Effect of levosimendan on myocardial contractility, coronary and peripheral blood flow, and arrhythmias during coronary artery ligation and reperfusion in the in vivo pig model

Abstract

Objective-To determine whether levosimendan, a calcium sensitiser that facilitates the activation of the contractile apparatus by calcium, improves myocardial contractile function during severe ischaemia and reperfusion without exacerbating the incidence of arrhythmias. Design-Pigs were pretreated orally twice daily for 10 days with 0.08 mg/kg levosimendan or placebo. On day 11 the left main coronary artery was ligated for 30 minutes, followed by 30 minutes of reperfusion. A bolus dose of levosimendan, 11.2 µg/kg intravenously, or placebo was given 30 minutes before coronary ligation, followed by a continuous infusion of 0.2 µg/kg/min levosimendan or placebo for the remainder of the experiment. Results-During the ischaemic period, cardiac output was higher in the levosimendan group than in the placebo group (mean (SD): 2.6 (0.5) v 2.0 (0.2) l/min, p < 0.05) and systemic vascular resistance was lower (2024 (188) (130) mm Hg/s, p < 0.05) were increased by levosimendan. The incidence of ischaemic ventricular fibrillation and tachycardia was similar in the two groups but there were more arrhythmic events (ventricular tachycardia and ventricular fibrillation) in the levosimendan treated group (8/12 levosimendan v 1/9 control p = 0.05). Conclusions-Levosimendan improved cardiac output and myocardial contractility during coronary artery ligation and reperfusion. However, it increased the number of arrhythmic events during ischaemia in this model of in vivo regional ischaemia. (Heart 2001;86:81-87)

Effects of Levosimendan on Myocardial Infarct Size and Hemodynamics in a Closed-Chest Porcine Ischemia–Reperfusion Model

“…The chronotropic effect of LEVO-infusion (0.2 mg/ kg/min) was more pronounced in our study than generally reported in patients with decompensated heart failure and in 30 kg pigs undergoing coronary ligation [18,35,36]. It probably represented a relative reflex tachycardia caused by vasodilatation as MAP was significantly reduced.…”

Levosimendan improves contractilityin vivoandin vitroin a rodent model of post-myocardial infarction heart failure

“…Others have reported that LEV is less arrhythmogenic than the traditional inotropes (Follath et al 2002, Nieminen 2003 or that LEV has an electrophysiologically neutral profile (Nijhawan et al 1999, Lilleberg et al 2004. Also in experimental animal studies the results are inconsistent (Du Toit et al 1999, du Toit et al 2001, Lepran & Papp 2003. In light of the novel data in this study and the lack of agreement in previous publications, this potential adverse effect of LEV in post-MI HF should be examined carefully in the future.…”

Myocardial ischemia-reperfusion and cardioprotection: a study with microdialysis in a porcine model

“…The effects were blocked with the KATP channel blocker glyburide (Kersten 2000). In pigs, during 30 min of coronary artery occlusion and 30 min of reperfusion, levosimendan initiated in advance of ischemia improved global cardiac performance and coronary flow in the peripheral ischemic zone as compared to control (du Toit 2001). No difference versus control was found on the myocardial tissue concentrations of ATP, and there were an increased number of arrhythmias in the levosimendan group (du Toit 2001).…”