Tracking protein function with sodium multi quantum spectroscopy in a 3D-tissue culture based on microcavity arrays.

The aim of this study was to observe the effects of strophanthin induced inhibition of the Na-/K-ATPase in liver cells using a magnetic resonance (MR) compatible bioreactor. A microcavity array with a high density three-dimensional cell culture served as a functional magnetic resonance imaging (MRI) phantom for sodium multi quantum (MQ) spectroscopy. Direct contrast enhanced (DCE) MRI revealed the homogenous distribution of biochemical substances inside the bioreactor. NMR experiments using advanced bioreactors have advantages with respect to having full control over a variety of physiological parameters such as temperature, gas composition and fluid flow. Simultaneous detection of single quantum (SQ) and triple quantum (TQ) MR signals improves accuracy and was achieved by application of a pulse sequence with a time proportional phase increment (TQTPPI). The time course of the Na-/K-ATPase inhibition in the cell culture was demonstrated by the corresponding alterations of sodium TQ/SQ MR signals.

Rapid detection of convallatoxin using five digoxin immunoassays.

CONTEXT: Cardiac glycosides of plant origin are implicated in toxic ingestions that may result in hospitalization and are potentially lethal. The utility of commonly available digoxin serum assays for detecting foxglove and oleander ingestion has been demonstrated, but no studies have evaluated the structurally similar convallatoxin found in Convallaria majalis (lily of the valley) for rapid laboratory screening, nor has digoxin immune Fab been tested as an antidote for this ingestion. OBJECTIVE: We aimed to (1) evaluate multiple digoxin assays for cross-reactivity to convallatoxin, (2) identify whether convallatoxin could be detected in vivo at clinically significant doses, and (3) determine whether digoxin immune Fab could be an effective antidote to convallatoxin. MATERIALS AND METHODS: Cross-reactivities of purified convallatoxin and oleandrin with five common digoxin immunoassays were determined. Serum from mice challenged with convallatoxin was tested for apparent digoxin levels. Binding of convallatoxin to digoxin immune Fab was determined in vitro. RESULTS: Both convallatoxin and oleandrin were detectable by a panel of commonly used digoxin immunoassays, but cross-reactivity was variable between individual assays. We observed measurable apparent digoxin levels in serum of convallatoxin intoxicated mice at sublethal doses. Convallatoxin demonstrated no binding by digoxin immune Fab. CONCLUSION: Multiple digoxin immunoassays detect botanical cardiac glycosides including convallatoxin and thus may be useful for rapid determination of severe exposures, but neutralization of convallatoxin by digoxin immune Fab is unlikely to provide therapeutic benefit.

[Clinical evaluation of intermittent strophanthin K therapy for congestive heart failure combined coronary artery disease].

OBJECTIVE: To evaluate the effects and safety of intermittent strophanthin K therapy (ISKT) for congestive heart failure combined coronary artery disease with sinus rhythm. METHODS: Two hundred patients divided into Group A (98 cases with maintenance digoxin therapy) and Group B (102 cases with ISKT). They were studied for 3 months and some of them for longer period. RESULTS: Comparing the pretreatment data: 1. heart rate (HR, bpm), 2. left ventricular ejection fraction (LVEF), 3. blood pressure (Bp, mmHg, calculated values as mean Bp for statistics). In group A, item 1. and 2. were significantly improved (item 1. 88 +/- 12 and 68 +/- 12, P < 0.01; item 2. 0.32 +/- 0.12 and 0.40 +/- 0.12, P < 0.01; item 3. showed no significant difference (126 +/- 21/90 +/- 6 and 128 +/- 21/80 +/- 5, P > 0.05). In group B, item 1., 2. and 3. were significantly improved (item 1. 90 +/- 10 and 70 +/- 11, item 2. 0.32 +/- 0.10 and 0.45 +/- 0.10, item 3. 128 +/- +/- 20/91 +/- 7 and 110 +/- 10/76 +/- 10, the p valves are the same < 0.01). As compared with the posttreatment data of both group A and B, HR, P > 0.05, there was no significant difference, LVEF, P < 0.05, there was significant difference, Bp, P < 0.01, there was significant difference. It showed no significant difference in total occurrence rate of digitalis overload or toxication between two groups also. CONCLUSION: ISKT for congestive heart failure combined coronary artery disease with sinus rhythm is effective and safe, with better improvement of heart function and Bp level.

[The rate of recovery of left atrial contractile function after the transition to sinus rhythm in patients with paroxysmal atrial fibrillation]. / Skorost' vosstanovleniia sokratitel'noi funktsii levogo predserdiia posle perekhoda k sinusovomu ritmu u bol'nykh s paroksizmami fibrilliatsii predserdii.

In the examination of 120 patients without valvular heart disease suffering from atrial fibrillation paroxysms mechanical function of the left atrium (LA) was assessed using Doppler echocardiography. The majority of the examinees had dilated LA which is thought to be arrhythmogenic. The recovery of the sinus rhythm is accompanied by electromechanical dissociation the longest duration of which took place in subjects exposed to electrical defibrillation. An inverse relationship was established between the time of the last fibrillation and recovery of LA mechanical function. The duration of the electromechanical dissociation of the atria holds prognostic importance in relation to recurrent fibrillation.

Long-term use of K-strophanthin in advanced congestive heart failure due to dilated cardiomyopathy: a double-blind crossover evaluation versus digoxin.

K-strophanthin or digoxin were added to diuretics (all cases) and vasodilators (most cases) for treating advanced congestive heart failure in 22 patients with dilated cardiomyopathy and sinus rhythm. K-strophanthin (0.125 mg intravenously) or digoxin (0.25 mg orally) were administered daily in two 3-month periods, during which vasodilators and diuretics were kept constant and patients received one of the two digitalis preparations in a double-blind fashion, crossing over to the alternative preparation in the next period. Blindness was assured throughout the trial with a daily intravenous injection of 10 ml normal saline solution either containing K-strophanthin or not, and with daily oral administration of either placebo or active digoxin. At the end of the run-in period, 15 days after starting active preparations, and thereafter every month for the next 6 months, we evaluated left ventricular pump function at rest and patients' functional performance by a cardiopulmonary exercise test. At Day 15, cardiac index and ejection fraction at rest, compared with run-in, were significantly raised with both glycosides; during exercise while on K-strophanthin, peak oxygen consumption was augmented by 1.4 ml/min/kg (p < 0.01) and oxygen consumption at anaerobic threshold by 2.2 ml/min/kg (p < 0.01); corresponding variations on digoxin (-0.1 and +0.3, respectively) were not significant versus run-in. These patterns were duplicated at repeated tests during follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of different concentrations of strophanthin K on the chrono- and inotropic parameters of the isolated myocardial preparation and its oxygen consumption]. / Vliianie razlichnykh kontsentratsii strofantina K na khronoinotropnye parametry izolirovannogo preparata miokarda i potreblenie im kisloroda.

The contraction rate and force of the myocardium and its oxygen consumption under the action of various strophanthin-K concentrations for 10 min after its administration into the cuvette were studied in the experiments on the isolated frog atria contracting in the isometric mode. There was a two-phase response of cardiac glycoside, which depended on the time of its action and concentration.

Effects of acute K-strophantidin administration on left ventricular relaxation and filling phase in coronary artery disease.

In 10 patients with coronary artery disease, preserved left ventricular (LV) performance and absence of previous myocardial infarction, the effects of an acute intravenous administration of k-strophantidin (0.005 mg/kg over 10 minutes) on selected parameters of both LV systolic and diastolic function, including relaxation, were evaluated. An increase in positive first derivative of LV pressure (dP/dt) and in the ratio between dP/dt and the pressure developed (dP/dt/P) (1,530 +/- 287) 1,600 +/- 329 mm Hg/s [p less than 0.05], and 30 +/- 6 to 34 +/- 8 s-1 [p less than 0.05], respectively) demonstrated the inotropic effect of k-strophantidin, whereas volumetric parameters of systolic function (end-systolic and stroke volume indexes, and ejection fraction) did not show any significant change. However, LV relaxation was impaired by k-strophantidin injection; in fact, mean values of T constant were significantly increased from 50 +/- 12 to 55 +/- 13 ms (p less than 0.01). Lowest LV and end-diastolic pressures increased from 8 +/- 4 to 11 +/- 4 mm Hg (p less than 0.05) and from 17 +/- 6 to 20 +/- 8 mm Hg (p less than 0.05), respectively. The end-diastolic volume and maximal rate of volumetric increase during the early and late filling phases were not modified by k-strophantidin. Mean aortic pressure increased from 110 +/- 10 to 120 +/- 12 mm Hg (p less than 0.001). Therefore, in patients with coronary artery disease and LV preserved performance, an acute intravenous administration of k-strophantidin appears to stimulate contractility and to worsen relaxation, and minimal LV and end-diastolic pressures.

[Reactions of the cardiovascular system to volume load and strophanthin administration in the early period after radical thoraco-abdominal surgical interventions in cancer patients]. / Reaktsii serdechno-sosudistoi sistemy na ob"emnuiu nagruzku i vvedenie strofantina v rannem periode posle radikal'nykh torakoabdominal'nykh khirurgicheskikh vmeshatel'stv u onkologicheskikh bol'nykh.

Cardiovascular reactions were assessed in 65 cancer patients who had been given volume load to the heart with sequential strophanthin in early postoperative period following thoraco-abdominal surgery. Positive hemodynamic reaction to the volume load was observed in 60% of cases whereas negative--in 35.4% while after strophanthin treatment the figures were 52.3 and 43.1%, respectively. Combination of values observed in the two tests proved indicative of the pathogenetic mechanism underlying postoperative circulatory disorders: cardiac failure, hypovolemia or syndrome of peripheral vasoconstriction. These data should be considered in choosing infusion and other medicinal treatment in early postoperative period.

[Chronopharmacodynamics of delayed-action cardiac glycosides and nitrates]. / Khronofarmakodinamika serdechnykh glikozidov i nitratov prolongi- rovannogo deistviia.

In 96 patients with coronary heart disease and stage II circulatory failure, the chronopharmacodynamics of strophanthin, corglycon, and nitrosorbide was studied by using acute clinical and pharmacological tests in the morning (8.00 a.m.), in the afternoon (2.00 p.m.), and in the evening (8.00 p.m.). Central and peripheral hemodynamic parameters were measured prior to and following 5, 15, 30, 60, and 120 min of intravenous injection of cardiac glycosides or sublingual administration of nitrosorbide in a dose of 10 mg for 240 min. The investigations showed that there were the most profound hemodynamic changes in the morning if strophanthin was used and in the afternoon if corglycon was given. The maximal reduction in heart pre- and afterload was seen in the morning when nitrosorbide was applied, the most improvement in central hemodynamic parameters was observed in the evening when nitrosorbide was used.

[Treatment of patients with ischemic heart disease in the initial stage of heart failure using strophanthin electrophoresis]. / Lechenie bol'nykh ishemicheskoi bolezn'iu serdtsa s nachal'noi stadiei serdechnoi nedostatochnosti élektroforezom strofantina.

It was established that strophanthine electrophoresis produced a positive inotropic effect associated with a pronounced improvement of the peripheral blood flow. It is concluded that strophantine electrophoresis is indicated as a method of maintenance treatment in patients with cardiac insufficiency.

Retinal toxicity in albino rabbits induced by intravitreal injection of strophanthin-K.

Time course and extent of strophanthin-K induced disturbances of flash electroretinogram (F-ERG) has been observed in 12 albino rabbits treated by a single dose of 1, 3 and 9 ug/0.1 ml of intravitreal injection. A phenomenon of the dependence of a- and b-wave amplitude changes on dosage was demonstrated. A 9 ug/0.1 ml dose caused a flat a- and b-wave showing the F-ERG wave could be completely suppressed by larger dose of strophanthin-K. Two parameters of "attenuation kinetics" are proposed to identify the pharmacodynamics and toxic kinetics on retina as time profile is concerned: 1) B (the slope of attenuation curve); 2) Et1/2 (half attenuative time). B and Et1/2 are helpful in making a tentative identification of the target cells on retina and in demonstrating a synergism or antagonism between drugs if any. The a-wave of F-ERG, having a steeper slope, is more sensitive than b-wave in terms of strophanthin-K toxicity bringing forth a quantitative criterion in visual pharmacology. The attenuation of amplitude in a-wave may therefore be considered as an early response to this drug. The direct pupillary response test were also done pre- and post-strophanthin-K, and the results of this test support that of F-ERG.

[Chronobiological approach to the diagnosis and therapy of cardiovascular diseases]. / O khronobiologicheskom podkhode k diagnostike i terapii zabolevanii serdechno-sosudistoi sistemy.

Some aspects of chronodiagnosis and chronotherapy of cardiovascular diseases were described. To reveal circadian cycles each examined person was observed for 3-5 days, the indices studied being measured every 4 h. The evaluation of a rhythm period was done using the dispersion analysis for the detection of non-sinusiodal rhythms and the approximation method for the detection of sinusoidal rhythms with a preset period (the cosignor analysis) and an unknown period (the least square method combined with the iteration method). Opportunities for the detection of changes or disorders of the time structure of examined function and approaches to chronotherapy were studied on clinical material.

[Dilatation (congestive) cardiomyopathy: clinical aspects, diagnosis and treatment]. / Dilatatsionnaia (zastoinaia) kardiomiopatiia: klinika, diagnostika i lechenie.

Clinical and electrocardiographic manifestations of congestive cardiomyopathy are considered on the basis of observations of 25 patients with this pathology of the myocardium. No clinico-electrocardiographic signs specific for this disease were found. Most characteristic were cardiomegaly, congestive cardiac failure and various disturbances of rhythm and conductivity. Thromboembolic complications in the lung and kidney vessels are frequently found. Cardiac glycosides, saluretics and vasodilators were employed in the treatment of patients with congestive cardiomyopathy but the prognosis was usually poor.

[Correction of protein metabolism in myocardial infarction according to the results of radionuclide studies with 131-albumin during during treatment with a number of drugs (retabolyl, methyluracil, panangin, strophanthin) and combinations of them]. / Korrektsiia belkovogo metabolizma pri infarkter miodarda po dannym radionuklidnykh issledovanii so 131I-albuminom pod vliianiem riada lekarstvennykh sredstv (retabolila, metiluratsila, panangina, strofantina) i ikh kombinatsii.

The effect of a series of drugs (retabolil, strophanthin, retabolil with strophanthin, retabolil with panangin , methyluracil with panangin ) on protein metabolism was investigated in 246 patients with acute myocardial infarction. Retabolil both alone and combined with panangin , and a methyluracil-- panangin combination were found to have anticatabolic and protein synthesizing effects. Strophanthin, when used in the acute period of myocardial infarction, contributes to an increase in the protein decay rate and a decrease in protein synthesis. When it is employed in combination with metabolism corrective agents (retabolil), the adverse effects of strophanthin mentioned above are eliminated.

Effect of cardiac glycosides on the coronaries: physiologic and morphologic studies in the dog heart.

The effect of K- strophanthoside on coronary blood flow (CBF) was studied in open chest dogs anaesthetized with pentobarbital sodium. K- strophanthoside (3.5 and 7.0 X 10(-8) mol X kg-1 i.v.) elicited a dose-dependent decrease of CBF and an increase of late diastolic coronary resistance. Intracoronary injections of the drug (1.2 X 10(-8) mol) produced selective coronary constriction. The haemodynamic pattern indicated a direct vasoconstrictor effect, independent of the extracoronary (cardiotonic) action of the drug. In the polarization microscope Romh anyi 's aldehyde bisulphite-toluidine blue (ABT) reaction as adapted for the detection of cardiac glycosides showed profuse binding of strophanthoside to the coronary vessel wall. K- strophanthoside significantly reduced the CBF increase elicited by adenosine infusion (2 X 10(-7) mol X kg-1) into the left heart. Verapamil (4 X 10(-7) mol X kg-1, i.v.), on the other hand, counteracted the strophanthoside action on CBF. The results suggest that restricted intracellular availability of Ca2+, a prerequisite of physiologic CBF increase, is opposed by cardiac glycosides.

[Pharmacological correction of cerebral circulation in experimental acute myocardial ischemia]. / Farmakologicheskaia korrektsiia krovoobrashcheniia mozga pri éksperimental'noi ostroi ishemii miokarda.

In acute experiments on anesthetized cats myocardial ischemia led to a reduction of the total brain circulation because of the increased resistance of brain vessels and lowered perfusion pressure. After administering curantyl, euphylline and nonachlazine myocardial ischemia brought about less pronounced decrease of the total brain circulation largely at the expense of elimination of brain vessels constriction. After administering strophanthine alone or combined with curantyl myocardial ischemia did not lead to any essential alterations in brain blood supply. It is likely that strophanthine and curantyl recover the compensatory mechanisms of the brain vessels lost during acute myocardial ischemia.