Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide☆☆☆

Caimmi, Philippe Primo; Molinari, Claudio; Uberti, Francesca; Micalizzi, Ezio; Valente, Guido; Mary, David A.S.G.; Vacca, Giovanni; Grossini, Elena

doi:10.1016/j.ejcts.2010.11.044

Cited by 35 publications

(41 citation statements)

References 23 publications

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“…In addition, renal blood flow at the end of reperfusion almost returned to control values without differences compared with what was observed in other groups of animals. Thus, the present findings confirmed previous observations in heart and cardiomyocytes (Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011) regarding the effects of levosimendan as an antioxidant, antiapoptotic, and prosurvival agent.…”

supporting

confidence: 81%

“…Moreover, levosimendan has been shown to protect cardiomyocytes from apoptotic cell death caused by I/R injuries (Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011). The anti-ischemic effects elicited by levosimendan could arise from its action on mitochondrial K ATP channels (Kaheinen et al, 2001;Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011), the modulation of NO release (Grossini et al, 2005(Grossini et al, , 2009, and mitochondrial function (Kaheinen et al, 2001;Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011). Taken together, these findings would suggest that renal protective effects caused by levosimendan occur not only through hemodynamic improvement but also by direct cellular action.…”

Section: Introductionmentioning

confidence: 59%

“…Hence, levosimendan, in addition to improving myocardial contraction and exerting vasodilation, has been demonstrated to have the potential to protect against I/R damage through a preconditioning-like effect (Kersten et al, 2000;Soeding et al, 2011) and the reduction of inflammatory and oxidative stress profiles (Avgeropoulou et al, 2005). Moreover, levosimendan has been shown to protect cardiomyocytes from apoptotic cell death caused by I/R injuries (Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011). The anti-ischemic effects elicited by levosimendan could arise from its action on mitochondrial K ATP channels (Kaheinen et al, 2001;Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011), the modulation of NO release (Grossini et al, 2005(Grossini et al, , 2009, and mitochondrial function (Kaheinen et al, 2001;Grossini et al, 2010;Caimmi et al, 2011b;Uberti et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Levosimendan Protection against Kidney Ischemia/Reperfusion Injuries in Anesthetized Pigs

Grossini¹,

Molinari²,

Pollesello³

et al. 2012

J Pharmacol Exp Ther

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Ischemia/reperfusion (I/R) injury is an important cause of acute renal failure because of oxidative, inflammatory, and apoptotic mechanisms. The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal I/R injury. In 40 anesthetized pigs (eight groups of five pigs each), I/R was induced by clamping-reopening the left renal artery. During ischemia, in three groups of pigs, levosimendan and the multiorgan preservation solution Custodiol, alone or in combination with levosimendan, were infused in the renal artery. In two other groups of animals, levosimendan in combination with Custodiol was administered after the intrarenal nitric-oxide (NO) synthase blocker N -nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K ϩ channel (K ATP channel) inhibitor 5-hydroxydecanoate (5-HD). In the other animals, saline, L-NAME, or 5-HD were administered alone. Throughout the experiments, urinary N-acetyl-␤-glucosaminidase (NAG) release was measured, and renal function was assessed. Moreover, renal biopsy samples were taken for the detection of apoptosis and tissue peroxidation. In pigs treated with levosimendan or the combination of levosimendan and Custodiol, NAG, peroxidation, and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and cell survival and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan alone or in combination with Custodiol exerted better protection against renal I/R injuries than Custodiol alone through antioxidant, antiapoptotic, and prosurvival actions depending on mitochondrial K ATP channels and NO-related mechanisms.

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supporting

confidence: 81%

Section: Introductionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

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Levosimendan Protection against Kidney Ischemia/Reperfusion Injuries in Anesthetized Pigs

Grossini¹,

Molinari²,

Pollesello³

et al. 2012

J Pharmacol Exp Ther

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“…This major finding of the LDDE test demonstrated that levosimendan improved the regional contractile function of stunned myocardium after the revascularisation therapy. The benefits of levosimendan may be attributed to its actions as an ATP-sensitive potassium (K ATP ) channel opener in coronary vascular smooth muscle [19,20] and the enhancement of coronary blood flow. In addition, levosimendan can inhibit phosphodiesterase III in the myocardium [12], but this may not be the major mechanism by which it causes coronary vasodilation, as with milrinone [21].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of Myocardial Function and Reduction of Injury with Levosimendan after Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Pilot Study

Yan

et al. 2014

Cardiology

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Objectives: To determine the short-term clinical effects of levosimendan in acute myocardial infarction (AMI) patients with myocardial stunning after emergency percutaneous coronary intervention (PCI). Methods: The study population consisted of 30 patients with AMI who received emergency PCI and satisfied the inclusion criteria. Levosimendan was given as a continuous infusion of 0.1 μg/kg/min for 24 h, and the remaining 10 patients received placebo treatment. The patients were observed with invasive haemodynamic monitoring and were evaluated biochemically and echocardiographically before and after the drug infusion. Results: Following treatment, biochemical indices (not including creatine kinase and its MB fraction) were significantly lower in the levosimendan group than in the placebo group. Meanwhile, left-ventricular (LV) end-systolic volume, mean pulmonary arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance were significantly reduced in the levosimendan group, whereas the early-to-late diastolic velocities ratio, LV ejection fraction, cardiac index and cardiac power index were increased. Troponin I levels were reduced and fewer stunned and infarction segments were observed in the patients treated with levosimendan. Conclusions: Levosimendan can significantly improve the myocardium function of patients with myocardial stunning after PCI.

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“…(5) Intracoronary (IC) administration of levosimendan was proposed as a possible strategy for effective regional myocardial drug distribution, facilitating favorable and avoiding potentially harmful drug effects. (6)(7)(8)(9) We present 10 cases of IC administration of levosimendan in ACS with decreased left ventricular ejection fraction (LVEF), manifested as ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI) or unstable angina pectoris (AP), requiring coronary artery bypass graft (CABG) surgery.…”

Section: Introductionmentioning

confidence: 99%

Intracoronary administration of levosimendan in patients with acute coronary syndromes and decreased left ventricular ejection fraction undergoing coronary artery bypass graft surgery

2017

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In cardiac surgery patients, intracoronary (IC) administration of levosimendan can provide optimal drug spread, enabling effective manifestation of favorable drug effects and avoiding potentially harmful systemic hypotension. This could be beneficial in acute coronary syndromes (ACS) with decreased left ventricular ejection fraction (LVEF). We present ten cases of IC administration of levosimendan in ACS manifested as ST segment elevation myocardial infarction, non-ST segment elevation myocardial infarction or unstable angina pectoris. All patients underwent coronary artery bypass graft (CABG) surgery, performed as an "off-pump" or "onpump"/"off-clamp" procedure (latter one with the use of cardiopulmonary bypass on the beating heart). Levosimendan was administered as an IC bolus (125-250 μg) in each coronary artery graft (2-3 grafts). Intravenous (IV) levosimendan infusion continued (0.1-0.2 μg•kg-1•min-1) after graft placements (24-48 h), with IV infusion of norepinephrine (0.1 mg•ml-1), if needed. Cardiac function was assessed using LVEF (%) (Teicholz), thermodilution cardiac index (CI) (ml•m-2), and systemic vascular 53.5 (45.7-59.2) %, respectively] (P=0.005), i.e. IC administration of levosimendan was associated with prompt improvement of intraoperative hemodynamics and cardiac contractility. IC administration of levosimendan may be a promising alternative method for improving decreased cardiac function in acute cardiac ischemia, besides necessary surgical revascularization.

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Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide☆☆☆

Cited by 35 publications

References 23 publications

Levosimendan Protection against Kidney Ischemia/Reperfusion Injuries in Anesthetized Pigs

Levosimendan Protection against Kidney Ischemia/Reperfusion Injuries in Anesthetized Pigs

Enhancement of Myocardial Function and Reduction of Injury with Levosimendan after Percutaneous Coronary Intervention for Acute Myocardial Infarction: A Pilot Study

Intracoronary administration of levosimendan in patients with acute coronary syndromes and decreased left ventricular ejection fraction undergoing coronary artery bypass graft surgery

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