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Garlic extract prevents acute platelet thrombus formation in stenosed canine coronary arteries
Volume Number
117 4
Fig. 3. Follow-through of right coronary injection demonstrating flow to left pulmonary artery. A, Early phase demonstrating tortuosity of fistulous vessels. B, Later phasedemonstrating early filling of pulmonary artery. C, Final phasewith filling of distal left lower lobe pulmonary artery (compare with Fig. 4).
possible explanation for the pulmonary emboli is a decreasedcardiac output leading to venous stasis,phlebitis, thrombosis, and emboli. Shortly thereafter, with paroxysmal atrial fibrillation, systemic embolization from the left heart may result in partial loss of vision and other unrecognized systemic emboli. Certainly this explanation is speculative, but it seemsto provide a unifying hypothesis.While the hemodynamic manifestations may not be threatening in the reported case, higher flow in other patients potentially may result in adverse consequences. One cannot exclude the possibility that the coronary artery-to-pulmonary artery fistula causedimpaired cardiac function, but the left ventriculogram has the appearance of a cardiomyopathy and the patient had no significant peripheral signs of heart failure. Corrective surgery has been recommendedin the medical literature>9 but is not without complication. One series9reported a 23% complication rate in 43 older patients, with myocardial infarction in 7 5%and death in 7% . Consequently, we chose afterload reduction as the best initial treatment for this patient. REFERENCES
1. Keith JD, Rowe RD, Vlad P. Heart disease in infancy and childhood. 3rd ed. New York: MacMillan Publishing Co, 19781014. 2. Hobbs RE, Millit HD, Raghavan RV, Moddie DS, Sheldon WC. Coronary artery fistulae: a ten-year review. Cleve Clin Q 1982;49:191-7. 3. Klinke WP, Pepine CJ, Conti CR. Demonstration of an inadvertently created aorto-coronary venous anastomosis: evidence against the clinical effectiveness of retrograde coronary venous perfusion. Cathet Cardiovasc Diagn 1979;5:36770. 4. Siepser SL, Kaltman AJ, Mills N, Pughkern T, Fox AC. Coronary collateral flow after traumatic fistula between right
Brief
Communications
973
Fig. 4. Posteroanterior (A) and lateral (6) chest x-ray
films with (C) pulmonary arteriogram demonstrating absenceof flow to left lower lobe.
5. 6. 7. 8.
9.
coronary artery and right atrium. N Engl J Med 1972; 287~754-6. Lowe JE, Oldham HN, Sabiston DC. Surgical management of congenital coronary artery fist&s. Ann Surg 1981;194:37380. Bairn DS, Kline H, Silverman JF. Bilateral coronary artery to pulmonary artery fistulas. Circulation 1982;65:810-15. Upshaw CB Jr. Congenital coronary arteriovenous fistula: report of a case with an analysis of 73 reported cases. AM HEART J 1962;63:399-404. Gobel FL, Anderson CF, Baltaxe HA, Amplatz K, Wang Y. Shunts between the coronary and pulmonary arteries with normal origin of the coronary arteries. Am J Cardiol 1970;25:655-61. Liberthson RR, Sager K, Berkoben JP, Weintraub RM, Levine FH. Congenital coronary arteriovenous fistula: report of 13 patients, review of the literature, and delineation of management. Circulation 1979;59:849-54.
Garlic extract prevents acute platelet thrombus formation in stenosed canine coronary arteries Laurence W. V. DeBoer, MD, and John D. Folts, PhD. Madison,
Wis.
From the Wisconsin
Cardiology Hospital
and
Section, Clinics.
Department
of Medicine,
University
Supported by Grant No. HL29586-05 of the National Institutes Bethesda, Maryland, and by a Grant-in-Aid from the Wisconsin of the American Heart Association. Reprint University 53792.
requests: John of Wisconsin
D. Felts, Hospital,
of
of Health, Affiliate
PhD, H6/379 Clinical Science Center, 600 Highland Ave., Madison, WI
April
974
Brief
Communications
American
Coronary thrombi form at sites of atherosclerotic plaque rupture, ulceration, or erosion, and a variety of agents have been proposed’ to inhibit or prevent acute platelet thrombus formation in diseasedhuman coronary arteries. We have developed a dog model of coronary artery stenosis with intimal damage that exposes subintimal tissuesto circulating platelets. Platelets accumulate at the site of stenosisand platelet thrombi enlargeover time and then embolize distally, causing periodic cyclical reductions in coronary blood Aow.~This model is thought to mimic in some ways the patient with coronary artery disease.We used this model to investigate the effects of garlic, a “food” known to contain antiplatelet substances, on acute platelet thrombus formation and periodic reductions in coronary blood flow. We tested the hypothesis that if garlic possessedantiplatelet substancesit might prevent acute platelet thrombus formation and cyclic flow reductions (CFRs) in our model of canine coronary artery stenosisand thrombosis.2-4 Methods. Eight anesthetized, adult mongrel dogs of either sex (weighing 25 to 30 kg) were studied aspreviously described.3z4 The left thorax was opened,the pericardium was incised, and the heart wasexposed.The proximal 2 to 3 cm of the left circumflex coronary artery were dissectedfree of the epicardium and an electromagnetic flow probe wasplaced around the coronary artery and was monitored with a flow meter (Statham SP2202,Gould Inc. Cardiovascular Products, Oxnard, Calif.). Distal to the flow probe, an external mechanical coronary stenosis (75% diameter reduction) was produced by placing a Lexan constricting cylinder (Cadillac Plastic and Chemical Co., Milwaukee, Wise.) around the coronary artery.“m4 During 30 minutes of observation, periodic coronary CFRs developeddue to periodic acute platelet thrombus formation, followed by embolization (Fig. 1). After the control observation, garlic wasgiven. Extract of cooked garlic was obtained from a commercial source (McCormick Spice, Inc., Baltimore, Md.). Prior to administration, the extract of five cloves of garlic was diluted to 10 cc with saline and 10% alcohol and given slowly intravenously. Since the platelet inhibiting compounds in garlic, including ally1 disulfide and ally1 trisulfide, represent approximately
clRcuMFLEx EPICAADIAL
1989
Heart Journal
0.3% to 0.4% of the total, this dose contained approximately 3 to 4 mg of active compounds.5We have previously determined3that this small amount of ethanol doesnot affect hemodynamic or hemostatic function in the dog. Heart rate, arterial blood pressure, and coronary blood flow were continuously monitored. Twenty minutes after the garlic had beengiven, epinephrine (0.4 pg/kg/min) was infused for 15 minutes to seeif the acute platelet thrombus formation would be renewed as we have previously shown.4 Results. In all eight dogs, acute platelet thrombus formation followed by distal embolization occurred, producing cyclical reductions in coronary blood flow (CFRs). The CFRs occurred at a frequency of 9 +- 3 per hour (Fig. 1). When garlic extract containing approximately 3 to 4 mg of active substance5-an amount that would flavor food strongly-was administered, there was no change in heart rate, blood pressure, or mean coronary blood flow, but CFRs due to acute platelet thrombus formation were abolished in seven of the eight dogs studied and diminished in the last. Whole blood platelet counts were 270,000/~1? 40,000/~1before and 255,000/~1+- 44,000/~1 after garlic administration (NS). In the sevendogsin which CFRs had been abolishedby garlic, platelet thrombus formation wasrenewed in five of the seven dogs by epinephrine administration (Fig. 2). Epinephrine infusion resulted in an increase in mean blood pressure from 110 t 19 to 128 -+ 16 mm Hg (p < 0.05), with a reflex slowingof the heart rate that was not statistically significant. Epinephrine overcame the antithrombotic effects of garlic, suggestingthat epinephrine exacerbatesplatelet thrombus formation by mechanisms other than those inhibited by garlic extract. The data are presented as mean it SD. Comments. The partially stenosed canine coronary artery with moderate intimal damageprovides a reasonable in vivo model to determine the effects of various interventions on the interaction of the vesselwall, platelets, and intraarterial platelet thrombi.2-4The CFRs following mechanicalstenosisof a coronary artery have been directly correlated with the size of the dislodged platelet thrombus collected downstream and are not due to vaso-
BED EGG
ml /min
Fig. 1. On the left, cyclical reductions in coronary blood flow (CFRs) due to acute intracoronary platelet thrombus formation are noted. On the right, the CFRs are abolished with intravenous garlic extract.
Volume
117
Number
4
Brief
Communications
975
CIRCUMFLEX BED EPlCARDlAL EC6 AORTIC BLOOD PRESSURE mm Hg. C lRCUMFLEX BLOOD FLOW ml./min.
Fig. 2. On the left, the CFRs due to acute platelet thrombus formation have been abolishedby the garlic. However, in the center, CFRs are renewedby the infusion of epinephrine (marked with arrows).
spasm.2This dog model hasbeen suitable for demonstrating the antithrombotic effects of such clinically used antiplatelet drugs as aspirin’s4and other nonsteroidal antiinflammatory agents.2The role of nonpharmacologic “dietary” interventions on platelet function is potentially very important but not well understood. We have shown* that tobacco smoke and intravenous nicotine increase platelet aggregation and increasethe tendency for occlusive platelet thrombi to form in this model. In addition, the intravenous infusion of the saturated fatty acid, oleic acid, also enhances acute platelet thrombus formation. Conversely, caffeine abolishes CFRs, perhaps as a result of inhibition of platelet phosphodiesterase and increased cyclic adenosine monophosphate (AMP) levels2 Also, ethanol at a blood alcohol concentration of greater than 0.20 mg/dl abolishescyclic flow reductions and acute coronary platelet thrombus formation in this model3 Our study of “garlic” wasprompted by the documented in vitro antiplatelet effects of garlic extracts.5.7Methanol extracts of raw garlic inhibit in vitro platelet aggregation responsesto stimuli such as: adenosine diphosphate (ADP), epinephrine, collagen, thrombin, arachidonate, platelet-activating factor, and the ionophore A-23187.5.6 Human platelet aggregation in vitro, using ADP and collagenasthe stimulus,wasinhibited with aslittle as0.25 pg of garlic extract7 In humans, ADP-stimulated ex vivo platelet activity significantly decreasedalso,following oral administration of this extract.6 Responsesto both epinephrine and collagen were inhibited. The extract suppressedthromboxane A, synthesisfrom (?-labeled arachidonic acid and a new arachidonic acid metabolite appeared.6Gas chromatography-mass spectroscopy demonstrated this metabolite as lo-, ll-, 12-HEPE, suggesting that garlic alters both the platelet cyclooxygenase and lipoxygenase pathways.6 In this in vivo model of platelet thrombus formation, the effects of intravenous epinephrine overcame garlic’s protective effect. Aspirin is widely prescribed as an anti-
platelet agent to prevent acute coronary thrombosis in patients with coronary artery disease.However, we4and others have shown that the ability of aspirin to inhibit human platelet activity in vitro, aswell asinhibiting acute thrombus formation in stenoseddog coronary arteries, can be renewed with elevated epinephrine levels. This epinephrine effect was also observed in these preliminary studies with garlic. In summary, we have shownthat antithrombotic activity is found in a commercial garlic extract at the equivalent of high dietary levels. This antiplatelet activity prevented acute platelet thrombus formation and CFRs in the stenosedcoronary artery of dogs.Under the stimulus of exogenousepinephrine, the inhibitory effects of garlic extract were partially reversed. It would seemworthwhile to continue to study nutritional substancesthat may increaseor decreaseplatelet activity in vivo. Such studies may aid in the understanding of the etiology and epidemiology of atherosclerosisand coronary artery thrombosis. REFERENCES
1. Buja LM, Willerson JT. Clinicopathologic correlates of acute ischemic heart disease syndrome. Am J Cardiol 1981;47: 343-9. 2. Folts JD. Experimental arterial platelet thrombosis, platelet inhibitors and their possible clinical relevance. Cardiovasc Rev Rep 1982;3:370-82. 3. Keller JW, Folta JD. Relative effects of cigarette smoke and ethanol on acute platelet thrombus formation in stenosed canine coronary arteries. Cardiovasc Res 1988;22:73-8. 4. Folts JD, Rowe GG. Epinephrine potentiation of in vivo stimuli reverses aspirin inhibition of platelet thrombus formation in stenosed canine coronarv arteries. Thromb Res 1988;50:507-16. 5. Noller CR. Chemistry of organic compounds. 3rd ed. Philadelphia: W. B. Saunders Co. 1965:316. 6. Apitz-Castro R, Cabrera S, Cruz MR, Ledesma E, Jain MK. Effect of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction, and platelet ultrastructure. Thromb Res 1983;32:155-60. 7. Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978;30:355-9.
117 4
Fig. 3. Follow-through of right coronary injection demonstrating flow to left pulmonary artery. A, Early phase demonstrating tortuosity of fistulous vessels. B, Later phasedemonstrating early filling of pulmonary artery. C, Final phasewith filling of distal left lower lobe pulmonary artery (compare with Fig. 4).
possible explanation for the pulmonary emboli is a decreasedcardiac output leading to venous stasis,phlebitis, thrombosis, and emboli. Shortly thereafter, with paroxysmal atrial fibrillation, systemic embolization from the left heart may result in partial loss of vision and other unrecognized systemic emboli. Certainly this explanation is speculative, but it seemsto provide a unifying hypothesis.While the hemodynamic manifestations may not be threatening in the reported case, higher flow in other patients potentially may result in adverse consequences. One cannot exclude the possibility that the coronary artery-to-pulmonary artery fistula causedimpaired cardiac function, but the left ventriculogram has the appearance of a cardiomyopathy and the patient had no significant peripheral signs of heart failure. Corrective surgery has been recommendedin the medical literature>9 but is not without complication. One series9reported a 23% complication rate in 43 older patients, with myocardial infarction in 7 5%and death in 7% . Consequently, we chose afterload reduction as the best initial treatment for this patient. REFERENCES
1. Keith JD, Rowe RD, Vlad P. Heart disease in infancy and childhood. 3rd ed. New York: MacMillan Publishing Co, 19781014. 2. Hobbs RE, Millit HD, Raghavan RV, Moddie DS, Sheldon WC. Coronary artery fistulae: a ten-year review. Cleve Clin Q 1982;49:191-7. 3. Klinke WP, Pepine CJ, Conti CR. Demonstration of an inadvertently created aorto-coronary venous anastomosis: evidence against the clinical effectiveness of retrograde coronary venous perfusion. Cathet Cardiovasc Diagn 1979;5:36770. 4. Siepser SL, Kaltman AJ, Mills N, Pughkern T, Fox AC. Coronary collateral flow after traumatic fistula between right
Brief
Communications
973
Fig. 4. Posteroanterior (A) and lateral (6) chest x-ray
films with (C) pulmonary arteriogram demonstrating absenceof flow to left lower lobe.
5. 6. 7. 8.
9.
coronary artery and right atrium. N Engl J Med 1972; 287~754-6. Lowe JE, Oldham HN, Sabiston DC. Surgical management of congenital coronary artery fist&s. Ann Surg 1981;194:37380. Bairn DS, Kline H, Silverman JF. Bilateral coronary artery to pulmonary artery fistulas. Circulation 1982;65:810-15. Upshaw CB Jr. Congenital coronary arteriovenous fistula: report of a case with an analysis of 73 reported cases. AM HEART J 1962;63:399-404. Gobel FL, Anderson CF, Baltaxe HA, Amplatz K, Wang Y. Shunts between the coronary and pulmonary arteries with normal origin of the coronary arteries. Am J Cardiol 1970;25:655-61. Liberthson RR, Sager K, Berkoben JP, Weintraub RM, Levine FH. Congenital coronary arteriovenous fistula: report of 13 patients, review of the literature, and delineation of management. Circulation 1979;59:849-54.
Garlic extract prevents acute platelet thrombus formation in stenosed canine coronary arteries Laurence W. V. DeBoer, MD, and John D. Folts, PhD. Madison,
Wis.
From the Wisconsin
Cardiology Hospital
and
Section, Clinics.
Department
of Medicine,
University
Supported by Grant No. HL29586-05 of the National Institutes Bethesda, Maryland, and by a Grant-in-Aid from the Wisconsin of the American Heart Association. Reprint University 53792.
requests: John of Wisconsin
D. Felts, Hospital,
of
of Health, Affiliate
PhD, H6/379 Clinical Science Center, 600 Highland Ave., Madison, WI
April
974
Brief
Communications
American
Coronary thrombi form at sites of atherosclerotic plaque rupture, ulceration, or erosion, and a variety of agents have been proposed’ to inhibit or prevent acute platelet thrombus formation in diseasedhuman coronary arteries. We have developed a dog model of coronary artery stenosis with intimal damage that exposes subintimal tissuesto circulating platelets. Platelets accumulate at the site of stenosisand platelet thrombi enlargeover time and then embolize distally, causing periodic cyclical reductions in coronary blood Aow.~This model is thought to mimic in some ways the patient with coronary artery disease.We used this model to investigate the effects of garlic, a “food” known to contain antiplatelet substances, on acute platelet thrombus formation and periodic reductions in coronary blood flow. We tested the hypothesis that if garlic possessedantiplatelet substancesit might prevent acute platelet thrombus formation and cyclic flow reductions (CFRs) in our model of canine coronary artery stenosisand thrombosis.2-4 Methods. Eight anesthetized, adult mongrel dogs of either sex (weighing 25 to 30 kg) were studied aspreviously described.3z4 The left thorax was opened,the pericardium was incised, and the heart wasexposed.The proximal 2 to 3 cm of the left circumflex coronary artery were dissectedfree of the epicardium and an electromagnetic flow probe wasplaced around the coronary artery and was monitored with a flow meter (Statham SP2202,Gould Inc. Cardiovascular Products, Oxnard, Calif.). Distal to the flow probe, an external mechanical coronary stenosis (75% diameter reduction) was produced by placing a Lexan constricting cylinder (Cadillac Plastic and Chemical Co., Milwaukee, Wise.) around the coronary artery.“m4 During 30 minutes of observation, periodic coronary CFRs developeddue to periodic acute platelet thrombus formation, followed by embolization (Fig. 1). After the control observation, garlic wasgiven. Extract of cooked garlic was obtained from a commercial source (McCormick Spice, Inc., Baltimore, Md.). Prior to administration, the extract of five cloves of garlic was diluted to 10 cc with saline and 10% alcohol and given slowly intravenously. Since the platelet inhibiting compounds in garlic, including ally1 disulfide and ally1 trisulfide, represent approximately
clRcuMFLEx EPICAADIAL
1989
Heart Journal
0.3% to 0.4% of the total, this dose contained approximately 3 to 4 mg of active compounds.5We have previously determined3that this small amount of ethanol doesnot affect hemodynamic or hemostatic function in the dog. Heart rate, arterial blood pressure, and coronary blood flow were continuously monitored. Twenty minutes after the garlic had beengiven, epinephrine (0.4 pg/kg/min) was infused for 15 minutes to seeif the acute platelet thrombus formation would be renewed as we have previously shown.4 Results. In all eight dogs, acute platelet thrombus formation followed by distal embolization occurred, producing cyclical reductions in coronary blood flow (CFRs). The CFRs occurred at a frequency of 9 +- 3 per hour (Fig. 1). When garlic extract containing approximately 3 to 4 mg of active substance5-an amount that would flavor food strongly-was administered, there was no change in heart rate, blood pressure, or mean coronary blood flow, but CFRs due to acute platelet thrombus formation were abolished in seven of the eight dogs studied and diminished in the last. Whole blood platelet counts were 270,000/~1? 40,000/~1before and 255,000/~1+- 44,000/~1 after garlic administration (NS). In the sevendogsin which CFRs had been abolishedby garlic, platelet thrombus formation wasrenewed in five of the seven dogs by epinephrine administration (Fig. 2). Epinephrine infusion resulted in an increase in mean blood pressure from 110 t 19 to 128 -+ 16 mm Hg (p < 0.05), with a reflex slowingof the heart rate that was not statistically significant. Epinephrine overcame the antithrombotic effects of garlic, suggestingthat epinephrine exacerbatesplatelet thrombus formation by mechanisms other than those inhibited by garlic extract. The data are presented as mean it SD. Comments. The partially stenosed canine coronary artery with moderate intimal damageprovides a reasonable in vivo model to determine the effects of various interventions on the interaction of the vesselwall, platelets, and intraarterial platelet thrombi.2-4The CFRs following mechanicalstenosisof a coronary artery have been directly correlated with the size of the dislodged platelet thrombus collected downstream and are not due to vaso-
BED EGG
ml /min
Fig. 1. On the left, cyclical reductions in coronary blood flow (CFRs) due to acute intracoronary platelet thrombus formation are noted. On the right, the CFRs are abolished with intravenous garlic extract.
Volume
117
Number
4
Brief
Communications
975
CIRCUMFLEX BED EPlCARDlAL EC6 AORTIC BLOOD PRESSURE mm Hg. C lRCUMFLEX BLOOD FLOW ml./min.
Fig. 2. On the left, the CFRs due to acute platelet thrombus formation have been abolishedby the garlic. However, in the center, CFRs are renewedby the infusion of epinephrine (marked with arrows).
spasm.2This dog model hasbeen suitable for demonstrating the antithrombotic effects of such clinically used antiplatelet drugs as aspirin’s4and other nonsteroidal antiinflammatory agents.2The role of nonpharmacologic “dietary” interventions on platelet function is potentially very important but not well understood. We have shown* that tobacco smoke and intravenous nicotine increase platelet aggregation and increasethe tendency for occlusive platelet thrombi to form in this model. In addition, the intravenous infusion of the saturated fatty acid, oleic acid, also enhances acute platelet thrombus formation. Conversely, caffeine abolishes CFRs, perhaps as a result of inhibition of platelet phosphodiesterase and increased cyclic adenosine monophosphate (AMP) levels2 Also, ethanol at a blood alcohol concentration of greater than 0.20 mg/dl abolishescyclic flow reductions and acute coronary platelet thrombus formation in this model3 Our study of “garlic” wasprompted by the documented in vitro antiplatelet effects of garlic extracts.5.7Methanol extracts of raw garlic inhibit in vitro platelet aggregation responsesto stimuli such as: adenosine diphosphate (ADP), epinephrine, collagen, thrombin, arachidonate, platelet-activating factor, and the ionophore A-23187.5.6 Human platelet aggregation in vitro, using ADP and collagenasthe stimulus,wasinhibited with aslittle as0.25 pg of garlic extract7 In humans, ADP-stimulated ex vivo platelet activity significantly decreasedalso,following oral administration of this extract.6 Responsesto both epinephrine and collagen were inhibited. The extract suppressedthromboxane A, synthesisfrom (?-labeled arachidonic acid and a new arachidonic acid metabolite appeared.6Gas chromatography-mass spectroscopy demonstrated this metabolite as lo-, ll-, 12-HEPE, suggesting that garlic alters both the platelet cyclooxygenase and lipoxygenase pathways.6 In this in vivo model of platelet thrombus formation, the effects of intravenous epinephrine overcame garlic’s protective effect. Aspirin is widely prescribed as an anti-
platelet agent to prevent acute coronary thrombosis in patients with coronary artery disease.However, we4and others have shown that the ability of aspirin to inhibit human platelet activity in vitro, aswell asinhibiting acute thrombus formation in stenoseddog coronary arteries, can be renewed with elevated epinephrine levels. This epinephrine effect was also observed in these preliminary studies with garlic. In summary, we have shownthat antithrombotic activity is found in a commercial garlic extract at the equivalent of high dietary levels. This antiplatelet activity prevented acute platelet thrombus formation and CFRs in the stenosedcoronary artery of dogs.Under the stimulus of exogenousepinephrine, the inhibitory effects of garlic extract were partially reversed. It would seemworthwhile to continue to study nutritional substancesthat may increaseor decreaseplatelet activity in vivo. Such studies may aid in the understanding of the etiology and epidemiology of atherosclerosisand coronary artery thrombosis. REFERENCES
1. Buja LM, Willerson JT. Clinicopathologic correlates of acute ischemic heart disease syndrome. Am J Cardiol 1981;47: 343-9. 2. Folts JD. Experimental arterial platelet thrombosis, platelet inhibitors and their possible clinical relevance. Cardiovasc Rev Rep 1982;3:370-82. 3. Keller JW, Folta JD. Relative effects of cigarette smoke and ethanol on acute platelet thrombus formation in stenosed canine coronary arteries. Cardiovasc Res 1988;22:73-8. 4. Folts JD, Rowe GG. Epinephrine potentiation of in vivo stimuli reverses aspirin inhibition of platelet thrombus formation in stenosed canine coronarv arteries. Thromb Res 1988;50:507-16. 5. Noller CR. Chemistry of organic compounds. 3rd ed. Philadelphia: W. B. Saunders Co. 1965:316. 6. Apitz-Castro R, Cabrera S, Cruz MR, Ledesma E, Jain MK. Effect of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction, and platelet ultrastructure. Thromb Res 1983;32:155-60. 7. Bordia A. Effect of garlic on human platelet aggregation in vitro. Atherosclerosis 1978;30:355-9.