Antithrombotic Diet Discussion Group | Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University

Kobe Gakuin University > Faculty of Nutrition > Laboratory of Physiology > Antithrombotic Diet Discussion Group

ANTITHROMBOTIC DIET DISCUSSION GROUP

1.Office

Laboratory of Physiology, Faculty of Nutrition, Kobe Gakuin University, Kobe, Japan
Junichiro Yamamoto

2.Start

Founded in January 2004 by Professor Junichiro Yamamoto PhD FRCPath

3.Aim

Thrombotic diseases such as stroke, myocardial infarction etc have been increasing not only in the aged but even in the young. Many factors are involved in the increase but undoubtedly change in diets is one of most important factors. Many studies have been done on “diet and thrombotic disease”. However, the guideline of dietary intake has been often forced to change. We have concluded to give some contribution in establishing the guideline to prevent thrombotic diseases. For this, firstly we have tried to find the most suitable tests. As we succeeded to select the tests, we have investigated to screen foods with antithrombotic activity and realized that the activity is different from varieties/accessions in even the same species. Further, we cannot eat experimentally demonstrated foods with antithrombotic activity unless corporation of researchers, farmers, food processing companies, nutritionists and medical doctors exists. “Antithrombotic Diet Discussion Group” consists of these people.

In more detail.
On the course of selecting foods with antithrombotic activity, we have noticed that we should pay much attention to “variety or accession, not just species”. At present most researchers/nutritionists are interested in nutritional components, especially content of polyphenolics and antioxidant activity. However, foods contain not only effective components but also components which scavenge their activity. “Is it true that foods with much polyphenolics and antioxidant activity are beneficial? Apart from supplements, we eat whole foods such as fruits and vegetables containing antioxidants and polyphenolics. In order to assess antithrombotic activity of whole foods, antithrombotic activity of whole foods has to be assessed by animal experiments at least. Surprisingly there are little publication which demonstrates significantly positive correlation between polyphenolics/ antioxidant contents and antithrombotic activity. There are publications which demonstrate that some purified polyphenolics and antioxidants are antithrombotic. We have demonstrated that positive correlation exists in some case but not in other case, indicating that the contents of polyphenolics and antioxidants in whole foods cannot be good indicators.

“Antithrombotic Diet Discussion Group” assesses antithrombotic activity of whole foods by shear-induced platelet reactivity/thrombolysis test called Global Thrombosis Test (Formerly Gorog Thrombosis Test) in vitro, subsequently; antithrombotic activity is assessed by helium-neon laser-induced thrombosis test (in vivo) after oral administration of foods. Heat resistance is also tested because of expected cooking and food processing.

After selecting foods with antithrombotic activity, there foods have to be harvested, sold and be served on the dish. In order to perform the aim, farmers, food processing companies and so on have to share a role. In addition, medical doctors and co-medical workers are also essential to assess thrombotic status of people not only patients bu healthy persons and to give nutritional advices to them. Members of “Antithrombotic Diet Discussion Group” exchange their information. This group might give additional benefits to agriculture and food industry.

4.Members

Researchers, clinicians, nurses, dietitians, pharmacists, farmers and businessman etc

5.Publication relating antithrombotic foods (mainly from Kobe Gakuin University)

35. Aki Naemura, Mayumi Ura, Tsutomu Yamashita, Ryo Arai and Junichiro Yamamoto. Long-term intake of rosemary and common thyme herbs inhibits experimental thrombosis without prolongation of bleeding time. Thrombosis Research 2008; 122: 517-522.
(http://www.ncbi.nlm.nih.gov/pubmed/18378282)

Dry powdered common thyme and rosemary which were demonstrated to have antithrombotic activity were given mice for 3 month and thrombotic status and bleeding time were assessed by He-Ne laser-induced mouse carotid artery thrombosis test (in vivo) and tail cut bleeding test (in vivo). These decreased thrombotic status but did not enhance bleeding time.

34. Taomoto K, Ohnishi H, Kuga Y, Nakashima K, Ichioka T, Kubota H, Kodama Y, Tominaga T, Hayashi M, Tanaka H, Yamashita T, Yamamoto J: Platelet Reactivity monitoring of patients with cerebral infarction－Platelet function and spontaneous thrombolytic activity by Gorog Thrombosis Test (GTT). The 13th European Congress of Neurosurgery MEDIMOND S.r.l. 2007; 537-543.

This is the first clinical report on thrombotic status of stroke patients assessed by Gorog Thrombosis Test. Platelet reactivity was significantly enhanced and spontaneous thrombolytic activity was suppressed at the attack of stroke. Enhanced platelet reactivity and suppressed spontaneous thrombolytic activity were gradually normalized by medication.

33. Yamamoto J, Naemura A, Ijiri Y, Ogawa K, Suzuki T, Shimada Y, Giddings JC: The antithrombotic effects of carrot filtrates in rats and mice. Blood Coagul Fibrinolysis. 2008 Dec;19(8):785-92.
(http://www.ncbi.nlm.nih.gov/pubmed/19002045)

and

32. Yamamoto J, Naemura A, Ijiri Y, Ogawa K, Suzuki T, Shimada Y: Testing various vegetables for anti-thrombotic effect: II. Carrots. XIV International Symposium on Atherosclerosis (June 2006, Rome, Italy)

Antithrombotic activity of juice from 15 varieties of carrots was screened by Gorog Thrombosis Test (in vitro), followed by He-Ne laser-induced mouse carotid artery thrombosis test (in vivo). Effect on platelet reactivity and spontaneous thrombolytic activity was different from variety to variety, some enhancing, some inhibiting and some no effect (in vitro). It was also demonstrated that effect on thrombosis in vivo was determined by the balance between activity on platelet reactivity and spontaneous thrombolytic activity. One variety showed strong antithrombotic activity and this activity was heat stable. This is a joint project with Sakata Seed Corporation, Kakegawa, Japan

31. Yamamoto J, Naemura A, Ura M, Ijiri Y, Yamashita T, Kurioka A, Koyama A: Testing various fruits for anti-thrombotic effect: I. Mulberries. Platelets 2006; 17: 555-564.
(http://www.informaworld.com/smpp/content~content=a762355523~db=all~order=page)

Antithrombotic activity of juice from 11 varieties of mulberry was screened by Gorog Thrombosis Test (in vitro), followed by He-Ne laser-induced mouse carotid artery thrombosis test (in vivo). Effect on platelet reactivity and spontaneous thrombolytic activity was different from variety to variety, some enhancing, some inhibiting and some no effect (in vitro). It was demonstrated that effect on thrombosis in vivo was determined by the balance between activity on platelet reactivity and spontaneous thrombolytic activity. This is a joint project with National Agriculture and Bio-oriented Research Organization, Japan

30. Naemura A, Ohira H, Ikeda M, Koshikawa K, Ishii H, Yamamoto J: An experimentally antithrombotic strawberry variety is also effective in humans. Pathophysiology of Haemostasis and Thrombosis 2006; 35: 398-404.
(http://www.ncbi.nlm.nih.gov/pubmed/17230043?ordinalpos=1&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Two kinds of strawberry juice from Nohime with antithrombotic activity and Nyoho without the activity and water were orally given to healthy volunteers. Thrombotic state was assessed by Gorog Thrombosis Test 2 hour after drinking (ex vivo). Water and Nyoho did not affect platelet reactivity and spontaneous thrombolytic activity. But Nohime inhibited platelet reactivity, but no effect on spontaneous thrombolysis. In addition, antithrombotic activity of Nohime was demonstrated in different four fields in the same year and yearly difference was not found in the same field. This is a joint project with Gifu Prefectural Research Institute for Agricultural Sciences, Gifu, Japan

29. Sawashita N: Effect of protein and peptide on thrombotic tendency. Master's Thesis of Kobe Gakuin Graduate School of Nutrition 2004.

and

28. Sawashita N, Naemura A, Shimizu M, Morimatsu F, Ijiri Y, Yuguchi K, Yamamoto J: Effect of dietary vegetable and animal proteins on atherothrombosis in mice. Nutrition 2006; 22: 661-667.
(http://www.ncbi.nlm.nih.gov/pubmed/16567078?ordinalpos=1&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Effect of purified animal and vegetable proteins on thrombotic tendency was assessed by giving diets containing their proteins to mice for 3months and by He-Ne laser-induced mouse carotid artery thrombosis test. No difference was found between animal and vegetable proteins. In addition, diets containing same percentage of protein, lipid and carbohydrate prepared from pork, chicken and fish were given mice and thrombotic tendency was assessed 3 months after feeding. No significant difference was demonstrated. Soy bean did show antithrombotic activity in all 6 varieties examined. This activity is independent from the skin colour. And no significant correlation between antithrombotic activity and isoflavone content was demonstrated. This is a joint project with Nippon Meat Packers, Inc., Tsukuba, Ibaraki, Japan.

27. Iwasaki :Master's Thesis of Kobe Gakuin Graduate School of Nutrition 2006.

and

26. Iwasaki , Naemura A, Yamashita T, Yamamoto J: Antithrombotic activity of grapes. The 28th Japanese Society on Thrombosis and Hemostasis. 2005.

Antithrombotic activity of 27 red grape varieties and 19 white varieties was assessed. Unexpectedly, only one variety showed antithrombotic activity. Rest of them enhanced platelet reactivity regardless red or white. In addition, activity on platelet reactivity did not correlate with polyphenol contents and antioxidant activity. This is the result of fresh grape fruits but raised a question whether red wine is really antithrombotic. Antithrombotic activity of wines remains to be solved in the future.

25. Daisuke Ichiura, Aki Naemura, Mayumi Ura, Motoyuki Mori, Junichiro Yamamoto: Anti-Thrombotic Effect of Potato in Animal Experiments. Food 3 (Special Issue 2) 2009; 8-12, Global Science Books.

and

24. Ichiura D: Search of carbohydrate rich food varieties with antithrombotic activity. Master's Thesis of Kobe Gakuin Graduate School of Nutrition 2005.

Antithrombotic activity of potato varieties was assessed by two methods. 1) Potato powders from 10 varieties were fed to mice for 3 months and their antithrombotic activity was assessed by He-Ne laser-induced mouse carotid artery thrombosis test. One variety showed the strongest antithrombotic activity among them. 2) Raw potato was grated and liquid was squeezed and collected. Antithrombotic activity of liquid was assessed by shear-induced platelet reactivity/thrombolysis test, Gorog Thrombosis Test, followed by He-Ne laser-induced mouse carotid artery thrombosis test after oral administration. Two varieties showed the strongest antithrombotic activity and this activity was heat-stable. Three varieties are cultivated by farmers and sold on the market. Farmers and consumers visit antithrombotic potato field, Laboratory of Physiology, Kobe Gakuin University (1, 2, 3).

23. Ijiri Y, Naemura A, Yamashita T, Ikarugi H, Meguro S, Tokimitsu I, Yamamoto J: Mechanism of the antithrombotic effect of dietary diacylglycerol in atherogenic mice. Pathophysiology of Haemostasis and Thrombosis 2006; 35: 380-387.
(http://www.ncbi.nlm.nih.gov/pubmed/17230040?ordinalpos=1&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

and

22. Ijiri Y, Naemura A, Yamashita T, Meguro S, Watanabe H, Tokimitsu I, Yamamoto J: Dietary diacylglycerol extenuates arterial thrombosis in apoE and LDLR deficient mice. Thrombosis Research 2006; 117: 411-417.
(http://www.ncbi.nlm.nih.gov/pubmed/15885757?ordinalpos=6&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Diacyl glycerol showed antithrombotic effect and this effect was due to endothelial function, as shown using laser-induced mouse carotid artery thrombosis test and experimental hyperemia. This is a joint project with Kao Co Ltd.

21. Naemura A, Mitani T, Ijiri Y, Tamura Y, Yamashita T, Yamamoto J: Anti-thrombotic effect of strawberries. Blood Coagulation & Fibrinolysis 2005; 16(7): 501-509.
(http://www.ncbi.nlm.nih.gov/pubmed/16175010?ordinalpos=2&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

The strongest antithrombotic activity was demonstrated in 3 varieties out of 17. The activity was heat-stable. This is a joint project with National Agriculture and Bio-oriented Research Organization, National Agricultural Research Centre for Kyushu Okinawa Region, Fukuoka, Japan

20. Yamashita T, Oda E, Sano T, Yamashita T, Ijiri Y, Giddings JC, Yamamoto J: Varying the ratio of dietary n-6/n-3 polyunsaturated fatty acid alters the tendency to thrombosis and progress of atherosclerosis in apoE-/-・LDLR-/- double knockout mouse. Thrombosis Research 2005; 116(5): 393-401.
(http://www.ncbi.nlm.nih.gov/pubmed/16122552?ordinalpos=1&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Diets with different ratio of n-6/n-3 were given to apoE-/-・LDLR-/- double knockout mice and thrombotic tendency was assessed. n-3 fatty acid rich diet showed antithrombotic effect.

19. Yamamoto J, Yamada J, Naemura A, Yamashita T, Arai R: Testing various herbs for anti-thrombotic effect. Nutrition 2005; 21(5): 580-587.
(http://www.ncbi.nlm.nih.gov/pubmed/15850964?ordinalpos=6&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Antithrombotic herbs were screened among various species. Common thyme and rosemary showed strong heat-stable antithrombotic activity. This is a joint project with S and B Foods Inc.

18. Sano T, Oda E, Yamashita T, Naemura A, Ijiri Y, Yamakoshi J, Yamamoto J: Anti-thrombotic effect of proanthocyanidin, a purified ingredient of grape seeds. Thrombosis Research 2005; 115(1-2): 115-121.
(http://www.ncbi.nlm.nih.gov/pubmed/15567462?ordinalpos=4&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Proanthocyanidin purified from grapes showed antithrombotic effect, as measured using laser-induced carotid artery thrombosis test. This is a joint project with Kikkoman Corporation, Japan.

17. Yamada K, Naemura A, Sawashita N, Noguchi Y, Yamamoto J: An onion variety has natural antithrombotic effect as assessed by thrombosis/thrombolysis models in rodents. Thrombosis Research 2004; 114(3): 213-220.
(http://www.ncbi.nlm.nih.gov/pubmed/15342218?ordinalpos=3 &itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

Antithrombotic onion varieties was assessed using in vitro and in vivo methods. TOYOHIRA showed strong activity and this activity was heat stable at 100C. This is the second study on screening antithrombotic fruits and vegetables in our laboratory. This is a joint project with National Agricultural Research Center for Hokkaido region, Japan.

16. Fukao H, Ijiri Y, Miura M, Hashimoto M, Yamashita T, Fukunaga C, Oiwa K, Kawai Y, Suwa M, Yamamoto J: Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagulation and Fibrinolysis 2004; 15(6): 441-446.
(http://www.ncbi.nlm.nih.gov/pubmed/15311151?ordinalpos=1&itool= EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

t-resveratrol purified from grapes showed antithrombotic effect, as measured using laser-induced carotid artery thrombosis test. This is a joint project with Sunstar Inc, Japan.

15. Yamashita T, Oda E, Giddings JC, Yamamoto J: The effect of dietary BNPP(Bacillus Natto Productive Protein) on in vivo endogenous thrombolysis. Pathophysiology of Haemostasis and Thrombosis 2003; 33(3): 138-143.
(http://content.karger.com/ProdukteDB/produkte.asp?Aktion= ShowAbstract&ArtikelNr=77822&Ausgabe=230056&ProduktNr=224034)

Spontaneous thrombolysis was assessed in rat mesenteric microvessels after long term intake of a kind of Nattokinase. Spontaneous thrombolysis was accelerated. This is a joint project with Daiwayakuhin Co Ltd.

14. Yamamoto J, Taka T, Yamada K, Ijiri Y, Murakami M, Hirata Y, Naemura A, Hashimoto M, Yamashita T, Oiwa K, Seki J, Suganuma H, Inakuma T, Yoshida T: Tomatoes have natural anti-thrombotic effects. British Journal of Nutrition 2003; 90(6): 1031-1038.
(http://www.ncbi.nlm.nih.gov/pubmed/14641962?ordinalpos=7&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Antithrombotic tomato varieties was screened with Haemostatometer (in vitro), followed by a laser-induced carotid artery thrombosis test (in vivo) after oral administration. A red Kagome 942 (Trade name: Kinukohime) showed the strongest antithrombotic activity. This activity was heat stable. This is the first paper screening antithrombotic fruits and vegetables among our papers. This is a joint project with National Cardiovascular Center, Japan, National Agricultural Research Organization, Japan and Kagome Co Ltd, Japan.

13. Sano T, Oda E, Yamashita T, Shiramasa H, Ijiri Y, Yamashita T, Yamamoto J: Anti-thrombotic and antiatherogenic effects of partially defatted flaxseed meal, using a laser-induced carotid artery thrombosis test in apolipoprotein E and low-density lipoprotein receptor deficient mice. Blood Coagulation and Fibrinolysis 2003; 14(8): 707-712.
(http://www.bloodcoagulation.com/pt/re/bcf/abstract.00001721-200312000-00003.htm;jsessionid=HKvp0cKX9J11XLGQ9phMnTBfZC6gn5jPFWzqZC6GXqzvj2dwCLJJ!-1297386286!181195629!8091!-1)

Antithrombotic and antiatherogenic activities of leavings of flaxseed produced after oil preparation were demonstrated using a laser-induced carotid artery thrombosis test in apolipoprotein E and low-density lipoprotein receptor deficient mice. This is a joint project with Yoshihara Oil Mill Ltd, Japan.

12. Yamamoto J, Kovacs IB: Review: Shear-induced in vitro haemostasis/ thrombosis tests: the benefit of using native blood. Blood Coagulation and Fibrinolysis 2003; 14(8): 697-702.
(http://www.bloodcoagulation.com/pt/re/bcf/abstract.00001721-200312000-00001.htm;jsessionid=HKvp0cKX9J11XLGQ9phMnTBfZC6gn5jPFWzqZC6GXqzvj2dwCLJJ!-1297386286!181195629!8091!-1)

This review paper describes the benefit of the test using non-anticoagulated blood and platelet activation with shear force.

11. Yamamoto J, Yamashita T, Ikarugi H, Taka T, Hashimoto M, Ishii H, Watanabe S, Kovacs IB: Gorog Thrombosis Test: A global in vitro test of platelet function and thrombolysis. Blood Coagulation and Fibrinolysis 2003; 14: 31-39.
(http://www.ncbi.nlm.nih.gov/pubmed/12544726?ordinalpos=7&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

This is the first paper which describes on an innovative, compact and bed-side aimed test called Global Thrombosis Test GTT which can assess platelet reactivity and thrombolytic activity sequentially with high reproducibility.

10. Yamamoto J. Q and A on thrombosis: Q44 About foods with antithrombotic activity. Thrombosis and Circulation 2001; 9: 422-424. (Japanese)

A notice on our study how to screen foods with antithrombotic activity.

9. Ijiri Y , Miura M, Hashimoto M, Taka T, Kubota A, Watanabe S, Oiwa K, Fukunaga C, Okuda T, Yamamoto J: Effect of isoflavone aglycone on thrombotic tendency using apoE-/-・LDLR-/- double knockout mice carotid artery method. Soyprotein Research 2001; 4: 107-115. (Japanese)

Isoflavone aglycone showed antithrombotic ativity demonstrated using He-Ne laser-induced mice carotid artery thrombosis method.

8. Ijiri Y , Miura M, Hashimoto M, Fukunaga C, Watanabe S, Kubota A, Oiwa K, Okuda T, Yamamoto J: A new model to evaluate the diet-induced prothrombotic state, using He-Ne laser-induced thrombogenesis in the carotid artery of apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagulation and Fibrinolysis 2002; 13: 497-504.
(http://www.ncbi.nlm.nih.gov/pubmed/12192301?ordinalpos=5&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

This has demonstrated that Western-style diet is prothrombotic compared with Japanese-style diet using low density lipoprotein receptor and apolipoprotein E double knockout mice and He-Ne laser-induced carotid artery mice model.(1, 2) This is important paper to study effect of diet on thrombotic tendency.

7. Yamamoto J (Main Organiser): Abstracts of papers presented at the Japanese-European Kobe Symposium on Thrombosis, 6-7 November 2000, Kobe Gakuin University, Kobe, Japan. Platelets 2001; 12: 172-186.
(http://www.informaworld.com/smpp/title~content=g713442163~db=all~tab=toc~order=page)

The Japanese-European Kobe Symposium on Thrombosis
(http://www.informaworld.com/smpp/title~content=g713442163~db=all)

6. Yamamoto J, Sasaki Y, Yamashita T, Taka T, Ikarugi H. A platelet reactivity test which uses non-anticoagulated blood - assessment of an in vitro test which reflects platelet reactivity in vivo. Japanese Journal of Thrombosis and Hemostasis. 2001; 12: 11-16. (Japanese)

This is a review paper which describes that haemostatometry using non-anticoagulated blood and shear force to activate platelets is very useful.

5. Ariga T, Tsuji K, Seki T, Moritomo T, Yamamoto J: Antithrombotic and antineoplastic effects of phyto-organosulfur compounds. Bio Factors 2000; 13: 251-255.
(http://www.ncbi.nlm.nih.gov/pubmed/11237190?ordinalpos= 4&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum)

This has demonstrated antithrombotic mechanism of the component(s) containing sulfur of garlic using He-Ne laser-induced thrombosis method. This is a joint project with Professor Ariga T, Nihon University

4. Yamamoto J, Taka T, Nakajima S, Ueda M, Sugimoto E, Sasaki S, Muraki T, Seki J, Watanabe S: A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects. Platelets 1999; 10: 178-184.
(http://www.informaworld.com/smpp/content~content=a713690673~db=all~order=page)

We made a Haemostatometer in our laboratory with help of Dr Kovacs and Dr Gorog. This is the first and important paper for us.

3. Ratnatunga CP, Edmondson SF, Rees GM, Kovacs IB: High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation. Circulation 1992; 85: 1077-1082.
(http://www.ncbi.nlm.nih.gov/pubmed/1537105?ordinalpos=2&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Dr Kovacs (St Bartholomew's Hospital, London) and Dr Gorog (The William Harvey Research Institute, London) developed a new instrument called Haemostatometer which enabled assessment of platelet reactivity after activation with shear force. This is an important and representative paper among a series of Haemostatometry studies. Highlight of this method is not to use anticoagulant and sequentially can assess platelet reactivity, coagulation activity and thrombolytic activity under flow condition. High dose aspirin inhibited platelet reactivity ex vivo.

2. Yamamoto J, Iizumi H, Hirota R, Shimonaka K, Nagamatsu Y, Horie N, Morita S: Effect of physical training on thrombotic tendency in rats: Decrease in thrombotic tendency measured by the He-Ne laser-induced thrombus formation method. Haemostasis 1989; 19: 260-265.
(http://www.ncbi.nlm.nih.gov/pubmed/2777138?ordinalpos=53&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

This is the first paper in which He-Ne laser technique was introduced and used in our laboratory. Aerobic exercise prevented prothrombotic state as assessed by the technique and rat mesenteric microvessels.

1.Kovacs IB, Tigyi-Sebes A, Trombitas K, Gorog P: Evans blue: an ideal energy-absorbing material to produce intravascular microinjury by HE-NE gas laser. Microvascular Research 1975; 10: 107-124.
(http://www.ncbi.nlm.nih.gov/pubmed/1143094?ordinalpos=70&itool=
EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)

Immediately after development of helium-neon (He-Ne) laser, Dr Kovacs (Semmelweis Medical College, Budapest) and Dr Gorog (EGYT Chemical Works, EGYT Chemical Works) developed an innovative apparatus which forms thrombi in microvessels of rats and mice by irradiating with He-Ne laser. This San Francisco Zoo poster gave them a hint to develop a new laser-induced thrombosis system. Blue colored balloon inside a transparent non-color balloon was broken by irradiation with a red He-Ne laser, but not outside non-color balloon. Blue dye absorbed laser energy and generated heat causing rupture. They injected Evans blue dye into animals and microvessels were irradiated with He-Ne laser, resulting in endothelial injury, followed by thrombus formation. This technique is very important because this technique is always used to demonstrate foods with or without antithrombotic activity in vivo after oral administration.

Antithrombotic Diet Discussion Group