Influence of the beta-1 selective blocker, metoprolol, on the development of pulmonary edema in tocolytic therapy.

Research on one group of nine anesthetized dogs pretreated with alpha-naphthyl-thiourea showed that doses of the beta-sympathicomimetic fenoterol such as those normally administered in clinical tocolysis (2 micrograms/kg per minute) lead to significant fluid displacement to the extravascular space of the lung in the sense of a preclinical interstitial edema. In a second group (N = 9) with the same pretreatment the addition of the beta-1 selective blocker, metoprolol (1.5 micrograms/kg per minute) served to antagonize the hemodynamic changes and possibly the increase of pulmonary capillary permeability induced by the beta-mimetic. Fluid displacement into the interstitium of the lung was prevented by metoprolol. These observations corroborate the hypothesis that pulmonary edema occurring during tocolytic therapy is largely a result of the use of beta-mimetics. In addition to its cardioprotective effect, the administration of the beta-1 selective blocker, metoprolol, may reduce the risk of the development of pulmonary edema in beta-sympathicomimetic therapy for premature labor.

[Diagnosis and differential diagnosis of breast cancer using intravenous DSA]. / Diagnose und Differentialdiagnose des Mammakarzinoms mittels intravenöser DSA.

Intravenous DSA of the breast is a new, hardly invasive, method for demonstrating carcinomas of the breast and for differentiating these from benign lesions. Carcinomas show distinct tumour-staining during the capillary phase, although the criteria which are used on conventional angiography are not recognisable. Semi-malignant tumours show feeble staining. Benign diseases such as fibro-adenomas and focal sclerosing adenosis are not demonstrated by I-V DSA. The indication for intravenous breast DSA is for the clarification of suspicious findings where less invasive methods, such as mammography and cytology, have failed to give a definitive diagnosis.

[Investigations in animal experiments into the influence of the beta-1-selective blocking agent metoprolol on the cardiovascular and metabolic side effects of the tocolytic fenoterol]. / Der Einfluss des Beta-1-selektiven Blockers Metoprolol auf die kardiovaskulären und die metabolischen Nebenwirkungen des Tokolytikums Fenoterol im Tierexperiment.

The influence of the highly selective beta-1-adrenergic blocker Metoprolol on cardiovascular and metabolic side effects of the beta-mimetic Fenoterol, used for labour inhibition, was investigated in anesthetized mongrel dogs. In a dosage of 1.5 microgram/kg BW/min Metoprolol antagonized the positive inotropic and chronotropic cardiac effects of Fenoterol (0.06 microgram/kg BW/min) thus compensating the impaired energetic balance of the myocardium. As expected, there was no influence on the beta-mimetic mediated metabolic alterations. Taking into account its pharmacologic actions, the additional application of Metoprolol in labour inhibition with beta-mimetics seems to be advantageous. On account of the proven results a reduction of the more or less considerable missensations and a cardioprotective effect may be expected.

[Gynecological laparoscopy. A 5-year retrospective study on laparoscopy at the Technical University of Munich]. / Gynäkologische Laparoskopie. Eine retrospektive 5-Jahres-Studie über die Eingriffe an der Frauenklinik der Technischen Universität München.

In a retrospective study we evaluated the results of 598 laparoscopies which had been carried out in the years 1973 through 1977 at the Women's hospital of the Technical University in Munich. A considerable increase in pelviscopic tube sterilizations could be observed. Severe complications resulting in a laparotomy occurred in 0,5% of the cases. For laparoscopic operations the medical indication was restricted, whereas it was generously applied for the differential diagnosis of an ectopic gravidity. The sterilization techniques most frequently used at the moment are the bi-polar high-frequency technique and--to a smaller extent--the light-current coagulation technique. The uni-polar high-frequency technique can be regarded as obsolete. As far as a restoration of fertility is concerned, the individual application of the various sterilization methods can be expected for the future.

Does the administration of the calcium-antagonist verapamil in tocolysis with beta-sympathicomimetics still make sense?

In tocolysis with beta-sympathicomimetics Verapamil is administered universally to reduce the subjective and objective cardiovascular side effects. The efficacy of the calcium-antagonist has not yet been substantiated. This has now re-emerged as an important issue due to the increasing occurrance of cardiopulmonary complications in tocolysis, some fetal. Nine mongrel German shepherds were anesthetized and relaxed, and their breathing was controlled at constant volume. After infusion of Fenoterol (0.06 microgram/kg/min) and subsequent administration of Verapamil (2 microgram/kg/min) a continuous record was made of the parameters of the pulmonary and systemic circulatory systems, the cardiac dynamics, the acid-base balance, the blood gases with O2 absorption and CO2 output, electrolytes and the colloid osmotic pressure. Furthermore, the intrapulmonary fluid volumes in the vascular system and the interstice were measured. During infusion with Fenoterol the changes expected from a beta-adrenergic were observed in the form of a hyperkinetic cardiac situation, metabolic acidosis and increased exchange of gases. Also pronounced fluid shifts in the lungs occurred from the intravascular space to the interstice. Subsequent administration of the calcium antagonist showed no influence on the beta-mimetic-induced changes demonstrated in the present work. The results agree with previous clinical investigations. According to the known dosage curve, the dosage of Verapamil would have to be increased multifold to achieve an effect, which is hardly possible due to the cardiodepression and peripheral circulation drop with hypotension that this would entail. The administration of Verapamil in tocolysis no longer appears expedient.

[The determination of verapamil in maternal and fetal blood (author's transl)]. / Nachweis von Verapamil im mütterlichen und fetalen Blut des Menschen.

During the late first stage of labor and during the second stage of labor seven women in labor received an intravenous infusion during 60-110 minutes of verapamil at 2 g/k/per minute. Immediately following delivery of the infant, maternal and cord blood was drawn and the verapamil level measured by gas chromatography. The serum levels in the maternal blood were from 5.4 to 33.6 ng/ml. (Mean value 19.3 +/- 3.3 ng/ml) and the cord blood concentrations were 4.3-17.8 ng/ml (Mean value 8.5 +/- 1.9 ng/ml). The mean fetal serum level of verapamil was 51.4% of the mean maternal value.

[Does the calcium antagonist verapamil protect from myocardial damage during tocolysis with beta-sympathicomimetics? (author's transl)]. / Bietet der Kalziumantagonist Verapamil bei der Tokolyse mit Beta-Sympathikomimetika den erwarteten Schutz vor Myokardschäden?

Under general anaesthesia nine mongrel dogs were first injected with fenoteral 0.06 mg/kg/per minute and later with fenoteral 0.06 mg/kg/per minute and verapamil 2 mg/kg/per minute. A microtip manometer was placed into the left ventricle and cardiac pressures continously monitored. The resulting pressure curves were used in micro-computer to calculate the cardiac pressure parameters including the inotropic measurements and the myocardical oxygen consumption. The intravenous infusion of the beta-mimetic fenoterol resulted in marked increase of the cardiac rate and contractility as measured in the different measurement of the ionotrophy. A corresponding increase of the myocardical oxygen consumption was found. The addition of the calcium antagonist verapamil did have no influence of the measured parameters. A protective effect of the calcium antagonist on the myocaridium was excluded in the animal experiment. A protective effect during tocolysis with beta-sympathicomimetics cannot be expected because of the expected low serum concentrations.

[Liquid shifts in the lung under fenoterol and verapamil. Experimental study on the origin of pulmonary oedema under tocolysis. III (author's transl)]. / Flüssigkeitsverschiebungen in der Lunge unter Fenoterol und Verapamil. Experimentelle Studie zur Entstehung des Lungenödems unter Tokolyse. III.

The question of the causal relationship between tocolysis and pulmonary edema has been unresolved up till now. Eight mongrel dogs were given infusions of Fenoterol (0.06 mcg/kg/min) and later of Fenoterol (0.06 mcg/kg/min) and Verapamil (2 mcg/kg/min). In the case of infusion of Fenoterol alone measurements by the thermo-dye-technique showed massive shifts of lung fluids from the intravascular to the extravascular space corresponding to interstitial edema. The addition of Verapamil induced no further changes. The intrapulmonary haemodynamical overload by increased cardiac output and pulmonary arterial pressure which we measured after infusion of Fenoterol must be regarded as the main cause of the shifts in fluid volumes. They seem to be amplyfied by central nervous-, metabolic- and localized toxical effects of the betamimetic drug. A direct cardiac cause as well as serious changes in electrolytes and colloidosmotic pressure could be excluded.

[Respiratory and circulatory parameters under fenoterol and verapamil. An experimental study on the origin of pulmonary oedema under tocolysis. II (author's transl)]. / Respiratorische und zirkulatorische Parameter unter Fenoterol und Verapamil. Experimentelle Studie zur Entstehung des Lungenödems unter Tokolyse. II.

In order to explain the development of pulmonary edema it is, in addition to determine shifts of lung fluids, indispensible that changes in the circulatory system be evaluated as well as changes in the breathing function by means of analysis of blood gases and acid and base status. The relevant parameters were continuously registrated for 8 anaesthesized mongrel dogs after the infusion of Fenoterol (0.06 mcg/kg/min) and later of Fenoterol (0.06 mcg/kg/min) and Verapamil (2 mcg/kg/min). A cardiac disfunction and irregularities in the ventilation process in the lung could be excluded. The proven changes such as an increase in cardiac output with increased venous backflow, and intrapulmonary shunt-formation as well as acidosis after an infusion of the betamimetic drug are to be regarded among the causes of a development of pulmonary edema. Verapamil produced no further changes in the evaluated parameters.

[Method for measuring physiological changes under fenoterol and verapamil. An experimental study on the origin of pulmonary oedema under tocolysis. I (author's transl)]. / Methodik zur Messung von physiologischen Veränderungen unter Fenoterol und Verapamil. Experimentelle Studie zur Entstehung des Lungenödems unter Tokolyse. I.

Fluidshifts in the lung seem to play an important role in labour inhibition with fenoterol and verapamil. Therefore the experimental procedure for an investigation of these drugs is discussed in detail. The Thermo-Dye-Technic is used for quantitating pulmonary extravascular water. Moreover methods for monitoring pulmonary and systemic hemodynamics, bloodgases and acid-base-balance, metabolic parameters and the realization of the experiment are described.

[Induction of fetal lung-maturity. Part III: surfactant-parameters in amniotic-fluid and fetal lung]. / Pharmakologische Beeinflussung der fetalen Lungenreife Teil III: Surfactantspezifische Parameter in Fruchtwasser und Fetenlunge.

In animal experiments we determined surfactant-specific parameters of premature fetal lungs and of samples of amniotic fluid taken fromthe same animal, and compared them with each other. These parameters were, among others: total phospholipids, lecithine and palmitic acid. In these experiments, 75 gravid Wistar rats were treated with NaCl (controls) or drugs in clinically relevant doses for stimulating the fetal synthesis of phospholipids like betamethasone, bromhexine metabolite VIII and D-L-carnitine hydrochloride. A relation between the amniotic fluid and the fetal lung with regard to the quantity of surfactant substances was found - with a security of 95% - with the controls only. The value of amniotic fluid analysis is discussed under this aspect.

[Secondary extra-uterine pregnancy (author's transl)]. / Sekundäre Bauchhöhlenschwangerschaft.

The article reports on a patient with secondary extra-uterine pregnancy during the 20th pregnancy week. The highly multifaceted symptoms and the diagnostic possibilities are discussed on the basis of this case. Laparoscopy is rated decisively important.

[Diaplacental transfer of verapamil in guinea pigs (author's transl)]. / Untersuchungen zur Plazentapassage von Verapamil beim Meerschweinchen.

Verapamil (1--50 mcg/kg/min) was given to guinea pigs by intravenous infusion for 30 minutes. The average clinical dosage amounts to 1 (0,5--2) mcg/kg/min. At doses of 1--10 mcg/kg/min we could not find pharmacologically effective concentrations of verapamil in plasma, although concentrations in mother rose corresponding to administered doses. Only at dosage 50 mcg/kg/min we found comparatively to the mother low, but clearly measurable concentrations also in fetal plasma. That means: Verapamil, administered to guinea pigs--hemomonochorial placentation like man--in dosage, given for tocolysis does not appear in fetal plasma with pharmacologically effective concentration.