Phosphodiesterase-5 inhibition mimics intermittent reoxygenation and improves cardioprotection in the hypoxic myocardium.

Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. AIM OF THE STUDY: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O₂) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. CONCLUSIONS: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms.

Quantification of the relation between surface morphodynamics and subsurface sedimentological product in sandy braided rivers

This study uses digital elevation models and ground-penetrating radar to quantify the relation between the surface morphodynamics and subsurface sedimentology in the sandy braided South Saskatchewan River, Canada. A unique aspect of the methodology is that both digital elevation model and ground-penetrating radar data were collected from the same locations in 2004, 2005, 2006 and 2007, thus enabling the surface morphodynamics to be tied explicitly to the associated evolving depositional product. The occurrence of a large flood in 2005 also allowed the influence of discharge to be assessed with respect to the processproduct relationship. The data demonstrate that the morphology of the study reach evolved even during modest discharges, but more extensive erosion was caused by the large flood. In addition, the study reach was dominated by compound bars before the flood, but switched to being dominated by unit bars during and after the flood. The extent to which the subsurface deposits (the product') were modified by the surface morphodynamics (the process') was quantified using the changes in radar-facies recorded in sequential ground-penetrating radar surveys. These surveys reveal that during the large flood there was an increase in the proportion of facies associated with bar margin accretion and larger dunes. In subsequent years, these facies became truncated and replaced with facies associated with smaller dune sets. This analysis shows that unit bars generally become truncated more laterally than vertically and, thus, they lose the high-angle bar margin deposits and smaller scale bar-top deposits. In general, the only fragments that remain of the unit bars are dune sets, thus making identification of the original unit barform problematic. This novel data set has implications for what may ultimately become preserved in the rock record.