TY - JOUR
T1 - Milrinone-Induced Postconditioning Requires Activation of Mitochondrial Ca2+-sensitive Potassium (mBKCa) Channels
AU - Behmenburg, Friederike
AU - Trefz, Lara
AU - Dorsch, Marianne
AU - Ströthoff, Martin
AU - Mathes, Alexander
AU - Raupach, Annika
AU - Heinen, André
AU - Hollmann, Markus W.
AU - Berger, Marc M.
AU - Huhn, Ragnar
PY - 2018
Y1 - 2018
N2 - Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced postconditioning involves activation of mBKCa channels in the rat heart in vitro. Randomized, prospective, blinded laboratory investigation. Experimental laboratory. Male Wistar rats. Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. At the onset of reperfusion, hearts were perfused with different concentrations of milrinone (0.3-100 μM) for determination of a dose-effect curve. In a second set of experiments, 3 μM milrinone was administered in combination with the mBKCa channel inhibitor paxilline (1 μM). Infarct size was determined by triphenyltetrazoliumchloride staining. In control animals, infarct size was 37 ± 7%. Milrinone at a concentration of 3 μM reduced infarct size to 22 ± 7% (p < 0.05 v control). Higher milrinone concentrations did not confer stronger protection. Paxilline completely blocked milrinone-induced cardioprotection whereas paxilline alone had no effect on infarct size. This study shows that activation of mBKCa channels plays a pivotal role in milrinone-induced postconditioning
AB - Cardioprotection by postconditioning requires activation of mitochondrial large-conductance Ca2+-sensitive potassium (mBKCa) channels. The involvement of these channels in milrinone-induced postconditioning is unknown. The authors determined whether cardioprotection by milrinone-induced postconditioning involves activation of mBKCa channels in the rat heart in vitro. Randomized, prospective, blinded laboratory investigation. Experimental laboratory. Male Wistar rats. Hearts of male Wistar rats were randomized, placed on a Langendorff system, and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to 33 minutes of global ischemia and 60 minutes of reperfusion. At the onset of reperfusion, hearts were perfused with different concentrations of milrinone (0.3-100 μM) for determination of a dose-effect curve. In a second set of experiments, 3 μM milrinone was administered in combination with the mBKCa channel inhibitor paxilline (1 μM). Infarct size was determined by triphenyltetrazoliumchloride staining. In control animals, infarct size was 37 ± 7%. Milrinone at a concentration of 3 μM reduced infarct size to 22 ± 7% (p < 0.05 v control). Higher milrinone concentrations did not confer stronger protection. Paxilline completely blocked milrinone-induced cardioprotection whereas paxilline alone had no effect on infarct size. This study shows that activation of mBKCa channels plays a pivotal role in milrinone-induced postconditioning
U2 - https://doi.org/10.1053/j.jvca.2017.11.048
DO - https://doi.org/10.1053/j.jvca.2017.11.048
M3 - Article
C2 - 29306618
SN - 1053-0770
VL - 32
SP - 2142
EP - 2148
JO - Journal of cardiothoracic and vascular anesthesia
JF - Journal of cardiothoracic and vascular anesthesia
IS - 5
ER -