当前位置： SCI文献检索 > BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS期刊下所有文献 > Activation of εPKC reduces reperfusion arrhythmias and improves recovery from ischemia: optical mapping of activation patterns in the isolated guinea-pig heart.

Activation of εPKC reduces reperfusion arrhythmias and improves recovery from ischemia: optical mapping of activation patterns in the isolated guinea-pig heart.

Abstract：

UNLABELLED:Pervious biochemical and hemodynamic studies have highlighted the important role of εPKC in cardioprotection during ischemic preconditioning. However, little is known about the electrophysiological consequences of εPKC modulation in ischemic hearts. Membrane permeable peptide εPKC selective activator and inhibitor were used to investigate the role of εPKC modulation in reperfusion arrhythmias. METHODS:Protein transduction domain from HIV-TAT was used as a carrier for peptide delivery into intact Langendorff perfused guinea pig hearts. Action potentials were imaged and mapped (124 sites) using optical techniques and surface ECG was continuously recorded. Hearts were exposed to 30 min stabilization period, 15 min of no-flow ischemia, followed by 20 min reperfusion. Peptides (0.5 μM) were infused as follows: (a) control (vehicle-TAT peptide; TAT-scrambled ψεRACK peptide); (b) εPKC agonist (TAT-ψεRACK); (c) εPKC antagonist (TAT-εV1). RESULTS:Hearts treated with εPKC agonist ψεRACK had reduced incidence of ventricular tachycardia (VT, 64%) and fibrillation (VF, 50%) compared to control (VT, 80%, P<0.05) and (VF, 70%, P < 0.05). However, the highest incidence of VT (100%, P < 0.05) and VF (80%) occurred in hearts treated with εPKC antagonist peptide εV1 compared to control and to εPKC agonist ψεRACK. Interestingly, at 20 min reperfusion, 100% of hearts treated with εPKC agonist ψεRACK exhibited complete recovery of action potentials compared to 40% (P < 0.05) of hearts treated with εPKC antagonist peptide, εV1 and 65% (P < 0.5) of hearts in control. At 20 min reperfusion, maps of action potential duration from εPKC agonist ψεRACK showed minimal dispersion (48.2 ± 9 ms) compared to exacerbated dispersion (115.4 ± 42 ms, P < 0.05) in εPKC antagonist and control (67 ± 20 ms, P<0.05). VT/VF and dispersion from hearts treated with scrambled agonist or antagonist peptides were similar to control. CONCLUSION:The results demonstrate that εPKC activation by ψεRACK peptide protects intact hearts from reperfusion arrhythmias and affords better recovery. On the other hand, inhibition of εPKC increased the incidence of arrhythmias and worsened recovery compared to controls. The results carry significant therapeutic implications for the treatment of acute ischemic heart disease by preconditioning-mimicking agents.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Restivo M,Kozhevnikov DO,Qu YS,Yue Y,Mochly-Rosen D,El-Sherif N,Boutjdir M

doi

10.1016/j.bbrc.2012.08.073

subject

Has Abstract

pub_date

2012-09-21 00:00:00

pages

237-41

issue

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(12)01592-6

journal_volume

426

pub_type

杂志文章

在线工具

Activation of εPKC reduces reperfusion arrhythmias and improves recovery from ischemia: optical mapping of activation patterns in the isolated guinea-pig heart.