Document Detail

Anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH reduces dispersion of action potential duration during ischemia/reperfusion in rabbit hearts.
MedLine Citation:
PMID:  12409986     Owner:  NLM     Status:  MEDLINE    
During ischemia, cardiac gap junctions close and neighboring cells uncouple. This leads to slow conduction, increased dispersion of APD90 (duration from action potential beginning to 90% of repolarization), nonuniform anisotropy, and unidirectional conduction block, all of which favor the induction of reentry arrhythmias. It has been suggested that anti-arrhythmic peptides increase gap junction conductance during states of reduced coupling. The aim of this study was to test the effect of the anti-arrhythmic peptide N-3-(4-hydroxyphenyl)propionyl Pro-Hyp-Gly-Ala-Gly-OH (HP-5) (10(-10) ) on dispersion of epicardial APD90 during both normokalemic and hypokalemic ischemia/reperfusion in isolated perfused rabbit hearts. HP-5 did not affect average APD90, heart rate, left ventricular contractility (LVP dP/dtmax), or mean coronary flow. HP-5 significantly reduced the epicardial APD dispersion during hypokalemic ischemia (HP-5 treated: 24.1 +/- 3.4 ms, untreated: 33.9 +/- 3.1 ms, p < 0.05 versus untreated) and during normokalemic reperfusion but not during normokalemic ischemia or control conditions. In addition, among untreated hearts subjected to hypokalemic ischemia/reperfusion, seven of 10 developed ventricular fibrillation, whereas only three of nine hearts perfused with HP-5 developed ventricular fibrillation. These results show that HP-5 is able to reduce APD90 dispersion during hypokalemic ischemia in rabbit hearts.
Anne Louise Kjølbye; Niels-Henrik Holstein-Rathlou; Jørgen Søberg Petersen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  40     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  2002 Nov 
Date Detail:
Created Date:  2002-10-31     Completed Date:  2003-03-04     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  770-9     Citation Subset:  IM    
Zealand Pharma, Glostrup, Denmark.
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MeSH Terms
Action Potentials / drug effects
Anti-Arrhythmia Agents / therapeutic use*
Heart / physiology*
Hemodynamics / drug effects*
Ischemia / drug therapy*
Myocardial Contraction / drug effects
alpha-Defensins / therapeutic use*
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 0/alpha-Defensins; 0/neutrophil peptide 5

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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