Document Detail

Nitric-oxide-induced reoxygenation injury in the cyanotic immature heart is prevented by controlling oxygen content during initial reoxygenation.
MedLine Citation:
PMID:  9071194     Owner:  NLM     Status:  MEDLINE    
Reintroduction of high levels of molecular oxygen after a hypoxic period is followed by a burst of nitric oxide (NO), peroxynitrite, and oxygen free radicals (OFR), which are highly cytotoxic. This study indicates that hyperoxic reoxygenation of cyanotic immature hearts on cardiopulmonary bypass (CPB) induces a reoxygenation injury and that, by reducing NO and OFR production during institution of CPB with subsequent reoxygenation under blood cardioplegic arrest, this oxygen-related damage can be avoided and biochemical and functional status improved. Of 25 immature piglets (3-5 kg, two to three weeks old), 6 underwent one hour of CPB including thirty minutes of aortic clamping with substrate-enriched modified blood cardioplegia (hypocalcemic, alkalotic, and hyperosmolar; warm induction-cold replenishment-warm reperfusion) without preceding hypoxia (controls). Nineteen others were made hypoxic (arterial [Po2] 20-30 mmHg) for up to two hours by lowering the fraction of inspired oxygen (FIO2) on ventilator. These hypoxic piglets were then reoxygenated on CPB at different Po2 levels (hyperoxic, normoxic, or hypoxic) for five minutes, followed by the aforementioned blood cardioplegic (BCP) arrest regimen. Myocardial conjugated diene (CD) production as a marker of lipid peroxidation, and NO production, determined as its spontaneous oxidation products, nitrite (NO2-) and nitrate (NO3-), were assessed during blood cardioplegic induction, and antioxidant reserve capacity was determined by incubating myocardium in the oxidant t-butylhydroperoxide (t-BHP). Myocardial function was evaluated from end-systolic elastance (Ees, conductance catheter). Blood cardioplegic arrest caused no functional or biochemical changes in normoxic control immature piglets. In contrast, brief reoxygenation at PO2 > 400 mmHg, followed by BCP-arrest (hyperoxic) resulted in marked CD production (42 +/- 4 vs 3 +/- 1 A233 nm/minute/100 g; P < 0.05), and NO production (4500 +/- 500 vs 450 +/- 32 mmol/minute/100 g; P < 0.05) during blood cardioplegic induction, reduced antioxidant reserve capacity (malondialdehyde [MDA] at 4.0 mM of t-BHP: 1342 +/- 59 vs 958 +/- 50 nM/g protein; P < 0.05), and caused profound myocardial dysfunction; Ees recovered only 21 +/- 2% (vs 104 +/- 7; P < 0.05), despite the blood cardioplegic regimen shown to be cardioprotective in control normoxic piglets. Conversely, controlling initial PO2 to normoxic (100 mmHg) or hypoxic (20-30 mmHg) levels reduced lipid peroxidation (CD production 16 +/- 2, 2 +/- 1 A233nm/minute/100 g) and NO production (1264 +/- 736, 270 +/- 182 mmol/minute/100 g), restored antioxidant reserve capacity (MDA at 4.0 mM of t-BHP: 940 +/- 95, 982 +/- 88 nM/g protein), and allowed significant functional recovery (58 +/- 11% and 83 +/- 8%), in a PO2-dependent fashion. The authors conclude that reoxygenation of hypoxemic immature hearts by initiating hyperoxic CPB causes oxidant-related damage characterized by lipid peroxidation, enhanced NO production, and reduced antioxidants, leading to functional depression that nullifies the cardioprotective effects of blood cardioplegia. These detrimental effects can be reduced in a PO2-dependent fashion by controlling initial PO2 on CPB and subsequent reoxygenation during blood cardioplegic arrest.
K Ihnken; K Morita; G D Buckberg; B Winkelmann; M Schmitt; L J Ignarro; M P Sherman
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Angiology     Volume:  48     ISSN:  0003-3197     ISO Abbreviation:  Angiology     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-04-09     Completed Date:  1997-04-09     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0203706     Medline TA:  Angiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  189-202     Citation Subset:  IM; S    
Department of Cardiovascular Surgery, Albert-Ludwigs-University Freiburg, Germany.
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MeSH Terms
Animals, Newborn
Anoxia* / therapy
Cardiopulmonary Bypass*
Free Radicals
Heart Arrest, Induced*
Heart Defects, Congenital / surgery*
Lipid Peroxidation
Myocardium / metabolism
Nitric Oxide / biosynthesis,  physiology*
Oxygen Consumption
Reg. No./Substance:
0/Free Radicals; 10102-43-9/Nitric Oxide

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