Short-term ingestion of purple grape juice improves FMD and reduces LDL susceptibility to oxidation in CAD patients. Improved endothelium-dependent vasodilation and prevention of LDL oxidation are potential mechanisms by which flavonoids in purple grape products may prevent cardiovascular events, independent of alcohol content.

This article provides an overview of current research on flavonoids as presented during a workshop entitled, "Flavonoids and Heart Health," held by the ILSI North America Project Committee on Flavonoids in Washington, DC, May 31 and June 1, 2005. Because a thorough knowledge and understanding about the science of flavonoids and their effects on health will aid in establishing dietary recommendations for bioactive components such as flavonoids, a systematic review of the science of select flavonoid classes (i.e., flavonols, flavones, flavanones, isoflavones, flavan-3-ols, anthocyanins, and proanthocyanidins) was presented. The objectives of the workshop were to 1) present and discuss current research on flavonoid intake and the relation between flavonoids and heart health; 2) develop information that could lead to expert consensus on the state-of-the-science of dietary intake of flavonoids on heart health; and 3) summarize and prioritize the research needed to establish the relations between specific flavonoids and heart health. Presentations included the basics of the biology of flavonoids, including the types and distribution in foods, analytical methodologies used to determine the amounts in foods, the bioavailability, the consumption patterns and potential biomarkers of intake, risk assessment and safety evaluation, structure/function claims, and the proposed mechanism(s) of the relation between certain flavonoids and heart health endpoints. Data presented support the concept that certain flavonoids in the diet can be associated with significant health benefits, including heart health. Research gaps were identified to help advance the science.

SUMMARY In 35 open chest anesthetized dogs coronary and aortic blood flow were measured with electromagnetic flowmeters while aortic and distal coronary blood pressure and an epicardial ECG were recorded. A fixed amount of stenosis (60-80%) was produced in the coronary artery by an externally applied plastic cylinder. In 24 of the 35 dogs the coronary blood flow showed cyclical reductions to near zero, with a sudden spontaneous return to near control levels. During reduced flow the epicardial ECG showed ST-segment depression suggestive of ischemia, and ventricular premature beats were often noted. Six animals died acutely during episodes of reduced flow.MANY STUDIES OF MYOCARDIAL INFARCTION AND SUDDEN DEATH from coronary heart disease have been reported. The significance of acute occlusive thrombi as a precipitating cause is widely debated.' 2 Acute coronary occlusion by thrombi were found in 21%' to 88%4 of those infarcted hearts examined at autopsy. These data vary with the investigative technique and material examined. In many patients with coronary artery disease and sudden death no acute thrombus or other mechanism for producing acute coronary insufficiency is demonstrated at post mortem examination and an episode of transient ischemia precipitating arrhythmia is often postulated.Platelet aggregation is involved in the formation of arterial thrombi and is not prevented by coumarin or heparin anticoagulant therapy.5 Mechanical damage of platelets can induce platelet aggregation in vitro6 and thrombosis occurs in areas of turbulent flow.7 It has been postulated that the turbulent flow produced at the sites of atherosclerotic plaques may play a role in thrombus formation by inducing platelet aggregation.' It has also been postulated that sudden coronary death may result from platelet aggregates in the epicardial arteries of man.8'9We present experimental evidence here that a fixed stenosis in a narrowed coronary artery promotes periodic in vivo platelet aggregation which transiently increases obstruction and decreases coronary blood flow. The possible significance of these observations to coronary disease in man is discussed.Material and Methods Thirty-five healthy adult mongrel dogs of both sexes were anesthetized with morphine sulfate (3 mg/kg) followed one hour later by sodium pentobarbital (30 mg/kg). Respiration was maintained using a positive pressure respirator, and the heart was exposed through a left thoracotomy at the fifth intercostal space in the usual fashion. After 35 mg/kg of aspirin were given intravenously the cyclical reductions in coronary blood flow were abolished and the in vitro platelet aggregations were reduced from a control of 62.1 ± 15 units (Born technique) to an average of 23.7 ± 12 units. Histologic sections of the narrowed coronary artery obtained when coronary flow was reduced show an amorphous mass in the lumen which was thought to be a platelet aggregate. Perhaps a similar process of platelet aggregation occurs in the stenosed coronary arteries in man, producing acute coronary...

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.

Coronary artery disease is responsible for much mortality and morbidity around the world. Platelets are involved in atherosclerotic disease development and the reduction of platelet activity by medications reduces the incidence and severity of disease. Red wine and grapes contain polyphenolic compounds, including flavonoids, which can reduce platelet aggregation and have been associated with lower rates of cardiovascular disease. Citrus fruits contain different classes of polyphenolics that may not share the same properties. This study evaluated whether commercial grape, orange and grapefruit juices, taken daily, reduce ex vivo platelet activity. In a randomized cross-over design, ten healthy human subjects (ages 26-58 y, five of each gender) drank 5-7.5 mL/(kg. d) of purple grape juice, orange juice or grapefruit juice for 7-10 d each. Platelet aggregation (whole blood impedance aggregometry, Chronolog Model #590) at baseline was compared to results after consumption of each juice. Drinking purple grape juice for one week reduced the whole blood platelet aggregation response to 1 mg/L of collagen by 77% (from 17.9 +/- 2.3 to 4.0 +/- 6.8 ohms, P = 0.0002). Orange juice and grapefruit juice had no effect on platelet aggregation. The purple grape juice had approximately three times the total polyphenolic concentration of the citrus juices and was a potent platelet inhibitor in healthy subjects while the citrus juices showed no effect. The platelet inhibitory effect of the flavonoids in grape juice may decrease the risk of coronary thrombosis and myocardial infarction.

Background-Moderate red wine consumption is inversely associated with coronary ischemia, and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events. Acute cardiac events are also associated with decreased platelet-derived nitric oxide (NO) release. In this study, the effects of PGJ and PGJ-derived flavonoids on platelet function and platelet NO production were determined. Methods and Results-Incubation of platelets with dilute PGJ led to inhibition of aggregation, enhanced release of platelet-derived NO, and decreased superoxide production. To confirm the in vivo relevance of these findings, 20 healthy subjects consumed 7 mL · kg Ϫ1 · d Ϫ1 of PGJ for 14 days. Platelet aggregation was inhibited after PGJ supplementation, platelet-derived NO production increased from 3.5Ϯ1.2 to 6.0Ϯ1.5 pmol/10 8 platelets, and superoxide release decreased from 29.5Ϯ5.0 to 19.2Ϯ3.1 arbitrary units (PϽ0.007 and PϽ0.05, respectively). ␣-Tocopherol levels increased significantly after PGJ consumption (from 15.6Ϯ0.7 to 17.6Ϯ0.9 mol/L; PϽ0.009), and the plasma protein-independent antioxidant activity increased by 50.0% (PϽ0.05). Last, incubation of platelets with select flavonoid fractions isolated from PGJ consistently attenuated superoxide levels but had variable effects on whole-blood aggregation, platelet aggregation, and NO release. Conclusions-Both in vitro incubation and oral supplementation with PGJ decrease platelet aggregation, increase platelet-derived NO release, and decrease superoxide production. These findings may be a result of antioxidant-sparing and/or direct effects of select flavonoids found in PGJ. The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol consumption, in cardiovascular disease. (Circulation. 2001;103:2792-2798.)

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IntroductionEndothelium-derived relaxing factor is important for vascular homeostasis and possesses qualities that may modulate vascular injury, including vasodilation, platelet inhibition, and inhibition of smooth muscle proliferation. S-nitrososerum albumin is a naturally occurring adduct of nitric oxide (NO) with a prolonged biologic half-life and is a potent vasodilator and platelet inhibitor. Given the avidity of serum albumin for subendothelial matrix and the antiproliferative effects of NO, we investigated the effects of locally delivered S-nitroso-bovine serum albumin (S-NO-BSA) and a polythiolated form of bovine serum albumin (pS-BSA) modified to carry several S-nitrosothiol groups (pS-NO-BSA) on neointimal responses in an animal model of vascular injury.Locally delivered S-NO-BSA bound preferentially to denuded rabbit femoral vessels producing a 26-fold increase in local concentration compared with uninjured vessels (P = 0.029). pS-NO-BSA significantly reduced the intimal/medial ratio (P = 0.038) and did so in conjunction with elevations in platelet (P < 0.001) and vascular cGMP content (P < 0.001). pS-NO-BSA treatment also inhibited platelet deposition (P = 0.031) after denuding injury. Comparison of BSA, S-NO-BSA, pS-NO-BSA, and control revealed a dose-response relationship between the amount of displaceable NO delivered and the extent of inhibition of neointimal proliferation at 2 wk (P < 0.001).Local administration of a stable protein S-nitrosothiol inhibits intimal proliferation and platelet deposition after vascular arterial balloon injury. This strategy for the local delivery of a long-lived NO adduct has potential for preventing restenosis after angioplasty. (J. Clin. Invest. 1995Invest. . 96:2630Invest. -2638