Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger, on myocardial ischemia–reperfusion injuries

Takahashi, Keiichi; Takahashi, Teisuke; Suzuki, Taizo; Onishi, Michihito; Tanaka, Yu; Hamano-Takahashi, Akiko; Ota, Tomomi; Kameo, Kazuya; Matsuda, Takehisa; Baba, Akemichi

doi:10.1016/s0014-2999(02)02732-2

Cited by 101 publications

(89 citation statements)

References 36 publications

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“…Protective effects of NHE inhibitors by posttreatment have been shown in previous studies in cardiac ischemic model [2,19]. Our results suggest that the effect of sabiporide may be involved in the reperfusion period, and similar results have been previously shown [2].…”

Section: Fig 2 Effect Of Sabiporide On Intracellular Casupporting

confidence: 91%

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

et al. 2005

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Section: Fig 2 Effect Of Sabiporide On Intracellular Casupporting

confidence: 91%

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

et al. 2005

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“…Similar, positive effects of NCX inhibition were reported from isolated guinea pig papillary muscles and rat hearts (Anderson, 2002;Schafer et al, 2001;Wang et al, 2007). NCX inhibitors were shown to attenuate myocardial reperfusion injury using in vivo experimental models (Takahashi et al, 2003). Under normal conditions or during ischemia 1 mM SEA0400 had no apparent effect on AP configuration, but improved the recovery of action potentials after reperfusion (Acsai et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion

Kormos¹,

Nagy²,

Acsai³

et al. 2014

European Journal of Pharmacology

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a b s t r a c tIn this study we evaluated the effects of selective Na þ /Ca 2 þ exchanger (NCX) inhibition by ORM-10103 on the [Ca 2 þ ] i transient (CaT), action potential (AP), and cell viability in isolated canine ventricular cardiomyocytes exposed to a simulated ischemia/reperfusion protocol performed either alone (modeling moderate low-flow ischemia) or with simultaneous strophantidine challenge (modeling more severe low-flow ischemia). CaTs were monitored using a Ca 2 þ -sensitive fluorescent dye, APs were recorded by intracellular microelectrodes, and anaerobic shifts in cellular metabolism were verified via monitoring native NADH fluorescence. Simulated ischemia increased the NADH fluorescence, reduced the amplitudes of the AP and CaT and induced membrane depolarization. APs moderately shortened, CaTs prolonged. Following the application of ORM-10103 the detrimental effect of ischemia/reperfusion on cell viability and the reperfusioninduced increase in AP and CaT variabilities were substantially reduced, but ischemia-induced shifts in AP morphology were barely influenced. In conclusion, selective NCX inhibition by ORM-10103 is highly effective against ischemia/reperfusion induced pathologic alterations in [Ca 2 þ ] i homeostasis, however, it fails to normalize untoward arrhythmogenic changes in AP morphology.

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“…Preischaemic administration of cariporide significantly attenuated ischaemia/reperfusion induced arrhythmogenesis in a variety of in vitro and in vivo models [54] while its post-ischaemic administration, though reduced the incidence of VF and subsequent cardiac death, the effect on mortality was not significant [59,64,65]. Our results obtained by the pre-ischaemic application of cariporide reflect the high antiarrhythmic efficacy of the treatment, and strongly support the conclusions of similar studies [30][31][32][33].…”

Section: Nhe Inhibition (Cariporide Alone)supporting

confidence: 84%

Prevention of intracellular calcium overload by blocking NCX

Szepesi¹

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b.) Conference presentations related to PhD topic Szepesi J, Sebők Zs, Tóth A Effect of NCX and NHE inhibition on the development and duration of postischemic arrhythmias (NCX és NHEgátlás hatása posztiszkémiás aritmiák kialakulására és időtartamára) CARDIOLOGIA HUNGARICA 42:(Suppl.A) p. A37. (2012) Szepesi J The effect of combined NCX1 and NHE1 blockade in acute ischemia/reperfusion injury in rat SEMINAR FOR YOUNG RESEARCHERS The physiology, pathophysiology and pharmacology of the cardiovascular system (2012) Posters Szepesi J The effect of NCX and NHE inhibition on the development and duration of post-ischemic arrhythmias  Sudden Cardiac Death & Cardioprotection conference and advanced workshop (2012) EHRA .......................................................................................................................... 51 10 ACKNOLEDGEMENTS ..............................................................................................

show abstract

Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger, on myocardial ischemia–reperfusion injuries

Cited by 101 publications

References 36 publications

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

Effects of sabiporide, a specific Na+/H+ exchanger inhibitor, on neuronal cell death and brain ischemia

Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion

Prevention of intracellular calcium overload by blocking NCX

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