Copyright © 2006, European Society of Cardiology
Neutrophil ablation with anti-serum does not protect against phase 2 ventricular arrhythmias in anaesthetised rats with myocardial infarction
aCardiovascular Division, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, UK
bPresent address: Loyola University Medical Center, Maywood, IL, USA
* Corresponding author. Tel.: +44 207 1881095. Email address: michael.curtis{at}KCL.AC.UK
Objectives: Arrhythmias, including ventricular fibrillation (VF), occur in two phases after coronary obstruction, the first during the reversible stage of acute myocardial ischaemia (phase 1) and the second during evolution of the infarct (phase 2). We tested the hypothesis that phase 2 arrhythmias are mediated by actions of neutrophils accumulating within the infarct.
Methods: Male rats (n=10 per group) were randomized to receive 2 ml/kg i.p. of either rabbit anti-rat neutrophil anti-serum or normal rabbit serum. After 17 h, single stage left coronary artery ligation was performed under pentobarbitone anaesthesia, and ischaemia was maintained for 240 min.
Results: Anti-serum pretreatment caused almost total neutropenia, reducing neutrophils in circulating blood from 2096±274x103 to 8±8x103 per ml (p<0.05). It also blocked neutrophil accumulation in the infarct, reducing cardiac myeloperoxidase activity from 74.7±27.4 to 9±3 mU per mg protein (p<0.05). Despite this, there was no significant difference between control and anti-serum-treated rats in the incidence of phase 2 VF (30% in each group) tachycardia (VT; 60% vs 80%) or number of ventricular premature beats (VPBs).
Conclusion: Neutrophil accumulation within the evolving myocardial infarct does not mediate phase 2 VF.
KEYWORDS Antiarrhythmic agents; Neutrophil; Myocardial infarction; Ischaemia; Nitric oxide; Reperfusion; Ventricular arrhythmias
Abbreviations: IL-8, interleukin 8 • PAF, myeloperoxidase • MPO, platelet activating factor • SCD, sudden cardiac death • TNF
, tumor necrosis factor • VF, ventricular fibrillation • VPB, ventricular premature beat • VT, ventricular tachycardia
Time for primary review 29 days
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