Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection.
OBJECTIVE
Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction.


METHODS
Male Wistar rats underwent 180 min bilateral lower limb ischemia followed by 4 or 24 hours of reperfusion. Intravenous Levosimendan was administered continuously (0.2μg/bwkg/min) throughout the whole course of ischemia and the first 3h of reperfusion. Results were compared with sham-operated and ischemia-reperfusion groups. Hemodynamic monitoring was performed by invasive arterial blood pressure measurement. Kidney and lower limb muscle microcirculation was registered by a laser Doppler flowmeter. After 4h and 24h of reperfusion, serum, urine and histological samples were collected.


RESULTS
Systemic hemodynamic parameters and microcirculation of kidney and the lower limb significantly improved in the Levosimendan treated group. Muscle viability was significantly preserved 4 and 24 hours after reperfusion. At the same time, renal functional laboratory tests and kidney histology demonstrated significantly less expressive kidney injury in Levosimendan groups. TNF-α levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion.


CONCLUSIONS
The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Peter
P
Onody
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Peter
P
Aranyi
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
Zsolt
Z
Turoczi
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Rita
R
Stangl
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Andras
A
Fulop
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Emese
E
Dudas
2nd Department of Pathology, Semmelweis University, Budapest, Hungary.
Gabor
G
Lotz
1st Department of Surgery, Semmelweis University, Budapest, Hungary.
Attila
A
Szijarto
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