Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp ender differences in the incidence of various types of ventricular arrhythmias have been reported. Torsades de pointes associated with long QT syndrome is more common in females than males. 1,2 The higher incidence of Brugada syndrome in males than females 3-5 is associated with gender differences in the early phase of ventricular repolarization, that is, the greater transient outward potassium current (Ito)-mediated phase 1 notch in the right ventricular epicardium in males than females. 6 Early repolarization syndrome is characterized by a prominent J wave and by ST-segment elevation in the left precordial leads; it is most commonly seen in young males. 7 Although the mechanisms underlying early repolarization syndrome remain unknown, it has been suggested to share notable cellular and ionic similarities with Brugada syndrome. 7-10Studies on gender-related repolarization differences have focused on the duration of repolarization, such as the longer QT 11,12 and JT intervals 13 in females than in males. While these sex differences in ventricular repolarization are not observed before, they become obvious after puberty, suggesting an important effect of sex hormone. In contrast, gender differences have been reported in the configuration of the ST segment in healthy subjects. 11 Previous studies showed that after puberty, the J point amplitude is higher and the ST segment angle is steeper in males. 14,15 However, little is currently known about age-and gender-related differences in the ST levels in the different leads that represent the right and left ventricles.Androgen-deprivation therapy, 16,17 a neoadjuvant treatment for prostate cancer, might strongly inhibit the hormonal modulation of not only prostate cells but also of cardiac ventricular myocytes. Although this therapy is associated with increased risks of cardiovascular death in patients with prostate cancer, 18,19 its effects on ventricular repolarization including the ST segment remain to be elucidated.We studied healthy subjects to identify age-and gender differences in the ST segments in leads V2 and V5, which are Background: ST-segment elevation in a structurally normal heart is observed in Brugada- and early repolarization syndrome. The incidence of both syndromes is much higher in males than females. Clinical and basic studies suggest that testosterone plays an important role in ventricular repolarization.

Reactive oxygen species (ROS) are important intracellular signaling molecules and are implicated in cardioprotective pathways including ischemic preconditioning. Statins have been shown to have cardioprotective effects against ischemia/reperfusion injury, however, the precise mechanisms remain to be elucidated. We hypothesized that ROS-mediated signaling cascade may be involved in pravastatin-induced cardioprotection. Cultured rat cardiomyocytes were exposed to H(2)O(2) for 30 min to induce cell injury. Pravastatin significantly suppressed H(2)O(2)-induced cell death evaluated by propidium iodide staining and the MTT assay. Incubation with pravastatin activated catalase, and prevented a ROS burst induced by H(2)O(2), which preserved mitochondrial membrane potential. Protective effects were induced very rapidly within 10 min, which was concordant with the up-regulation of phosphorylated ERK1/2. L-NAME, 5HD, N-acetylcysteine (NAC) and staurosporine inhibited ERK1/2 phosphorylation and also reduced pravastatin-induced cardioprotection, suggesting NO, mitochondrial K(ATP) (mitoK(ATP)) channels, ROS and PKC should be involved in the cardioprotective signaling. We also demonstrated that pravastatin moderately up-regulated ROS generation in a 5HD-inhibitable manner. In isolated perfused rat heart experiments, pravastatin administered 10 min prior to no-flow global ischemia significantly improved left ventricular functional recovery, and also reduced infarct size, which were attenuated by the treatment with NAC, 5HD, L-NAME or staurosporine. Administration of pravastatin from the beginning of reperfusion also conferred cardioprotection. Pravastatin protected the cardiomyocytes against oxidative stress by preventing the ROS burst and preserving mitochondrial function. Moderately up-regulated ROS production by mitoK(ATP) channels opening is involved in the pro-survival signaling cascade activated by pravastatin.

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp eperfusion therapy by primary percutaneous coronary intervention or thrombolysis is the most effective strategy to reduce mortality and improve the clinical outcome in acute myocardial infarction (AMI). However, reperfusion itself is associated with a risk of lethal ventricular arrhythmias. In fact, reperfusion-induced arrhythmias were identified in 30% of patients with successful reperfusion by thrombolysis. 1 Furthermore, in the majority of cases, successful restoration of coronary flow by primary angioplasty is accompanied by reperfusion-induced arrhythmias, including bradyarrhythmias, ventricular premature contractions (VPC), ventricular tachycardia (VT) and ventricular fibrillation (VF). 2 VT and VF by spontaneous recanalization are especially critical and underlie many cases of sudden cardiac death before hospital arrival. In a previous study of 12 patients who developed VF before the arrival of the ambulance, only one patient was discharged alive. 3 The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are attracting much attention because of their putative pleiotropic effects. We have reported that administration of atorvastatin in the early phase of an AMI improves cardiac function and attenuates B-type natriuretic peptide increase, and these effects were assumed to be independent of the drug's lipid-lowering effect. 4 Consistently, other reports have shown that early statin treatment for AMI patients decreases the risk of congestive heart failure and long-term mortality. 5,6 Several large clinical trials have also shown that statins reduce sudden cardiac death in patients with coronary