Document Detail


Poly-ADP-ribose polymerase inhibition protects against myocardial and endothelial reperfusion injury after hypothermic cardiac arrest.
MedLine Citation:
PMID:  14502135     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Free radical production and related cytotoxicity during ischemia and reperfusion might lead to DNA strand breakage, which activates the nuclear enzyme poly-ADP-ribose synthetase and initiates an energy-consuming and inefficient cellular metabolic cycle with transfer of the adenosine diphosphate-ribosyl moiety of nicotinamide adenine dinucleotide (NAD(+)) to protein acceptors. We investigated the effects of poly-ADP-ribose synthetase inhibition on myocardial and endothelial function during reperfusion in an experimental model of cardiopulmonary bypass. METHODS: Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6) or PJ34 (10 mg/kg), a potent poly-ADP-ribose synthetase inhibitor (n = 6). Biventricular hemodynamic variables were measured by means of a combined pressure-volume conductance catheter, and the slope of the end-systolic pressure-volume relationships was calculated at baseline and after 60 minutes of reperfusion. Left anterior descending coronary blood flow, endothelium-dependent vasodilatation to acetylcholine, and endothelium-independent vasodilatation to sodium nitroprusside were also determined. RESULTS: The administration of PJ34 led to a significantly better recovery of left and right ventricular systolic function (P <.05) after 60 minutes of reperfusion. In addition, the inotropic adaptation potential of the right ventricle to an increased afterload was better preserved in the PJ34 group. Coronary blood flow was also significantly higher in the PJ34 group (P <.05). Although the vasodilatory response to sodium nitroprusside was similar in both groups, acetylcholine resulted in a significantly higher increase in coronary blood flow in the PJ34 group (P <.05). CONCLUSIONS: Poly-ADP-ribose synthetase inhibition improves the recovery of myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest.
Authors:
Gábor Szabó; Volker Buhmann; Terézia Andrási; Nicole Stumpf; Susanne Bährle; Violetta Kékesi; Siegfried Hagl; Csaba Szabó; Alexander Juhász-Nagy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  126     ISSN:  0022-5223     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-22     Completed Date:  2003-11-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  651-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiac Surgery, University of Heidelberg, In Neuenheimer Feld 110, 69120 Heidelberg, Germany. dzsi@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Circulation
Dogs
Endothelium, Vascular*
Heart Arrest, Induced / adverse effects*
Hemodynamics
Myocardial Reperfusion Injury / etiology,  prevention & control*
Poly(ADP-ribose) Polymerases / antagonists & inhibitors*
Vascular Diseases / etiology,  prevention & control
Ventricular Function
Grant Support
ID/Acronym/Agency:
R01 HL 59266/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 2.4.2.30/Poly(ADP-ribose) Polymerases
Comments/Corrections
Comment In:
J Thorac Cardiovasc Surg. 2004 Aug;128(2):323-4; author reply 324-5   [PMID:  15282474 ]

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


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