the intracellular composition of the tumor cells. Also, the possible role of cytotoxic agents in potentiating the inhibitory effect of cesium on tumors was discussed. cesium inhibits growth of Sarcoma I tumors.doc

Rubidium and cesium chlorides accelerated cAMP synthesis in rat brain cortex membranes, while other alkali metal chlorides had no influence on the rate of this process. The effect was dose-dependent and yielded above 2-fold activation of adenylate cyclase.cesium and Rb activate cAMP synthesis.doc

Title

Cesium therapy in cancer patients.

Author

Sartori HE

Source

Pharmacol Biochem Behav, 21 Suppl 1():11-3 1984

Abstract

Females may absorb or need more cesium than males. In a study where dogs were given radioactive 137Cs: "The middle-aged dogs died significantly earlier due to complications of hematological dyscrasia compared to the juvenile and young adult dogs, and the middle-aged females died significantly earlier than the middle-aged males. cesium--effects of 137Cs on age and sex in dogs.doc

Maternal exposure to either alkali metal reduced brain and testis weights of the developing offspring mice compared to controls. This suggests a delayed toxic effect on the CNS and endocrine organs. Coadministration of both salts negated this effect. cesium-lithium interaction in maternal mice.doc

Cesium (up to 20 mM) had no effect on the late inward current or the mechanical activity, but decreased the early outward current by 80 +/- 12%. Manganese (25 mM), which blocks sodium-calcium exchange, abolished the late inward current and the mechanical activity. Manganese also reduced the early outward current by 27 +/- 10%. Manganese and cesium together blocked all the effects of sodium removal. We conclude that removal of extracellular sodium interrupts a cesium-sensitive "background current, that may be related to the time-dependent pacemaker current, If. Sodium removal also causes gradual activation of a nonspecific conductance, which can ultimately depolarize the cells, and which may be gated by cytoplasmic calcium. cesium and manganese effects on sodium removal.doc

Zinc-, copper-, cobalt, and nickel hexacyanoferrates(II), despite showing a high caesium sorption capacity in vitro, were less effective in rats and are not suited for in vivo application, also because they may produce toxic side effects. As a consequence, the orally administered colloidal-soluble iron(III) hexacyanoferrates(II) (NH4Fe[Fe(CN)6] and KFe[Fe(CN)6]) have to be considered as the most valuable countermeasure against radiocaesium absorption for humans and domestic animals in the case of a severe nuclear accident in the future. Manganese oxide, a non-hexacyanoferrate(II) compound with known in vitro caesium binding capacity, showed no inhibitory effect on radiocaesium absorption in rats. cesium binding by manganese and hexacyanoferrates.doc

The effect of a mixture of calcium alginate, iron (III) ferrocyanide and potassium iodide added to rat diet on 85Sr, 137Cs and 131I metabolism and health was investigated in female rats after four weeks of treatment. The retention of these radioisotopes was determined in the whole body and critical organs six days after 85 Sr and 137CS and one day after 131I oral administration. The health effect of the mixture was evaluated by measuring body weights, haematological parameters, concentrations of iron, zinc and manganese in the kidneys, liver and femur, bone parameters (femur composition and morphometry) and by a histopathological examination. The mixture reduced 85Sr retention in the femur 11 times, 137Cs retention in the thigh muscle 102 times and 131I retention in the thyroid 134 times. Treated animals were in good health and the only differences found between the control and experimental rats were slightly lower haemoglobin values in the blood and a slightly lower iron concentration in the liver. It is concluded that the mixture was very efficient for decreasing body retention of three important fission products and that it can be used over long periods without causing adverse health effects. cesium retention factors.doc

The author has treated 370 cases of skin cancer of the nose with Cesium-137 brachytherapy. The excellent results with a low recurrence rate of 3% and good cosmetic results are compared with those reported on the literature. The method is more elegant than any reconstructive surgery, which should be reserved for extensive cases. cesium and skin cancer of the nose.doc

The experiments were carried out on 35 male (M) and female (F) rats contaminated by ingestion of Cesium--137(Cs) for 38 or 84 days; the total Cs activity was 288 Bq 460 Bq, and respectively. The duration of forced swimming decreased significantly in the contaminated groups as compared with controls (n = 16). The active avoidance reaction in the shuttle-box shows an increase in F groups and a decrease in M groups. The total latency time of the same reaction was lower in F and M treated rats on the first day of learning. The score of aggressive behavior rose significantly, especially in group F. These results can be explained by the sex dependence of Cs accumulation and by the neurotoxic action of the radionuclide on several central neural areas including monoaminergic and endocrine mechanisms. cesium--sex differences in accumulation.doc

The effect of postnatal maternal ingestion of LiCl, CsCl or both during weaning period on the developing newborn was studied in the albino mouse. Maternal exposure to CsCl alone or in combination with LiCl reduced the weanling body weight from corresponding control which persisted for a subsequent 2 weeks after separation of the offspring from maternal breast feeding. This was compared to a moderate reduction in offspring growth by maternal Li-exposure during alkali metal-free period. Exposure of nursing dams to either alkali metals studied, but not their combination, decreased brain weight of the developing mouse. The maternal Li-exposure caused a marked increase in female but not male offspring spleen weight as compared to a reduction of kidney weight from corresponding controls. Coadministration of CsCl with LiCl negated this sex-dependent Li-mediated changes of the offspring's tissue weights. The maternal Li-treatment caused sex-dependent induction of offspring hepatic aldehyde dehydrogenase but not alcohol dehydrogenase. The results suggest that breast feeding by nursing dams ingesting these alkali metals could cause retarded growth during development. The Cs+ appears to negate some of the changes produced by Li on brain and kidney weights. The interaction between Cs+ and Li+ may prove useful in minimizing some of the neonatal toxicity studied. cesium and sex effects on lithium toxicity.doc

Since cesium is found in muscles more than in other tissues, it seems logical that muscle building would use up more cesium. Also, males will have a higher reservoir of cesium than females because of their higher muscle mass. This may offer partial explanation why females are more subject to thyroid disease than males: "It was found that significantly higher contents of 137Cs were present in the athletes. Furthermore, it was found that within the groups of athletes male subjects had significantly higher internal 137Cs contamination per kilogram of body mass than the female subjects. An explanation for this is the different nutrition and the higher relative muscle mass of the athletes." cesium incorporation higher in male athletes.doc

Mass spectrographic and isotope studies have shown that potassium, rubidium, and especially cesium are most efficiently taken up by cancer cells. This uptake was enhanced by Vitamins A and C as well as salts of zinc and selenium. The quantity of cesium taken up was sufficient to raise the cell to the 8 pH range. Where cell mitosis ceases and the life of the cell is short. Tests on mice fed cesium and rubidium showed marked shrinkage in the tumor masses within 2 weeks. In addition, the mice showed none of the side effects of cancer. Tests have been carried out on over 30 humans. In each case the tumor masses disappeared. Also all pains and effects associated with cancer disappeared within 12 to 36 hr; the more chemotherapy and morphine the patient had taken, the longer the withdrawal period. Studies of the food intake in areas where the incidences of cancer are very low showed that it met the requirements for the high pH therapy. cesium--high pH therapy for cancer.doc

We studied the effects of permeant ions on the gating of the large conductance Ca(2+)-activated K+ channel from rat skeletal muscle. Rb+ blockade of inward K+ current caused an increase in the open probability as though Rb+ occupancy of the pore interferes with channel closing. In support of this hypothesis, we directly measured the occupancy of the pore by the impermeant ion Cs+ and found that it strongly correlates with its effect on gating. This is consistent with the "foot-in-the-door model of gating, which states that channels cannot close with an ion in the pore. However, because Rb+ and Cs+ not only slow the closing rate (as predicted by the model), but also speed the opening rate, our results are more consistent with a modified version of the model in which the channel can indeed close while occupied, but the occupancy destabilizes the closed state. Increasing the occupancy of the pore by the addition of other permeant (K+ and Tl+) and impermeant (tetraethylammonium) ions did not affect the open probability. To account for this disparity, we used a two-site permeation model in which only one of the sites influenced gating. Occupancy of this "gating site interferes with channel closing and hastens opening. Ions that directly or indirectly increase the occupancy of this site will increase the open probability. potassium channel gating and blocking by Ca, Rb, Cs.doc

The mechanism by which magnesium therapy suppresses some ventricular tachyarrhythmias characterized by a prolonged QT interval (e.g., torsades de pointes) is unknown. Since early afterdepolarizations have been proposed as a cause of the long QT syndrome and the related ventricular tachyarrhythmias, we hypothesized that magnesium therapy would suppress both the early afterdepolarizations and the ventricular arrhythmias. The present study was performed to test that hypothesis. Using monophasic action potentials (MAP) recorded with a contact electrode from the right ventricular endocardium to demonstrate early afterdepolarizations, cesium chloride (168 mg/kg iv) was administered before, during, and 1 to 2 hr after discontinuation of a magnesium infusion (1 to 2 mg/kg/min for 20 to 30 min). Before magnesium infusion, cesium induced early afterdepolarizations that were 49.7 +/- 1.6% (mean +/- SE) of the amplitude of the corresponding monophasic action potential. The amplitude of the early afterdepolarization decreased to 31.2 +/- 3.8% of the MAP amplitude during magnesium infusion (p less than .003) and increased to 48.0 +/- 4.0% 1 to 2 hr after termination of the magnesium infusion (p less than .003). Cesium induced sustained monomorphic ventricular tachycardia, torsades de pointes, or ventricular fibrillation in 12 of 13 dogs before magnesium infusion, and in eight of 11 dogs 1 to 2 hr after stopping infusion, but in only three of 13 dogs during magnesium infusion. Cesium prolonged the corrected QT interval from 338 +/- 16 msec (control) to 387 +/- 14 msec before (p less than .003), 356 +/- 12 msec during (p less than .003), and 406 +/- 16 msec after stopping the magnesium infusion (p less than .003).(ABSTRACT TRUNCATED AT 250 WORDS) cesium induced tachyarrythmias stopped by magnesium.doc