Milrinone-induced postconditioning reduces hepatic ischemia-reperfusion injury in rats: the roles of phosphatidylinositol 3-kinase and nitric oxide

Abstract

(237 words)Background: Ischemic postconditioning (PostC) protects the liver against ischemia-reperfusion (IR)

A novel role for milrinone in neonatal acute limb ischaemia: successful conservative treatment of thrombotic arterial occlusion without thrombolysis

“…There are also animal data to suggest a role of PDE3 inhibitors such as milrinone in promoting insulin secretion,15 which is a potential explanation for the hypoglycaemia observed in our patient. Animal studies have revealed a role for milrinone in ameliorating ischaemia-reperfusion injury in multiple organs, including the kidney16 and liver 4. Cycles of controlled ischaemia and reperfusion prior to an ischaemia-reperfusion event (preconditioning), or following an ischaemic event (postconditioning), are recognised methods to reduce organ injury secondary to ischaemia-reperfusion.…”

“…Cycles of controlled ischaemia and reperfusion prior to an ischaemia-reperfusion event (preconditioning), or following an ischaemic event (postconditioning), are recognised methods to reduce organ injury secondary to ischaemia-reperfusion. Beneficial effects of milrinone as an adjunct to preconditioning and postconditioning have both been described 4. Effects during preconditioning are mediated by activation of intracellular cyclic adenosine monophosphate (c-AMP) and c-AMP-dependent protein kinase A (PKA) 4 16.…”

“…Beneficial effects of milrinone as an adjunct to preconditioning and postconditioning have both been described 4. Effects during preconditioning are mediated by activation of intracellular cyclic adenosine monophosphate (c-AMP) and c-AMP-dependent protein kinase A (PKA) 4 16. A similar mechanism during postconditioning is postulated via a PKA-activated pathway-dependent Akt, which has antiapoptotic effects 4.…”

“…Effects during preconditioning are mediated by activation of intracellular cyclic adenosine monophosphate (c-AMP) and c-AMP-dependent protein kinase A (PKA) 4 16. A similar mechanism during postconditioning is postulated via a PKA-activated pathway-dependent Akt, which has antiapoptotic effects 4. An inhibitory effect on platelet aggregation and anti-inflammatory properties may be additional benefits of PDE inhibition in this setting in reducing the extent of thrombus 4 16.…”

“…Milrinone is a phosphodiesterase-3 (PDE3) inhibitor increasingly used in neonatology for its vasodilatory effects on the systemic and pulmonary vasculature 3. There is also emerging translational evidence for benefit of milrinone in ischaemic postconditioning, or amelioration of ischaemia-reperfusion injury following an ischaemic event 4. Milrinone has not previously been described as a treatment modality for NLI.…”