Levosimendan Administration in Limb Ischemia: Multicomponent Signaling Serving Kidney Protection

AIMS AND OBJECTIVES: 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 (0.2mug/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-alpha levels were significantly less elevated in the Levosimendan group 4 hours after reperfusion. CONCLUSION: The results claim a protective role for Levosimendan administration during major vascular surgeries to prevent renal complications

Távoli szervi kondicionálás: rövid távú hepatoprotectiv hatások patkánymodellben [Remote ischemic conditioning: short-term effects on rat liver ischemic-reperfusion injury]

Bevezetés: Az ischaemiás-reperfúziós károsodások mérséklésére kipróbált módszerek között újszerű elképzelés a célszervi ischaemia alatt alkalmazott távoli szervi ischaemiás perkondicionálás. Célkitűzés: Patkánymáj ischaemiás-reperfúziós modellben alkalmazni ezen újszerű kondicionálási technikát. Módszer: Hím Wistar patkányok (n = 30, 10/csoport) 60 perc parciális ischaemiában, majd 60 perc reperfúzióban részesültek. Egy csoportban perkondicionálás került alkalmazásra a májischaemia utolsó 40 percében, az infarenalis aortán. A máj és az alsó végtag mikrokeringésének regisztrálása lézeres Doppler-áramlásmérővel történt. A reperfúziót követően a máj szövettani elváltozásainak analízise és a májszöveti hősokkfehérje-72-expresszió mérése mellett a szérumtranszamináz-aktivitások, továbbá a redox-homeosztázis állapotának meghatározása történt. Eredmények: A máj és az alsó végtag mikrocirkulációt jellemző paraméterei szignifikáns (p<0,05) javulást mutattak a perkondicionált csoportban a kontrollhoz képest. A szérum-alanin-transzamináz-aktivitás és a májszövettani vizsgálatok, továbbá a májszöveti redox-homeosztázis vonatkozásában egyaránt szignifikánsan enyhébb károsodás volt megfigyelhető a perkondicionált csoportban a kontrollhoz képest. Következtetés:A perkondicionálás alkalmas lehet a máj ischaemiás-reperfúziós károsodásának mérséklésére. Introduction: Several techniques have been developed to reduce ischemic-reperfusion injury. A novel method is the remote ischemic perconditioning, applied parallel with target organ ischemia. Aim: The aim of the study was to determine the extent of liver ischemic-reperfusion injury via the application of this novel method. Methods: Male Wistar rats (n = 30, 10/group) were subjected to 60-minute partial liver ischemia and 60-minute reperfusion. Rats in the perconditioned group received conditioning treatment during the last 40 minutes of liver ischemia by infrarenal aortic clamping. Hepatic and lower limb microcirculation was monitored by laser Doppler flowmeter during reperfusion. After reperfusion, liver samples were taken for routine histological examination and redox-state assessment. Serum transaminase activities and liver tissue heat-shock protein-72 expression were measured. Results: Parameters of microcirculation showed significant (p<0.05) improvement in the perconditioned group in comparison with the control. Besides the significant improvement observed in the serum alanine amino-transferase activities, significantly milder tissue injury was detected histologically in the liver sections of the perconditioned group. Moreover, significant improvement was found in the redox-state parameters. Conclusion: Perconditioning may be a reasonable possibility to reduce liver ischemic-reperfusion injury

Postconditioning Protects Skeletal Muscle Against a Long-Lasting Vascular Occlusion

ABSTRACT Purpose/Aim of the Study: Long-lasting lower limb arterial occlusion is a condition with high incidence and complication rates. With the absence of appropriate treatment to cure advanced complications, mortality rates are high. Postconditioning (PC) might be capable of limiting the degree of ischemic-reperfusion (IR) injuries, thus reducing complications and mortality rates. The aim of this study was to evaluate the impact of postconditioning during the first postoperative day on skeletal muscle after a long-lasting arterial occlusion. Materials and Methods: Male Wistar rats (n = 72) underwent 8 hr of infrarenal aortic occlusion followed by 2, 6, 12, or 24 hr of reperfusion. In one group of each reperfusion period, postconditioning was applied. Muscle samples were collected for histological examinations. Furthermore, muscle fiber viability and muscle wet-to-dry ratio were assessed. Blood samples were taken for creatine-kinase measurements. Results: Postconditioning strongly reduced morphological injury compared to the corresponding ischemic-reperfusion group (p < .001). Serum creatine-kinase levels showed a peak at 6 hr post-ischemia (IR: 6702.2 +/- 797.5; PC: 5523.3 +/- 769.3 IU/l) and decreased to normal level by the end of the experiment (Sham: 171.5 +/- 71.6; IR: 186.2 +/- 82.7; PC: 174.2 +/- 72.4 IU/l). Creatine-kinase levels were significantly reduced by postconditioning (p2hr = .028; p6hr = .06; p12hr = .042). A marked decrease in viability was observed in the ischemic-reperfusion groups (2 hr: 11.0 +/- 4.1; 6 hr: 10.3 +/- 3.6; 12 hr: 9.4 +/- 3.3; 24 hr: 8.6 +/- 2.8%), whereas with postconditioning, viability was preserved (2 hr: 26.4 +/- 5.5; 6 hr: 24.6 +/- 4.5; 12 hr: 24.5 +/- 6.8; 24 hr: 26.2 +/- 6.1%; p < .001); moreover, a significant decrease in the wet-to-dry ratio was achieved (p < .001). Conclusion: Postconditioning was able to reduce local complications after a long-lasting lower limb vascular occlusion