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Effects of Levosimendan on Myocardial Infarct Size and Hemodynamics in a Closed-Chest Porcine Ischemia–Reperfusion Model

  • Basic Pharmacology
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Abstract

Introduction

Levosimendan is a positive inotropic drug with vasodilator action and proposed myocardioprotective properties. In a canine model, levosimendan increased coronary collateral flow and reduced myocardial infarct size (IS). We investigated the effect of levosimendan on IS and hemodynamics in the closed-chest porcine ischemia–reperfusion model, which is devoid of coronary collaterals.

Methods

Infusion with levosimendan (0.2 μg/kg/min following a bolus of 24 μg/kg) or saline was initiated 30 min prior to ischemia in anaesthetized pigs (n = 10 in both groups). Balloon occlusion of the left anterior descending coronary artery for 45 min was followed by 2 1/2 h of reperfusion. Hemodynamics were monitored with a Swan-Ganz catheter and a left ventricular pressure micromanometer. Left ventricular systolic and diastolic function was estimated by dP/dtmax and τ, respectively. Myocardial area at risk (AAR) and IS were assessed in vivo by myocardial perfusion imaging (MPI) and ex vivo by histopathology (fluorescein staining for AAR, tetrazolium staining for IS).

Results

Prior to ischemia, levosimendan improved left ventricular systolic and diastolic function with coincident preload and afterload reduction. Cardiac output increased by 10 ± 4% (p = 0.04), dP/dtmax by 15 ± 5% (p = 0.01). Pulmonary capillary wedge pressure decreased by 18 ± 3% (p = 0.04), τ by 11 ± 2% (p = 0.001), and mean arterial pressure by 11 ± 2% (p < 0.001). A similar trend was observed during ischemia–reperfusion. The ratio of IS/AAR was not reduced by levosimendan compared to saline as evaluated by histopathology (76 ± 4% vs. 64 ± 7%, p = 0.12) and by MPI (94 ± 2% vs. 87 ± 5%, p = 0.14).

Conclusion

Levosimendan improves hemodynamics but does not reduce IS in an ischemia–reperfusion model without coronary collaterals.

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Abbreviations

AAR:

area at risk

CO:

cardiac output

CVP:

central venous pressure

dP/dtmax :

estimate of left ventricular systolic function

HR:

heart rate

IS:

infarct size

KATP channels:

ATP-sensitive potassium channels

LAD:

left anterior descending coronary artery

LEVO:

levosimendan

LVP:

left ventricular pressure

MAP:

mean arterial pressure

MBq:

mega Becquerel

MPI:

myocardial perfusion imaging

PAP:

pulmonary artery pressure

PCWP:

pulmonary capillary wedge pressure

PVR:

pulmonary vascular resistance

SV:

stroke volume

SVR:

systemic vascular resistance

Tau (τ):

estimate of left ventricular diastolic function

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Authors and Affiliations

  1. Department of Cardiology B, Research Unit, Skejby Sygehus, Aarhus University Hospital, Brendstrupgaardsvej 100, DK-8200, Aarhus, Denmark

    Martin Busk, Michael Maeng, Jens Kristensen, Ulrik Markus Mortensen, Torsten Toftegaard Nielsen & Jens Erik Nielsen-Kudsk

  2. Department of Cardiothoracic and Vascular Surgery, Skejby Hospital, Aarhus University Hospital, Aarhus, Denmark

    Jette Scheby Berg

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  1. Martin Busk
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  2. Michael Maeng
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  3. Jens Kristensen
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Correspondence to Martin Busk.

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Busk, M., Maeng, M., Kristensen, J. et al. Effects of Levosimendan on Myocardial Infarct Size and Hemodynamics in a Closed-Chest Porcine Ischemia–Reperfusion Model. Cardiovasc Drugs Ther 20, 335–342 (2006). https://doi.org/10.1007/s10557-006-0294-0

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