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Background and Purpose At present there are no small molecule inhibitors that show strong selectivity for the Na +/Ca 2+ exchanger ( NCX). Hence, we studied the electrophysiological effects of acute administration of ORM-10103, a new NCX inhibitor, on the NCX and L-type Ca2+ currents and on the formation of early and delayed afterdepolarizations. Experimental Approach Ion currents were recorded by using a voltage clamp technique in canine single ventricular cells, and action potentials were obtained from canine and guinea pig ventricular preparations with the use of microelectrodes. Key Results ORM-10103 significantly reduced both the inward and outward NCX currents. Even at a high concentration (10 μ M), ORM-10103 did not significantly change the L-type Ca2+ current or the maximum rate of depolarization ( dV/dtmax), indicative of the fast inward Na+ current. At 10 μ M ORM-10103 did not affect the amplitude or the dV/dtmax of the slow response action potentials recorded from guinea pig papillary muscles, which suggests it had no effect on the L-type Ca2+ current. ORM-10103 did not influence the Na+/ K+ pump or the main K+ currents of canine ventricular myocytes, except the rapid delayed rectifier K+ current, which was slightly diminished by the drug at 3 μ M. The amplitudes of pharmacologically- induced early and delayed afterdepolarizations were significantly decreased by ORM-10103 (3 and 10 μ M) in a concentration-dependent manner. Conclusions and Implications ORM-10103 is a selective inhibitor of the NCX current and can abolish triggered arrhythmias. Hence, it has the potential to be used to prevent arrhythmogenic events. Linked Article This article is commented on by Terracciano and Hancox, pp. 765-767 of this issue. To view this commentary visit [ABSTRACT FROM AUTHOR]

Aim: In diabetes mellitus, several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models, changes in these parameters were reported, but only limited relevant information is available in other species, having cardiac electrophysiological properties more resembling the human, including the rabbit. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and the underlying transmembrane potassium currents in rabbit hearts. Methods: Diabetes was induced by a single injection of alloxan (145 mg kg−1 i.v.). After the development of diabetes (3 weeks), electrophysiological studies were performed using whole cell voltage clamp and ECG measurements. Results: The QTc interval in diabetic rabbits was moderately but statistically significantly longer than measured in the control animals (155 ± 1.8 ms vs. 145 ± 2.8 ms, respectively, n = 9–10, P < 0.05). This QTc-lengthening effect of diabetes was accompanied by a significant reduction in the density of the slow delayed rectifier K+ current, IKs (from 1.48 ± 0.35 to 0.86 ± 0.17 pA pF−1 at +50 mV, n = 19–21, P < 0.05) without changes in current kinetics. No differences were observed either in the density or in the kinetics of the inward rectifier K+ current ( IK1), the rapid delayed rectifier K+ current ( IKr), the transient outward current ( Ito) and the L-type calcium current ( ICaL) between the control and alloxan-treated rabbits. Conclusion: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization. Diabetes attenuates the repolarization reserve by decreasing the density of IKs current, and thereby may enhance the risk of sudden cardiac death. [ABSTRACT FROM AUTHOR]

Many investigators have proved the usefulness of acetazolamide provocation and the carbon dioxide test for assessment of the local cerebrovascular reactivity by measurement of the regional cerebral blood flow in patients with occlusive cerebrovascular disease. Data originating from a comparison of these two different vasomotor stimuli as concerns the differences in sensitivity to them in various parts of the central nervous system are scarce. Our aim was to compare the cerebral blood flow responses to hypercapnic and acetazolamide stimuli in different brain regions.The cerebral blood flow was measured in the cerebrum (cortex and caudate nucleus) and cerebellum (cortex), as measured by a hydrogen clearance method in anaesthetized, artificially ventilated rabbits.In normocapnia, the cerebral blood flow values in the cerebrum and the cerebellum differed significantly. The cerebral blood flow responses to both vasodilatory stimuli were to be significantly higher in the cerebrum than in the cerebellum, but the relative increases, i.e. the mean relative reactivities, were similar in the different regions measured.The regional dissimilarity might explain to some extent the different sensitivities of the various brain areas to sudden blood pressure changes (infarction or haemorrhage). The results further suggest that heterogeneity in cerebrovascular reactivity should be considered in the assessment of vasoreactivity in patients with occlusive cerebrovascular disease. Since the comparison of the carbon dioxide and acetazolamide– induced cerebrovascular reactivities revealed a strong linear relationship, it was concluded that acetazolamide provocation is equivalent to the carbon dioxide test in the evaluation of cerebrovascular reactivity. [ABSTRACT FROM AUTHOR]