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CLINICAL RESEARCH: MYOCARDIAL ISCHEMIA/INFARCTION

The calcium sensitizer levosimendan improves the function of stunned myocardium after percutaneous transluminal coronary angioplasty in acute myocardial ischemia

Steffen Sonntag^*,*, Stig Sundberg, PhD, Lasse Antero Lehtonen, MD and Franz Xaver Kleber, MD^*

^* UKB Berlin and Free University Berlin, Berlin, Germany
Orion Corporation, Espoo, Finland
Helsinki University Central Hospital, Helsinki, Finland

Manuscript received December 2, 2002; revised manuscript received January 18, 2004, accepted February 18, 2004.

^* Reprint requests and correspondence: Steffen Sonntag, Department Internal Medicine, UKB Berlin, Academic Teaching Hospital, Free University Berlin, Warener Strasse 07, D-12683 Berlin, Germany.
steffen.sonntag{at}snafu.de

OBJECTIVES: We assessed the effects of levosimendan on left ventricular (LV) function in patients with acute myocardial ischemia and after coronary angioplasty.

BACKGROUND: The calcium sensitizer levosimendan improves the function of myocardium in experimental stunning.

METHODS: Twenty-four patients with an acute coronary syndrome underwent angioplasty followed by double-blinded, randomized treatment with 24 µg/kg of levosimendan (n = 16) or placebo (n = 8). Left ventricular pressures and volumes were recorded by cineventriculography and micromanometer-tipped catheters 10 min after angioplasty before drug administration (baseline) and 20 min after drug administration. Left ventricular function was assessed by the pressure–volume loop, and regional function analysis by the Slager method.

RESULTS: The number of hypokinetic segments decreased with levosimendan, from 8.9 ± 0.9 to 6.5 ± 1.1 (mean ± SEM), as compared with an increase from 7.8 ± 1.0 to 8.5 ± 1.1 with placebo (p = 0.016). A leftward and/or upward shift of the systolic part of the pressure–volume loop, indicating improved systolic function, was observed in eight of 16 of the levosimendan-treated and one of eight of the placebo patients (p = 0.178). In addition, the single-beat elastance was increased by levosimendan (p = 0.045). The pressure–volume area (p = 0.001), end-systolic pressure (p = 0.002), and volume index (p < 0.001) were decreased by levosimendan, but there was no change in the end-systolic pressure–volume ratio. End-diastolic pressure remained unchanged, whereas the end-diastolic volume index was decreased by levosimendan (p = 0.002). The time constant of isovolumic LV pressure fall decreased with levosimendan (p = 0.001).

CONCLUSIONS: Levosimendan improved the function of stunned myocardium without obvious impairment of diastolic function.

Abbreviations and Acronyms   ACS = acute coronary syndrome   LV = left ventricle/left ventricular   TIMI = Thrombolysis In Myocardial Infarction

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