Effects of Acetaminophen on Left Atrial Contractility

Jun-Hei Chang; Pao-Yun Cheng; Chih-Hsueng Hsu; Yao-Chang Chen; Po-Da Hong

doi:10.6515/acs20150823a

Effects of Acetaminophen on Left Atrial Contractility

Acta Cardiol Sin. 2016 Jul;32(4):485-90. doi: 10.6515/acs20150823a.

Authors

Jun-Hei Chang¹, Pao-Yun Cheng², Chih-Hsueng Hsu³, Yao-Chang Chen⁴, Po-Da Hong¹

Affiliations

¹ Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology;
² Department of Physiology and Biophysics, National Defense Medical Center;
³ Division of Cardiology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center;
⁴ Department of Biomedical Engineering and Institute of Physiology, National Defense Medical Center, Taipei, Taiwan.

Abstract

Background: It has been observed that acetaminophen shows cardioprotective efficacy in mammals. In this study, we investigated the electromechanical effects of acetaminophen on the left atrium (LA).

Methods: Conventional microelectrodes were used to record the action potentials (AP) in rabbit LA preparations. The action potential duration (APD) at repolarization levels of 90%, 50% and 20% of the AP amplitude (APD90, APD50, and APD20, respectively), resting membrane potential, and contractile force were measured during 2 Hz electrical stimulation before and after sequential acetaminophen administration to the LA.

Results: Acetaminophen (0.1, 0.3, 1, and 3 mM) reduced APD20 from 9.4 ± 1.2 to 8.0 ± 1.1 (p < 0.05), 7.1 ± 0.8 (p < 0.05), 7.8 ± 1.1, and 6.8 ± 1.2 ms (p < 0.05), respectively, and APD50 from 20.2 ± 1.9 to 17.4 ± 2.0, 15.6 ± 1.8 (p < 0.05), 15.8 ± 2.2 (p < 0.05), and 14.1 ± 2.4 ms (p < 0.05), respectively, in a concentration-dependent manner. APD90 was reduced from 72.0 ± 3.6 to 64.7 ± 4.2, 61.9 ± 4.3, 60.5 ± 3.7, and 53.4 ± 4.4 ms (p < 0.05), respectively. Acetaminophen increased LA contractility from 45 ± 9 to 52 ± 10 (p < 0.05), 55 ± 9 (p < 0.01), 58 ± 9 (p < 0.01), and 60 ± 9 mg (p < 0.01), respectively, in a concentration-dependent manner. In the presence of the NOS inhibitor L-NAME or PKG-I inhibitor DT-2, additional acetaminophen treatment did not significantly increase LA contractility.

Conclusions: Acetaminophen modulated the electromechanical characteristics of LA by inhibiting the NOS and PKG I pathway, and then contributed to the positive inotropic effect.

Keywords: Acetaminophen; Contractility; Left atrium.