Arterial t-PA-concentrations.

<p>Absolute t-PA concentrations in arterial blood are shown for pre-ischemia (baseline), as well as for the period after 10 min of ischemia and 10 min of reperfusion. Both the treated group (filled squares, n = 12) and the control group (open squares, n = 10) are shown. Data are presented as mean ± SEM. No differences were noted within groups over time, or between groups at any of the time intervals (mixed between-within subjects ANOVA). There was no sign here that the valproic acid treatment led to higher systemic blood levels of t-PA in the resting state. These results also showed that the coronary t-PA release did not affect systemic arterial t-PA levels.</p

Hemodynamic results.

<p>HR =  heart rate (bpm); MAP =  mean arterial pressure (mm Hg); CSF  =  coronary sinus blood flow (mL/min). Control group (n = 10), treated group (n = 12). Data are presented as mean ± 95% SEM. * = p<0.05 using repeated measures ANOVA and when significant was followed by paired t test vs. baseline. A between-groups t test was performed, but no differences were found.</p

Coronary t-PA-flux.

<p>Coronary t-PA fluxes are shown in Panel A for pre-ischemia (baseline), after 10 min of ischemia followed by 10 min of reperfusion for treated group (filled squares, n = 12) and for control group (open squares, n = 10). These are point measurements for observed t-PA fluxes at minutes 1, 3, 5, 7, and 10. One can note that there are different baselines for the two groups. The main result is derived from Panel A, and presented as the cumulative t-PA release over time in Panel B, as area under the curve (AUC). There is a clearly higher cumulative t-PA release for the VPA treated group (mixed between-within subjects ANOVA, p = 0.023); treated group (filled diamonds, n = 12) and control group (open diamonds, n = 10) data presented as mean ± SEM. There were also differences between groups (larger cumulative t-PA release in the treatment group) for specific measurements at minutes 10, 7, and 5 (t-test).</p

Absolute values of coronary lactate-fluxes.

<p>These are shown for pre-ischemia (baseline), after 10 min of ischemia followed by 10 min of reperfusion for treated group (filled squares, n = 12) and for control group (open squares, n = 10). Data are presented as mean ± SEM. Sampling of the ischemic area, as confirmed by positive lactate flux (regional myocardial lactate production in response to the local coronary occlusion), was observed in all animals (not shown individually) and is reflected by the immediate high positive lactate flux noted at reperfusion minute 1. This regional lactate flux was quickly ‘washed out’. No difference was found between groups (p = 0.853, mixed between-within subjects ANOVA).</p

Forearm t-PA net release on the same day, first and second measurements.

<p>Panel A demonstrates non-treatment grouped t-PA fluxes during ISP stimulation for the first measurement sequence (Control-1, filled diamond, n = 16), and second (Control-2, open diamond, n = 15). Panel B shows the VPA treated grouped t-PA fluxes for the first measurement sequence (VPA-1, filled square, n = 15) and second (VPA-2, open square, n = 15). First, there are linear and progressive increases in t-PA release during the course of the ISP stimulation in the VPA group (Panel B), but not in the Control group (Panel A) It is notable that for Control, there are lower t-PA fluxes at each time point (3–18 minutes) during the second (same day) stimulation, but that this is not the case for the VPA grouped measures, until 18 minutes of stimulation. There is clear lower level in the response for the second stimulation (one hour later) for Controls that is not observed with VPA treatment. Data are presented as mean with 95% confidence intervals. # indicates p value less than 0.05 using repeated measured ANOVA within groups for change in values during the interval between 3–18 minutes. * indicates p value less than 0.05 using repeated paired t tests.</p

Demographic data.

<p>Abbreviations: kg = kilogram, m² = square meter, bpm = beats per minute, mm Hg = millimeters of mercury, g = gram, L = liter, μmol = micromole, mmol = millimole. Results shown as mean ± SD, (n = 16).</p><p>Demographic data.</p

CONSORT subject flow diagram.

<p>Subjects were placed initially in one of two groups, where one group was treated for 4 weeks with VPA before being measured, and the other group was measured directly as Controls. After the first measurement, the VPA treated group rested for 4 weeks with a washout period before being measured again Control. The subjects that first were Controls, were measured again after 4 weeks of VPA treatment. The subjects first treated with VPA were measured and then observed a 4 week washout and rest period before they were studied again as Controls. All subjects measured with VPA were combined for grouped analysis (same for Control measurements).</p

Coagulation and inflammation.

<p>Abbreviations: CI = confidence interval, μmol = micromole, g = gram, L = liter, mg = milligram, s = second, ng = nanogram, ml = milliliter. Comparisons made with a paired t test. Data shown as mean with 95% CI, (n = 16).</p><p>Coagulation and inflammation.</p

Work-flow diagram of EV isolation from porcine blood, followed by evaluation of EV purity and DNA isolation and analysis.

<p>Work-flow diagram of EV isolation from porcine blood, followed by evaluation of EV purity and DNA isolation and analysis.</p

Gene fragment quantification.

<p>The Y-axis shows the number of sequenced gene fragments (reads) isolated in EV before (black) and after IPC (grey). The x-axis shows the 3000 genes (not all named) with most reads in decreasing number of read frequency before IPC. The genes detected after IPC are presented in the same order as the genes before IPC, in order to illustrate possible differences for numbers of reads. Due to the high number of genes, the x-axis shows only a few of these (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0159105#pone.0159105.s002" target="_blank">S2 Fig</a> for the complete data). The lines are closely located and do not show any significant difference between before and after IPC.</p