Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries.

BACKGROUND Moderate daily consumption of alcoholic beverages is a negative risk factor for the development of atherosclerosis and coronary artery disease (CAD), especially in France and other Mediterranean areas where red wine is regularly consumed with meals. Platelets contribute to the development of atherosclerosis, CAD, and acute arterial thrombus formation. METHODS AND RESULTS Anesthetized dogs were prepared with the Folts model of mechanically stenosed coronary arteries and intimal damage. Periodic acute platelet-mediated thrombus formation occurred, causing cyclic flow reductions (CFRs) in coronary blood flow. The CFRs were eliminated by the administration of 1.62 +/- 1.12 mL/kg red wine intravenously (IV) and 4.0 mL/kg intragastrically (IG). The CFRs were abolished by 2.04 +/- 1.42 mL/kg of grape juice IV and 10 mL/kg IG. White wine did not have significant results in eliminating the CFRs, either IV (2.0 mL/kg) or IG (4.0 mL/kg), decreasing the slopes of the CFRs only slightly. CONCLUSIONS Pure ethanol has been shown to inhibit platelet aggregation in vitro, ex vivo, and in vivo, although a blood alcohol content (BAC) of > or = 0.2 g/dL is usually required. The BAC of dogs administered the red wine-saline solution intravenously was 0.028 g/dL, much less than is usually necessary for platelet inhibition with pure ethanol. Because red wine and grape juice, but not white wine, abolished the CFRs, this suggests there are compounds present in red wine and grape juice that are not present or are present in a lower concentration in white wine. Wine and grape juice contain a wide variety of naturally occurring compounds, including fungicides, tannins, anthocyanins, and phenolic flavonoids (including flavonols and flavones). These compounds have shown platelet inhibition in vitro by a variety of proposed mechanisms. Perhaps the biological activity of these compounds can explain the platelet-inhibitory properties of red wine and grape juice that are observed without high levels of ethanol.

[1]  W. Willett,et al.  Moderate alcohol intake, increased levels of high-density lipoprotein and its subfractions, and decreased risk of myocardial infarction. , 1993, The New England journal of medicine.

[2]  J. Maffrand,et al.  Combined ADP and Thromboxane A2 Antagonism Prevents Cyclic Flow Variations in Stenosed and Endothelium‐Injured Arteries in Nonhuman Primates , 1993, Circulation.

[3]  J. Stamler,et al.  Sodium Nitroprusside, an Endothelium‐Derived Relaxing Factor Congener, Increases Platelet Cyclic GMP Levels and Inhibits Epinephrine‐Exacerbated In Vivo Platelet Thrombus Formation in Stenosed Canine Coronary Arteries , 1993, Journal of cardiovascular pharmacology.

[4]  E. Parks,et al.  Inhibition of oxidation of human low-density lipoprotein by phenolic substances in red wine , 1993, The Lancet.

[5]  A. Klatsky,et al.  Alcoholic beverage choice and risk of coronary artery disease mortality: do red wine drinkers fare best? , 1993, The American journal of cardiology.

[6]  S. Renaud,et al.  Wine, alcohol, platelets, and the French paradox for coronary heart disease , 1992, The Lancet.

[7]  J. Cutler,et al.  Alcohol Use and Mortality from Coronary Heart Disease: The Role of High-Density Lipoprotein Cholesterol , 1992, Annals of Internal Medicine.

[8]  R. Langer,et al.  Lipoproteins and Blood Pressure as Biological Pathways for Effect of Moderate Alcohol Consumption on Coronary Heart Disease , 1992, Circulation.

[9]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[10]  S. Bergmann,et al.  Inhibition of cyclic flow variations and reocclusion after thrombolysis in dogs by a novel antagonist of platelet-activating factor. , 1991, Journal of the American College of Cardiology.

[11]  T. Ulbricht,et al.  Coronary heart disease: seven dietary factors , 1991, The Lancet.

[12]  V. Turitto,et al.  Effect of aspirin and epinephrine on experimentally induced thrombogenesis in dogs. A parallelism between in vivo and ex vivo thrombosis models. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[13]  J. Folts.  An in vivo model of experimental arterial stenosis, intimal damage, and periodic thrombosis. , 1991, Circulation.

[14]  L. Bush,et al.  In vivo models of arterial thrombosis and thrombolysis , 1990, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[15]  D. Mikhailidis,et al.  The effect of ethanol on platelet function and vascular prostanoids. , 1990, Alcohol.

[16]  P. Ribereau-gayon,et al.  Effect of the consumption of alcohol, white wine and red wine on platelet function and serum lipids , 1990 .

[17]  T. Ockhuizen,et al.  Effects of moderate alcohol consumption on platelet aggregation, fibrinolysis, and blood lipids. , 1987, Metabolism: clinical and experimental.

[18]  J. Folts,et al.  Relative effects of cigarette smoke and ethanol on acute platelet thrombus formation in stenosed canine coronary arteries. , 1988, Cardiovascular research.

[19]  R. Gryglewski,et al.  On the mechanism of antithrombotic action of flavonoids. , 1987, Biochemical pharmacology.

[20]  M. Criqui.  Alcohol consumption, blood pressure, lipids, and cardiovascular mortality. , 1986, Alcoholism, clinical and experimental research.

[21]  O'Rourke St,et al.  Inhibition of canine platelet aggregation by barbiturates. , 1986 .

[22]  R D Moore,et al.  Moderate Alcohol Consumption and Coronary Artery Disease: A REVIEW , 1986, Medicine.

[23]  A. Nanji.  Alcohol and ischemic heart disease: wine, beer or both? , 1985, International journal of cardiology.

[24]  J. Maclouf,et al.  Interference of some flavonoids and non-steroidal anti-inflammatory drugs with oxidative metabolism of arachidonic acid by human platelets and neutrophils. , 1985, Biochimica et biophysica acta.

[25]  W. Campbell,et al.  Effects of the selective thromboxane synthetase inhibitor dazoxiben on variations in cyclic blood flow in stenosed canine coronary arteries. , 1984, Circulation.

[26]  M J Davies,et al.  Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. , 1984, The New England journal of medicine.

[27]  M. Steiner,et al.  Modification of platelet function and arachidonic acid metabolism by bioflavonoids. Structure-activity relations. , 1984, Biochemical pharmacology.

[28]  M. Silver,et al.  A Quick Method for Screening Platelet Dysfunctions Using the Whole Blood Lumi-Aggregometer , 1984, Thrombosis and Haemostasis.

[29]  M. Steiner,et al.  Inhibition in vitro of platelet aggregation and arachidonic acid metabolism by flavone. , 1984, Biochemical pharmacology.

[30]  G. Pozza.  Diet, diabetes, and atherosclerosis , 1984 .

[31]  J. Cazenave,et al.  Role of cyclic AMP in the inhibition of human platelet aggregation by quercetin, a flavonoid that potentiates the effect of prostacyclin. , 1982, Biochemical pharmacology.

[32]  W. Willett,et al.  Effects of beer, wine, and liquor in coronary deaths. , 1979, JAMA.

[33]  A. Qureshi,et al.  Quantitation of potential flavoring compounds in worts and beers by HPLC , 1979 .

[34]  J. M. Mansour,et al.  Structure/activity studies of flavonoids as inhibitors of cyclic AMP phosphodiesterase and relationship to quantum chemical indices. , 1979, Molecular pharmacology.

[35]  A. Cochrane,et al.  FACTORS ASSOCIATED WITH CARDIAC MORTALITY IN DEVELOPED COUNTRIES WITH PARTICULAR REFERENCE TO THE CONSUMPTION OF WINE , 1979, The Lancet.

[36]  M. Ruckstuhl,et al.  Flavonoids are selective cyclic GMP phosphodiesterase inhibitors. , 1979, Biochemical pharmacology.

[37]  V. L. Singleton,et al.  Phenolic substances in grapes and wine, and their significance. , 1969, Advances in food research. Supplement.