BACKGROUND: Acute myocardial infarction (AMI) is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumor necrosis factor-α (TNF-α) on ventricular arrhythmias induced by AMI in rats in vivo. METHODS: Two hundred and forty male Wistar rats were randomized into a sham-operation group, an AMI group, and a recombinant human tumor necrosis factor receptor:Fc fusion protein(rhTNFR:Fc) group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery (LAD), and there was no ligation but operation in the sham-operation group. The rhTNFR:Fc group was treated with rhTNFR:Fc(10 mg/kg), a TNF-α antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-α among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. RESULTS: Expression of TNF-α increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR:Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR:Fc group showed a lesser expression of TNF-α protein and a lower incidence of ventricular arrhythmias (P<0.05). There was no obvious change in the sham-operation group. CONCLUSION: The expression of TNF-α induced by AMI could contribute to the onset of ventricular arrhythmias.
BACKGROUND:Acute myocardial infarction (AMI) is an acute cardiovascular emergency. This study was undertaken to assess the effect of tumornecrosis factor-α (TNF-α) on ventricular arrhythmias induced by AMI in rats in vivo. METHODS: Two hundred and forty male Wistar rats were randomized into a sham-operation group, an AMI group, and a recombinant humantumornecrosis factor receptor:Fc fusion protein(rhTNFR:Fc) group. Acute anterior wall myocardial infarction was produced in the AMI group by ligating the left anterior descending coronary artery (LAD), and there was no ligation but operation in the sham-operation group. The rhTNFR:Fc group was treated with rhTNFR:Fc(10 mg/kg), a TNF-α antagonist, 24 hours before LAD ligation. The spontaneous and induced programmed electrical stimulation ventricular arrhythmias were recorded at baseline and 10 minutes, 20 minutes, 30 minutes, 60 minutes, 3 hours, 6 hours and 12 hours after ligation. At the same time the protein and mRNA expression levels of TNF-α among different groups were detected by histochemistry and real-time fluorescent quantitative PCR. RESULTS: Expression of TNF-α increased markedly from 10 minutes after infarction, peaked at 20-30 minutes, and returned to baseline gradually in the AMI group and rhTNFR:Fc group. The time-windows of spontaneous and induced ventricular arrhythmias were similar. Compared with the AMI group, the rhTNFR:Fc group showed a lesser expression of TNF-α protein and a lower incidence of ventricular arrhythmias (P<0.05). There was no obvious change in the sham-operation group. CONCLUSION: The expression of TNF-α induced by AMI could contribute to the onset of ventricular arrhythmias.
Entities:
Keywords:
Acute myocardial infarction; Fc fusion protein (rhTNFR: Fc); Recombinant human tumor necrosis factor receptor; Tumor necrosis factor-α; Ventricular arrhythmia
Authors: Yuanna Cheng; Kent A Mowrey; Vladimir Nikolski; Patrick J Tchou; Igor R Efimov Journal: Am J Physiol Heart Circ Physiol Date: 2002-06 Impact factor: 4.733
Authors: Polina S Petkova-Kirova; Erdal Gursoy; Haider Mehdi; Charles F McTiernan; Barry London; Guy Salama Journal: Am J Physiol Heart Circ Physiol Date: 2005-12-09 Impact factor: 4.733
Authors: Barry London; Linda C Baker; Joon S Lee; Vladimir Shusterman; Bum-Rak Choi; Toru Kubota; Charles F McTiernan; Arthur M Feldman; Guy Salama Journal: Am J Physiol Heart Circ Physiol Date: 2002-10-17 Impact factor: 4.733