R. Coronel

Reperfusion arrhythmias in isolated perfused pig hearts. Inhomogeneities in extracellular potassium, ST and TQ potentials, and transmembrane action potentials.

We recorded direct current electrograms and local [K+]o at multiple sites and transmembrane potentials at selected sites during reperfusion after 5 minutes and 10 minutes of regional ischemia in isolated perfused pig hearts. After 10 minutes of ischemia, the incidence of ventricular fibrillation (VF) was 38%. At 80-90 seconds after reperfusion, [K+]o was 0.8 mM less than in normal tissue in half of the reperfused tissue, especially in the border zone. This was associated with TQ elevation of +4.5 mV and large peaked T waves. The latter was caused by an abrupt decrease of action potential duration in reperfused tissue, leading to a difference of up to 165 msec with normal tissue. Reperfusion VF started with a closely coupled ventricular premature beat. Activation block between reperfused and normal tissue permitted reentrant activation, leading to VF. Pretreatment with ryanodine (10(-6) M) and reperfusion with elevated [K+] (both of which prevent delayed afterdepolarizations) did not prevent closely coupled ventricular premature beats or VF. Five minutes of ischemia never caused VF. K+ depletion and TQ elevation in the reperfused zone was less frequent and smaller (-0.4 mM and 1.8 mV, respectively). Peaked T waves did not occur, and shortening of the action potential duration was less. We conclude that extracellular K+ depletion and marked action potential duration shortening in the reperfused tissue play a role in the genesis of reperfusion VF, which is caused by reentry. The closely coupled ventricular premature beat that initiates reentry is not caused by delayed afterdepolarizations but most likely by intramural reentry.

The significance of the peer review process against the background of bias: priority ratings of reviewers and editors and the prediction of citation, the role of geographical bias

Editors are facing larger numbers of submitted manuscripts than they can publish [1]. In their selection process of papers they depend on the advice of one or more peer reviewers [1]. It is thus important that the process is fair and as unbiased as possible. The origin of ‘peer review’ dates back to 1752, when the Royal Society of London obtained the fiscal responsibility for the Philosophical Transactions [2]. There are few historical accounts of the evolution of editorial peer review [3]. Today, specialized research on the peer review system is only just starting to emerge and has been the topic of four world congresses [4–7]. This type of research focuses—amongst many other issues—on themes as whether or not masking the identity of authors to reviewers influences the reports of reviewers and whether or not anonymity of reviewers is a relevant topic [4–7]. Previous reports on the editorial process of Radiology [8] and the Journal of Clinical Investigation [9], have indicated that reviewers set markedly different standards in their appreciation of manuscripts. The concordance between reviewers on identical manuscripts is limited [9]. The fact that in the social sciences published papers have an almost 90% chance to be rejected when resubmitted to other journals casts doubt on the validity of the peer review system [10]. Such data are to our knowledge not available for the biomedical sciences. However, there is circumstantial evidence that peer review can successfully discriminate between manuscripts that have a greater chance to be cited in the future. Thus, Wilson showed that papers rejected by the Journal of Clinical Investigation were cited at lower frequency if published by other journals [11]. Manuscripts rejected by Cardiovascular Research were also cited at significantly lower frequency, even if published by … * Corresponding author. Tel.: +31-30-253-8900; fax: +31-30-253-9036

Electrophysiological changes in heart failure and their implications for arrhythmogenesis

Heart failure is the final common pathway of various cardiac pathologies and is associated with sudden cardiac death, mostly caused by ventricular arrhythmias. In this paper we briefly review the electrophysiological remodeling and the alterations in intracellular calcium handling, and the resulting arrhythmogenic mechanisms associated with heart failure. Intercellular uncoupling and fibrosis are identified as a major arrhythmogenic factors. Diet and ventricular wall stretch are discussed as modulating factors. Finally, emphasis is placed on the hitherto poorly studied aspects of right ventricular failure. This article is part of a Special Issue entitled: Heart failure pathogenesis and emerging diagnostic and therapeutic interventions.

Intrinsic heterogeneity in repolarization is increased in isolated failing rabbit cardiomyocytes during simulated ischemia

OBJECTIVE Myocardial ischemia and ventricular arrhythmias often complicate congestive heart failure. Ischemia-induced dispersion in repolarization is an important arrhythmogenic factor that might be caused by intrinsic cellular differences in response to simulated ischemia (SI) or by changed coupling of myocytes. We hypothesized that intrinsic heterogeneity in action potential duration (APD) or the occurrence of rigor is larger in failing than in normal rabbit myocytes during SI. METHODS Heart failure (HF) was induced with volume and pressure overload. Left ventricular myocytes from apex, free wall and base were enzymatically isolated and exposed to SI with NaCN. RESULTS There were no baseline differences in APD before SI. During SI no differences in time to inexcitability occurred but the range in APD increased more in HF than in normal cells. Rigor occurred after 16.8+/-3.5 and 23.0+/-7.5 min (P<0.05) in normal and HF myocytes, with no differences between apical, free wall or base cells. Variance in time to rigor was larger in HF than in normal cells (55.7 versus 12.4 min(2)). Blockade of anaerobic reserve decreased variance in time to rigor, also when normalized to mean, in HF and normal myocytes. In coupled normal and HF cell pairs, no delay in action potential propagation or differences in APD occurred during SI, and time to rigor was synchronized (P<0.05 vs. single cells). CONCLUSIONS Intercellular differences in APD and in time of rigor arise in normal and HF myocytes subjected to SI, and are inhibited by blockade of anaerobic glycolysis. Dispersion in APD and tolerance to SI is increased in HF cells. APD and time to rigor are completely synchronized in coupled cell pairs.

Defining heart failure

The definition of heart failure is hampered by the wide variability of the clinical symptoms and signs, and of their etiologies. Many attempts have been made to come up with a general set of criteria that describe heart failure [1–7]. These criteria include clinical, epidemiological, pathophysiological, and exercise-related criteria and criteria derived from the patients response to therapy. The need for a more circumscript definition reflects the hope to be able to stratify patient groups, to detect heart failure at an earlier stage and to optimally treat patients. At the basis of this need is our wish to understand heart failure as a pathogenetic entity. Moreover, to attain this purpose a clear definition is required for the design of adequate experimental protocols. From medical history we know that the understanding of diseases often has started with the recognition of consistency in a set of symptoms and signs. The starting point for our knowledge therefore is the definition of such a set of characteristics. Here, pathophysiological and medical objectives may, however, lead to conflicts: those searching for a pathophysiologic entity may produce a common denominator of the characteristics, whereas those concerned with the optimal treatment of their patients may come up with a description that covers all possible appearances of the phenomenon. Debates between followers of the standpoint of comprehensiveness and those of brevity continue [4–7]. In order to uncover the dilemmas in the definition of heart failure, the editors of Cardiovascular Research have recently performed a survey amongst the Journals reviewers. A letter was sent to 2238 active reviewers with a request for confirmation of data stored in the Journals database. In the same letter the reviewers were asked to give a definition of heart failure in less than 150 words. In the 2 months following the mailing … *Corresponding author. Tel.: +31-20-566-3267; fax: +31-20-697-5458 r.coronel{at}amc.nl

Productivity in science: more more and more?

During the first 60–70 years of the last century it was more or less possible to read everything that was published worldwide in whatever scientific speciality. This is no longer true. De Jong and Schaper [1] published a paper on the number of publications in clinical cardiovascular science including the citation of those papers over a 12-year period from 1981 to 1992. Of the 137 000 papers published during that period 46% remained uncited with a remarkable geographical variability from 31% for Norway to 69% for Japan. It should be realized that even a single citation by the authors themselves (self-citation) during such a long period would classify a paper in the cited category. Low citation is not synonymous with low scientific quality over brief periods (as used for popular bibliometric parameters as the ‘impact factor’) [2,3]. However, zero citation of about 62 000 papers over a 6-year period after publication [1], raises the question whether the scientific community should try to limit this flood of publications. This question becomes even more relevant when it is realized that electronic publishing will probably alleviate the burden of page limitations imposed on journal editors, and may lead to rejection rates that are more in agreement with reviewer’s recommendations [4]. It has been pointed out previously that rejection rates are much higher than what is actually advised by reviewers [4]. Fig. 1 shows the number of … * Corresponding author. Tel.: +31-30-253-8900; fax: +31-30-253-9036.