Pyruvate Potentiatesβ-Adrenergic Inotropism of Stunned Guinea-Pig Myocardium

This study tested the hypotheses that the sensitivity of stunned myocardium toβ-adrenergic stimulation is diminished, and that metabolic intervention with pyruvate can restoreβ-adrenergic responsiveness to pre-ischemic levels. Isolated working guinea-pig hearts metabolizing 10 m glucose were stunned by 45 min of low flow ischemia, and pyruvate and/or isoproterenol treatments were initiated 15 and 30 min after reperfusion, respectively. The dose:response for cardiac power from 0.1–100 n isoproterenol was significantly shifted to the right in stunned hearts: EC50(n ) increased from 0.3±0.06 to 5.2±1.86. Pyruvate (5 m ) largely restored isoproterenol responsiveness of stunned myocardium, lowering EC50to 1.1±0.34 n . Maximum power was similar in each group. Additional stunned hearts were treated with intermediate (2 n ) or high (30 n ) isoproterenol concentrations with or without pyruvate. Combining treatments produced a significant interaction at the low dose of isoproterenol, increasing cardiac power (mJ•min−1•g−1) to 149±20, twice the sum of the individual treatments (2 n isoproterenol: 34±11; pyruvate: 33±8). Cyclic AMP content was unaltered by isoproterenol or pyruvate alone but was increased 41% by the combination. Power was maximized by 30 n isoproterenol, which tripled cyclic AMP content; pyruvate did not augment these responses, but lessened the isoproterenol-induced decline in cytosolic phosphorylation potential.Conclusions: β-adrenergic inotropism is attenuated in stunned myocardium, although the maximal response is unchanged. Pyruvate potentiated the effects of sub-maximal doses of isoproterenol without depleting cellular energy reserves further, and attenuated energy depletion by high doses of isoproterenol. Pyruvate may allow restoration of contractile performance with lower, energetically less costly doses of β-adrenergic agents.