Inotropic, vasodilating and preconditioning actions of levosimendan in the heart.
BACKGROUND
Levosimendan improves ventricular function, induces vasodilation and induces myocardial preconditioning. We determined the external efficiency and assessed the effects on arrhythmias.


METHODS
In isolated, blood-perfused rabbit hearts, levosimendan (0.75 micromol) or placebo was administered, while hemodynamics were recorded. After no-flow ischemia and reperfusion, data were recorded again.


RESULTS
Placebo in normoxic hearts did not affect measurements, while levosimendan increased heart rate (+ 18 %) and improved coronary output (+ 52 %), stroke volume (+ 28 %), maximal left ventricular pressure (+ 30 %), maximal rate of pressure increase (+ 36 %), work (+ 68 %), minimal rate of pressure increase (+ 53 %), coronary blood flow (+ 41 %), coronary resistance (- 19 %) and external efficiency (33 %; P < 0.05). During reperfusion, hemodynamics in the levosimendan group were significantly better preserved compared with the placebo group. Early reperfusion arrhythmias were decreased (levosimendan group: 7 +/- 3 % vs. placebo group: 25 +/- 17 %; P < 0.05).


CONCLUSIONS
Levosimendan does not impair diastole, dilates coronary vessels, induces pharmacological preconditioning, improves external efficiency and exerts antiarrhythmic properties during reperfusion. As this drug protects the heart from reperfusion injury, it seems well suited for treating dysfunctional hearts after cardiac surgery.
Meyer
K
K
Research Group Experimental Surgery, University Hospital Düsseldorf, Düsseldorf, Germany.
Schipke
J D
JD
Klocke
R C
RC
Gams
E
E
Korbmacher
B
B
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists; D011724:Pyridazines / Q000494:pharmacology*; D011817:Rabbits; D000077464:Simendan; D014665:Vasodilator Agents / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D006835:Hydrazones; D015221:Potassium Channels; D011724:Pyridazines; D014665:Vasodilator Agents; C117780:mitochondrial K(ATP) channel; D000077464:Simendan; D002118:Calcium