Levosimendan Increases Portal Blood Flow and Attenuates Intestinal Intramucosal Acidosis in Experimental Septic Shock

Abstract

It has been proposed that vasodilatory therapy may increase microcirculatory blood flow and improve tissue oxygenation in septic shock. The authors aimed to evaluate the effects of levosimendan in systemic and splanchnic hemodynamics in a porcine model of septic shock in a randomized animal controlled study. This study was performed in an animal research facility in a university hospital. Anesthetized pigs were monitored with a pulmonary artery catheter and an ultrasonic blood flow probe in the portal vein for measurement of systemic and portal blood flows and with a tonometer placed in the small intestine for measurement of the intramucosal-arterial PCO2 gap. Three groups of pigs were studied: nonseptic (n = 7), septic (n = 7), and septic treated with levosimendan (n = 7). Levosimendan was administered i.v. at t = -10 min (200 microg/kg in i.v. bolus followed by 200 microg/kg per h). Sepsis was induced at t = 0 min by the administration of live Escherichia coli. Vascular reactivity was tested by the hemodynamic response to noradrenaline. Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap. Systemic blood pressure and vascular resistance did not differ as compared with the septic untreated group. Responses to noradrenaline significantly improved in animals treated with levosimendan. Treatment with levosimendan in this animal model of sepsis attenuated pulmonary vasoconstriction and improved portal blood flow, intestinal mucosal oxygenation, pulmonary function, and vascular reactivity.

Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study

“…The role of levosimendan in severe sepsis or septic shock is still not fully elucidated and remains controversial [12,14-16,20-26]. However, there is increasing evidence that under normovolemic conditions, continuous infusion with levosimendan attenuates septic myocardial dysfunction [6-10,27,28] without aggravating hemodynamic instability.…”

“…In addition, levosimendan exerts anti-ischemic, anti-inflammatory, and anti-apoptotic properties, thereby affecting important pathways in the pathophysiology of septic shock [12-14]. It has been speculated that, owing to these beneficial effects, levosimendan may positively affect myocardial performance and regional hemodynamics, thereby improving microcirculatory perfusion [6-10,12,15,16]. …”

Pharmacological targets in the renal peritubular microenvironment: Implications for therapy for sepsis-induced acute kidney injury

“…The therapeutic potential of levosimendan as a single therapy or in combination with other inotropes or pressor agents is still controversial because its effects appear to be related to the model used. In porcine LPS infusion models of endotoxemia, levosimendan showed little improvements (Chew, et al, 2011; Cunha-Goncalves, et al, 2009); however, levosimendan attenuated the increase in pulmonary resistance, improved portal blood flow, and improved urine output following infusion of live E. coli in a porcine model (Garcia-Septien, et al, 2010). In the rat subjected to single injection of LPS, levosimendan did reduce serum creatinine, a marker of renal injury (Zager, et al, 2006).…”

Effects of Combined Levosimendan and Vasopressin on Pulmonary Function in Porcine Septic Shock

“…On the other hand, pulmonary arterial hypertension is a common clinical feature of ALI/ARDS and increased pulmonary arterial hypertension is associated with poor prognosis [11]. Previous studies have demonstrated that both levosimendan and AVP infusion result in a significant decrease of pulmonary artery pressure in septic shock [6,11,18]. In this regard, a lower MPAP might be expected in levosimendan+AVP+norepinephrine group.…”