Abstract 13: Baicalein Rescues Delayed Therapeutic Hypothermia in Cardioprotection
Introduction: Therapeutic hypothermia (TH) is a highly promising cardioprotective treatment for cardiac arrest and ischemia/reperfusion (I/R) injury. Our prior work showed that TH conferred cardioprotection associated with enhanced Akt phosphorylation that was abrogated by delayed-TH (DL-TH). The optimal timing of TH appears critical. We previously demonstrated that baicalein, a flavonoid derived from Scutallaria baicalensis Georgi, protected against I/R injury in murine cardiomyocytes. Therefore, we hypothesize that baicalein rescues cells from I/R injury when cooling is delayed and this protection is attributed to activation of Akt.
Methods: Cardiomyocytes isolated from 1-2-day old C57BL6 mice were exposed to 90 min ischemia and 180 min reperfusion. The intra-cooling (32oC) was applied to cells during the last 20 min of ischemia and the first hour of reperfusion. DL-TH was initiated at 20 min of reperfusion and maintained for a similar duration. For 20 min DL-TH, baicalein was given to the cells at the time of reperfusion and cooling introduction. Cell viability was assessed by propidium iodide and Akt phosphorylation (p-Akt) was detected by western blot.
Results: I/R resulted in an increased cell death compared to control (45.6 ± 4.4 % vs. 8.2 ± 1.8 %, p < 0.001) and intra-cooling reduced cell death to 24.5 % ± 2.8 (n = 8, p < 0.01). In contrast, DL-TH increased cell death (55.6 ± 3.3 %, n = 6). Baicalein, given at the time of reperfusion and cooling introduction, decreased cell death to 29.3 ± 2.6% (n = 6, p < 0.01). Moreover, failed hypothermia (DL-TH) was associated with a decrease in p-Akt that was reversed and increased by the combined treatment of baicalein and DL-TH.
Conclusions: Results show that the DL-TH abrogates TH-induced protection in cardiomyocytes. Adjunctive therapy with baicalein during DL-TH improves cell survival. This strategy may be clinically relevant in patients with heart I/R injury who receive delayed cooling.
- © 2012 by American Heart Association, Inc.