Functional and Antiischaemic Effects of the Phosphodiesterase Inhibitor Levosimendan in Isolated Rabbit Hearts

Several phosphodiesterase inhibitors have been reported to possess antiischaemic properties by improving myocardial oxygen demand/supply balance. Levosimendan is a new phosphodiesterase inhibitor with calcium-sensitizing properties. We investigated the functional and anliischaemic properties of levosimendan in isolated electrically-driven rabbit hearts (Langendorff, constant perfusion pressure: 70 cm H2O, Tyrode solution, Ca++ 1.8 mmol/1, 37°, 200 beats/min.). Acute regional myocardial ischaemia was induced by ligature of a circumflex artery branch and quantified from epicardial NADH-fluorescence photography. Results: The left ventricular pressure was similarly enhanced by levosimendan 10−7 M or 5 × 10−6 M (+15%) (P 0.05). Epicardial NADH-fluorescence area and intensity were significantly diminished by levosimendan (-20%) (P 0.05). Conclusion: Levosimendan is an inotrope with coronary dilator activity, showing antiischaemic effects in isolated rabbit hearts. These may be caused by (1) phosphodiesterase-inhibition and improvement of myocardial perfusion and/or (2) by oxygen-sparing effects, related to calcium sensitization of myofilaments, particularly at lower concentrations associated with a lower coronary dilator activity.