Background: 

Cell injury resulting from myocardial infarction (MI) leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage, a process that contributes to tissue injury throughout the ventricle. We previously demonstrated, that released, natural extracellular RNA significantly increases the permeability across microvascular endothelial cells through a vascular endothelial growth factor (VEGF)-dependent mechanism. In the present study we therefore evaluated changes of vascular permeability, edema formation and myocardial infarction size following a depletion of extracellular RNA after in vivo induction of MI.

Methods and Results: 

The left coronary artery (LAD) of C57/Bl 6 was ligated and RNase (100mg) or control buffer was administered intravenously 30 min, 3 and 6 hours following LAD ligation. Wet and dry weight of heart slices were measured for analysis of myocardial edema, and evans blue dye and tetrazolium were used to delineate the area at risk and infarction size within the myocardium 24h after ligation. Cardiac function as measured by fractional shortening was assessed by echocardiography.

RNase treatment had no effect on blood pressure, total plasma protein or albumin levels, peripheral blood cell counts or glucose levels. However, edema formation was significantly decreased in RNAse treated mice as measured by wet/dry ratio (3.38 0.19 vs. 3.93 0.27; P<0.05). Since risk zone sizes were similar between groups, the percentage infarction of the risk zone was significantly smaller in RNase treated mice (P<0.05). Moreover, Fractional shortening analysis determined by echocardiography revealed a significantly enhanced myocardial contractility in RNase treated mice (25.3 2.6% vs. 13.8 2.6%; P<0.05). Furthermore application of RNase led to an significant increase of survival of mice following MI.

Conclusion: 

These results identify extracellular RNA as a novel natural permeability factor which augments ischemia-induced edema formation and myocardial infarction. Moreover, RNase treatment serving as a novel vessel-protective modality, prevents MI-induced edema formation and tissue injury and thus significantly improves survival following MI.