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

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zhi Zhang ◽  
Che Cheng ◽  
Satoshi Masutani ◽  
Tiankai Li ◽  
Xiaowei Zhang ◽  
...  
Keyword(s):  
Alcohol Intake ◽  
Alcohol Exposure ◽  
Cardiac Response ◽  
Conscious Dogs ◽  
Ethanol Ingestion ◽  
Chronic Alcohol ◽  
Functional Responses ◽  
Cell Contractility ◽  
Cardiac Depression ◽  
Ras Activation

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.

scholarly journals Cerebral Hemorrhage and Alcohol Exposure: A Review

2019 ◽  
Vol 55 (1) ◽  
pp. 20-27 ◽  
Author(s):  
Jialing Peng ◽  
Hongxuan Wang ◽  
Xiaoming Rong ◽  
Lei He ◽  
L Xiangpen ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Alcohol Intake ◽  
Literature Search ◽  
Heavy Drinking ◽  
Alcohol Exposure ◽  
Chronic Alcohol ◽  
Chronic Alcohol Abuse ◽  
Pubmed Database ◽  
The Impact ◽  
The Relationship

Abstract Aims To investigate the dose–response relationships between alcohol and intracerebral hemorrhage (ICH), the impact of alcohol on the outcome of ICH and possible mechanisms underlying hypertensive ICH (HICH) caused by heavy drinking. Methods Literature search from 1985 to August 2019 in the PubMed database. Results The relationship between low-middle alcohol consumption and ICH remains controversial for various reasons, whereas chronic heavy drinking increases the incidence of ICH and exerts worse outcome. More attention is needed to clarify the characteristics of chronic alcohol intake and binge drinking. Chronic alcohol abuse tends to elevates blood pressure, resulting in increased occurrence of HICH and exaggerated HICH-contributed brain injury. Conclusion It is important to develop strategies to promote reasonable intake categories, prevent alcoholism and thus reduce the risk of ICH.

Chronic Alcohol Intake Exacerbates Cardiac Dysfunction After Myocardial Infarction

2020 ◽  
Vol 55 (5) ◽  
pp. 524-530
Author(s):  
Yu Liang ◽  
Xuewen Xu ◽  
Qin Li ◽  
Yan Deng ◽  
Maodi Xie ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mitochondrial Function ◽  
Cardiac Dysfunction ◽  
Alcohol Intake ◽  
Alcohol Exposure ◽  
Heart Weight ◽  
Vehicle Group ◽  
Coronary Artery Ligation ◽  
Chronic Alcohol

Abstract Aims Alcohol intake is a risk factor for cardiovascular diseases. This study was designed to investigate whether chronic alcohol intake affects myocardial infarction (MI)-induced cardiac remodeling and heart failure. Methods Eight-week-old male C57BL/6 mice were randomly divided into four groups: Sham group (Sham), MI plus drinking water group (MI + Vehicle), and MI plus daily alcohol intake for 6 weeks with or without gavage of additional alcohol every 3 days (MI + Alcohol and MI + Alcohol + G). The MI were induced by permanent left anterior descending (LAD) coronary artery ligation surgery before vehicle or alcohol treatment. The blood alcohol concentration (BAC), cardiac function, release of cardiac enzymes, pathological changes and mitochondrial function were measured. Results As expected, supplementation of alcohol in drinking water significantly increased random BAC in mice. Long-term exposure to alcohol further reduced body weight, ejection fraction and fractional shortening in comparison with the MI + Vehicle group. Histopathological data showed that alcohol increased fibrosis in infarct zone, which was well correlated with the functional decline. Also, as compared to the MI + Vehicle group, the adenosine diphosphate-supported respiratory function of freshly isolated cardiac mitochondria was inhibited in the MI + Alcohol + G group. Besides, upon MI-induced cardiac damage, we did not observe further changes in heart weight, cardiomyocyte enlargement in remote zone, exercise capacity, lung edema and the release of cardiac enzyme after chronic alcohol intake. Conclusions Our study demonstrated that chronic daily alcohol exposure exacerbated MI-induced cardiac dysfunction, which is related to promoted myocardial fibrosis and inhibited mitochondrial function.

CB1R Promotes Chronic Alcohol-Induced Neuronal Necroptosis in Mice Prefrontal Cortex

2020 ◽  
Author(s):  
Lin Ye ◽  
Shuhao Li ◽  
Xiaochen Liu ◽  
Dingang Zhang ◽  
Liliang Li ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Protein Level ◽  
Cannabinoid Receptors ◽  
Alcohol Exposure ◽  
Global Burden ◽  
Dependent Manner ◽  
Chronic Alcohol ◽  
Inverse Agonists ◽  
Alcohol Vapor ◽  
Chronic Alcohol Exposure

Abstract Aims Alcohol abuse induces multiple neuropathology and causes global burden to human health. Prefrontal cortex (PFC) is one of the most susceptible regions to alcohol-induced neuropathology. However, precise mechanisms underlying these effects on PFC remain to be elucidated. Herein, we investigated whether RIP1/RIP3/MLKL-mediated necroptosis was involved in the alcohol-induced PFC injury, and explored the effect that cannabinoid receptors (CBRs) exerted on the neurotoxicity of alcohol. Methods In this study, dynamic development of neuronal necroptosis in the PFC region was monitored after 95% (v/v) alcohol vapor administration for 15 and 30 days, respectively. Selective CBRs agonists or inverse agonists were pretreated according to the experimental design. All the PFC tissues were isolated and further examined by biochemical and histopathological analyses. Results It was found that chronic alcohol exposure increased the protein level of MLKL and also the phosphorylated levels of RIP1, RIP3 and MLKL in a time-dependent manner, all of which indicated the activation of necroptosis signaling. Particularly, compared to astrocytes, neurons from the PFC showed more prototypical necrotic morphology in response to alcohol insults. In parallel, an increased protein level of CB1R was also found after 15 and 30 days alcohol exposure. Administration of specific inverse agonists of CB1R (AM251 and AM281), but not its agonists or CB2R modulators, significantly alleviated the RIP1/RIP3/MLKL-mediated neuronal necroptosis. Conclusion We reported the involvement of RIP1/RIP3/MLKL-mediated necroptosis in alcohol-induced PFC neurotoxicity, and identified CB1R as a critical regulator of neuronal necroptosis that enhanced our understanding of alcohol-induced neuropathology in the PFC.

scholarly journals Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms

2014 ◽  
Vol 307 (9) ◽  
pp. G941-G949 ◽  
Author(s):  
Padmanabhan Srinivasan ◽  
Rubina Kapadia ◽  
Arundhati Biswas ◽  
Hamid M. Said
Keyword(s):  
Transgenic Mice ◽  
Chronic Exposure ◽  
Methylation Status ◽  
Acinar Cells ◽  
Alcohol Exposure ◽  
Significant Inhibition ◽  
Pancreatic Acinar Cells ◽  
Chronic Alcohol ◽  
Wild Type ◽  
Chronic Alcohol Exposure

Chronic exposure to alcohol affects different physiological aspects of pancreatic acinar cells (PAC), but its effect on the uptake process of biotin is not known. We addressed this issue using mouse-derived pancreatic acinar 266-6 cells chronically exposed to alcohol and wild-type and transgenic mice (carrying the human SLC5A6 5′-promoter) fed alcohol chronically. First we established that biotin uptake by PAC is Na+ dependent and carrier mediated and involves sodium-dependent multivitamin transporter (SMVT). Chronic exposure of 266-6 cells to alcohol led to a significant inhibition in biotin uptake, expression of SMVT protein, and mRNA as well as in the activity of the SLC5A6 promoter. Similarly, chronic alcohol feeding of wild-type and transgenic mice carrying the SLC5A6 promoter led to a significant inhibition in biotin uptake by PAC, as well as in the expression of SMVT protein and mRNA and the activity of the SLC5A6 promoters expressed in the transgenic mice. We also found that chronic alcohol feeding of mice is associated with a significant increase in the methylation status of CpG islands predicted to be in the mouse Slc5a6 promoters and a decrease in the level of expression of transcription factor KLF-4, which plays an important role in regulating SLC5A6 promoter activity. These results demonstrate, for the first time, that chronic alcohol exposure negatively impacts biotin uptake in PAC and that this effect is exerted (at least in part) at the level of transcription of the SLC5A6 gene and may involve epigenetic/molecular mechanisms.

Propolis Prevents the Effects of Chronic Alcohol Intake on Ocular Tissues

2009 ◽  
Vol 42 (3) ◽  
pp. 147-151 ◽  
Author(s):  
Sinan Emre ◽  
Zümrüt Yılmaz ◽  
Feral Öztürk ◽  
M. Hanifi Emre
Keyword(s):  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Ocular Tissues

Decrease in the Number of Muscarinic Receptors in Rat Pancreas after Chronic Alcohol Intake

1989 ◽  
Vol 64 (4) ◽  
pp. 356-359 ◽  
Author(s):  
Juha M. Grönroos ◽  
Timo Kaila ◽  
Heikki J. Aho ◽  
Timo J. Nevalainen
Keyword(s):  
Muscarinic Receptors ◽  
Alcohol Intake ◽  
Chronic Alcohol ◽  
Rat Pancreas

EFFECTS OF CHRONIC ALCOHOL EXPOSURE ON GROWTH AND NUTRITION IN RATS

1976 ◽  
Vol 273 (1 Work in Progr) ◽  
pp. 205-211 ◽  
Author(s):  
Jack Wang ◽  
Mark Marvin ◽  
Bruce Abel ◽  
Richard N. Pierson
Keyword(s):  
Alcohol Exposure ◽  
Chronic Alcohol ◽  
Growth And Nutrition ◽  
Chronic Alcohol Exposure
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