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Curriculum Vitae

Nama : Prof. Dr. dr H. Djanggan Sargowo SpPD,SpJP(K), FIHA., FACC., FAPSC

Tempat/Tgl lahir : Sragen, 21 September 1947

Alamat : Wilis Indah E-10 Malang


Telp. 0341-552395
Pendidikan :
1. Lulus Dokter dari UGM, tahun 1974
2. Lulus Cardiologist dari Univ. Indonesia, tahun 1983
3. Lulus Internist dari Univ. Airlangga, tahun 1986
4. Lulus Doktor, Univ. Airlangga, tahun 1996
5. Advanced Cardiology Course, Univ. Hongkong, tahun 1984
6. Senior Visiting Program, Institut Jantung Negara, Kualalumpur, 1996
7. Fellow American College of Cardiology (FACC), September 2006.
8. Fellow Collage Asia Pacific Society of Cardiology (FAPSC), Desember 2007

Jabatan :
1. Direktur Program Pascasarjana Universitas Brawijaya
2. Ketua Ikatan Dokter Indonesia Cabang Malang Raya
3. Ketua PERKI Cabang Malang Raya
4. Ketua Kolegium Kardiovaskuler Indonesia 1
ORAL FIBRINOLYTIC NATTOKINASE
ON ACUTE CORONARY SYNDROME

Djanggan Sargowo

Malang
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ACS: TIP OF THE ATHEROTHROMBOTIC ICEBERG
Acute Plaque Rupture ACS (UA/NSTEMI/STEMI)

Clinical

Subclinical

Persistent Hyperreactive
Platelets
Presence of Multiple Vascular
Coronary Plaques Inflammation

ACS, acute coronary syndrome; UA, unstable angina; NSTEMI, non-ST-segment elevation myocardial
infarction; STEMI, ST-segment elevation myocardial infarction.
Adapted from Goldstein JA. J Am Coll Cardiol. 2002;39:1464-1467.
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REDOX REGULATION OF ENDOTHELIAL
DYSFUNCTION & ACTIVATION

O2 NO Activity
H2O2 G-Protein Function
OH Protein Kinase C

Oxidation Endothelial Dysfunction

(D. Sargowo) 4
ENDOTHELIAL DYSFUNCTION AND
ACUTE CORONARY SYNDROMES

Vasoconstriction Endothelial Dysfunction


Platelet Aggregation
Plaque Rupture
SMC Proliferation
Leukocyte Adhesion Thrombosis
LDL Oxidation
Activation of MMPs Matrix Remodeling

(D. Sargowo) 5
ENDOTHELIAL DYSFUNCTION AND
ACUTE CORONARY SYNDROMES

Vasospasm
ACUTE
Plaque Rupture CORONARY
SYNDROMES
Thrombosis

Matrix Remodeling

(D. Sargowo) 6
MECHANISMS OF CORONARY THROMBUS FORMATION
ATHEROSCLEROSIS

DYSFUNCTIONAL
PLAQUE RUPTURE
ENDOTHELIUM

Intraplaque Release of Exposure of Turbulent Vasodilator Anti thrombotic


hemorrhage Tissue Factor subendothelial blood flow effect effect
collagen

PLATELET
ACTIVATION &
AGGREGATION
Vessel Activation of Vasoconstriction
umen the coagulation
diameter cascade

CORONARY THROMBOSIS 7
UNSTABLE PLAQUE = VULNERABLE PLAQUE

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RISK FACTORS FOR PLAQUE RUPTURE
Local Factors Systemic Factors
Cap Smoking
Fatigue
Cholesterol
Atheromatous Core
(size/consistency)
Diabetes
Mellitus Fibrinogen
Cap
Thickness/
Consistency
Cap Homocysteine
Impaired
Inflammation
Fibrinolysis

Plaque
Rupture

Fuster V, et al. N Engl J Med. 1992;326:310-318.


Falk E, et al. Circulation. 1995:92:657-671. 9
THROMBOTIC PROCESS PATHOPHYSIOLOGY
THROMBUS FORMATION / COAGULATION

Factor Factor Prothrom


VII Xa bin

Promotes :
Tissue factors
Adhesive molecules
Smooth muscle
Leukocyte activation Thrombin Fibrinogen
Platelet aggregation (II)
Release reaction
Fibrin

Alexander JH, Harrington RA, 1997


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THROMBOSIS : PLATELET AND THE COAGULATION SYSTEM

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Inflammation

Repair

Unstable plaque Stable plague

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Unstable Coronary Thrombus forms and
Artery Disease (II) extends into the lumen

Thrombus

Lipid core

Adventitia

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CONSEQUENCES OF CORONARY THROMBUS
CORONARY THROMBUS

Small thrombus Partially occlusive Occlusive


(non-flow limiting) thrombus thrombus
Transient
ischemia Prolonged
ischemia
No ECG
changes ST segment
Depression and/or ST elevation
T wave inversion (Q wave later)

Healing and
Plaque enlargement Negative
Serum Positive Positive
biomarkers Serum Serum
biomarkers biomarkers

UNSTABLE NON-ST SEGEMENT ST SEGMENT


ANGINA ELEVATION ELEVATION 15
ACUTE CORONARY THROMBOSIS IN ACS
Plaque Rupture
or Erosion

ASA Platelet Coagulation Heparin


Low molecular
Activation Cascade weight heparin
Ticlopidine
Clopidogrel
Direct
Adhesion/ Fibrin Thrombin
Glycoprotein Aggregation Formation Inhibitors
IIb/IIIa
Inhibitors

Platelet-Rich
Thrombolytic
Thrombus
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UNSTABLE ANGINA/NSTEMI
THERAPEUTIC GOALS
Anti-ischemic therapy
nitrates, beta blockers, calcium
antagonists
Anti-thrombotic therapy
Anti-platelet therapy
aspirin, clopidogrel
GP IIb/IIIa inhibitors
Anti-coagulant therapy
heparin, low molecular weight heparin
(LMWH), warfarin, hirudin, hirulog
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THROMBOLISIS & LYSIS
Protein C & S

Vit K tPA SK-


Plasminogen Plasminogen
Reteplase
inhibitors
Tenecteplase
WARFARIN etc CLOT LYSIS
plasmin
HIRUDIN
thrombin
Thrombin fibrin fibrin
Pro-
Fibrin thrombin
thrombin
+ thrombin fibrin
thrombin fibrin thrombin

Thrombin
Platelet
13 activation
Platelet aggregation and
Antithrombin-III adhesion to vessel wall
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HEPARIN molecule Gp IIb/IIIa INHIBITORS


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Treatment Focus

THROMBUS/EMBOLUS
Precipitating Factor of UAP

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WHAT IS NATTO ?

Natto is a popular Japanese cheese


made from fermented soybeans

Natto is found by the warrior Minamoto


no Yoshiie a thousand years ago
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WHAT IS NATTO ??

End of Y1867, Natto had become a


regular part of Japanese cuisine
Used as a folk remedy for heart and
vascular diseases
No secret that Japanese
Live longer
Have less cardiovascular diseases
Not affected by heart attack & stroke as
frequently as Western people
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WHAT IS Bacillus subtilis

Originally named Vibrio subtilis and


in 1872 renamed Bacillus subtilis by
Ferdinand Cohn
Produce the proteolytic enzyme subtilisin
Gram-positive, not pathogen & commonly
found in soil
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( like this. )

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WHAT IS NATTOKINASE

A potent fibrinolytic enzyme complex,


extracted & highly purified from Natto
Produced when Bacillus subtilis acts
on the soybeans
Support the body in breaking up and
dissolving the unhealthy coagulation
of blood
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NATTOKINASE DISCOVERY
In 1980, Japanese researcher Hiroyuki Sumi
from Chicago University Medical School,
discovered
Nattokinase was dropped onto an artificial
thrombus
Over the next 18 hours, the thrombus
arround the nattokinase completely
dissolved

Sumi remarks that Nattokinase shows :


A Potency matched by no other enzyme 1,2
Ref : 1. Prevent Heart Attack and Stroke with Potent Enzyme that Dissolves Deadly Blood
Clots in Hours. Health Sciences Institute, March 2002
2. Hager, K. et.al. Fibrinogen and Aging. Aging (Milano) 1994, 6:133-138 25
HOW NATTOKINASE WORKS
Nattokinase acts directly on the fibrin
Nattokinase binds platelets and red
blood cells to form the clots
Nattokinase has ability to dissolve
fibrin thus releasing platelets and
unclotting areas of unnecessary blood
flow restriction
Nattokinase also acts as a coagulation
preventative
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NATTOKONASE BENEFITS

Thrombolytic Effect 3
Blood Pressure 4
Circulating Enhancement 5

Ref : 3. Sumi, H. et al. A novel fibrinolytic enzyme in the vegetable cheese Natto Experientia 1987, 43:1110-11
4. Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS, 1995
5. Sumi H. Healthy Microbe Bacillus Natto. Japan Bio Science Laboratory Co. Ltd

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THROMBOLYTIC EFFECT
12 healthy Japanese volunteers
6 men & 6 women, between 21 and 55 yrs old
Given 30 mg nattokinase extract before
breakfast
Time needed to dissolve the clots was
cut in half within 2 hours of treatment
compared to the control group
The volunteers retained & enhanced
ability to dissolve blood clots for up to 8
hours 6
Ref : 6. Sumi, H. et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta haematol 1990, 84:134-43 28
THROMBOLYTIC EFFECT
2 groups of male dogs with blood clots
Given either 4 capsules of 250mg
nattokinase or 250mg placebo
Angiograms shows that the blood
clots was completely dissolved within
5 hours with nattokinase whilst no
sign of dissolving 18 hours to placebo
group 6

Ref : 6. Sumi, H. et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta haematol 1990,
84:134-43 29
BLOOD PRESSURE
5 volunteers with high blood pressure

Given 30mg nattokinase extract for 4 days

4 out of 5 volunteers, the blood pressure


decreased on average 1,6,7 :

systolic = from 173.8 to 154.8


diastolic = from 101.0 to 91.2

Ref : 1. Prevent Heart Attack and Stroke with Potent Enzyme that Dissolves Deadly Blood Clots in Hours. Health Sciences Institute, March 2002
6. Sumi, H. et al. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta haematol 1990, 84:134-43
7. Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS, 1995

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CIRCULATING ENHANCEMENT

A 58-year-old man with retina blood clots


Caused fluid build up, bleeding & losing vision
Given 3 ounce dose of natto during bed time
Over the 10th day, the bleeding stopped
Over the 20th day, his vision returned
The next 2 months treatment, the clots was
completely gone 8

Ref : 8. Nishimura, K. et al. Natto diet was apparently effective in a case of incipient central retinal vein occlusion. Japan Rev Clin Opthalmol 1994, 88:1381-85 31
SIDE EFFECTS
Nattokinase has been used for
nearly 20 years
Nattokinase has no known side
effects
Nattokinase has not been recoqnized
to cause any allergic reactions
Nattokinase has never been any
reports of toxicity
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Which one ??
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DRUG INTERACTIONS

Nattokinase contains vitamin K

Might interfere with the actions


of blood thinning drugs :
warfarin
aspirin
Need to consult & dosage reduction

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TROBESCO FEATURE

COMPOSITION
Nattokinase 50 mg

INDICATION
Natural fibrinolytic agent
Ajuvan treatment for cardiovascular &
cerebro disorders

DOSAGE
1 2 capsule/ day
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