Daisuke Kambayashi

Effects of ACE inhibition on myocardial apoptosis in an ischemia-reperfusion rat heart model.

Myocardial ischemia–reperfusion injury involves necrosis and apoptosis. The inhibition of angiotensin-converting enzyme (ACE) has been reported to suppress infarct size. In this study, it was investigated whether an ACE inhibitor affected myocardial apoptosis and apoptosis-related proteins in rats with experimental myocardial infarction. Anesthetized Sprague-Dawley rats were divided into four groups. Group I underwent 30 minutes of left coronary artery occlusion followed by 24 hours of reperfusion (control group); Group II underwent oral administration of the ACE inhibitor quinapril (10 mg/kg/day) before coronary occlusion (quinapril group); Group III underwent administration of the bradykinin B2-receptor antagonist Hoe 140 (250 &mgr;g/kg/day, subcutaneously) with quinapril (quinapril + Hoe 140 group); and Group IV underwent administration of Hoe 140 alone (Hoe 140 group). After reperfusion, myocardial infarct size was determined by triphenyltetrazolium chloride staining. Myocardial apoptosis was detected immunohistologically using terminal deoxynucleotidyl transferase–mediated nick end labeling staining and DNA electrophoresis. Myocardial caspase-3 activation was analyzed by Western blot and the expressions of Bcl-xL and Bax proteins were detected immunohistochemically. Quinapril significantly reduced the ratio of myocardial infarct size in the ischemic area at risk. In addition, quinapril significantly suppressed the incidence of apoptotic myocytes around the necrotic region (from 18.9 ± 0.8% to 8.6 ± 1.0%;P < 0.0001), the intensity of DNA ladder formation, and the activation of caspase-3. Hoe 140 attenuated these protective effects of quinapril. In the immunohistochemical study, Bax and Bcl-xL were expressed in myocytes, and ischemia–reperfusion abolished both proteins in the center region of ischemia. The Bax staining was equally observed among all groups. However, Bcl-xL staining remained in the ischemic area widely after quinapril treatment. In addition, Hoe 140 also depleted this effect of quinapril. These results suggest that inhibition of ACE reduces myocardial infarction and apoptosis via the bradykinin B2 receptor in part. The antiapoptotic effect of the ACE inhibitor is attributed to the changing expression of Bcl-xL.

Nifekalant and disopyramide in a patient with short QT syndrome: evaluation of pharmacological effects and electrophysiological properties.

We assessed several pharmacological effects on electrocardiogram parameters and effective refractory period (ERP) in a patient with a short QT syndrome (SQTS). Pharmacological challenge tests revealed that disopyramide and selective Ikr blocker, nifekalant normalized QT interval, and ERP of the atrial and ventricular myocardium. This study suggested that disopyramide and nifekalant should be feasible for the drug treatment of the SQTS. Moreover, QT interval was paradoxically prolonged at higher heart rates induced with isoproterenol infusion or an exercise test, although the mechanism of this QT prolongation remains to be investigated.

Focal ablation for atrial fibrillation originating from the inferior vena cava and the posterior left atrium

We identified a case of paroxysmal atrial fibrillation (AF) originating from inferior vena cava (IVC) and the low-posterior left atrium (LA). Both foci, the IVC and the low-posterior LA, simultaneously served not only as trigger but also as driver for maintenance of AF. During AF, the IVC and the low-posterior LA continuously demonstrated the rapid and fractionated potentials that exit into both atria with conduction block. Focal ablation for ectopic beats within the IVC and the low-posterior LA completely eliminated the storm of AF.