Insulin mitigates acute ischemia–induced atrial fibrillation and sinoatrial node dysfunction ex vivo
Huiliang Qiu, Fan Li, Hannah Prachyl, Alejandra Patino-Guerrero, Michael Rubart, Wuqiang Zhu
Huiliang Qiu, Fan Li, Hannah Prachyl, Alejandra Patino-Guerrero, Michael Rubart, Wuqiang Zhu
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Research Article Cardiology Therapeutics

Insulin mitigates acute ischemia–induced atrial fibrillation and sinoatrial node dysfunction ex vivo

Abstract

Acute atrial ischemia is a well-known cause of postoperative atrial fibrillation (POAF). However, mechanisms through which ischemia contributes to the development of POAF are not well understood. In this study, ex vivo Langendorff perfusion was used to induce acute ischemia/reperfusion in the heart to mimic POAF. Inducibility of atrial fibrillation (AF) was evaluated using programmed electrical stimulation and verified with open-atrium optical mapping. Compared with the control group without ischemia, 25 minutes of ischemia substantially increased the incidence of AF. The right atrium was more susceptible to AF than the left atrium. Administering insulin for 30 minutes before ischemia and during reperfusion with 25 minutes of ischemia greatly reduced the vulnerability to AF. However, insulin treatment during reperfusion only did not show substantial benefits against AF. Optical mapping studies showed that insulin mitigated ischemia-induced abnormal electrophysiology, including shortened action potential duration and effective refractory period, slowed conduction velocity, increased conduction heterogeneity, and altered calcium transients. In conclusion, insulin reduced the risk of acute ischemia/reperfusion–induced AF via improving the electrophysiology and calcium handling of atrial cardiomyocytes, which provides a potential therapy for POAF.

Authors

Huiliang Qiu, Fan Li, Hannah Prachyl, Alejandra Patino-Guerrero, Michael Rubart, Wuqiang Zhu

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Figure 8

Insulin reduces cardiomyocyte apoptosis.

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Insulin reduces cardiomyocyte apoptosis. (A) Cell apoptosis is measured ...
(A) Cell apoptosis is measured by TUNEL staining. Cell nuclei were counterstained by DAPI. Bar = 100 μm. (B) Quantification of TUNEL positively staining nuclei of cardiomyocytes and nonmyocytes, respectively. The numbers of apoptotic cell nuclei were normalized to the total number of nuclei for cardiomyocytes and nonmyocytes, respectively. Data were represented as mean ± SEM. n = 5 (biological repeats) in each group. One-way ANOVA with Tukey’s multiple-comparison test. (C) H&E was performed to observe cardiac inflammation and gross morphology. Bar = 100 μm. Fast green/Sirius red staining was performed to determine the interstitial fibrosis. Bar = 100 μm. Immunostaining using antibodies against cardiac troponin T (cTnT) was performed to visualize cardiomyocyte morphology. Bar = 25 μm. (D) Quantification of interstitial fibrosis. Data were represented as mean ± SEM. n = 5 (biological repeats) in each group. One-way ANOVA with Tukey’s multiple-comparison test.