Treatment with the ω-3 polyunsaturated fatty acids (PUFAs) docosahexanoic acid (DHA) and eicosapentanoic acid (EPA) exerts cardioprotective effects, and suppresses Ca2+-induced opening of the mitochondrial permeability transition pore (MPTP). These effects are associated with increased DHA and EPA, and lower arachidonic acid (ARA) in cardiac phospholipids. While clinical studies suggest the triglyceride lowering effects of DHA and EPA are equivalent, little is known about the independent effects of DHA and EPA on mitochondria function. We compared the effects of dietary supplementation with the ω-3 PUFAs DHA and EPA on cardiac mitochondrial phospholipid fatty acid composition and Ca2+-induced MPTP opening. Rats were fed a standard lab diet with either normal low levels of ω-3 PUFA, or DHA or EPA at 2.5% of energy intake for 8 weeks, and cardiac mitochondria were isolated and analyzed for Ca2+-induced MPTP opening and phospholipid fatty acyl composition. DHA supplementation increased both DHA and EPA and decreased ARA in mitochondrial phospholipid, and significantly delayed MPTP opening as assessed by increased Ca2+ retention capacity and decreased Ca2+-induced mitochondria swelling. EPA supplementation increased EPA in mitochondrial phospholipids, but did not affect DHA, only modestly lowered ARA, and did not affect MPTP opening. In summary, dietary supplementation with DHA but not EPA, profoundly altered mitochondrial phospholipid fatty acid composition and delayed Ca2+-induced MPTP opening.
Intake of fish oil containing docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) prevents heart failure; however, the mechanisms are unclear. Mitochondrial permeability transition pore (MPTP) opening contributes to myocardial pathology in cardiac hypertrophy and heart failure, and treatment with DHA ϩ EPA delays MPTP opening. Here, we assessed: 1) whether supplementation with both DHA and EPA is needed for optimal prevention of MPTP opening, and 2) whether this benefit occurs in hypertrophied myocardium. Rats with either normal myocardium or cardiac hypertrophy induced by 8 weeks of abdominal aortic banding were fed one of four diets: control diet without DHA or EPA or diets enriched with either DHA, EPA, or DHA ϩ EPA (1:1 ratio) at 2.5% of energy intake for 17 weeks. Aortic banding caused a 27% increase in left ventricular mass and 25% depletion in DHA in mitochondrial phosopholipids in rats fed the control diet. DHA supplementation raised DHA in phospholipids ϳ2-fold in both normal and hypertrophied hearts and increased EPA. DHA ϩ EPA supplementation also increased DHA, but to a lesser extent than DHA alone. EPA supplementation increased EPA, but did not affect DHA compared with the control diet. Ca 2ϩ -induced MPTP opening was delayed by DHA and DHA ϩ EPA supplementation in both normal and hypertrophied hearts, but EPA had no effect on MPTP opening. These results show that supplementation with DHA alone effectively increases both DHA and EPA in cardiac mitochondrial phospholipids and delays MPTP and suggest that treatment with DHA ϩ EPA offers no advantage over DHA alone.
Functional imaging modalities, such as functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), are rapidly changing the scope and practice of neuroradiology. While these modalities have long been used in research, they are increasingly being used in clinical practice to enable reliable identification of eloquent cortex and white matter tracts in order to guide treatment planning and to serve as a diagnostic supplement when traditional imaging fails. An understanding of the scientific principles underlying fMRI and DTI is necessary in current radiological practice. fMRI relies on a compensatory hemodynamic response seen in cortical activation and the intrinsic discrepant magnetic properties of deoxy- and oxyhemoglobin. Neuronal activity can be indirectly visualized based on a hemodynamic response, termed neurovascular coupling. fMRI demonstrates utility in identifying areas of cortical activation (i.e., task-based activation) and in discerning areas of neuronal connectivity when used during the resting state, termed resting state fMRI. While fMRI is limited to visualization of gray matter, DTI permits visualization of white matter tracts through diffusion restriction along different axes. We will discuss the physical, statistical and physiological principles underlying these functional imaging modalities and explore new promising clinical applications.
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