Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial ischemia/reperfusion injury.

Molecular Determinants of Na+/Ca2+ Exchange (NCX1) Inhibition by SEA0400

“…Previously we have observed that KB-R7943 at a low dose (ϳ10 M) has virtually no effect on Ca 2ϩ transients corresponding to spontaneous beating in cultured cardiomyocytes (24). In addition, SEA0400 as well as KB-R7943 has been shown to exhibit no or negative effects on heart rate, contractile function, and coronary flow (24,26,27,31,42,43). In these cases, these agents should produce Ca 2ϩ i accumulation or cardiac positive inotropy if the forward mode of the exchanger (i.e.…”

“…Since 1996, KB-R7943 has been widely used as a pharmacological tool to study the roles of the exchanger at the cellular and organ levels. For example, KB-R7943 has been shown to efficiently guard against toxicity by cardiac glycosides (26,30) and ischemia/reperfusion injury of the heart (24,27,(31)(32)(33), kidney (34,35), and brain (36,37). More recently, however, nonspecific effects of KB-R7943 have been suggested.…”

Sodium Calcium Exchange as a Target for Antiarrhythmic Therapy

“…11. In the latter condition, cardioprotective and antiarrhythmic effects could be documented in multicellular or intact heart preparations (Mukai et al 2000;Nakamura et al 1998;Satoh et al 2003). Further antiarrhythmic effects were shown in Na + overload induced by glycosides or Na-channel openers (Amran et al 2004;Satoh et al 2003).…”

Cardiac Na + -Ca 2+ Exchange

“…Third, reverse-mode NCX activity has been implicated as the cause of Ca 2ϩ overload associated with cardiac ischemia/reperfusion. 12 Recent studies have provided evidence that KB-R7943 at 3 to 20 mol/L is effective in reducing cytosolic Ca 2ϩ and Na ϩ overload, cell injury, and arrhythmias that are associated with ischemia/ reperfusion, the Ca 2ϩ paradox, and substrate-free hypoxia/ reoxygenation in different types of cardiac preparations (rat cardiomyocytes, 121,133 guinea pig papillary muscle, 127 and Langendorff-perfused rat hearts 133,134 ). KB-R7943 has also been reported to be significantly protective against anoxia/ reoxygenation or ischemia/reperfusion damage in brain 135 and kidney.…”