A little gap junctional uncoupling too much.

See article by Pollard et al. [15] (pages 381 –392) in the ischemic zone and with corresponding heterogeneous this issue. depressed excitability [9]. The mechanism of the 1B phase of arrhythmias is as of Ventricular fibrillation (VF) in the setting of acute today not fully understood. Kaplinsky et al., in the seminal myocardial ischemia and infarction remains an enormous paper mentioned above, interpreted the absence of epicarburden for society, with |300,000 deaths each year in the dial conduction delay as absence of reentrant activity [6]. United States alone [1,2]. The chance of surviving an event There are, however, reports that confirm that intramural of ischemia-induced VF is inversely proportional to the [10,11] and subepicardial reentry [12] does take place and time elapsing until defibrillation is applied [3]. Therefore, might form the underlying mechanism of VF during the 1B automatic external defibrillators are now more and more phase. being introduced in public areas. However, the vast The spontaneous occurrence of 1B-VF has been demonmajority of cases of sudden death occur at home [4]. strated to coincide with the onset of cellular uncoupling as Therefore, despite the numerous number of studies measured by the rise in tissue impedance and with the 1 published in recent decades, there is still a need for better second rise in [K ] [13]. Smith et al. showed that in open o understanding of the mechanism of ischemia-induced chested pigs, VF occurred within a time window between arrhythmias. The information that is available to date 19 and 30 min of occlusion [13]. Cinca et al. demonstrated concerns predominantly the mechanism of arthat both uncoupling (i.e. the rise in tissue impedance) as rhythmogenesis in the first 10 to 15 min of coronary the occurrence of ventricular arrhythmias could be postocclusion (for review see Janse and Wit [5]). However, poned by ischemic preconditioning [14]. These findings Kaplinsky et al. reported in 1979 that premature ventricuare of particular interest, not only because they further lar beats, ventricular tachycardias and VF occur in two support the association between impedance rise and ardistinct phases in dogs subjected to coronary occlusion [6]. rhythmias, but also because this might provide a therapeuThey named these immediate and delayed arrhythmias, tic target in the future. respectively [6]. These phases of arrhythmias, now often In this issue of Cardiovascular Research, Pollard et al. referred to as 1A and 1B [7], are present in many species [15] report a modification of the Luo-Rudy dynamic subjected to myocardial ischemia, including pig, rat and membrane equations (LRd) [16] in which they focus on sheep although the distribution of arrhythmic event might the source–sink relationships and the role of cellular differ in individual animals [8]. coupling on the occurrence of phase 1B arrhythmias. The main interest of the presence of the bimodal The authors have modified the LRd ionic concentrations, distribution of arrhythmias lies in the conjecture that the sarcolemmal currents and sarcoplasmic reticulum (SR) 21 two early phases have different electrophysiological mechCa uptake and release to levels that promoted sponta21 anisms. The first, 1A phase starts |2 min after coronary neous SR Ca release. Parameters were adjusted accordocclusion and lasts until 10 min. Its mechanism relates to ing to the degree of hyperkalemia, acidosis and hypoxia macro reentry that is facilitated by depression of excitabilithat has been reported for 15 to 25 min of ischemia. At that 1 1 ty [5]. Heterogeneous increase in [K ] is associated with time, the second rise of [K ] [17,18] and the onset of o o different degrees of depolarization of the myocytes within cellular uncoupling have started [19]. For detailed description of the changes imposed upon the LRd model, the reader is referred to the paper itself [15]. *Tel.: 131-20-566-3266; fax: 131-20-697-5458. E-mail address: [email protected] (J.R. de Groot). The modifications of the LRd model result in conditions