Effects of hypoxia on the guinea-pig myocardium following inhibition of adenosine deaminase by coformycin.

The effect of moderate and severe hypoxia on the electrical and mechanical activity of isolated left atria of guinea-pigs was compared in the presence and absence of coformycin, a highly specific and tight-binding inhibitor of adenosine deaminase. The myocardial actions of hypoxia (reduction in the duration of intracellularly recorded action potentials and decrease in isometric tension, maximum velocity of contraction and relaxation as well as in time to peak tension) were significantly enhanced by coformycin, when applied in a concentration of 7 mumol/l producing nearly complete inhibition of adenosine deaminase in atrial muscle. These effects of coformycin were moderate during early hypoxia (0-5 min) and became pronounced during the late phase of oxygen deprivation (5-16 min). The results are in favour of the previous assumption that under hypoxic conditions the increased tissue level of adenosine might contribute to the functional impairment of the guinea-pig myocardium.