Contribution of mechanical activity and electrical activity to cellular electrical uncoupling in ischemic rabbit...

We separated mechanical and electrical activity during ischemia and we assessed the contribution of each of these variables to ischemia induced cellular electrical uncoupling. In two groups of rabbit papillary muscles, mechanical and electrical activity at the onset of ischemia was abolished. We determined how this affected the time of onset of uncoupling. Also, action potential duration (APD80), conduction velocity and extracellular pH were recorded. In the first group, the BDM group, mechanical arrest was achieved with 10 mM BDM (2,3-butanedione monoxime). This had no effect on APD80 and conduction velocity. In the second group, the quiescent group, electrical as well as mechanical arrest was obtained by not stimulating the muscles. The effect of electrical arrest was estimated as the difference between this group and the BDM group. Mechanical arrest delayed uncoupling significantly (control: 14.6 +/- 0.9 (min), mean +/- S.E.M., n = 10; BDM: 19.3 +/- 1.1, n = 10; P < 0.025). Electrical arrest caused an even greater delay (quiescent: 41.6 +/- 4.6, n = 7; P < 0.001 v control and BDM). In the BDM group, these effects were not associated with a difference of APD80 during ischemia, but with a smaller decrease of conduction velocity. Delay of uncoupling correlated with delay of extracellular acidosis. We conclude: (1) mechanical and electrical activity both are significant determinants of ischemia induced uncoupling; (2) delay of uncoupling is associated with delay of extracellular acidosis, indicating a reduced rate of metabolism.