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Abstract 13050: Acute Alcohol-Induced Enhanced Cardiac Depression in a Canine Model of Chronic Alcohol Consumption: Adverse Effects on Left Ventricle and Myocyte Contraction, [Ca
 2+
 ]
 i
 Transient and Ca
 2+
 Current


 Background:
 Acute alcohol ingestion produces transient RAS activation. Alcoholics have an enhanced RAS activation after acute ethanol ingestion. Thus, chronic alcohol users may have enhanced cardiac functional responses to acute alcohol intake. However, it is unclear whether and how chronic alcohol intake alters cardiac response to acute alcohol exposure. We tested the hypothesis that acute alcohol may exacerbate cardiac depression and [Ca
 2-
 ]
 i
 dysregulation, thus play important role in development of irreversible cardiomyopathy in alcoholics.
 
 
 Methods:
 We compared LV and cardiomyocyte response to acute alcohol in 6 chronically-instrumented conscious dogs before and 6 months after the once daily ingestion of alcohol (400 ml, 22% providing 33% of total daily caloric intake).
 
 
 Results:
 In conscious dogs, 6 months of alcohol significantly decreased LV contractility by 48% measured by the slopes of pressure-volume relations (E
 ES
 , 48%, 4.4 vs 8.4 mmHg/ml and M
 SW
 , 50.8 vs 98.6 mmHg) and increased the time constant of relaxation (τ, 78%, 47.8 vs 26.9 ms). In the alcoholic animals, when compared with the same animals prior to alcohol, acute alcohol (0.2 g/kg, iv, plasma level 62.3 ± 8 mg/dL) caused a greater decrease in LV contractility (47% vs 23%) and increase in τ (27% vs11%). In isolated myocytes, abrupt exposure to alcohol (250 mM) produced significant decreases in cell contraction, [Ca
 2+
 ]
 i
 transient ([Ca
 2+
 ]
 i
 ) and Ca
 2+
 current (I
 Ca,L
 ) in both normal and alcoholic myocytes. However, compared with the isolated cells obtained from LV biopsied tissues of the same animals prior to alcohol, the acute alcohol-induced decrease in I
 Ca,L
 (alcoholic: 50%, 1.3 vs 2.6; normal: 29%, 4.0 vs 5.6 pA/pF) was much greater in the alcoholic myocytes, the resulting reductions in the cell contractility, dL/dtmax (alcoholic: 46%, 36vs67; normal: 24%, 82vs108 μm/s), the percent shortening (49% vs 24%) and relengthening, dR/dtmax were doubled.
 
 
 Conclusion:
 In chronically alcohol-fed dogs, acute alcohol produces increased direct inhibition in LV and myocyte contractility, relaxation and exacerbates [Ca
 2+
 ]
 i
 hemostasis. The chronic alcohol-induced increased cardiac sensitivity to acute alcohol may play an important role in the functional impairment in alcoholic cardiomyopathy.
