Figure 1.
Schematic image of the in vivo heart preparation.
The left anterior descending artery and corresponding vein are depicted. A coronary snare is placed in the mid region of this artery, and when drawn, this generates a region of ischemia corresponding to a larger part of the anterior left ventricle. The coronary venous catheter is introduced through the right atrium, coronary sinus, and finally placed with the sampling tip in the proximal great cardiac vein, draining the left anterior descending vascular region (ischemic area).
Figure 2.
Absolute values of coronary lactate-fluxes.
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).
Table 1.
Hemodynamic results.
Figure 3.
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.
Figure 4.
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).