Mode of perfusion influences infarct size, coronary flow and stress kinases in the isolated mouse heart

Abstract

Aim: The isolated, retrogradely perfused heart (modified Langendorff model) is a widely used method in experimental heart research. The presence of an intraventricular balloon is necessary to get functional measurements. We have previously shown that the balloon induces phosphorylation of some suggested cardioprotective mitogen activated protein kinases (MAPK): P38-MAPK, ERK 1/2 and JNK. We hypothesized that the balloon could influence cardioprotection, protect against ischemia reperfusion injury and interfere with coronary flow. Methods and results: Isolated mouse hearts were perfused for 5, 10, 20, 40 and 60 minutes with a balloon in the left ventricle. We found a wavelike phosphorylation of all MAPK while AKT displayed a gradual dephosphorylation when compared to non-perfused hearts. Hearts were subjected to 20 minutes of stabilization with or without the balloon, followed by 35 minutes of ischemia and 120 minutes of reperfusion. Although the MAPK were phosphorylated, the infarcts were larger in the balloon group. When the balloon was present during the entire protocol, compared to removal at the end of ischemia, the infarct size was also larger, especially in the endocardial layer. The balloon reduced post ischemic endocardial coronary flow, despite a higher average flow, indicating a hyperperfused epicard. Blocking the balloon-induced ERK 1/2 phosphorylation during stabilization did not affect infarct size. The effect of postconditioning was influenced by the balloon, showing reduced infarct size when the balloon was present. Conclusion: The balloon used for pressure measurements may contributes to cell death possibly by reducing endocardial coronary flow. The final version of this research has been published in Acta Physiologica. © 2017 Wiley