Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model

Hein, Marc; Zoremba, Norbert; Bleilevens, C.; Bruells, Christian S.; Rossaint, Rolf; Röhl, Anna Bettina

doi:10.1186/1471-2377-13-106

Cited by 29 publications

(17 citation statements)

References 38 publications

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“…Previous nonclinical studies have shown some effects of levosimendan on the brain (Hein et al, 2013;Roehl et al, 2012). 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).…”

Section: Discussionmentioning

confidence: 98%

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: 98%

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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“…Because of the narrow time window as demonstrated in experimental studies, one has to consider that such a drug, for induction of postconditioning, should be administered before reperfusion so that it is circulating in blood at the time of onset of reflow (Andreadou 2008). Literature is replete with studies involving neuroprotection with pharmacological agents administered at the start of reperfusion (Sicard et al 2009;Du et al 2010;Tong et al 2011;Hein et al 2013;Bouhidel et al 2014;Zhang et al 2016). However, it has been debated whether this approach can be described as 'pharmacological postconditioning' or 'post-reperfusion treatment' (Sandu and Schaller 2010).…”

Section: Discussionmentioning

confidence: 99%

Effects of resveratrol postconditioning on cerebral ischemia in mice: role of the sirtuin-1 pathway

Grewal

Singh

2019

Can. J. Physiol. Pharmacol.

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Evidence has demonstrated that resveratrol preconditioning exhibits neuroprotection against cerebral ischemia–reperfusion (IR) injury. The current investigation aimed to explore whether pharmacological postconditioning, by administering resveratrol, after a sustained ischemia and prior to prolonged reperfusion abrogates cerebral IR injury. Cerebral IR-induced injury mice model was employed in this study to evaluate the neuroprotective effects of pharmacological postconditioning with resveratrol (30 mg/kg; i.p.) administered 5 min before reperfusion. We administered sirtinol, a SIRT1/2 selective inhibitor (10 mg/kg; i.p.) 10 min before ischemia (17 min) and reperfusion (24 h), to elucidate whether the neuroprotection with resveratrol postconditioning depends on SIRT1 activation. Various biochemical and behavioural parameters and histopathological changes were assessed to examine the effect of pharmacological postconditioning. Infarct size is estimated using TTC staining. It was established that resveratrol postconditioning abrogated the deleterious effects of IR injury expressed with regard to biochemical parameters of oxidative stress (TBARS, SOD, GSH), acetylcholinesterase activity, behavioural parameters (memory, motor coordination), infarct size, and histopathological changes. Sirtinol significantly reversed the effect of resveratrol postconditioning. We conclude that induced neuroprotective benefits of resveratrol postconditioning may be the consequence of SIRT1 activation and resveratrol can be considered, for further studies, as potential agent inducing pharmacological postconditioning in clinical situations.

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“…Possibly owing to this unique characteristic, several clinical trials or meta-analyses have implied favorable benefits, including improved cardiac function and reduction of mortality or length of hospital stay, upon levosimendan treatment when compared with dobutamine treatment in critically ill patients or those with a cardiology setting (34)(35)(36)(37). The neuroprotective effect of levosimendan has been recently demonstrated in a TBI in vitro model (38), and in a cerebral reperfusion and spinal cord injury in vivo model (39,40). The exact mechanism is unclear, and is possibly attribute to the opening of ATP-sensitive K + channels (mitoKATP channels) and to the suppression of nitric oxide synthase expression, cell death and inflammatory response upon the application of levosimendan (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review

Lin

Wang

et al. 2016

Experimental and Therapeutic Medicine

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Neurogenic pulmonary edema (NPE) is occasionally observed in patients with traumatic brain injury (TBI); however, this condition is often underappreciated. NPE is frequently misdiagnosed due to its atypical clinical performance, thus delaying appropriate treatment. A comprehensive management protocol of NPE in patients with TBI has yet to be established. The current study reported the case of a 67-year-old man with severe TBI who was transferred to our intensive care unit (ICU). On day 7 after hospitalization, the patient suddenly suffered tachypnea, tachycardia, systemic hypertension and hypoxemia during lumbar cistern drainage. Intravenous diuretics, tranquilizer and glucocorticoid were administered due to suspected left heart failure attack. Chest radiography examination supported the diagnosis of pulmonary edema; however, hypotension and hypovolemia were subsequently observed. Pulse index continuous cardiac output (PiCCO) hemodynamic monitoring and bedside echocardiography were performed, which excluded the diagnosis of cardiac pulmonary edema, and thus the diagnosis of NPE was confirmed. Goal-directed therapy by dynamic PiCCO monitoring was then implemented. In addition, levosimendan, an inotropic agent, was introduced to improve cardiac output. The patient had complete recovered from pulmonary edema and regained consciousness on day 11 of hospitalization. The current case demonstrated that PiCCO monitoring may serve a central role in the integrated management of NPE in patients with TBI. Levosimendan may be a potential medicine in treating cardiac dysfunction, along with its benefit from improving neurological function in NPE patients.

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Levosimendan limits reperfusion injury in a rat middle cerebral artery occlusion (MCAO) model

Cited by 29 publications

References 38 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

Effects of resveratrol postconditioning on cerebral ischemia in mice: role of the sirtuin-1 pathway

Role of PiCCO monitoring for the integrated management of neurogenic pulmonary edema following traumatic brain injury: A case report and literature review

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