In vivo evidence of positive inotropism of EMD 57033 through calcium sensitization.

The previous separation of the racemic cardiotonic thiadiazinone derivative EMD 53998 yielded two enantiomers with different pharmacologic properties: EMD 57,033, a potent Ca2+ sensitizer with some residual phosphodiesterase III (PDE III) inhibition, and EMD 57,439, a pure PDE III inhibitor. Although numerous in vitro studies demonstrated the ability of EMD 57,033 to increase the responsiveness of cardiac contractile proteins to Ca2+, in vivo evidence for such an action is lacking. Because there is no possibility of directly proving Ca2+ sensitization in vivo, we attempted to exclude PDE III inhibition as a major contributing component of the positive inotropic action of EMD 57,033.

Antagonistic effects of bisoprolol on several beta-adrenoceptor-mediated actions in anaesthetized cats.

The beta-adrenoceptor antagonistic activity of i.v. administered bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy] -3-isopropylamino-2-propanol, hemifumarate) was studied under two different sets of experimental conditions in anaesthetized cats and compared to the activity of atenolol and propranolol.

High beta 1-selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol.

Bisoprolol, (+/-)1-(4-[(2-isopropoxyethoxy)-methyl]-phenoxy)-3-isopropyl-amino -2- propanol-hemifumarate, is a new, highly selective beta 1-adrenoceptor blocking agent without intrinsic sympathomimetic activity and low to moderate local anaesthetic activity. As demonstrated in binding experiments, and in classical pharmacological studies using rats, guinea pigs, cats, and dogs, bisoprolol markedly differentiated between beta 1-adrenoceptors of the heart, or the renal juxtaglomerular apparatus, and the beta 2-subtype in arterial blood vessels, bronchi, liver, or skeletal muscle. Up to concentrations nearly 100-fold higher than the therapeutic plasma levels in humans, bisoprolol did not affect the functional refractory period of the heart, and was devoid of a direct suppressive effect on myocardial contractility and of calcium antagonistic properties in heart and vascular muscle.

Beta 1-selectivity of bisoprolol, a new beta-adrenoceptor antagonist, in anesthetized dogs and guinea pigs.

The beta-adrenoceptor activity of the newly synthesized antagonist bisoprolol [+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy]-3-isopropylamino-2- propranol, hemifumarate), has been compared with the effect of several reference compounds in anesthetized dogs and guinea pigs. In anesthetized, bivagotomized dogs, isoprenaline dose-response relations for increase in heart rate and decrease in diastolic blood pressure were established. Bisoprolol had the largest beta 1/beta 2 ratio, i.

[Does methylmethacrylate induce cardiovascular complications during alloarthroplastic surgery of the hip joint? (AUTHOR'S TRANSL)].

Cardiovascular experiments in dogs and rabbits under various conditions demonstrated that monomethylacrylate has no direct cardiac depressant activity. The transient decrease in blood pressure and heart rate of patients receiving endoprostheses and experimental animals is elicited by a vagotropic effect of the methacrylates and can be antagonized by prophylactic application of atropine. Severe cardiovascular incidents involving an acute cor pulmonale are induced via the steep rise in pressure within the bone-marrow canal during the forcing in of the endoprosthetic shafts, leading to intravasation of bone marrow and its thromboplastine like compounds, thus resulting in a partial coagulation.