A double-blind placebo controlled trial of diltiazem in Duchenne dystrophy.

The role of calcium accumulation in the pathogenesis of Duchenne muscular dystrophy (DMD) has already been discussed. Several trials with different calcium-blocking drugs have revealed no clinical benefit. In addition, the present study includes histological investigations and computer tomography to verify therapeutic effects. In a randomized placebo-controlled double-blind study, 13 DMD patients aged from 3-10 years (mean, 7 years) were treated with 5 mg/kg diltiazem daily for 1 year. Compared with before therapy, the number of calcium-positive muscular fibres was remarkably reduced in the treated DMD patients, but not in the placebo group. The evaluation of all other biochemical and clinical parameters revealed no significant effects of the diltiazem therapy. The muscular X-ray density measured by computer tomography decreased under treatment. After the evaluation of the double-blind study, the code was broken. Therapy, however, was continued in the treated group and started in the placebo group. After 3 years of diltiazem therapy the clinical status of all 26 patients of the study and 20 additional DMD patients who were treated with diltiazem was compared with 46 untreated DMD patients of the same age and stage in our department. No obvious clinical benefit of diltiazem therapy could be observed.

[Acute heart failure in pheochromocytoma in childhood. Case report and demonstration of therapeutic possibilities]. / Akute Herzinsuffizienz bei Phäochromozytom im Kindesalter. Fallbericht und Darstellung von Therapiemöglichkeiten.

A noradrenaline-secreting phaeochromocytoma of extra-adrenal origin was found as cause of acute cardiac insufficiency in a 12-year-old child. After i.v. treatment with diuretics, digitalis and oral alpha-sympathicolysis with phenoxybenzamine the tumor was surgically removed several days later without further complications.

Primary systemic carnitine deficiency under successful therapy: clinical, biochemical, ultrahistochemical and renal clearance studies.

Systemic carnitine deficiency is an often fatal, but treatable metabolic disorder which should be considered in any child with repeated episodes of a Reye-like syndrome or a cardiomyopathy. A 4-year-old girl with a typical history and clinical findings was successfully treated with oral carnitine. Despite low liver carnitine, ketogenesis upon fasting was normal. Normal muscle function under therapy was associated with unchanged low muscle carnitine levels. Improvement of mitochondrial structure and function was demonstrated by controlled ultrahistochemical studies. A renal carnitine leak, evident from renal clearance studies, may contribute to the pathogenesis of systemic carnitine deficiency.

[The angiocardiographic image following determination of axial-oblique projection with 2-dimensional echocardiography]. / Kardioangiographische Darstellungen nach Bestimmung der axial-schrägen Projektionsrichtung mit zweidimensionaler Echokardiographie.

A precise prediction of axial-oblique angulation in cineangiocardiography by noninvasive investigation is possible. A simple method is described using two-dimensional echocardiography to determine the cross-sectional plane. The perpendicular X-ray beam presents the angiocardiographic feature related to the echocardiographically determined plane. The described method is most helpful in diagnosis of simple morphological changes (ASD, VSD) as well as in complex congenital heart defects. To our knowledge this is the first report of the application of two-dimensional echocardiography to cardioangiographic axial-oblique angulation.

[The percutaneous cardiac catheterization in the diagnosis of congenital cardiac failure (author's transl)]. / Die perkutane Herzkathetereinführung in der Diagnostik kongenitaler Herzfehler.

The results of a modified percutaneous approach of 113 cardiac catheterizations will be reported. The success rate for the right heart catheterization from the unselected cases in 63% in infants, 84% in those one to five years old and 96% in those children older than five years. For the retrograde left heart catheterization, the percutaneous approach was successful in infants in 91% (except one patient with aortic coarctation) and successful in all patients older than one year.

The influence of hypoxia and metabolic inhibitors on the excitation process in atrioventricular node.

In small specimens prepared from the atrioventricular node of rabbits, the influence of hypoxia and metabolic inhibitors (Na-cyanide, 2.4 dinitrophenol, 2-desoxyglucose) on the av-node action potential was studied. The action potentials in these specimens proved to be of slow response type regardless of their origin, either the N or the NH-region of the node. 1. Following superfusion with O2-poor Tyrode solution, Vmax of the atrioventricular action potential gradually declined within 90 min and attained finally a new steady state. A mean decrease of 30.2 +/- 9.4% was obtained. Frequency a automatic impulse formation went down by almost the same amount within only 20 min. On return to an oxygenated Tyrode solution, or in the continued presence of O2 deficiency after an increase of the external glucose concentration from 11 mM to 33 mM, full recovery of these effects occurred. 2. After administration of Na-cyanide (1 X 10(-3) M), a similar Vmax decrease of 29.0 +/- 7.0% appeared. It took only 20 min for full development and was accompanied by a decrease reversible within 10-20 min on return to a cyanide-free medium. Poisoning the atrioventricular cell with 2.4 dinitrophenol (1 X 10(-3) M) led to the same result. Treatment with 2-desoxyglucose (3 X 10(-2) M) evoked a more pronounced Vmax diminution of 50%. 3. The inhibitor of K conductance, 4-aminopyridine (2 X 10(-3) M) did not remove the metabolically induced changes of Vmax of the atrioventricular action potential. After poisoning of oxydative phosphorylation, this compound caused in some cases evan a further reduction of Vmax. 4. The beta-adrenergic compound isoproterenol (9.2 X 10(-6) M) restored the hypoxia or cyanide-induced suppression of both Vmax and frequency of automatic impulse formation. The particularly pronounced response of Vmax led to an increase far exceeding the initial control values obtained under normal metabolic conditions of the atrioventricular cell.

[Stereovectorcardiography. Analysis of congenital excitation-conduction anomalies using a new type of microelectronic equipment (author's transl)]. / Stereo-Vektorkardiographie. Analyse kongenitaler Reizleitungsanomalien mit einer neuen mikroelektronischen Technik.

The results of the first clinical trial of a stereo-VCG used for the quantitative and qualitative analysis of congenital anomalies of excitation-conduction are elaborated and discussed. Normal values for paediatric cardiological patients were calculated for the following parameters with the help of measurements from 78 patients: Pmax, Rmax, Tmax-stereovectors, their elevation and azimut, the stereo-angle between Rmax/Tmax, Pmax/Tmax and Pmax/Rmax as well as the periods from the beginning of the ventricular excitation until Rmax and Tmax. The patients were divided into 4 age groups. The group of normal individuals was compared with 22 patients having anomalies of conduction. The results show that this new technique allows more differentiated analyses of the vector loops registered according to Frank's orthogonal corrected registering system than the conventional measurements in cases of congenital anomalies.

Influence of low extracellular pH upon the Ca inward current and isometric contractile force in mammalian ventricular myocardium.

In isolated papillary muscles of cats the changes in Ca inward current and isometric contractile force following a decrease of extracellular pH from 7.4 to 5.5 were studied. The Ca current was analyzed (a) by measuring the upstroke velocity of Ca-mediated action potentials and (b) in voltage clamp experiments using the double sucrose gap technique. 1. At a pH of 5.5 the upstroke velocity of the Ca-mediated action potential decreased to 65% of the control, while overshoot and action potential duration remained almost unchanged. Furthermore, the relative refractory period was prolonged and in some cases, a "Wenckebach-like" phenomenon occurred. In voltage clamp experiments, the slow inward current was found to be diminished to 50-60% of the initial control value and over a broad voltage range the current voltage relationship curve was shifted to weaker currents. Acidosis did not influence the steady state inactivation but altered the kinetics of inactivation of the slow inward current and induced an increase of tauinactivation and taurecovery. This indicates that acidosis exerts a complex effect on the slow membrane channel. 2. The normal response of the Ca current towards variations of the extracellular Ca concentration (0.5-4 mM) or towards the addition of the beta-stimulating compound isoproterenol (2 mg/l) was not altered by the lowered extracellular pH. 3. In the acid medium, isometric contractile force declined to 40% of the control value within 25 min and, thus, reacted stronger than the Ca current. This indicates that those forms of acidosis used in the present experiments caused their negative inotropic effect not exclusively via a depression of the Ca current. Rather an additional intracellular effect has to be assumed which finally leads to a reduced activity of the contractile system. 4. At pH 5.5 excess Ca (4 mM) induced the same quantitative response of the contractile system as obtained at normal pH. In contrast, the positive-inotropic effect of 2 mg/l isoproterenol was more pronounced, whilst the sensitivity of the Ca inward current towards this beta-stimulating compound remained unchanged.

The response of Ca-mediated action potentials and contractile activity in mammalian ventricular myocardium towards alkalosis.

Alkalosis (pH 7.8) produced by reduction of CO2 concentration augmented both upstroke velocity of Ca action potentials and isometric contractile force of mammalian heart muscle. If the increase of pH to 7.8 was achieved by a raise of HCO3 concentration (with simultaneous reduction of CO2 concentration), the positive inotropic response was not accompanied by an augmented Ca current. Obviously, the well-known positive inotropic effect of alkalosis does not only depend upon the enhancement of transmembrane Ca influx during excitation, but can be mediated alone by affecting intracellular Ca movements as well.