25th Annual Computational Neuroscience Meeting: CNS-2016

Abstracts of the 25th Annual Computational Neuroscience Meeting: CNS-2016 Seogwipo City, Jeju-do, South Korea. 2–7 July 201

Cardiovascular effects of the novel Ca2+-sensitiser EMD 57033 in pigs at rest and during treadmill exercise.

1. To date no study has described the cardiovascular effects of increased myofilament Ca(2+) responsiveness in awake animals both under resting conditions and during treadmill exercise. In the present study we therefore investigated the systemic, pulmonary and coronary haemodynamic actions of the Ca(2+) sensitizer EMD 57033 in 16 chronically instrumented awake pigs at rest and during treadmill exercise, and compared these to the haemodynamic actions of the Ca(2+) sensitizer/phosphodiesterase inhibitor pimobendan. 2. Under resting conditions EMD 57033 (0.2, 0.4 and 0.8 mg kg(−1) min(−1), i.v.) produced dose-dependent increases in LVdP/dt(max) (up to 65±17% (mean ±s.e.mean), P⩽0.05) and stroke volume (up to 20±3%, P⩽0.05), with an increase in heart rate only after the highest dose (22±5%, P⩽0.05), while mean aortic blood pressure and LVdP/dt(min) were not altered. EMD 57033 had also no effect on pulmonary vascular resistance, but produced dose-dependent decreases in systemic vascular resistance (32±4%, P⩽0.05), and coronary vascular resistance (44±2%, P⩽0.05). These effects were essentially unchanged when animals were pretreated with non-selective β-adrenoceptor blockade, indicating that phosphodiesterase inhibition did not contribute to the positive inotropic actions of EMD 57033. 3. During exercise at 2, 3, and 4 km h(−1), the positive inotropic actions of EMD 57033 gradually waned at higher levels of exercise. This may have been caused by the exercise-induced increase in β-adrenergic activity, because after pretreatment with propranolol the positive inotropic actions of EMD 57033 were preserved at all levels of exercise. In contrast, the positive inotropic and chronotropic effects of pimobendan were amplified during exercise, but were abolished (at rest) or markedly attenuated (during exercise) after pretreatment with propranolol. 4. The responses to EMD 57033 during exercise after combined α- and β-adrenergic receptor blockade were not different from those after β-adrenergic receptor blockade alone, indicating that the positive inotropic actions of EMD 57033 were not mediated via or did not depend on intact α-adrenergic receptor activity. 5. In conclusion, EMD 57033 increases left ventricular myocardial contractility in awake pigs. During exercise this effect is partially offset by the increased β-adrenergic activity, with no effect of α-adrenergic activity, suggesting that EMD 57033 may be most effective in patients with severe loss of β-adrenergic responsiveness

On a new diatomyid (Rodentia, Mammalia) from the Paleogene of south-east Serbia, the first record of the family in Europe

A new diatomyid genus and species, Inopinatia balkanica, from the early Oligocene of south-east Serbia is described, and the affinities between the Diatomyidae and Ctenodactylidae are discussed. Inopinatia balkanica nov. gen. nov. sp. seems to have retained its deciduous teeth throughout life just as all other species of the family. The only other diatomyid described from outside south-east Asia which is Pierremus explorator López-Antoñanzas, 2010 is transferred to the thryonomyid species Paraphiomys knolli