Evoked Changes in Cardiovascular Function in Rats by Infusion of Levosimendan, OR-1896 [(R)-N-(4-(4-Methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-Aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], Dobutamine, and Milrinone: Comparative Effects on Peripheral Resistance, Cardiac Output, dP/dt, Pulse Rate, and Blood Pressure

Segreti, Jason A.; Marsh, Kennan C.; Polakowski, James S.; Fryer, Ryan M.

doi:10.1124/jpet.107.132530

Cited by 40 publications

(37 citation statements)

References 41 publications

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“…Compared with placebo, mean arterial BP decreased with increasing concentrations of levosimendan, which confirms a similar systemic vasodilatory effect of levosimendan in all groups (although nonsignificant in the MCT group), as described previously in healthy rats. 20 We found no changes in RV dP/dt max or other functional parameters at equivalent levels of BP reduction caused by nitroprusside (Fig. 4).…”

Section: Discussionmentioning

confidence: 65%

Acute Effects of Levosimendan in Experimental Models of Right Ventricular Hypertrophy and Failure

et al. 2014

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Pulmonary arterial hypertension (PAH) is a fatal disease, and the ultimate cause of death is right ventricular (RV) failure. In this study, we investigated the acute hemodynamic effects of levosimendan in two rat models of RV hypertrophy and failure. Wistar rats were randomized to receive sham surgery (n ¼ 8), pulmonary trunk banding (PTB; n ¼ 8), or monocrotaline injection (MCT; n ¼ 7). RV function was evaluated at baseline and after injection of placebo and two concentrations of levosimendan (12 and 60 μg/kg) using magnetic resonance imaging, echocardiography, and invasive pressure recordings. PTB and MCT injection caused hypertrophy, dilatation, and failure of the RV compared with sham surgery. Levosimendan increased RV end systolic pressure (sham surgery: 16.0% AE 3.8% [P ¼ 0.0038]; MCT: 9.9% AE 3.1% [P ¼ 0.018]; PTB: 24.5% AE 3.3% [P ¼ 0.0001]; mean AE SEM) compared with placebo. Levosimendan markedly increased RV stroke volume (SV) in the MCT group (29.1% AE 8.3%; P ¼ 0.012), did not change RV SV in the PTB group (0.4% AE 4.5%; P ¼ 0.93), and decreased RV SV in the sham surgery group (−10.9% AE 3.7%; P ¼ 0.020). Nitroprusside, which was used to mimic the systemic arterial vasodilator action of levosimendan, did not influence RV function. These data demonstrate that levosimendan acutely improves the failing right heart in a MCT model of PAH and that the mechanism involves a direct acute positive inotropic effect on the hypertrophic and failing RV of the rat.

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Section: Discussionmentioning

confidence: 65%

Acute Effects of Levosimendan in Experimental Models of Right Ventricular Hypertrophy and Failure

et al. 2014

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“…Diastolic function is not impaired by levosimendan [18][19][20] potentially because of the mild degree of Ca 2+ -sensitization, and probably also because dissociation of Ca 2+ from the cTnC molecule at the diastolic level of intracellular Ca 2+ precludes its interaction with levosimendan [21]. The active metabolite OR-1896 exhibits comparable hemodynamic effects to those of levosimendan via Ca 2+ -sensitization [22][23][24]: similar interactions between OR-1896 and cTnC can therefore be postulated. However, structural biochemical data for the interaction between OR-1896 and cTnC are not yet available.…”

Section: Ca 2+ -Sensitizationmentioning

confidence: 95%

Levosimendan: Molecular mechanisms and clinical implications

Papp

Édes

Fruhwald

et al. 2012

International Journal of Cardiology

256

125

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“…levosimendanın 0,1 µg/kg/dk dozlarından itibaren KAH'ı artırdığını, yüksek dozlarda ise OAB'yi düşürdüğünü bildirmişlerdir. 22 Çalışma-mıza benzer şekilde, Aittomaki ve ark., Scheirman ve ark. ile Segreti ve ark.nın çalışmalarında, levosimendan uygulaması sonucu KAH artışı saptanmış-tır.…”

Section: şEki̇lunclassified

“…ile Segreti ve ark.nın çalışmalarında, levosimendan uygulaması sonucu KAH artışı saptanmış-tır. [20][21][22] Kalp atım hızı artışında, Harkin ve ark. vazodilatasyon ile indüklenmiş baroreseptör refleks aktivasyonunun rol oynayabileceğini bildirmişler-dir.…”

Section: şEki̇lunclassified

Hemodynamic Effects of Levosimendan on Dexmedetomidine Infusion in Rats Under Isoflurane Anesthesia

Çağlar¹,

Hepağuşlar²,

Girgin³

et al. 2012

Turkiye Klinikleri J Med Sci

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A An na ah ht ta ar r K Ke el li im me el le er r: : İzofluran; deksmedetomidin; simendan; kalp hızı; kan basıncı; sıçanlar A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : In this study, hemodynamic effects of levosimendan (L) on dexmedetomidine (D) infusion in rats were investigated under isoflurane (I) anesthesia. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : A total of eighteen female Wistar-Albino rats were divided into 3 groups. Rats were artificially respirated following cannulation and tracheostomy. At the end of the stabilization period (15 min), initial hemodynamic values were recorded and (i) I (1.4%) was administered to Group I; (ii) I (1.4%) and D (1 µg/kg/dk) were administered to Group ID and (iii) I (1.4%), D (1 µg/kg/dk) and L (0.3 µg/kg/dk) were administered to Group IDL for 60 min. Heart rate (HR)(bpm), systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) (mmHg) were recorded with 5 min intervals were and given as mean and/or %. One way variance analysis, Tukey-Kramer and paired t tests were used, p< 0.05 was considered the level of significance. R Re es su ul lt ts s: : No difference was found between groups in terms of initial hemodynamic values. On the contrary, significant differences were found in HR (p= 0.03) and DAP (p= 0.03) at the end of the infusion period between groups. The differences were correlated to the lower HR in Group ID (176) Group I and HR (206 vs. 176 [85%], p= 0.008) decreased significantly in Group ID at the end of the infusion period when compared to baseline values. C Co on nc cl lu us si io on n: : In rats, I led to a decrease in systemic arterial pressure; and D in the presence of I led to a decrease in HR. Isoflurane-related systemic arterial pressure decrease was prevented by using of D and combination of D and L. Additionally, D-related HR decrease in the presence of I was prevented by using L. In this study, positive effects of D and DL utilization were observed when systemic arterial pressure dropped due to I. Besides, positive effect of L utilization was observed when HR decreased due to D in the presence of I in rats.K Ke ey y W Wo or rd ds s: : Isoflurane; dexmedetomidine; simendan; heart rate; blood pressure; rats

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Abstract: Levosimendan enhances cardiac contractility primarily via Ca 2ϩ

Cited by 40 publications

References 41 publications

Acute Effects of Levosimendan in Experimental Models of Right Ventricular Hypertrophy and Failure

Acute Effects of Levosimendan in Experimental Models of Right Ventricular Hypertrophy and Failure

Levosimendan: Molecular mechanisms and clinical implications

Hemodynamic Effects of Levosimendan on Dexmedetomidine Infusion in Rats Under Isoflurane Anesthesia

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