Role of some components of ischemia in the genesis of spontaneous ventricular arrhythmias

Senges, Jochen; Seller, H.; Brachmann, Johannes; Braun, Wolfgang; Mayer, E; Rizos, Ioannis; Kübler, W.

doi:10.1007/bf01935808

Cited by 3 publications

(1 citation statement)

References 20 publications

(17 reference statements)

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“…removal of lacta te and hyd rogen ions during cardioplegic reperfu sion considerably improves the conditions for anaerobic energy supply during a subsequent interval of ischemia (7) . While it is impossible to decide whet her the lactate and hydrogen ions in the coronary perfusate are due to th e unphysiologically high intra-extracellular concentra tion gradient caused by ischemia or arc a sign of abnormal memb rane permeability, the loss of potassium from the myocardial cell during or following an ischemic stress does represent a compromised function of the outer cell membrane ( 17). After 100 minut es of ischemia at 17°C under IITK prot ection .…”

Section: Ad Imentioning

confidence: 99%

Different Effects of Cardioplegic Solution HTK during Single or Intermittent Administration

Gebhard¹,

Preusse²,

Schnabel³

et al. 1984

Thorac cardiovasc Surg

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Since intermittent cardioplegic reperfusion during an ischemic period may reduce the ischemic stress of the heart at least by lowering myocardial temperature, we compared the post-ischemic recovery of the dog heart following cardioplegia and subsequent continuous ischemia of 1 X 300 minutes at 22 +/- 1 degree C (model 1) and following cardioplegia and subsequent 3 X 100 minutes of ischemia at 17 +/- 1 degree C with intermittent 4-minute cardioplegic reperfusion every 100 minutes (model 2). The parameters of post-ischemic recovery were the cardiac O2 consumption per beat at work (MVO2-E0): HR), the stability of cardiac rhythm, the left ventricular content of high-energy phosphates, and ultrastructure. Solution HTK with a magnesium concentration of 9 mM/L, in clinical use up to the beginning of 1984, resulted in a significantly better post-ischemic recovery in model 1, despite about 40% lesser ischemic stress in model 2. A reduction of Mg concentration from 9 to 4 mM/l, as in the HTK solution clinically tested since February 1984, did facilitate the post-ischemic recovery in model 1 as indicated by the stability of cardiac rhythm but led to a significant improvement of all parameters of recovery in model 2. Moreover, recovery in model 2 after reduced Mg was also clearly better than in model 1 corresponding to the lesser ischemic stress. The parameters myocardial O2 consumption (MVO2) and potassium loss during HTK perfusion containing 9 and 4 mM/l, respectively, gave indications of specific membrane labilizing effects of Mg in the cardioplegic solution HTK.

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Section: Ad Imentioning

confidence: 99%

Different Effects of Cardioplegic Solution HTK during Single or Intermittent Administration

Gebhard¹,

Preusse²,

Schnabel³

et al. 1984

Thorac cardiovasc Surg

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General mechanism of chronic diseases

Yabrov

1987

Medical Hypotheses

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Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart

Smith

Visweswaran

Talkachova

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Smith RM, Visweswaran R, Talkachova I, Wothe JK, Tolkacheva EG. Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart. Am J Physiol Heart Circ Physiol 305: H9 -H18, 2013. First published May 3, 2013 doi:10.1152/ajpheart.00915.2012.-Alternans of action potential duration (APD) and intracellular calcium ([Ca 2ϩ ]i) transients in the whole heart are thought to be markers of increased propensity to ventricular fibrillation during ischemia-reperfusion injuries. During ischemia, ATP production is affected and the mitochondria become uncoupled, which may affect alternans formation in the heart. The aim of our study was to investigate the role of mitochondria on the formation of APD and [Ca 2ϩ ]i alternans in the isolated rabbit heart. We performed dual voltage and [Ca 2ϩ ]i optical mapping of isolated rabbit hearts under control conditions, global no-flow ischemia (n ϭ 6), and after treatment with 50 nM of the mitochondrial uncoupler FCCP (n ϭ 6). We investigated the formation of alternans of APD, [Ca 2ϩ ]i amplitude (CaA), and [Ca 2ϩ ]i duration (CaD) under different rates of pacing. We found that treatment with FCCP leads to the early occurrence of APD, CaD, and CaA alternans; an increase of intraventricular APD but not CaD heterogeneity; and significant reduction in conduction velocity compared with that of control. Furthermore, we demonstrated that FCCP and global ischemia have similar effects on the prolongation of [Ca 2ϩ ]i transients, whereas ischemia induces a significantly larger reduction of APD compared with that in FCCP treatment. In conclusion, our results demonstrate that uncoupling of mitochondria leads to an earlier occurrence of alternans in the heart. Thus, in conditions of mitochondrial stress, as seen during myocardial ischemia, uncoupled mitochondria may be responsible for the formation of both APD and [Ca 2ϩ ]i alternans in the heart, which in turn creates a substrate for ventricular arrhythmias.alternans; FCCP; calcium; action potential; mitochondria; ischemia T-WAVE ALTERNANS and alternans of action potential duration (APD) in the whole heart are thought to be markers of increased propensity to ventricular arrhythmias during ischemiareperfusion injuries (21,29,40). Repolarization T-wave alternans has been considered to be a strong marker of electrical instability and a precursor for ventricular arrhythmias (25,42,46,51,53), which is a major cause of sudden cardiac death (3, 4, 63). At the whole heart level, T-wave alternans, seen on the electrocardiogram, has been shown to correspond to a beat-tobeat variation in the APD at the single-cell level, a phenomenon known as APD alternans (46,63). It has been shown that APD and intracellular calcium ([Ca 2ϩ ] i ) transients are closely related. An action potential triggers a calcium influx leading to a release of calcium from the sarcoplasmic reticulum, whereas [Ca 2ϩ

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Role of some components of ischemia in the genesis of spontaneous ventricular arrhythmias

Cited by 3 publications

References 20 publications

Different Effects of Cardioplegic Solution HTK during Single or Intermittent Administration

Different Effects of Cardioplegic Solution HTK during Single or Intermittent Administration

General mechanism of chronic diseases

Uncoupling the mitochondria facilitates alternans formation in the isolated rabbit heart

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