CARDIOPLEGIA ON THE CONTRACTILE APPARATUS LEVEL - EVALUATION OF A NEWCONCEPT FOR MYOCARDIAL PRESERVATION IN PERFUSED PIG HEARTS

The concept of a reversible desensitization of the myocardial contract ile apparatus for calcium by 2,3 Butanedione Monoxime (BDM) as a metho d to improve the myocardium's tolerance to cold ischemia was evaluated in normal pig hearts (n = 14). The results were compared to those obt ained after application of Bretschneider's HTK cardioplegic solution. Methods: Series I) After BDM treatment (concentrations: 0-30 mmol/L) t he isometric force output and the intracellular calcium transients (me asured using the FURA-2 ratio method) of electrically driven (1 Hz) is olated left-ventricular muscle strips excised from beating pig hearts (n = 14) were recorded simultaneously in order to analyse the mode of action of BDM; Series II) The cardioprotective effects of BDM (30 mmol /L) and Bretschneider's cardioplegic solution (HTK) were compared in a large-animal model: after ''in situ perfusion'' of pig hearts with ei ther 2000 ml ice-cold BDM solution (30 mmol/L) (n = 7) or 2000 ml HTK (n = 7) the hearts were explanted and stored at 4 degrees C in the sam e solutions for up to 42 h. The contractile properties of muscle fibre s, excised after storage periods of 8, 24, and 42 h from these hearts were analyzed in terms of isometric force development and isotonic sho rtening. 280 muscle fibres from 14 pigs were used for measurements. Re sults: Series I) In pig myocardium a dose-dependent reduction of isome tric force development was found after BDM application. The shape and the amplitude of the intracellular calcium transient were also affecte d by BDM. At 30 mmol/L BDM no force development could be elicited desp ite the presence of an intracellular calcium transient (amplitude < 70 % of the control). Series II) Shortening, calcium transient, and forc e of left-ventricular muscle strips of pig myocardium excised after st orage periods for up to 42 h showed complete recovery when BDM was app lied. In contrast HTK perfusion allowed complete recovery of these par ameters when the storage period did not exceed 6 hours. Conclusion: Un der the given experimental conditions reversible desensitization of th e contractile apparatus for calcium results in a considerable prolonga tion of the tolerance to cold ischemia in explanted pig hearts. The pr esent study shows that the protective effects of BDM are not only pres ent when isolated muscle fibres were stored (and the extracellular spa ce is large) but also after storage of complete hearts in a solution c ontaining BDM. Thus BDM may become a useful agent to enlarge the stora ge period of donor hearts in heart transplantation considerably.