Effects of selective dopamine D1- and D2-type receptor antagonists on the development of behavioral sensitization to 7-OH-DPAT.

The primary objective of this study was to determine whether the development of behavioral sensitization to the putative dopamine D3 receptor agonist 7-OH-DPAT could be prevented by either selective D1-type or D2-type dopamine receptor antagonists. In three experiments, male Wistar rats (250-350 g) were given seven to nine injections (at 48-h intervals) of 7-OH-DPAT (1.0 mg/kg, SC) or vehicle in combination with the D2-type dopamine antagonist eticlopride (0.3 mg/kg, SC), the D1-type dopamine antagonist SCH 23390 (0.1 or 0.2 mg/kg, SC), or vehicle. After the injections, the rats were tested for locomotor activity in photocell arenas for 2 h. In the first two experiments, after seven injections, all rats were tested for activity following vehicle injections to test for possible conditioning effects. In each experiment, after the last pre-exposure session, all rats were given a challenge injection of 7-OH-DPAT (1.0 mg/kg, SC) and tested for activity. Major findings were as follows: a) 7-OH-DPAT treatments produced a progressively greater increase in locomotor activity with repeated treatment; b) concurrent treatment with eticlopride or SCH 23390 (0.1 and 0.2 mg/kg) blocked the acute locomotor-activating effects of 7-OH-DPAT across days; c) eticlopride, but not SCH 23390, completely blocked the development of behavioral sensitization to 7-OH-DPAT. Although the low dose of SCH 23390 (0.1 mg/kg) produced a partial attenuation of sensitization, the higher dose (0.2 mg/kg) of SCH 23390 appeared to augment, rather than block, sensitization to 7-OH-DPAT; d) rats previously treated with SCH 23390 (0.2 mg/kg, but not 0.1 mg/kg) without 7-OH-DPAT displayed a hyperactive response to the 7-OH-DPAT challenge injection; and e) after vehicle injections, rats previously given 7-OH-DPAT, SCH 23390, or eticlopride either alone or in combination were more active than vehicle control rats. These findings suggest that the neurochemical mechanisms mediating the development of behavioral sensitization to 7-OH-DPAT may differ from those of other dopamine D2-type agonists such as quinpirole or bromocriptine. Moreover, these results demonstrate that hyperactivity responses following vehicle injections in drug-pretreated animals do not necessarily reflect conditioning mechanisms.

[Antiarrhythmic drugs in chronic ventricular extrasystole (author's transl)]. / Antiarrhythmika bei chronischer ventrikulärer Extrasystolie. Vergleichende Untersuchung zur Wirksamkeit von Lidocain, Ajmalin, Propafenon und Org 6001.

Several class I antiarrhythmic drugs were used in an intraindividual comparative study in 15 patients with chronic stable ventricular extrasystole of various origins. In a randomised sequence lidocaine, ajmalin and, in a cross-over double blind study with placebo, the new antiarrhythmic Org 6001 were tested. Propafenon was given as a final preparation. Each substance was administered parentally in therapeutic doses. A significant placebo effect could be excluded, baseline control values before administration of individual substances correlated well. Comparing mean values obtained over one hour before and after administration of the substance it was shown that the effectiveness of drugs decreased as follows: ajmalin, propafenon, lidocaine, Org 6001. Whereas suppression of extrasystole was most marked after ajmalin, propafenon showed the longest period of activity. After Org 6001 divergent activity of arrhythmia could be observed; in some patients good antiarrhythmic effects could be demonstrated. For evaluation of effectiveness and validity of new antiarrhythmic substances intraindividual comparison with placebo and well established standard antiarrhythmic drugs is advisable.

[Dopamine and dobutamine in the treatment of severe cardiac failure (author's transl)]. / Dopamin und Dobutamin in der Behandlung der schweren Herzinsuffizienz.

Ten patients in severe cardiac failure were treated with dopamine (4 microgram/kg . min) and dobutamine (7.5 microgram/kg.min). Both drugs brought about a similar increase in stroke volume and cardiac output of about 50% and 60%, respectively, accompanied by a fall in peripheral vascular resistance of about 33%. On dopamine the heart rate increased by 12%, but remained unaltered on dobutamine. There was a significant fall in the preload of both ventricles with dobutamine, while ventricular filling pressure during dopamine infusion was only slightly decreased, unchanged or even increased. The pulmonary (wedge) pressure during dopamine infusion averaged 9 mm Hg higher than during dobutamine (P less than 0.001). There is thus the potential danger with dopamine of aggravating pulmonary congestion. Furthermore, the improvement in cardiac function due to dopamine is at the expense of a higher oxygen demand than with dobutamine. Dobutamine is, therfore, preferable to dopamine in the treatment of advanced myocardial failure.

[Lithium-powered cardiac pacemakers. A survey of 3 years' clinical experience (author's transl)]. / Herzschrittmacher mit Lithiumbatterien. 3 Jahre klinische Erfahrung.

In addition to the lithium-iodine cell which has been in clinical use since 1972, the following lithium-based power sources for cardiac pacemakers are available: The lithium-silver chromate cell (SAFT), the lithium-thionylchloride-battery (G.T.E.), the lithium-cupric sulfide cell (DuPont) and the lithium-lead iodide cell (Mallory). These batteries differ not only in their energy providing chemical reaction and their components (liquid electrolyte or not), but also in their capacity and discharge characteristics. Out of 244 lithium-powered pacemakers implanted during the past 3 years, 5 pulse generators had to be removed due to electronic circuit failure, whereas battery failure has not been observed up till now. Sensing problems were registered in 8 cases probably due to the specific properties of the entrance filter and entrance resistance of the pacer. In some cases, however, they were caused by poor electrode position. One pacemaker model, powered with the WGL702 cell, frequently gave rise to skin necrosis, Newer models have more favourable dimensions and lower specific weight. The capacity of their batteries is sufficient for middle to long-term stimulation when using current saving electrodes. Because of the well-known advantages of the lithium-cells in comparison to conventional Mallory batteries, together with the favorable clinical results, only lithium-powered pacemakers have been implanted in our hospital since 1977.

[Prolonging the life of an implanted pacemaker by reducing impulse duration (author's transl)]. / Verlängerung der Funktionszeit implantierter Herzschrittmacher durch Reduzierung der Impulsdauer

The current drain of a pacemaker depends on the electrical charge delivered to the heart during stimulation, the energy being determined by amplitude and width of the stimulating pulse. On investigating how far pulse duration can be shortened without jeopardizing reliability of cardiac stimulation, how much the current drain can be reduced and how this might influence pacemaker life, it was found that pulse width could be reduced to 0.3 ms in over 80% of cases with an increase in pacemaker life, if powered by conventional mercury batteries, to about 60 months.