Flavonols and Flavones - Protecting Against Myocardial Ischemia/Reperfusion Injury by Targeting Protein Kinases.

In acute myocardial infarction (AMI), the first line of treatment is to rapidly restore blood flow to the ischemic myocardium to limit infarct size. It is now well established that though clearly beneficial, the positive outcomes of this intervention are limited by injury in response to the reperfusion itself in addition to the prior ischemia. This process is described as reperfusion injury and is considered to contribute to the arrhythmias, microvascular dysfunction and impaired cardiac contractility that is observed even after the restoration of coronary blood flow.

Protection against reperfusion injury by 3',4'-dihydroxyflavonol in rat isolated hearts involves inhibition of phospholamban and JNK2.

Background: Flavonols, including 3',4'-dihydroxyflavonol (DiOHF), reduce myocardial ischemia and reperfusion (I/R) injury but their mechanism remains uncertain. To better understand the mechanism of the cardioprotective actions of flavonols we investigated the effect of DiOHF on cardiac function and the activation of protective and injurious signalling kinases after I/R in rat isolated hearts.

Methods: We assessed the effect of global ischemia (20min) and reperfusion (5-30min) on cardiac function and injury in rat isolated, perfused hearts in the absence or presence of DiOHF (10μM) during reperfusion.

Protective actions of des-acylated ghrelin on brain injury and blood-brain barrier disruption after stroke in mice.

The major ghrelin forms, acylated ghrelin and des-acylated ghrelin, are novel gastrointestinal hormones. Moreover, emerging evidence indicates that these peptides may have other functions including neuro- and vaso-protection. Here, we investigated whether post-stroke treatment with acylated ghrelin or des-acylated ghrelin could improve functional and histological endpoints of stroke outcome in mice after transient middle cerebral artery occlusion (tMCAo).

Characterisation of a mouse cerebral microvascular endothelial cell line (bEnd.3) after oxygen glucose deprivation and reoxygenation.

Studies have utilised immortalised mouse cerebral endothelial cells (bEnd.3) exposed to oxygen glucose deprivation (OGD) to study blood-brain barrier (BBB) disruption after ischaemia. However, there is a paucity of literature describing the duration of OGD (and reoxygenation [RO]) required to best simulate BBB disruption in vivo.

The HNO donor Angeli's salt offers potential haemodynamic advantages over NO or dobutamine in ischaemia-reperfusion injury in the rat heart ex vivo.

Available inotropic pharmacotherapy for acute heart failure (HF) remains largely ineffective at ameliorating marked impairments in contractile function. Nitroxyl (HNO), the redox sibling of NO•, has recently attracted interest as a therapeutic approach for acute HF. We now compare the impact of ischaemia-reperfusion (I-R) injury on acute haemodynamic responsiveness of the HNO donor, Angeli's salt (AS), to that of NO and dobutamine.

New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury.

Background: Early reperfusion of the blocked vessel is critical to restore the blood flow to the ischemic myocardium to salvage myocardial tissue and improve clinical outcome. This reperfusion strategy after a period of ischemia, however, may elicit further myocardial damage named myocardial reperfusion injury. The manifestations of reperfusion injury include arrhythmias, myocardial stunning and micro-vascular dysfunction, in addition to significant cardiomyocyte death.

The concomitant coronary vasodilator and positive inotropic actions of the nitroxyl donor Angeli's salt in the intact rat heart: contribution of soluble guanylyl cyclase-dependent and -independent mechanisms.

Background And Purpose: The NO redox sibling nitroxyl (HNO) elicits soluble guanylyl cyclase (sGC)-dependent vasodilatation. HNO has high reactivity with thiols, which is attributed with HNO-enhanced left ventricular (LV) function. Here, we tested the hypothesis that the concomitant vasodilatation and inotropic actions induced by a HNO donor, Angeli's salt (sodium trioxodinitrate), were sGC-dependent and sGC-independent respectively.