Alcoholic Liver Disease Role Of Free Radicals
A substantial body of evidence exists to support the contention that ROS generated during ethanol metabolism may be involved in the pathogenesis of alcoholic liver disease (ALD). Decades ago, it was already emphasized by Lieber that the induction of cytochrome P450 is a critical event with respect to the development of ALD 85 , If free radical production and lipid peroxidation play a role in the development of ALD, depletion of dietary antioxidants such as vitamin E or an increase in oxidants...
Human and nonhuman primate studies
Apolipoprotein A-I is the most abundant protein in HDL and plays an important role in maintaining the structure of HDL and activating lecithin cholesterol acyltransferase (LCAT), an enzyme involved in converting cholesterol to cholesterol ester. HDL appears to be primarily cardioprotective by transporting cholesterol from the periphery to the liver for export as bile acids. This process is termed reverse cholesterol transport. From epidemiological studies, higher levels of HDL cholesterol are...
Fatty Acid Ethyl Esters
The majority of ingested alcohol is rapidly absorbed from the small intestine into the bloodstream, and is distributed to tissues that possess high water content and blood flow, e.g., myocardium 5J. Once ethanol has reached myocardium, it has been shown to affect both the sarcolemma (muscle cell membrane) and the sarcoplasmic reticulum (SR). In rat myocytes, chronic alcohol intake creates sarcolemma leaking along with an intracellular calcium increase 23,24 , Several studies also exhibited...
Effects
Watson Alcohol, the most consumed drug in the world, is often not recognized as a drug or addictive by the public and the media, because of its legal use and acceptance. The public, on the other hand, recognizes cocaine as an addictive drug with traumatic effects on its users. Some users of cocaine begin to mix cocaine with alcohol as together they extend the euphoric sensation. Cocaine plus concomitant ethanol use results in cocaethylene, a compound synthesized...
Models
The rat model continues to be one of the primary models of choice for the study of the cardiovascular effects of cocaine. Recently, the rat model has been utilized to study the acute and chronic effects of cocaine self-administration behavior on cardiovascular function 81 . When rats were self-administered injections of cocaine 0.5 mg kg there was a significant increase in blood pressure. Tolerance developed to this effect within 3 daily sessions. During saline-substitution sessions, a...
Ethanol And Smooth Muscle Cell Proliferation
Excessive proliferation of arterial SMC plays an important role in the process of atherogenesis and hypertension 14 , Therefore, inhibition and stimulation of VSMC proliferation may be crucial for preventing and exacerbating, respectively, the development of cardiovascular disease. One key regulatory enzyme pathway for control points within the cell cycle has been identified as mitogen-activated protein kinases (MAPKs) 51 , They are serine threonine protein kinases that are activated by dual...
Effect Of Ethanol On Prostacyclin
The effects of ethanol on PGI2, another endothelium-derived vasodilator and potent inhibitor of platelet aggregation, have also been investigated. Ethanol increased PGI2 production in cultured human umbilical vein endothelial cells and elevated plasma levels ofPGI2 in volunteers administered ethanol 29 , Guivernau et al. found that while ethanol did not affect vascular PGI2 release in control rats, in aortas from alcohol-fed animals ethanol stimulated PGI2 production 30 , These data imply that...
Specific Effects Of Ethanol Consumption On Platelets
From the foregoing, although it is clear that consumption of alcoholic beverages inhibits platelet function in humans, several questions remain regarding the nature of the effect. Duration of the effect and dose-response relationships, for example, are not established, and even the fundamental question of whether ethanol itself has a direct role in the effects of alcoholic beverages on platelet function has not been sufficiently investigated. Thus, we recently performed a study in human...
Alcohol And The Heart
Ethanol has important effects on the cardiovascular system and particularly on anti-oxidant systems (reviewed in 75,158 ). Although the relative incidence of alcohol consumption reduces the overall risk of cardiovascular disease by a number of mechanisms (for example, increasing HDL LDL ratio, reducing platelet function and aggregation 140,159 ) excessive alcohol is damaging and can lead to the development of alcoholic cardiomyopathy 160-163 , Paradoxically, moderate alcohol consumption has...
References
Preclinical cardiac malfunction in chronic alcoholism. Comparison with matched normal controls and with alcoholic cardiomyopathy. N. Engl. J. Med. 1972 287 677-680. 2 Wu CF, Sudhaker M, Ghazanfar J, Ahmed SS, Regan TJ. Preclinical cardiomyopathy in chronic alcoholics a sex difference. Am. HeartJ. 1976 91 281-286. 3 Richardson PJ, Wodak AD, Atkinson L, Saunders JB, Jewitt DE. Relation between alcohol intake, myocardial enzyme activity, and myocardial function...
Apolipoprotein B
Apolipoprotein B is the major structural protein for triglyceride-rich particles including chylomicrons and very low density lipoprotein (VLDL) as well as intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). VLDL is sequentially metabolized to IDL and LDL by hydrolysis of the triglycerides. There are two forms of apolipoprotein B, apolipoprotein B100 and apolipoprotein B48. Apolipoprotein B48 derives from mRNA editing of apolipoprotein B100 mRNA. In the intestine, where...
Alcoholism In Women And Incidence Of Ahmd
Compared to men, women drink less and experience less alcohol-related medical problems 6 , However, one third of all alcoholics in the United States are women 6 , Over the last two decades, there is no evidence of any major increase in total alcohol consumption by women, however there has been an important change in the drinking patterns and prevalence of alcohol usage among women 7J. With regard to drinking patterns, younger women report frequent heavy drinking and frequent bouts of...
Cryptogenic Stroke
Finally, ischemic brain infarcts of unknown origin (cryptogenic stroke) have also been described in connection with heavy drinking of alcohol 41,42 , Alcohol also has complex effects on cerebral blood flow and autoregulation. Whether or not these mechanisms play a significant role is unclear. Thus far, we have not found an alcoholic binge to result in marked hypotension and watershed infarcts. We believe that many of the cryptogenic ischemic brain infarcts are due to emboli of unknown origin.
Introduction
Prognosis for both spontaneous intracerebral hemorrhage (ICH) 1-4 and aneurysmal subarachnoid hemorrhage (SAH) 4-7 , despite improvements in medical and neurosurgical treatment, has largely remained unaffected. Outcome of both these main hemorrhagic stroke subtypes, which together account for approximately 20 of all strokes, is still determined mainly by the severity ofbleeding, and overall case-fatality still reaches 40-50 2,3,7 , Hence, identification of modifiable risk factors for ICH and...
Mechanisms of cocaine cardiotoxicity
Cocaine abuse induces coronary vasospasm 1-5 , myocardial infarction 6-8 , hypertension 9,10 , stroke 7,H , and fatal cardiac rhythm disorders, including ventricular fibrillation 12-15 , Chronic cocaine abuse has also been shown to cause dilated cardiomyopathy 16,17 , and left ventricular hypertrophy in normotensive cocaine users 18-20 , It is only since modern electrocardiographic techniques have come into widespread use that the effect of cocaine on cardiac rhythm has been effectively...
Are Female Animal Models Of Alcoholism Helpful In Evaluating The Adverse Effects Of Alcohol
Female animal models of alcoholism should be used to study the effects oflong-term alcohol exposure. However, investigators need to consider variables such as the level concentration of ethanol intake, the pattern of weight gain as well as the absolute weight gain, and hormone levels. As noted above, we have found that female rodents drink less alcohol than male rodents (Table 4.6). Our findings differ from those of others, who have reported that female rodents drink more than male rodents...
Cardiogenic Brain Embolism
Stroke admission rates have been observed to be high among heavy drinkers 10 , Some studies also suggest that alcohol abuse may associate with ischemic stroke recurrence 11,12 . A study on recent alcohol intake showed that heavy drinking is an independent risk factor for most subtypes of ischemic stroke and particularly a risk factor for cardiogenic brain embolism 13 . Table 7.1 Previously published and new case histories illustrating several different mechanisms that could link alcohol abuse...
Baroreceptors
In this series of experiments, we addressed the question whether ethanol-evoked attenuation of the baroreflex bradycardic response is dependent on either or both sets of the baroreceptor afferents. In the first study, bilateral transection of the aortic nerves in the cervical region, Figure 21.1 Bar graphs showing that ethanol (0.1, 0.5 and 1.0 g kg) produces graded decreases in regression coefficient (baroreflex slopes beats min mmHg) in SO, but not in aortic barodenervated (ABD) rats. Values...
Development Of Ahmd
There have been many reasons postulated to explain the differences between males and females, in terms of sensitivity to alcohol-related medical consequences. Several of the reasons are briefly reviewed below. A more comprehensive review is published elsewhere 40 , Female alcoholics develop a multitude of symptoms more rapidly than male alcoholics during the first few years of drinking, a phenomenon which is refered to as 'telescoping' 41,42 , Lewis et al. examined the effect of other...
Baroreflexes
We have previously shown that systemically administered ethanol attenuated the bradycardic and depressor responses to stimulation of the aortic nerve in sinaortic denervated rats 36 , These findings provided indirect evidence of a possible ethanol-evoked impairment of the central pathways that mediate the baroreceptor reflex control ofheart rate. In a subsequent study, we examined the effects of microinjection of ethanol in some CNS sites that are possibly involved in the baroreceptor reflex...
Alcohol Abuse And Cardiovascular Disease
Although there is considerable evidence that moderate drinking protects against mortality and morbidity from coronary heart disease 21,22 , heavy consumption is shown to have deleterious cardiovascular effects. It exerts its adverse effects by increasing the risks of cardiomyopathy, hypertension, and stroke 23 , Chronic ethanol consumption has been linked to the prevalence of hypertension, which contributes to an increased incidence of stroke. Heavy drinkers have alO mmHg higher systolic blood...
Tobacco
Studies on interactions between alcohol and tobacco are most challenging, not only because of the complexity of the effects of either factor, but also because of many inherent methodological problems. Epidemiologic studies on alcohol and tobacco are prone to imprecision in measurements and various biases, their interactions thus being even harder to evaluate in a reliable and valid manner. Alcohol consumption and smoking are usually self-reported and the measurement of either habit is...
The Effect Modification Of Alcohol By Smoking
There are only two epidemiologic studies on the effect modification of alcohol by smoking and neither of them examines it in relation to the risk of stroke. In a Japanese cohort of 19,231 men, alcohol consumption and all-cause mortality had a J-shaped association in nonsmokers but not in smokers 78 , In a cross-sectional study of 5,312 German men and women, the rise in blood pressure associated with drinking was higher in smokers than in nonsmokers 79 , Some studies have instead examined the...
Conclusions
Two thirds of Americans report using alcohol and since social drinking is a potentially modifiable behavior, the relation between alcohol consumption and cardiovascular disease is a subject of considerable importance. Although the literature is not unanimous, evidence from large epidemiologic studies leads to the conclusion that moderate alcohol intake decreases risk of non-fatal and fatal CHD and ischemic stroke. The observed differences in the shape of the relationship between various studies...
Pancreas
Injury to the pancreas has important metabolic consequences, due to its central role in endocrinological and nutritional homeostasis. Susceptibility of pancreatic tissue to damage by ROS may be due to the relatively low activities of endogenous antioxidant enzymes such as glutathione peroxidase, and comparatively low cellular levels of ATC 93 , Certainly, pancreatic islet cells are profoundly sensitive to vitamin E deficiency, as reflected by reduced Mn-superoxide dismutase and increased...
Drinking patterns and beverage types
Drinking patterns have been studied surprisingly little. Yet, drinking patterns vary and are of obvious health relevance. The frequency of drunkenness, the frequency ofhangover and morning drinking have been found to be related to mortality from several causes 54 , Changes in drinking between years may influence mortality 9,55 . Most reports classify participants using a total consumption variable (e.g., drinks per day) based on estimates of customary drinking frequency and amount of alcohol...
Cardioprotective Effect Of Moderate Wine Drinking
There is evidence that moderate wine consumption protects against CAD. Two studies linked the beneficial effects of moderate drinking only to wine 13,14 , Red wine contains several flavonoids and phenolic compounds with significant antioxidant properties. The protection effects against atherogenesis suggested that antioxidants in wine might play a role through modification of LDLs 15 , However, it seems unlikely that the cardioprotective effects are due solely to the antioxidant properties of...
Function
As discussed elsewhere in this volume, quite a few epidemiological studies have examined the association between morbidity and mortality from CHD and moderate alcoholic beverage consumption, and an inverse association has been established in studies involving nearly a million subjects 29 , One example of such reports is a study of American Cancer Society volunteers, which showed that the rate of death from all cardiovascular diseases was 30-40 lower among men and women who consumed at least one...
Cocaine Cardiotoxicity
As cocaine abuse has become widespread, the number of cocaine related cardiovascular events, such as angina pectoris, myocardial ischemia and infarction, cardiac myopathy, left ventricular hypertrophy, and sudden death has increased substantially 1-15 , These occur in young subjects, a significant percentage of whom had no evidence of atherosclerotic coronary artery disease on subsequent angiography 10,11,18-21 . Twice as many men as women experience cocaine related cardiac ischemic events, at...
Alcoholic versus viral or idiopathic chronic dilated cardiomyopathy DCM
The most prevalent confusion with the alcoholic heart disease caused by thiamine and nutritional deficiency is with viral or idiopathic chronic DCM. Between 20 and 35 of all cases ofDCM are thought to occur because of excessive ethanol intake 25 , However, in both alcoholic and idiopathic chronic DCM, the clinical picture is similar. In the early stages of both categories of congestive heart failure, the patients often show some response to bedrest, salt restriction, diuretics, and digitalis....
Dependence Of Ethanolevoked Attenuation Of Baroreflex Sensitivity On The Ovarian Hormones
Very few studies dealt with the acute effects of ethanol on cardiovascular reflexes in the female population. Even when female subjects were included 27 , the small sample size did not permit conclusions of whether the action of ethanol on baroreflexes is sexually dimorphic. Our recent studies have demonstrated that ethanol causes a dose-related attenuation ofbaroreflex-mediated bradycardia in female rats 54 , even though the baseline baroreflex sensitivity was significantly lower in female...
Figures
4.1 Survival curves of cardiac deaths in male patients with alcoholic dilated cardiomyopathy DCM . Solid line indicates patients with alcoholic DCM and alcohol abstinence, large dashed line indicates patients with alcoholic DCM without abstinence and small dashed line indicates idiopathic DCM. Used with permission from Fauchier etal. European Heart J. 2000 21 306-314 37 4.2 Representative echocardiograms from control and ethanol-fed female rat 40 4.3 Representative echocardiograms from control...
