[Ineffective anticoagulation prior to elective electric cardioversion for atrial fibrillation. Results of transesophageal echocardiography]. / Ineffektive Antikoagulation vor elektiver elektrischer Kardioversion von Vorhofflimmern. Befunde der transösophagealen Echokardiographie.

BACKGROUND AND OBJECTIVE: Anticoagulation (AC) should be given for 3 to 4 weeks before elective electrical cardioversion to reduce thromboembolic events. During this period ineffective AC is a common problem. The aim of our study was to investigate the influence of the duration of ineffective AC on the incidence of left atrial thrombi (LAT) or spontaneous echocontrast (SEC) induced by hemostasis detected by transesophageal echocardiography (TEE). PATIENTS AND METHODS: 56 consecutive patients (39 men) at the age of 64 +/- 9 years with non-rheumatic atrial fibrillation who were scheduled for electrical cardioversion after 3 to 4 weeks of AC and a documented ineffective AC underwent TEE. Cardioversion was performed after exclusion of a LAT by TEE or in patients with LAT after 4 more weeks of AC and repeated TEE. All patients received AC and were observed for at least 4 weeks after cardioversion. Echocardiographic, demographic and clinical parameters and available values of AC were recorded. RESULTS: In 5/56 (9 %) patients a LAT, in 10 (18 %) patients SEC was detected. No patient had both. In patients with LAT the duration of ineffective AC was 15 +/- 10 days (range 5 - 28) and did not differ significantly from patients without LAT (17 +/- 8 days; range 0 - 28) or to the group with SEC (23 +/- 6 days; range 12 - 28). There was no significant difference of demographic, echocardiographic and clinical parameters between these groups. There was no embolic event during follow-up. CONCLUSIONS: Neither the duration of ineffective AC nor clinical, epidemiologic or echocardiographic parameters could differentiate patients with or without LAT in our observed groups with small numbers of patients. In case of an ineffective AC patients who are to undergo electrical cardioversion should have TEE. In our study patients with SEC were not at a higher thromboembolic risk.

Femoral injection of echo contrast medium may increase the sensitivity of testing for a patent foramen ovale.

OBJECTIVE: The diagnosis of a patent foramen ovale (PFO) as a cause of stroke is of increasing interest especially in young (<45 years) patients. METHODS: We studied potential right-to-left shunting using transesophageal echocardiography (TEE) and bilateral transcranial Doppler sonography (TCD) of the middle cerebral artery (MCA) simultaneously in 44 patients. All patients were younger than age 45 years and suffered from an acute ischemic stroke or transient ischemic attack. Other possible etiologies were excluded. Echo contrast medium was injected in an alternating mode via antecubital or femoral veins. Tests were performed with and without the Valsalva maneuver. The criteria for a PFO were that the contrast pass from the right to the left atrium (TEE) and early detection (<10 seconds) of more than 10 micro air bubbles in at least one MCA by TCD. RESULTS: A PFO was diagnosed in 22 patients (50%). The detection rate with TEE/TCD was 11.4%/4.5% via antecubital injection, 18%/13.6% via antecubital injection plus the Valsalva maneuver, 38.6%/36% via femoral injection alone, and 50%/50% via femoral injection plus the Valsalva maneuver. The difference between femoral and antecubital injections was significant with and without the Valsalva maneuver (p < 0.01, chi2 test). There were no differences between TEE and TCD after femoral injection with the Valsalva maneuver. The brain transit time was 4.6 +/- 2.1 seconds for femoral injection and 6.3 +/- 4.1 seconds for antecubital injection. CONCLUSIONS: The sensitivity in detecting a PFO was markedly increased by femoral injection. This may be caused by different inflow patterns to the right atrium: inferior vena caval flow is directed to the right atrial septum, whereas superior vena caval flow is directed to the tricuspid valve. Thus, femoral injection may help to improve the detection of PFO and may explain the differences between TEE and TCD findings in previous studies.

Facilitating influence of procainamide on conversion of atrial flutter by rapid atrial pacing.

In a prospective, double-blind, randomized, placebocontrolled study we investigated the facilitating influence of intravenous procainamide on conversion of atrial flutter by rapid atrial pacing. Fifty consecutive patients with spontaneous sustained atrial flutter were 1:1 randomized into two homogenous groups: group A received 10 mg.kg-1 procainamide intravenously, group B placebo. After infusion there was a significant (P < 0.01) lengthening of the flutter cycle with respect to baseline in group A, exceeding the flutter cycle length of the control group (P < 0.05). The overall success rate of rapid atrial pacing in restoring sinus rhythm was significantly higher after pre-treatment with procainamide compared to placebo (100% vs 76%; P < 0.05): 20 patients of group A reverted immediately after pacing to sinus rhythm, the remaining five after a brief episode of atrial fibrillation. In the placebo group, 16 patients showed a prompt conversion to sinus rhythm and three after transient atrial fibrillation. In the remaining six patients, due to sustained pacing-induced atrial fibrillation, direct current cardioversion was necessary. After administration of procainamide a less aggressive stimulation protocol with significantly (P < 0.01) longer paced cycles to interrupt atrial flutter was achievable. In conclusion, intravenous procainamide augments the efficacy of atrial pacing to convert atrial flutter to sinus rhythm.

Low energy transvenous cardioversion of short duration atrial tachyarrhythmias in humans using a single lead system.

The purpose of this study was to investigate the efficacy and safety of atrial cardioversion using an endocardial single lead system presently used for ventricular defibrillation. The study population consisted of 26 recipients of an ICD in combination with a conventional endocardial single lead system with the proximal spring electrode as anode in the SVC and the distal as cathode in the apex of the RV. Atrial tachyarrhythmias were induced by right atrial burst pacing. If the arrhythmia sustained > 1 minute, biphasic shocks synchronized with the R wave were delivered using the implanted device, beginning with an energy of 4 J. If 4 J failed to terminate the arrhythmia, energy was increased stepwise, if the first shock was successful, a step-down testing was performed after reinduction of atrial tachyarrhythmias. The mean atrial defibrillation threshold was 2.3 +/- 1.2 J (range, 0.5-5 J). A total of 154 shocks were delivered and no adverse effects were observed. The mean defibrillation threshold for atrial flutter was somewhat lower than that for AF (1.8 +/- 1 J vs 2.7 +/- 1.4 J, P = 0.08). There was no correlation between the atrial defibrillation threshold and a history of previously occurring atrial tachyarrhythmias, the kind of the underlying heart disease, a prescription of antiarrhythmic drugs, the dimension of the LA, the LVEF, or the ventricular DFT. Internal atrial cardioversion of short duration atrial tachyarrhythmias using a transvenous single lead system designed for ventricular defibrillation is feasible and safe at low energies, and may have important clinical applications.

[Amiodarone-induced pulmonary toxicity]. / Amiodaroninduzierte Lungenveränderungen.

Amiodarone is highly effective in suppressing ventricular and supraventricular tachyarrhythmias. The most serious adverse reaction is pulmonary toxicity. The mechanisms involved in amiodarone-induced pulmonary injury are incompletely understood. Several forms of pulmonary disease occur including interstitial pneumonitis, fibrosis or organizing pneumonia. The incidence is generally lower with lower maintenance doses (

[Initial clinical experiences with low energy internal cardioversion of chronic atrial fibrillation after unsuccessful external cardioversion]. / Erste klinische Erfahrungen mit der niederenergetischen internen Kardioversion von chronischem Vorhofflimmern nach erfolgloser externer Kardioversion.

Between January and September 1995, 54 consecutive patients (male: 34, age: 66 +/- 10 years) with symptomatic chronic atrial fibrillation (median duration: 4.5 months) were referred for external electrical cardioversion to our hospital. Mean left atrial diameter was 49 +/- 9 mm, heart disease was apparent in 81%. All patients were under antiarrhythmic drugs (class III: 85%). In 49 patients (91%) sinus rhythm was achieved. In five patients atrial fibrillation persisted after delivery of 360 Joules. These five patients were characterized by a significantly higher body weight in comparison to patients with successful external cardioversion. All five patients underwent low energy internal cardioversion the following day: biphasic R-wave synchronous shocks were delivered through catheters positioned in the right atrium and the coronary sinus using stepwise increased energy levels. Internal cardioversion was successful in all patients resistant to external cardioversion: stable sinus rhythm was established at a mean energy level of 13 +/- 6.7 Joules. No complications were observed. During the follow-up, each patient revealed a relapse of symptomatic atrial fibrillation within 2 weeks after internal cardioversion despite antiarrhythmic therapy, whereas only 16 patients (33%) lost sinus rhythm during the same period of time after external cardioversion (p < 0.01). During a mean follow-up of 283 +/- 72 days 21 patients (43%) preserved stable sinus rhythm after external cardioversion. Internal low energy cardioversion seems to be effective and safe in conversion of chronic atrial fibrillation resistant to external cardioversion. The clinical value of this invasive, time- and material-consuming therapy seems to be limited in this setting because of the high early relapse-rate in the investigated patient population. Further clinical studies in a larger cohort of patients are necessary.

[Diurnal distribution of spontaneous ventricular tachyarrhythmias in patients with implanted cardioverter defibrillator]. / Tageszeitliche Verteilung von spontanen ventrikulären Tachyarrhythmien bei Patienten mit implantierbarem Kardioverter-Defibrillator.

The purpose of this study was to analyze temporal patterns of spontaneous ventricular tachyarrhythmias in patients (p) with implantable cardioverter-defibrillator (ICD). By reading out the ICD-data logs 725 arrhythmic episodes (e) from 43 patients were investigated. After grouping the episodes into four defined time periods (period 1: midnight to 6 a.m., period 2: 6 a.m. to noon, period 3: noon to 6 p.m., period 4: 6 p.m. to midnight) according to the data stored by the device, the percentage of episodes per time period has been calculated for each patient who experienced at least 10 arrhythmic events (n = 22). A significant peak occurrence (mean 34%) could been demonstrated for the morning hours (period 2). Analyzing patients individually, 4 subgroups could be identified: group 1 with an episode peak in period 2 (9 p, 277 e, p < 0.01), group with an episode peak in period 3 (4 p, 83 e, p < 0.01), group 3 with a peak occurrence in period 4 (3 p, 110 e, p < 0.01) and group 4 with an equal episode distribution over all four time periods (6 p, 187 e). Comparing sustained and nonsustained tachyarrhythmias, the nonsustained episodes were found to be distributed much more equally, meanwhile the circadian variation for fast (HR > or = 240/min) and slower (HR < 240/min) arrhythmias was identical. Regarding episodes of patients on beta-blocker or class III-antiarrhythmic therapy the same circadian variation has been found. There was no significant difference between the subgroups of patients with an episode peak in period 2 and the other patients concerning age, sex, cardiac disease, left ventricular ejection fraction, clinical arrhythmia, beta-blocker or class III-antiarrhythmics, number of recorded episodes or follow-up time. Further studies are needed to determine a possible correlation between these findings and different circadian variations in individual psychovegetative activity.

Binding of 3H-aldosterone and 3H-dexamethasone in primary monolayer cultures of kidney cortical collecting tubule (CCT) cells.

Specific binding of corticosteroids in cultured CCT cells was measured as a function of time, of temperature, of pH, and of concentration. Scatchard analysis revealed the existence of two species of binding sites for both, 3H-aldosterone type I A: KD = 2.3.10(-9) M, N = 33.10(-17) mol/10(4) cells; type I B: KD = 51.10(-9) M, N = 55.10(-17) mol/10(4) cells) and dexamethasone (type II A: KD = 4.7.10(-9) M, N = 2.3.10(17) mol/10(4) cells; type II B: KD = 22.10(-9) M, N = 6.5.10(-17) mol/10(4) cells). The data demonstrate that CCT cells in primary monolayer culture express corticosteroid binding sites similar to cells of the CCT in vivo.

Protein content in rabbit periodontal ligament fibroblasts during growth in culture.

The protein content of an individual periodontal ligament fibroblast decreases with increasing cell density during growth in culture. A mean total protein concentration of 3.3 +/- 0.4 micrograms per 10(3) cells was calculated. This reference value can be used in studies evaluating enzyme activities, transport rates or metabolic functions.

Transport and metabolic functions in cultured renal tubule cells.

The study tool of cultured tubule epithelia has been applied to new areas in nephron cell biology, such as the evolution of epithelial membrane asymmetry. Studies utilizing monoclonal antibodies against plasma membrane glycoproteins in MDCK revealed that the development of surface cell polarity is a continuous process requiring intact tight junctions and their electrical resistor function [101]. The role of the junctional complex to establish and maintain distinct membrane protein domains had been suggested earlier from work utilizing the apical aminopeptidase [102] and fluorescent membrane probes [103]. Cultured tubule epithelia lend themselves for the evaluation of cell-specific membrane protein synthesis [104] and antigenic determinants [105]. Human renal epithelia, from normal [106, 107] and defined abnormal kidney [108], have been maintained functional in primary and passage culture [106]. Pathophysiological mechanisms may be examined in cultured tubule epithelia, as shown first [109] by studies on the recovery from ischemic failure, where anoxia and substrate deprivation resulted in cell swelling which was prevented in culture by an oncotic agent. This article has not attempted to give an exhaustive account of the studies in which cultured tubule cells have served as a tool. Instead, the investigations quoted herein represent some principal lines of study, as seen from renal physiology, which may disclose details in culture of complex in vivo phenomena. It was Bernard [110] who, in 1865, suggested that "physiological events must be isolated outside the organism . . . to better understand the deepest associations of the phenomena."

Protein content of epithelial cells of rabbit renal cortical collecting tubules (CCT) during growth in culture.

Protein content per cell in epithelial monolayers derived from cortical collecting tubules (CCT) of the rabbit kidney decreases with increasing cell density during growth in culture. When expressed per 500 cells in culture (this number of cells is present per mm of segmental length in vivo, a total protein concentration of 149 +/- 18 ng was measured. In the in vivo CCT nephron segment, total protein concentration was 172 +/- 16 ng per mm of segmental length.

p-Aminohippurate (PAH) transport and Na-K-ATPase activity in rat renal cortical slices during postnatal maturation and drug-induced stimulation.

PAH transport and Na-K-ATPase activity markedly increase during the first month of postnatal life. Pretreatment of rats with PAH or cyclopenthiazide induces a stimulation of in vitro PAH accumulation in renal cortical slices, whereas Na-K-ATPase activity is unchanged in comparison to saline-pretreated controls. 5 mM ouabain in the incubation medium reduces PAH accumulation. Developmental pattern and stimulation effects are pronounced as in controls. The ouabain-insensitive component of net PAH accumulation progressively increases with age and is significantly enhanced following drug pretreatment, whereas the ouabain-sensitive component of net PAH accumulation shows relatively slight modifications. Consequently, Na-K-ATPase seems not to be linked with postnatal maturation or drug-induced stimulation in tubular PAH transport.

[Stimulation of the renal transport of foreign substances following unilateral nephrectomy]. / Stimulation des renalen Fremdstofftransportes nach unilateraler Nephrektomie.

During the phase of compensation of parenchyma loss two different mechanisms can be stated causing an improvement of renal tubular transport capacity. Besides an increase of tubular transport ratio in kidney slices from nephrectomized rats an increased mass of kidney tissue participated in the augmented transport capacity. 24 h after unilateral nephrectomy TmPAH is elevated from 0.40 +/- 0.10 to 0.61 +/- 0.13 mg/min x g kidney weight. The simultaneous increase in slice-to-medium ratio of renal cortical slices demonstrate the increase in specific transport capacity of regenerating kidney tissue. Furthermore the increase in kidney mass is the reason for an elevated transport capacity. Stimulation of renal PAH excretion by repeated pretreatment with cyclopenthiazide shortened the phase of compensation and raised the extent of tubular transport capacity following partial loss of kidney tissue. The specific accumulation of PAH in renal cortical slices from nephrectomized, cyclopenthiazide pretreated rats is distinctly elevated 96 h after unilateral nephrectomy from 19.4 +/- 2.7 to 24.3 +/- 0.6 micrograms/g kidney weight. Obviously there are different mechanisms for the increased PAH transport caused by stimulation and by regeneration after unilateral nephrectomy, because additional effects can be stated in regenerating rats by additional stimulation of renal tubular transport.

Stimulation of kidney function in rats injured by nephrotoxic agents.

After single administration of potassium dichromate or glycerol, renal PAH excretion was markedly reduced in adult, but not in newborn and infant rats. As already demonstrated in rats with intact kidney functions, repeated administration of PAH or cyclopenthiazide stimulates also renal PAH excretion in rats with acute renal failure. In detail, after PAH or cyclopenthiazide treatment of rats the duration of injury is shortened whereas the intensity of the nephrotoxic effects is not changed. However, the stimulation depends on the age of animals as well as on the nephrotoxic agent administered.

In vitro analysis of postnatal maturation of tubular p-aminohippurate transport in rat kidney.

Factors responsible for the developmental pattern in renal tubular PAH transport were analysed. The apparent Michaelis constant for PAH uptake is the same in all ages, whereas the maximum steady-state PAH uptake as well as the PAH efflux are increasing with age. In consideration of the significant differences in PAH efflux, the age-related differences in maximum steady-state PAH uptake do not accurately reflect the postnatal maturation of the transport mechanism. Therefore, the actual PAH uptake was calculated in renal cortical slices from rats of different ages. The data were related to units of wet weight, protein, and DNA. In conclusion, for the increasing renal tubular PAH transport with age both a quantitative increase in functional transport sites as well as an enhancement in the turnover-rate of the transport mechanism seem to be responsible.

Succinate dehydrogenase activity in rat kidney after repeated administrations of p-aminohippurate or sodium chloride.

During PAH excretion and 18 h after repeated PAH administrations to rats, renal cortical SDH activity was unchanged in comparison with untreated controls. On the other hand, 18 h after repeated administrations of 0.9% or 1.8% NaCl solution, SDH activity was decreased by about 20% in kidney cortex. In outer medulla SDH activity was decreased 18 h after all pretreatments. The decline of SDH activity was observed whenever an increased urinary Na excretion occurred, except that PAH was repeatedly administered. The probability is discussed that substrate-induced stimulation of the carrier system for weak organic acids is accompanied by an increase of mitochondrial activity in kidney cortex.

Stimulation of kidney function in rats of different ages injured by nephrotoxic agents.

Intensity and duration of nephrotoxic effects can be characterized by measurement of renal p-aminohippurate (PAH) excretion. Single administration of potassium dichromate or glycerol is followed by a marked decrease of renal PAH excretion in dependence on the time after the administration as well as on the dosage used. Both agents are without effect in young rats with an immature tubular transport system for organic anions. As observed previously in rats with intact kidney function, renal PAH excretion can also be stimulated in rats with potassium dichromate or glycerol induced kidney damage. Stimulation of renal PAH excretion is possible in injured rats by repeated administrations of PAH and cyclopenthiazide, respectively. Exactly, the duration of injury is shortened whereas the intensity of the nephrotoxic effect is not changed. However, this effect depends on the age of rats as well as on the nephrotoxic agent administered.

Enhancement of p-aminohippurate accumulation in renal cortical slices after repeated administrations of various organic anionic drugs to rats of different ages.

After repeated administrations of various organic anionic drugs to rats of different ages, an enhancement of paminohippurate accumulation was observed in renal cortical slices from adult but not from newborn and infant rats. The effect can be interpreted as specific substrate-induced stimulation of the organic anion transport.