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The myocardial protective effect of nicorandil, N-(2-hydroxyethyl) nicotinamide nitrate ester, against hypoxia was examined in comparison with that of nitroglycerin in 22 open chest dogs. The regional ventricular myocardium was perfused for 5 min with a hypoxic solution in 8 dogs (Group 1), with a hypoxic solution containing 0.5 or 2.5 mg/dl of nicorandil in 7 dogs (Group 2) and with a hypoxic solution containing 0.5 mg/dl of nitroglycerin in 7 dogs (Group 3). In Group 2, the ATP content of the hypoxic myocardium was 3.14 +/- 0.37 mumol/g, which was less than that in the uninvolved myocardium (4.31 +/- 0.57 mumol/g) but significantly higher than those of the hypoxic myocardium in Groups 1 and 3 (2.09 +/- 0.45 and 2.39 +/- 0.33 mumol/g, respectively). The lactate content of the hypoxic myocardium in Group 2 (5.05 +/- 1.13 mumol/g) was less than those of the hypoxic myocardium in Groups 1 and 3 (8.77 +/- 2.34 and 8.98 +/- 2.08 mumol/g, respectively). This protective effect was not caused by the hemodynamic changes. In contrast, nitroglycerin did not show any protective effects on the hypoxic myocardium.
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