Effect of diltiazem on the oxymyoglobin level of myocardial cells in the isolated, perfused rat heart during hypoxia

Summary

The effect of diltiazem on the oxymyoglobin level was studied in the isolated rat heart during hypoxia. The heart was perfused with Krebs-Henseleit solution equilibrated with a gas mixture containing 95% O₂+5% CO₂ (normoxic perfusion solution) at a constant flow rate (9 ml/min) according to Langendorff's method. All the hearts were paced at 300 beats/min. The myocardial oxymyoglobin level (i.e., intracellular oxygen level) of the left ventricular surface was continuously measured by means of an optical technique. Diltiazem (infused into the aortic cannula for 10 minutes at concentrations of 0.72, 2.41, or 4.82 μM, expressed as the final concentration in the solution) decreased, the left ventricular pressure (LVP) and perfusion pressure (PP) dose dependently, and did not change the oxymyoglobin (MbO₂) level during normoxic perfusion. Hypoxic perfusion (using a gas mixture containing 30% O₂+5% CO₂+65% N₂) decreased the MbO₂, LVP, and PP. Diltiazem (infused 5 minutes after the hypoxic perfusion) at a concentration of 2.41 or 4.82 μM increased the MbO₂ level and further decreased the LVP, without affecting the PP. The low concentration (0.72 μM) of diltiazem, however, had practically no effect on these parameters. In summary, diltiazem in high concentrations decreased the LVP and increased the intracellular oxygen level of the myocardial cells during hypoxia, but not during normoxia.