Regional differences of superoxide dismutase activity enhance the superoxide–induced electrical heterogeneity in rabbit hearts

Abstract

During myocardial ischemia and the subsequent reperfusion, free radicals are important intermediates of the cellular damage and rhythm disturbances. We examined the effects of superoxide radicals or hydrogen peroxide (H(2)O(2)) on the action potentials in isolated rabbit Purkinje fibers, atrial muscle and ventricular muscle. Reactive oxygen species (ROS) donors such as adriamycin, xanthine/xanthine oxidase and menadione induced prolongation of APD(90) in Purkinje fibers. Menadione (30 microM), the most specific superoxide radical donor, prolonged the action potential duration at 90% repolarization (APD(90)) by 17% in Purkinje fibers, whereas it shortened the APD by 57% in ventricular muscle, and it did not affect the atrial APD. All these menadione-induced effects were completely blocked by 2,2,6,6-tetramethyl- 1-peperadinyloxy, a superoxide radical scavenger. Superoxide dismutase (SOD) activity was lowest in Purkinje fibers, it was moderate in atrial muscle and highest in ventricular muscle. H(2)O(2) shortened the APDs of all three cardiac tissues in a concentration-dependent manner. These results suggest that the different electrical responses to O(2) ([Symbol: see text]-) in different cardiac regions may result from the regional differences in the SOD activity, thereby enhancing the regional electrical heterogeneity.

Effects of superoxide donor menadione in adult Rat myocardium are associated with increased diastolic intracellular calcium

“…Menadione reduced the duration of APD 80 in the LV of isolated whole rat hearts. These findings are consistent with the findings of Choi et al (2005) and Ha et al (2007). However, Barrington, Meier and Weglicki (1988) provided evidence that H 2 O 2 prolonged the APD of canine ventricular myocytes and Cerbai et al (1991) have shown that dihydroxyfumaric acid (DHF), a general donor of ROS species, prolongs the APD of guinea pig ventricular myocytes.…”

“…Menadione is a potent superoxide donor (Choi et al, 2005) that has a negative inotropic effect on isolated hearts, which, it has been suggested, is linked to intracellular Ca 2+ ([Ca 2+ ]i) regulation (Anderson and Dutta, 1991). In addition, it has been demonstrated that menadione alters the electrical response of cardiac tissue preparations (Choi et al, 2005;Ha et al, 2007).…”

“…Menadione is a potent superoxide donor (Choi et al, 2005) that has a negative inotropic effect on isolated hearts, which, it has been suggested, is linked to intracellular Ca 2+ ([Ca 2+ ]i) regulation (Anderson and Dutta, 1991). In addition, it has been demonstrated that menadione alters the electrical response of cardiac tissue preparations (Choi et al, 2005;Ha et al, 2007). However, the simultaneous measurement of the mechanical and electrical effects of menadione has not previously been reported, nor has its effects on [Ca 2+ ] i transients in intact adult myocytes been measured.…”

Sodium Channel Gating Modes During Redox Reaction

“…Thus, H 2 O 2 and DTT also could indirectly change sodium channel gating by modulating the activity of PKC. In summary, we suppose that the redox states could adjust the activity of the sodium channel by acting on the cysteine residues of the cellular sodium Figure 7C), which is consistent with most of the previous researches [41][42][43][44] but different from report of Choi et al [45]. The disparity may be attributed to species differences.…”

Dynamic changes in nitric oxide and mitochondrial oxidative stress with site-dependent differential tissue response during anoxic preconditioning in rat heart

“…•Ϫ dismutase distribution, action potential duration, and myosinactin dynamics lead to regional differences in ischemia and reperfusion-induced heart injuries (5,28). However, the process of regional injury localization during global ischemia is not completely understood.…”