Abstract
Aims and ObjectivesAcute 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.MethodsMale 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.ResultsSystemic 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.ConclusionThe results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications.
Highlights
The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications
Lower limb ischemic injuries may represent serious clinical situations where profound cell destructions lead to substantial hemodynamic disturbances, systemic inflammatory changes and consequentially, severe multi-organ injuries [1]
Rats (n = 44) were distributed randomly into two main groups defined by the proposed length of reperfusion (4 and 24 hours), and were further divided into three subgroups according to the operation type (Sham-operation, IR and Levosimendan, 6-8-8 animals each group, respectively). (Fig 1)
Summary
Lower limb ischemic injuries (such as acute limb ischemia or even major vascular surgery on lower limb arteries) may represent serious clinical situations where profound cell destructions lead to substantial hemodynamic disturbances, systemic inflammatory changes and consequentially, severe multi-organ injuries [1]. Levosimendan is described as a dual-acting positive inotropic and vasodilatory agent developed for treatment of severe acute heart failure.[3] The agent exerts its positive inotropic effect through sensitizing the myocardium to Ca2+ by binding to and stabilizing the Ca2+ saturated troponin C.[4] The vasodilatory effect is related to the potential to open the ATP-sensitive K+ (KATP) channels, localized in the sarcolemma of vascular smooth muscle cells in small resistance vessels[5] as well as in the venous side of the circulation[6], leading to reduced cardiac afterload and preload.[7] In the large conductance vessels, other (voltage-gated[8] and Ca2 +-dependent[9]) subtypes of potassium channels have been proposed to be opened by the drug though with equivocal clinical relevance
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