Abstract 9746: Differential Impact of Dose-Related Chronic Alcohol Ingestion on Action Potential Upstroke, Systolic Myocardial Function and Cardiac Pro-inflammatory Factors mRNA Expression in Male C57BL/6 Mice

Abstract

Background Cardiomyopathy elicited by ethanol or the toxic metabolites after chronic excessive alcohol intake had been well documented. However, to what extent of such dose-related chronic alcohol (Alc) ingestion on myocardial systolic performance and electrical disturbance remained unclear. Methods Totally 40 C57BL/6 male mice of 6 weeks old were fed with a liquid diet containing 4% (n=13) or 6% (n=14) alcohol and normal diet (CTRL, n=13) for 12 weeks. In vivo cardiac function was examined by echocardiography at baseline and before animal sacrifice. Optical mapping (Lecia MZ FLIII system, Heidelberg, Germany) and single cardiomyocyte patch clamp were used to assess conduction velocity of ventricular surface and action potential of single cardiomyocyte, respectively. Extent of myocardial macrophage infiltration and fibrosis were examined by immunostaining with the mRNA content of pro-inflammatory factors determined by real-time PCR. Results Both 4% and 6% Alc groups had reduced conduction velocity (47±3 cm/s and 28±8 cm/s vs Ctrl: 71±7 cm/s, p<0.05)) and a more perturbated activation spread. Echocardiography demonstrated enlarged cardiac dimension and worsened fractional shortening in both Alc groups while only 6% Alc mice demonstrated a significant decline of systolic myocardial velocity (Ctrl vs 6%: 1.14±0.03 vs 0.97±0.03, p<0.05). Reduced action potential upstroke velocity (Figure) and abnormal resting membrane potential were shown in both Alc groups. Markedly increased macrophage infiltration and fibrosis zone (6% vs Ctrl: 3.1±0.3 vs 1.3±0.1 mm 2 /cm 2 , p<0.05) were accompanied by significantly elevated pro-inflammatory (including TNF-α, ΙL-6, and ΜΜP-2) factors mRNA expression only in 6% Alc mice. Conclusion These results showed a differential impact of myocardial electromechanical disturbance in response to dose-specific Alc ingestion and that overt inflammation response may start to take place in more severely damaged myocardium.