Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium : A review

Coronary heart disease (CHD) remains the greatest killer in the Western world, and although the death rate from CHD has been falling, the current increased prevalence of major risk factors including obesity and diabetes, suggests it is likely that CHD incidence will increase over the next 20 years. In conjunction with preventive strategies, major advances in the treatment of acute coronary syndromes and myocardial infarction have occurred over the past 20 years. In particular the ability to rapidly restore blood flow to the myocardium during heart attack, using interventional cardiologic or thrombolytic approaches has been a major step forward. Nevertheless, while 'reperfusion' is a major therapeutic aim, the process of ischemia followed by reperfusion is often followed by the activation of an injurious cascade. While the pathogenesis of ischemia-reperfusion is not completely understood, there is considerable evidence implicating reactive oxygen species (ROS) as an initial cause of the injury.

ROS formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks, all potentially damaging to normal cellular function. ROS have been shown to be generated following routine clinical procedures such as coronary bypass surgery and thrombolysis, due to the unavoidable episode of ischemia-reperfusion. Furthermore, they have been associated with poor cardiac recovery post-ischemia, with recent studies supporting a role for them in infarction, necrosis, apoptosis, arrhythmogenesis and endothelial dysfunction following ischemia-reperfusion. In normal physiological condition, ROS production is usually homeostatically controlled by endogenous free radical scavengers such as superoxide dismutase, catalase, and the glutathione peroxidase and thioredoxin reductase systems. Accordingly, targeting the generation of ROS with various antioxidants has been shown to reduce injury following oxidative stress, and improve recovery from ischemia-reperfusion injury.

This review summarises the role of myocardial antioxidant enzymes in ischemia-reperfusion injury, particularly the glutathione peroxidase (GPX) and the thioredoxin reductase (TxnRed) systems. GPX and TxnRed are selenocysteine dependent enzymes, and their activity is known to be dependent upon an adequate supply of dietary selenium. Moreover, various studies suggest that the supply of selenium as a cofactor also regulates gene expression of these selenoproteins. As such, dietary selenium supplementation may provide a safe and convenient method for increasing antioxidant protection in aged individuals, particularly those at risk of ischemic heart disease, or in those undergoing clinical procedures involving transient periods of myocardial hypoxia.

Effect of sodium selenite-enriched reperfusion solutions on rat cardiac ischemia reperfusion injury

Cardiac surgery often generates oxidative stress leading to ischemia reperfusion injury (I-R). Antioxidants have been shown to prevent this injury and have been added to cardioplegic solutions to assist in recovery. In this study, we tested the effectiveness of sodium selenite in protecting against ischemia reperfusion injury and investigated the mechanisms behind this protection. Hearts from male Wistar rats were subjected to ischemia reperfusion using the Langendorf model. Krebs-Henseleit perfusion solutions were supplemented with 0,0.1, 0.5, 1.0, and 10μM sodium selenite. Hearts were perfused for 30 min and then subjected to 22.5 min of global ischemia followed by 45 min reperfusion. Heart rate, ischemic contracture, end diastolic pressure, and developed ventricular pressure were monitored. At the completion of the experiment, hearts were homogenized and tissue extracts were assayed for glutathione peroxidase (GSH-Px) and thioredoxin reductase (Thx-Red) activity. Sodium selenite, at a concentration of 0.5 μM, demonstrated a protective effect on the recovery of cardiac function following I-R, as evidenced by a lower end diastolic pressure and enhanced recovery of rate pressure product. There was no beneficial effect observed in hearts perfused with 0.1 μM sodium selenite-supplemented buffer, whereas poorer functional recovery was observed in hearts perfused with 10 μM sodium selenite-supplemented buffer. The beneficial effect of sodium selenite was not mediated through increased activity of GSH-Px or Thx-Red. This study demonstrates that the addition of sodium selenite to reperfusion solutions, at an optimal concentration of 0.5 μM, assists in cardiac recovery following ischemia reperfusion.

The theoretical underpinnings of rural injury and its impact on prevention programs

Many observations support the concept of an entity that could be described as ‘rural injury,’ yet the nature and limits of this concept are little explored. We demonstrate the complexity through descriptions along a single dimension: place.

Rural injury may be considered as consisting of both ‘Rural specific injury’ (Farm/agricultural, Forestry and Mining related injuries and Injuries in state/national parks) and also rural instances of ‘Injury which is not location specific’. Examples of the latter category include water related (especially boating & fishing), other industrial, Road Trauma, Sporting and Domestic injuries.

Pretend play of children with acquired brain injury : an exploratory study

Objective: This exploratory study aimed to describe the self-initiated pretend play of three children who had sustained an acquired brain injury (ABI). No previous research was found.

Methods: Three children aged 3.0–6.0 years were recruited through purposive sampling. Pretend play ability was assessed using the Child-Initiated Pretend Play Assessment.

Results: Two of the three children scored below the range expected for children their age and one child scored above the range, indicating a wide range of pretend play ability for the children. None of the children could sustain their engagement in pretend play to complete the time of the assessment.

Conclusion: Complex pretend play ability is a functional assessment of cognitive ability involving sequential planning, problem-solving, language and social understanding. Cognitive fatigue is argued to explain the children's limited ability to engage in play for the time expected for their ages. More research is required.