Inhibition of hypoxic myocardial contracture by Cobalt in the rat

We studied the relationship between the slow inward current, tissue ATP content, and the development of hypoxic myocardial contracture in the rat. Resting tension and active isometric tension were measured using isolated left ventricular papillary muscle preparations. Action potentials and membrane currents were studied using a single sucrose gap voltage clamp technique. The slow inward current (isi) was partially inhibited by verapamil and completely inhibited by cobalt but was not reduced by ryanodine. Active tension was reduced by all three drugs. Non-stimulation, verapamil, and ryanodine did not prevent contracture development with hypoxia, but contracture was markedly reduced by pre-treatment with cobalt. Despite contrasting effects on contracture, both non-stimulation and cobalt partially prevented ATP depletion with hypoxia, suggesting that contracture is not directly related to total muscle ATP content. Cobalt appears to block hypoxic contracture via a mechanism other than simple blockade of isi, inhibition of contraction, or preservation of tissue ATP content.