The role of Levosimendan in cardiopulmonary resuscitation

Varvarousi, Giolanda; Stefaniotou, A.; Varvaroussis, Dimitrios; Aroni, Filippia; Xanthos, Theodoros

doi:10.1016/j.ejphar.2014.06.024

Cited by 10 publications

(10 citation statements)

References 88 publications

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“…Moreover, a recent report showed that levosimendan was beneficial in a model of injury to the immature brain following cardiopulmonary bypass (Namachivayam et al, 2014). Finally, Varvarousi et al (2014) described positive effects of levosimendan in post-cardiac arrest brain injury, and Bleilevens et al (2014) showed that levosimendan treatment significantly reduces cerebral infarct size in the cortex in a rat model.…”

Section: Discussionmentioning

confidence: 95%

Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

Levijoki

Kivikko

Pollesello

et al. 2015

European Journal of Pharmacology

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The effects of levosimendan on cerebrovascular lesions and mortality were investigated in models of primary and secondary stroke. We aimed to determine whether the effects of levosimendan are comparable to and/or cumulative with those of valsartan, and to investigate whether levosimendan-induced vasodilation has a role in its effects on stroke. In a primary stroke Dahl/Rapp rat model, mortality rates were 70% and 5% for vehicle and levosimendan, respectively. Both stroke incidence (85% vs. 10%, P<0.001) and stroke-associated behavioral deficits (7-point neuroscore: 4.59 vs. 5.96, P<0.001) were worse for vehicle compared to levosimendan. In a secondary stroke model in which levosimendan treatment was started after cerebrovascular incidences were already detected, mean survival times were 15 days with vehicle, 20 days with levosimendan (P=0.025, vs. vehicle), 22 days with valsartan (P=0.001, vs. vehicle), and 31 days with levosimendan plus valsartan (P<0.001, vs. vehicle). The respective survivals were 0%, 16%, 20% and 59%, and the respective incidences of severe lesions were 50%, 67%, 50% and 11%. In this rat model, levosimendan increased blood volume of the cerebral vessels, with significant effects in the microvessels of the cortex (∆R=3.5±0.15 vs. 2.7±0.17ml for vehicle; P=0.001) and hemisphere (∆R=3.2±0.23 vs. 2.6±0.14ml for vehicle; P=0.018). Overall, levosimendan significantly reduced stroke-induced mortality and morbidity, both alone and with valsartan, with apparent cumulative effects, an activity in which the vasodilatory effects of levosimendan have a role.

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Section: Discussionmentioning

confidence: 95%

Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

Levijoki

Kivikko

Pollesello

et al. 2015

European Journal of Pharmacology

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“…After resuscitation, a complex series of events occur during reperfusion, which leads to secondary brain damage 10 . The beneficial effects of levosimendan have been the subject of numerous studies 11 that have reported increased ROSC rates 3 , 12 and reduced rates of post-resuscitation myocardial dysfunction 13 , brain injury 4 , and kidney ischemia/reperfusion injury 14 . The combination of hypothermia and levosimendan has a positive effect on cardiac function, and survival has been shown to improve following CA in the rat 15 .…”

Section: Discussionmentioning

confidence: 99%

Levosimendan increases brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion

García-Bardon

Kamuf

Ziebart

et al. 2021

Sci Rep

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Prompt reperfusion is important to rescue ischemic tissue; however, the process itself presents a key pathomechanism that contributes to a poor outcome following cardiac arrest. Experimental data have suggested the use of levosimendan to limit ischemia–reperfusion injury by improving cerebral microcirculation. However, recent studies have questioned this effect. The present study aimed to investigate the influence on hemodynamic parameters, cerebral perfusion and oxygenation following cardiac arrest by ventricular fibrillation in juvenile male pigs. Following the return of spontaneous circulation (ROSC), animals were randomly assigned to levosimendan (12 µg/kg, followed by 0.3 µg/kg/min) or vehicle treatment for 6 h. Levosimendan-treated animals showed significantly higher brain PbtO2 levels. This effect was not accompanied by changes in cardiac output, preload and afterload, arterial blood pressure, or cerebral microcirculation indicating a local effect. Cerebral oxygenation is key to minimizing damage, and thus, current concepts are aimed at improving impaired cardiac output or cerebral perfusion. In the present study, we showed that NIRS does not reliably detect low PbtO2 levels and that levosimendan increases brain oxygen content. Thus, levosimendan may present a promising therapeutic approach to rescue brain tissue at risk following cardiac arrest or ischemic events such as stroke or traumatic brain injury.

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“…After resuscitation, a complex series of events begins during reperfusion, leading to secondary brain damage [13]. The beneficial effects of levosimendan were subject of different studies [14] showing increased ROSC-rates [3,15], and less post-resuscitation myocardial dysfunction [16], brain injury [4], and kidney ischemia/reperfusion injury [17]. All these positive effects were attributed to enhanced cardiac output [14] or CBF [4] as underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

Levosimendan improves brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion

García-Bardon

Kamuf

Ziebart

et al. 2019

Preprint

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Background: Prompt reperfusion is essential to rescue ischemic tissue, but in itself represents a key pathomechanism contributing to poor outcome after cardiac arrest. Experimental data suggest levosimendan as a therapeutic drug to limit ischemia-reperfusion injury by improving cerebral microcirculation and thereby reducing neuronal injury. However, recent studies question its effect on cardiac output and cerebral microcirculation in normally pumping hearts. The present study was designed to investigate the influence of levosimendan on hemodynamic parameters, cerebral perfusion, and cerebral oxygenation after cardiac arrest and resuscitation.Methods: Ventricular fibrillation was induced in anesthetized juvenile male pigs for 7 min, followed by cardiopulmonary resuscitation. After return of spontaneous circulation (ROSC) animals were randomly assigned to levosimendan (12µg/kg, followed by 0.3µg/kg/min) or vehicle (normal saline) treatment for 6 hours. Cerebral oxygen saturation and brain tissue oxygen levels were determined with near-infrared spectroscopy (NIRS) and fluorescence quenching tissue PbtO 2 probes. Cerebral and kidney perfusion were quantified by fluorescent-labeled microspheres and laser-doppler flowmetry. Results: Compared to vehicle, levosimendan treated animals showed significantly higher brain tissue oxygen levels after ROSC. This effect was not accompanied by changes in cardiac output, cardiac preload and afterload, arterial blood pressure, nor cerebral microcirculation, indicating a local levosimendan-mediated effect in the brain.Conclusions: Cerebral oxygenation is key to minimizing neurological damage during and after cardiac arrest. Therefore, current concepts aim at improving impaired cardiac output or cerebral perfusion pressure. In the present study we provide evidence that NIRS fails to reliably detect low brain tissue oxygen levels and that levosimendan improves brain oxygen content. Levosimendan may therefore present a promising therapeutic approach to rescue brain tissue at risk in patients after cardiac arrest or other causes of cerebral ischemia or malperfusion such as stroke or traumatic brain injury.

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The role of Levosimendan in cardiopulmonary resuscitation

Cited by 10 publications

References 88 publications

Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

Levosimendan increases brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion

Levosimendan improves brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion

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