Time-dependent efficacy of initial reperfusion with 2,3 butane-dione monoxime (BDM) on release of cytosolic enzymes and ultrastructural damage in isolated hearts

Citation
J. Voigtlander et al., Time-dependent efficacy of initial reperfusion with 2,3 butane-dione monoxime (BDM) on release of cytosolic enzymes and ultrastructural damage in isolated hearts, THOR CARD S, 47(4), 1999, pp. 244-250
Citations number
23
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
THORACIC AND CARDIOVASCULAR SURGEON
ISSN journal
0171-6425 → ACNP
Volume
47
Issue
4
Year of publication
1999
Pages
244 - 250
Database
ISI
SICI code
0171-6425(199908)47:4<244:TEOIRW>2.0.ZU;2-P
Abstract
Background: Reperfusion injury after cardioplegia may not be sufficiently a ddressed by conventional cardioplegic techniques in open heart surgery. 2,3 -butanedione monoxime (BDM) has the potential to reduce myocardial reperfus ion injury by uncoupling myocyte contraction from the intracellular calcium concentration, thus reducing reperfusion contracture. The aim of this stud y was to investigate the effects of different application periods of BDM du ring initial reperfusion on myocardial tissue injury after cardioplegia. Me thods: Isolated guinea-pig hearts underwent 50 min of cardioplegic arrest i n St. Thomas' Hospital II solution at 37 degrees C. Control hearts (n=8) we re immediately reperfused with normal Krebs-Henseleit solution for 30 min. In the therapy groups BDM-5, BDM-20, and BDM-40 (n=8, each), hearts were in itially reperfused with BDM (20 mmol/L) for either 5, 20, or 40 min, respec tively, followed by 30 min of reperfusion with normal Krebs-Henseleit solut ion. Coronary venous effluent was collected to estimate myocardial tissue d amage through release of cytosolic enzymes (LDH and CK) and cardiac troponi n I. Ultra-structural alterations were qualitatively assessed by electron m icroscopy. Results: Initial reperfusion with BDM markedly reduced LDH and C K release, as long as BDM was present. After washout of the protective agen t a rebound of enzyme release occurred in BDM-5 hearts which was effectivel y reduced in BDM-20 and BDM-40 hearts. Traponin I release was similarly inc reased in all groups at the onset of reperfusion and rapidly decreased ther eafter. Myocardial ultrastructural damage was most pronounced in control he arts, intermediate in BDM-5 and BDM-40 hearts, but markedly attenuated in B DM-20 hearts. Conclusions: Both 20 and 40 min of initial reperfusion effect ively protected the hearts from reperfusion damage as indicated by cytosoli c enzyme release, while 5 min of treatment were clearly insufficient. Toxic effects of BDM during the longer treatment period of 40 min or induction o f edema by the long-term perfusion of non-beating hearts in this group may account for the worse preservation of myocardial ultrastructure in BDM-40 h earts. Thus, contraction uncoupling during initial reperfusion by BDM or si milarly acting drugs may prove a viable principle for reduction of myocardi al reperfusion injury. However, the ideal duration of treatment for the bes t therapeutic effect must be carefully evaluated.