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Abstract-Intracellular Ca 2ϩ waves (CaWs) of cardiomyocytes are spontaneous events of Ca 2ϩ release from the sarcoplasmic reticulum that are regarded as an important substrate for triggered arrhythmias and delayed afterdepolarizations. However, little is known regarding whether or how CaWs within the heart actually produce arrhythmogenic membrane oscillation because of the lack of data confirming direct correlation between CaWs and membrane potentials (V m ) in the heart. On the hypothesis that CaWs evoke arrhythmogenic oscillatory depolarization when they emerge synchronously and intensively in the heart, we conducted simultaneous fluorescence recording of intracellular Ca 2ϩ ([Ca 2ϩ ] i ) dynamics and V m of ventricular myocytes on subepicardial surfaces of Langendorff-perfused rat hearts using in situ dual-view, rapid-scanning confocal microscopy. In intact hearts loaded with fluo4/acetoxymethyl ester and RH237 under perfusion with cytochalasin D at room temperature, individual myocytes exhibited Ca 2ϩ transients and action potentials uniformly on ventricular excitation, whereas low-K ϩ -perfused (2.4 mmol/L) hearts exhibited CaWs sporadically between Ca 2ϩ transients without discernible membrane depolarization. Further [Ca 2ϩ ] i loading of the heart, produced by rapid pacing and addition of isoproterenol, evoked triggered activity and subsequent oscillatory V m , which are caused by burst emergence of CaWs in individual myocytes. Such arrhythmogenic membrane oscillation was abolished by ryanodine or the Na ϩ -Ca 2ϩ exchanger inhibitor SEA0400, indicating an essential role of CaWs and resultant Na ϩ -Ca 2ϩ exchanger-mediated depolarization in triggered activity. In summary, we demonstrate a mechanistic link between intracellular CaWs and arrhythmogenic oscillatory depolarizations in the heart. Our findings provide a cellular perspective on abnormal [Ca 2ϩ ] i handling in the genesis of triggered arrhythmias in the heart. (Circ Res. 2008;103:509-518.)Key Words: Ca 2ϩ wave Ⅲ delayed afterdepolarization Ⅲ triggered activity Ⅲ Na ϩ -Ca 2ϩ exchange Ⅲ confocal microscopy I ntracellular Ca 2ϩ waves (CaWs) in cardiomyocytes are wave-like propagation of spontaneous, local Ca 2ϩ -release events from the sarcoplasmic reticulum (SR) within the cells as a result of Ca 2ϩ overload. [1][2][3][4][5] Previous electrophysiological studies in isolated ventricular myocytes suggested that CaWs can evoke triggered arrhythmias by generating oscillatory depolarization via Ca 2ϩ -activated transient inward currents, 5 which consist of the Na ϩ -Ca 2ϩ exchanger (NCX) current 6,7 and other Ca 2ϩ -activated currents. 8,9 When the depolarized membrane potential (V m ) reaches the threshold of firing, myocytes exhibit nondriven action potentials (APs) and subsequent oscillations called triggered activity and delayed afterdepolarizations (DADs), respectively. 6,10 -12 Although extensive studies have been conducted on CaWs for their electrogenic and proarrhythmic potentials, most studies were focused on isolated cardiomyocytes or sma...

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Aim The association of outdoor air pollution and meteorological elements with primary care visits at night due to asthma attack was studied. Methods A case-crossover study was conducted in a primary care clinic in Himeji City, Japan. The subjects were 956 children aged 0-14 years who visited the clinic with an asthma attack between the hours of 9 p.m. and 6 a.m. Daily concentrations of particulate matter, ozone, nitrogen dioxide, and a number of meteorological elements were measured, and a conditional logistic regression model was used to estimate odds ratios (ORs) of primary care visits per unit increment of air pollutants or meteorological elements. The analyses took into consideration the effects of seasonality. Results Of the 956 children, 73 (7.6 %) were aged \2 years and 417 (43.6 %) were aged 2-5 years. No association between daily ozone levels and primary care visits due to asthma attack at night in the spring or summer was found. An inverse relation between suspended particulate matter and primary care visits due to asthma attack was detected in the winter. ORs in the summer per degree increment in daily mean temperature was 1.31 [95 % confidential interval (CI) 1.09-1.56], and ORs in the autumn per hourly increment in daily hours of sunshine was 0.94 (95 % CI 0.90-0.99). Conclusion The findings of our study fail to support any association between daily mean concentration of air pollutant and primary care visits at night. However, we did find evidence indicating that certain meteorological elements may be associated with primary care visits