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

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Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats. / Levijoki, Jouko; Kivikko, Matti; Pollesello, Piero; Sallinen, Jukka; Hyttilä-Hopponen, Minja; Kuoppamäki, Mikko; Haasio, Kristiina; Gröhn, Olli; Miettinen, Riitta; Puoliväli, Jukka; Tähtivaara, Leena; Yrjänheikki, Juha; Haapalinna, Antti.

In: European Journal of Pharmacology, Vol. 750, 05.03.2015, p. 132-40.

Research output: Contribution to journalArticleScientificpeer-review

Harvard

Levijoki, J, Kivikko, M, Pollesello, P, Sallinen, J, Hyttilä-Hopponen, M, Kuoppamäki, M, Haasio, K, Gröhn, O, Miettinen, R, Puoliväli, J, Tähtivaara, L, Yrjänheikki, J & Haapalinna, A 2015, 'Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats' European Journal of Pharmacology, vol. 750, pp. 132-40. https://doi.org/10.1016/j.ejphar.2015.01.037

APA

Levijoki, J., Kivikko, M., Pollesello, P., Sallinen, J., Hyttilä-Hopponen, M., Kuoppamäki, M., ... Haapalinna, A. (2015). Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats. European Journal of Pharmacology, 750, 132-40. https://doi.org/10.1016/j.ejphar.2015.01.037

Vancouver

Levijoki J, Kivikko M, Pollesello P, Sallinen J, Hyttilä-Hopponen M, Kuoppamäki M et al. Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats. European Journal of Pharmacology. 2015 Mar 5;750:132-40. https://doi.org/10.1016/j.ejphar.2015.01.037

Author

Levijoki, Jouko ; Kivikko, Matti ; Pollesello, Piero ; Sallinen, Jukka ; Hyttilä-Hopponen, Minja ; Kuoppamäki, Mikko ; Haasio, Kristiina ; Gröhn, Olli ; Miettinen, Riitta ; Puoliväli, Jukka ; Tähtivaara, Leena ; Yrjänheikki, Juha ; Haapalinna, Antti. / Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats. In: European Journal of Pharmacology. 2015 ; Vol. 750. pp. 132-40.

Bibtex - Download

@article{a986c7ad6dfc4a91adb835c17fd2ea68,
title = "Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats",
abstract = "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.",
keywords = "Animals, Blood Pressure, Blood Volume, Brain, Drug Interactions, Hydrazones, Male, Pyridazines, Rats, Rats, Inbred Dahl, Stroke, Valsartan, Vasodilator Agents, Journal Article, Research Support, Non-U.S. Gov't",
author = "Jouko Levijoki and Matti Kivikko and Piero Pollesello and Jukka Sallinen and Minja Hyttil{\"a}-Hopponen and Mikko Kuoppam{\"a}ki and Kristiina Haasio and Olli Gr{\"o}hn and Riitta Miettinen and Jukka Puoliv{\"a}li and Leena T{\"a}htivaara and Juha Yrj{\"a}nheikki and Antti Haapalinna",
note = "INT=sgn,{"}Miettinen, Riitta{"}",
year = "2015",
month = "3",
day = "5",
doi = "10.1016/j.ejphar.2015.01.037",
language = "English",
volume = "750",
pages = "132--40",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Levosimendan alone and in combination with valsartan prevents stroke in Dahl salt-sensitive rats

AU - Levijoki, Jouko

AU - Kivikko, Matti

AU - Pollesello, Piero

AU - Sallinen, Jukka

AU - Hyttilä-Hopponen, Minja

AU - Kuoppamäki, Mikko

AU - Haasio, Kristiina

AU - Gröhn, Olli

AU - Miettinen, Riitta

AU - Puoliväli, Jukka

AU - Tähtivaara, Leena

AU - Yrjänheikki, Juha

AU - Haapalinna, Antti

N1 - INT=sgn,"Miettinen, Riitta"

PY - 2015/3/5

Y1 - 2015/3/5

N2 - 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.

AB - 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.

KW - Animals

KW - Blood Pressure

KW - Blood Volume

KW - Brain

KW - Drug Interactions

KW - Hydrazones

KW - Male

KW - Pyridazines

KW - Rats

KW - Rats, Inbred Dahl

KW - Stroke

KW - Valsartan

KW - Vasodilator Agents

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.ejphar.2015.01.037

DO - 10.1016/j.ejphar.2015.01.037

M3 - Article

VL - 750

SP - 132

EP - 140

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

ER -