Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection

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.

Wenshen Jianpi recipe, a blended traditional Chinese medicine, ameliorates proteinuria and renal injury in a rat model of diabetic nephropathy

“…The microcirculatory blood flow measurements were performed in the renal cortex in each animal by laser doppler flowmeter (Moor, UK) and it was expressed as ml·min − 1 ·g − 1 [20]. The blood samples were obtained from heart and heparin anticoagulant tubes were used as the sampling tubes.…”

Kidney Microcirculation as a Target for Innovative Therapies in AKI

“…These combinations, used in modern intensive care, are reasonable approaches to improving survival in patients who have multiple organ dysfunction necessitating multiple organ-supportive techniques. In many studies, there were promising results for the restoration of microcirculation after cardiac arrest, decreasing post-cardiac arrest syndrome and preventing renal and intestinal damage by maintaining perfusion as well as positive inotropic and vasodilatory effects on the cardiopulmonary system and its effects on decreasing ischemic-reperfusion damage on erythrocytes [ 91 , 92 , 93 ]. To date, there is limited clinical literature and an absence of evidence from randomized trials that addresses the use of levosimendan for cardiogenic shock requiring ECMO support and weaning as well as for preventing AKI.…”