Alcohol abuse is positively associated with cardiovascular disease. Dietary low-carbohydrate/high-protein (LCHP) intake confers a greater mortality risk. Here, the impact of ethanol consumption in combination with dietary LCHP intake on left ventricular (LV) systolic function and lethal ventricular arrhythmia susceptibility were investigated in apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice. The underlying mechanisms, cardiac sympathovagal balance, beta-adrenergic receptor (ADRB) levels, and gap junction channel protein connexin 43 (Cx43) expression, were examined. Male AL mice fed an LCHP diet with or without ethanol were bred for 16 weeks. Age-matched male AL and wild-type mice received standard chow diet and served as controls. The following were used to assess LV systolic function, lethal ventricular arrhythmia susceptibility, cardiac sympathovagal balance, Cx43 expression, and ADRB levels:

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echocardiography

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electrocardiography and a ventricular arrhythmia-evoked test

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LV tyrosine hydroxylase (TH) expression shown by a fluorescence immunohistochemical examination and the ratio of low-frequency power to high-frequency power (LF/HF) as indicated by the heart rate variability (HRV)

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Cx43 expression in both a fluorescence immunohistochemical examination and polymerase chain reaction (PCR); and ADRB1 and ADRB2 expressions in fluorescence immunohistochemical examination

The results demonstrated that ethanol consumption in combination with dietary LCHP intake worsened LCHP-induced LV systolic dysfunction in AL mice and enhanced their susceptibility in the ventricular arrhythmia-evoked test. There were concomitant increases in LV weight, LF/HF ratio shown by HRV, TH, ADRB1, ADRB2, and Cx43 expressions by LV fluorescence immunohistochemistry, and LV Cx43 messenger ribonucleic acid expression by PCR. In AL mice, alcohol consumption combined with dietary LCHP intake may thus promote a shift in cardiac sympathovagal balance toward sympathetic predominance, the increases in beta-adrenergic receptors (ADRB1 and ADRB2), and then affect the gap junction channel protein Cx43, which in turn could contribute to increased risks of LV systolic dysfunction and susceptibility to lethal ventricular arrhythmia.

酗酒与心血管疾病呈正相关。膳食低碳水化合物/高蛋白 (LCHP) 摄入量会增加死亡风险。在这里，在载脂蛋白 E/低密度脂蛋白受体双基因敲除 (AL) 小鼠中研究了乙醇消耗与膳食 LCHP 摄入相结合对左心室 (LV) 收缩功能和致死性室性心律失常易感性的影响。检查了潜在机制、心脏交感迷走神经平衡、β-肾上腺素能受体 (ADRB) 水平和间隙连接通道蛋白连接蛋白 43 (Cx43) 表达。用含或不含乙醇的 LCHP 饮食喂养雄性 AL 小鼠饲养 16 周。年龄匹配的雄性 AL 和野生型小鼠接受标准食物并作为对照。以下用于评估 LV 收缩功能，

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超声心动图

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心电图和室性心律失常诱发试验

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由荧光免疫组织化学检查显示的 LV 酪氨酸羟化酶 (TH) 表达和由心率变异性 (HRV) 指示的低频功率与高频功率 (LF/HF) 的比率

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Cx43 在荧光免疫组织化学检查和聚合酶链反应 (PCR) 中的表达；荧光免疫组化检查中ADRB1和ADRB2的表达

结果表明，乙醇消耗与膳食 LCHP 摄入相结合会加重 AL 小鼠中 LCHP 诱导的 LV 收缩功能障碍，并增强其在室性心律失常诱发试验中的易感性。LV 荧光免疫组织化学显示的 HRV、TH、ADRB1、ADRB2 和 Cx43 表达显示的 LV 重量、LF/HF 比率同时增加，LV Cx43通过 PCR 表达信使核糖核酸。在 AL 小鼠中，饮酒与膳食 LCHP 摄入相结合可能会促进心脏交感迷走神经平衡向交感神经优势转变，β-肾上腺素能受体（ADRB1 和 ADRB2）增加，然后影响间隙连接通道蛋白 Cx43，进而影响可能会增加左室收缩功能障碍的风险和对致死性室性心律失常的易感性。