On augmentation of adenosine-mediated negative dromotropic effect by K+ released during myocardial ischemia.

The present study was designed to investigate mechanisms of adenosine (ADO)-mediated prolongation of conductivity through the atrioventricular (AV) node during myocardial ischemia. Using the Langendorff preparation of the guinea pig heart, we tested the hypothesis that extracellular potassium concentration elevated due to ischemia could augment ADO effect. Exposure of the heart preparation to either stop-flow or hypoxic Krebs-Henseleit solution (KH) inhibited AV node conductivity observed as an increase in SH interval, and finally resulted in AV block. Superficial potassium concentration ([K+]s), recorded simultaneously increased in response to each stop-flow or hypoxia. Application of 0.1 mM BaCl2 markedly increased the SH interval, yet it did neither protect the heart from hypoxia-evoked AV block nor did it prevent hypoxia-induced [K+]s elevation. Neither did perfusion of the myocardium with modified KH containing 8 mM K+ affect the hypoxic AV block and [K+]s increase. The hypoxic effects were not affected by adenosine A1 agonist N6-cyclopentyl-adenosine (CPA, 30 nM). In the presence of CPA, application of high-K+ KH, where potassium was elevated to the value of hypoxic level, did not affect the SH interval. On the other hand, adenosine deaminase (ADA, 4 U/ml) significantly attenuated the hypoxic AV block. This indicated an involvement of endogenous ADO. Yet, in the presence of both ADA and CPA, the application of the high-K+ KH did not affect the SH interval. We concluded that increased extracellular [K+], elevated due to hypoxia, did not participate in the hypoxia-induced AV block mediated by ADO.