[A new concept of cardioplegic protection in cardiac surgery: iron chelation].
Hydroxyl is one of the most cytotoxic of all oxygen-derived free radicals produced during the myocardial ischaemia-reperfusion sequence. The purpose of the present study was to determine the effects of various interventions aimed at diminishing the production of hydroxyl radicals by reducing either one of their precursors (hydrogen peroxide) or the metal (ferric iron) which catalyzes the reaction generating these radicals. Sixty isolated and perfused rat hearts with isovolaemic contraction were studied. Except for non-ischaemic controls, these hearts were subjected to a 3-hour cardioplegic arrest in hypothermia (15-18 degrees C) followed by a 45-min reperfusion. The following interventions were performed: pretreatment with peroxidase, a hydrogen peroxide scavenger; pretreatment with peroxidase combined with deferoxamine, an ironchelating agent; pretreatment with peroxidase followed by addition of deferoxamine to the cardioplegic solution; addition of deferoxamine to the cardioplegic solution without pretreatment with the enzyme. Judging from the post-ischaemic values of developed pressure (maximum systolic pressure--diastolic pressure), left ventricular dP/dt and diastolic pressure and coronary flow rate, it appeared that the best myocardial protection was provided by deferoxamine-enriched cardioplegia. This study confirms that hydroxyl radicals most probably play a role in the genesis of the myocardial lesions associated with global ischaemia followed by reperfusion. Moreover, our results highlight the potential value of deferoxamine added to cardioplegic protection in heart surgery performed under extracorporeal circulation.
Menasché
P
P
Service de chirurgie cardio-vasculaire et INSERM U 127, hôpital Lariboisière, Paris.
Grousset
C
C
Gauduel
Y
Y
Mouas
C
C
Piwnica
A
A
D000818:Animals; D006348:Cardiac Surgical Procedures; D002314:Cardioplegic Solutions / Q000378:metabolism*; D003327:Coronary Disease / Q000503:physiopathology*; D003676:Deferoxamine / Q000008:administration & dosage / Q000378:metabolism*; D005112:Extracorporeal Circulation; D005609:Free Radicals; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000008:administration & dosage; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010544:Peroxidases / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002314:Cardioplegic Solutions; D005609:Free Radicals; D007502:Iron Chelating Agents; D007501:Iron; D010544:Peroxidases; D003676:Deferoxamine
Un nouveau concept de la protection cardioplégique en chirurgie cardiaque: la chélation du fer.