| Mesenteric injury after cardiopulmonary bypass: role of poly(adenosine 5'-diphosphate-ribose) polymerase. | |
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MedLine Citation:
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PMID: 15599141 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: To investigate the effects of the ultrapotent poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) inhibitor INO-1001 on cardiac and mesenteric function during reperfusion in an experimental model of cardiopulmonary bypass with cardioplegic arrest. DESIGN: Prospective, randomized, and blinded experimental study. SETTING: Research laboratory. SUBJECTS:: Twelve anesthetized dogs underwent cardiopulmonary bypass with hypothermic cardioplegic cardiac arrest. INTERVENTIONS: After 60 mins of hypothermic cardiac arrest, either PARP inhibitor INO-1001 (1 mg/kg, n = 6) or vehicle (control, n = 6) was administered during reperfusion. MEASUREMENTS AND MAIN RESULTS: Left ventricular hemodynamic variables were measured by combined pressure-volume-conductance catheters. Coronary and mesenteric blood flow and vasodilatory responses to acetylcholine and sodium nitroprusside as well as mesenteric lactate and creatinine phosphokinase release were also determined. The administration of INO-1001 led to a significantly improved recovery of left ventricular systolic function (p < .05) after 60 mins of reperfusion. Coronary and mesenteric blood flow were also significantly higher in the INO-1001 group (p < .05). Although the vasodilatory response to sodium nitroprusside was similar in both groups before and after cardiopulmonary bypass and similar in response to acetylcholine before cardiopulmonary bypass, PARP-inhibited dogs had lower mesenteric vascular resistance after cardiopulmonary bypass (p < .05). Mesenteric lactate and creatinine phosphokinase release was significantly lower in the PARP inhibitor treated group (p < .05). CONCLUSION: PARP inhibition with INO-1001 improves the recovery of myocardial function and prevents mesenteric vascular dysfunction and tissue injury after cardiopulmonary bypass with hypothermic cardiac arrest. |
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Authors:
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Gábor Szabó; Pál Soós; Susanne Mandera; Ulrike Heger; Christa Flechtenmacher; Leila Seres; Zsuzsanna Zsengellér; Falk-Udo Sack; Csaba Szabó; Siegfried Hagl |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Critical care medicine Volume: 32 ISSN: 0090-3493 ISO Abbreviation: Crit. Care Med. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-12-15 Completed Date: 2005-01-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 2392-7 Citation Subset: AIM; IM |
Affiliation:
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Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Biopsy, Needle Cardiopulmonary Bypass / adverse effects*, methods Coronary Circulation / drug effects Disease Models, Animal Dogs Dose-Response Relationship, Drug Drug Administration Schedule Female Heart Arrest, Induced Hemodynamics / drug effects, physiology Immunohistochemistry Mesentery / drug effects*, injuries*, pathology Myocardial Reperfusion Injury / drug therapy*, pathology Poly(ADP-ribose) Polymerases / antagonists & inhibitors*, metabolism Probability Random Allocation Reference Values Sensitivity and Specificity |
| Grant Support | |
ID/Acronym/Agency:
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R01HL59266/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
| Comments/Corrections | |
Comment In:
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Crit Care Med. 2004 Dec;32(12):2543-4
[PMID:
15599165
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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