Levosimendan cardioprotection in acutely beta-1 adrenergic receptor blocked open chest pigs.
BACKGROUND
Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. beta-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect.


METHODS
Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues.


RESULTS
At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups.


CONCLUSIONS
The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by beta-1 adrenergic receptor antagonism with metoprolol.
Metzsch
C
C
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Lund University, Lund, Sweden. carsten.metzsch@med.lu.se
Linnér
R
R
Steen
S
S
Liao
Q
Q
Algotsson
L
L
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002985:Clinical Protocols; D005260:Female; D005947:Glucose / Q000032:analysis; D005990:Glycerol / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000008:administration & dosage*; D019344:Lactic Acid / Q000032:analysis; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011724:Pyridazines / Q000008:administration & dosage*; D019289:Pyruvic Acid / Q000032:analysis; D000077464:Simendan; D013552:Swine; D019616:Thoracic Surgical Procedures / Q000379:methods*; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019344:Lactic Acid; D000077464:Simendan; D019289:Pyruvic Acid; D008790:Metoprolol; D005947:Glucose; D005990:Glycerol