Mechanisms of ranolazine pretreatment in preventing ventricular tachyarrhythmias in diabetic db/db mice with acute regional ischemia-reperfusion injury.

ABSTRACT: Studies have demonstrated that diabetic (db/db) mice have increased susceptibility to myocardial ischemia-reperfusion (IR) injury and ventricular tachyarrhythmias (VA). We aimed to investigate the antiarrhythmic and molecular mechanisms of ranolazine in db/db mouse hearts with acute IR injury. Ranolazine was administered for 1 week before coronary artery ligation. Diabetic db/db and control db/+?mice were divided into ranolazine-given and -nongiven groups. IR model was created by 15-min left coronary artery ligation and 10-min reperfusion. In vivo electrophysiological studies showed that the severity of VA inducibility was higher in db/db mice than control (db/?+) mice. Ranolazine suppressed the VA inducibility and severity. Optical mapping studies in Langendorff-perfused hearts showed that ranolazine significantly shortened action potential duration, Cai transient duration, Cai decay time, ameliorated conduction inhomogeneity, and suppressed arrhythmogenic alternans induction. Western blotting studies showed that the expression of pThr17-phospholamban, calsequestrin 2 and voltage-gated sodium channel in the IR zone was significantly downregulated in db/db mice, which was ameliorated with ranolazine pretreatment and might play a role in the anti-arrhythmic actions of ranolazine in db/db mouse hearts with IR injury.

SUBMITTER: Chou CC 

PROVIDER: S-EPMC7674419 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature