Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs

Abstract

1 The distribution of cardiac output during administration of levosimendan, a new myofilament calcium sensitizer, is unknown. We examined and compared the effects of levosimendan, pimobendan, and milrinone on regional tissue perfusion by use of the radioactive microsphere technique in barbiturate-anaesthetized dogs. 2 Haemodynamics and regional blood flow were determined before and during infusions of levosimendan (0.75, 1.5, and 3.0 Mg kg-' min-'), pimobendan (10, 20, and 40 ig kg-' min-'), or milrinone (1.0, 2.0, and 4.0 ,ug kg-' min-'). 3 All three drugs caused similar increases in heart rate, cardiac output, and left ventricular + dP/dt and decreases in end-diastolic pressure and systemic vascular resistance. No changes in subendocardial, midmyocardial, and subepicardial blood flow occurred during administration of levosimendan. However, a redistribution of blood flow from subendocardium to subepicardium was observed. Pimobendan increased midmyocardial and subepicardial blood flow and reduced the endo/epi ratio to a greater degree than levosimendan. Milrinone did not affect myocardial perfusion. 4 Levosimendan increased blood flow to the renal medulla and decreased renal medullary and cortical vascular resistance. Levosimendan increased blood flow to the small intestine and liver and reduced vascular resistance in these organs. Pimobendan increased hepatic blood flow to a greater degree than levosimendan but did not alter small intestinal perfusion. All three drugs decreased splenic blood flow to similar degrees. Levosimendan and pimobendan reduced cerebral vascular resistance. Levosimendan and milrinone reduced skeletal muscle vascular resistance. 5The results indicate that levosimendan, pimobendan, and milrinone cause subtlety different alterations in regional tissue perfusion while producing similar haemodynamic effects.

Outcome of Prophylactic Use of Levosimendan andMilrinone in Open Heart Surgery With CompromisedVentricular Function–A Comparative Study

“…Experimental reports have also observed increased blood flow with levosimendan to various tissues including the gastric mucosa, renal medulla, small intestine, and liver. [25,26] Levosimendan has an active metabolite which has similar hemodynamic effects [10][11][12] and has a long elimination half life of around 70 to 80 hours. [12] This can be an explanation of its positive hemodynamic effects lasted even after the 24-hour infusion, Levosimendan may constitute a cost effective option as it decreases significantly ICU and hospital stay and consequent risk of complications after open-heart surgery in high risk patients with compromised cardiac function.…”

Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due to inotropic drugs in isolated hearts

“…At higher concentrations, levosimendan also acts as a cardiac phosphodiesterase III inhibitor, resulting in elevated cAMP and subsequently in increased [Ca 2ϩ ] (23,24). Levosimendan increased phasic LVP and [Ca 2ϩ ] before but not after ischemia.…”

Effects of Milrinone on Hemodynamics and Regional Blood Flow in the Hypoxic Dog

“…Tolerance to milrinone is rare, as is arrhythmogenesis as a result of its use [8,17]. It is also reported that milrinone increases regional blood flow in the renal cortex, brain, endocardium and epicardium [15]. Nevertheless, investigations of these effects of milrinone were almost all conducted under normoxia, and few reports have investigated how milrinone affects the hemodynamics and redistribution of regional blood flow under severe hypoxia.…”