Terminal warm blood cardioplegia improves cardiac function through microtubule repolymerization

To elucidate the mechanisms responsible for the beneficial effects of terminal warm blood cardioplegia, we studied dynamic change in microtubules induced by cold cardioplegia followed by rewarming. Further, we investigated the relationship between cardiac function and morphologic changes in microtubules caused by hyperkalemic, hypocalcemic warm cardioplegia during initial reperfusion.

In protocol 1 isolated rat hearts were perfused at 37 degrees C with Krebs-Henseleit buffer (KHB). After 3 hours of hypothermic cardiac arrest at 10 degrees C, hearts were reperfused at 37 degrees C with one of two buffers: group C, 60-minute reperfusion with KHB (K+, 5.9 mmol/L; Ca2+, 2.5 mmol/L); and group TC, 10-minute initial reperfusion with modified KHB (K+, 15 mmol/L; Ca2+, 0.25 mmol/L), followed by 50 minutes of reperfusion with KHB. Cardiac function after reperfusion was determined as a percentage of the prearrest value. In protocol 2 hearts were perfused at 37 degrees C with KHB containing colchicine (10(-5) mol/L) for 60 minutes.

There was spontaneous contractile recovery after 10 minutes of initial reperfusion in hearts from group TC as well as improved cardiac function after 15, 30, and 60 minutes of reperfusion compared with that in group C. Immunohistochemical staining and immunoblot analysis demonstrated microtubule depolymerization during hypothermic cardiac arrest and complete repolymerization after 10 minutes of reperfusion with warm buffers in both groups. Colchicine-induced microtubule depolymerization is associated with deterioration of cardiac function.

One mechanism responsible for improved cardiac function mediated by terminal warm blood cardioplegia is the restart of contraction after complete microtubule repolymerization.