This document summarizes Mrinal Dewanjee's work over 25 years developing methods to continuously measure and image platelet thrombi and emboli in live animals and patients. He created algebraic equations to quantify thrombi on cardiovascular prostheses like mechanical heart valves, vascular grafts, and components of heart lung machines. This helped reduce mortality from platelet thrombi during cardiopulmonary bypass procedures and improved prosthetic device design. He collaborated with surgeons and engineers to evaluate thrombus formation and new designs, helping advance cardiovascular surgery and treatment.

1. Reduction of Platelet Thrombi in
Cardiovascular Prostheses: Mechanical and
Tissue Heart Valves, Vascular Graft and
Components of Heart Lung Machine
Mrinal K. Dewanjee, MSc, PhD, FAHA, FAIMBE
Mrinal K Dewanjee, PhD, FAHA, FAIMBE
Neurobiology, Neurodegeneration & Repair
Laboratory, National Eye Institute, NIH,
Bethesda, MD 20892, USA

2. In the absence of any tools or methods, the cardiovascular surgeons,
neurologists, cardiologists could only speculate about the role of
thrombi and emboli.
I made two major Algebraic equations that changed the world of
thrombi and emboli on drug evaluation and reduction of thrombi on
cardiovascular prostheses (CVPs: Mechanical and Tissue Heart Valves,
Vascular Graft and Components of Heart Lung Machine) that also
reduced mortality from platelet thrombi during cardiopulmonary bypass
(CPB) procedure, essential for implantation of CVPs by continous
measurements of thrombi: Non-invasive Imaging of thrombi in live
animals and patients with a gamma camera and measurements of small
amount of radioactivity with a gamma counter using In-111 tagged
autologous platelets. Similar measurements were made for the clotting
factors, fibrinogen, thrombin with I-125/123/131 labeled radionuclides.
High shear rate in hollow-fiber fragmented platelets thus reducing their
chance of thrombi and emboli in brain and other perfused organs during
CPB and hemodialysis.

3. Cross-calibration of Gamma camera, Dose-calibrator and
Gamma counter
Gamma camera could image large thrombi with large amount
of radioactivity. Dose-calibrator measures large and medium
amount of radioactivity (millicurie to microcurie). Small
amount of radioactive thrombi is measured with a gamma
counter (Counts per min: CPM). By cross-calibration, we could
account for all platelets: Thrombi, Emboli and their
fragments.
The Equation, I developed, converted platelet-bound
radioactive count into number of platelets.
Mayo Clinic, NHLBI and Corporate sponsors supported my
studies for 25 years.

4. Human Imaging
X-ray: CT
Gamma ray: SPECT/CT MRI
Fused PET-CT-MRI
Ultrasound
Fluor-IR: Optical
?
Fusion Imaging
CT: Structure/Resolution
PET/MRI: Function
3D Imaging of Organs by Miracle Machines of 21th Century

6. Indium chemistry is similar to that of a trivalent
Cation, like Ferric ion: Fe3+

7. BestBest 111111
InIn--complex for Cell Labelingcomplex for Cell Labeling
Make platelets GLOW with RadiationMake platelets GLOW with Radiation

9. Quantification of platelet retention in aortocoronary femoral vein bypass graft in dogs treated
with dipyridamole and aspirin. pg. 350-356. Circulation 69, No. 2, 350-356, 1984.
Dewanjee, Mrinal K. Ph.D.; Tago, Mamoru M.D.; Josa, Miguel M.D.; Fuster, Valentin M.D.; Kaye,
Michael P. M. D.

10. We used Idonne-125 for in vitro measurements and I-123
and I-131 for clotting factors: fibrinogen, thrombin and
other proteins.

11. BestBest 111111
InIn--complex for Cell Labelingcomplex for Cell Labeling
Make platelets GLOW with RadiationMake platelets GLOW with Radiation

21. Quantitation of Platelet Thrombi with 111In-platelets on stainless steel retainer
for pyrolitic carbon disk, Dacron sewing ring, Teflon-felt-sutures and injured valve
annulus in Medtronic Hall Valve Prostheses (22-mm, 24 hour after implantation)
in a Duroc-Yorkshire Pig model

25. Imaging Thrombus on Dacron Graft (15 yr. after Repair
of Abdominal Aortic Aneurysm, 24 hr after IV
administration of 111In-platelets, 850 microcuries)
Dewanjee: Sem Nucl Med 14: 154-187,1984

32. Medtronic-Hall Single Disc Mechanical Heart Valve
Disc opens and closes around the Central Pivot
Pig Model (24 hr)

33. Platelet Thrombi on Components of Mechanical Heart Valve
(Pig Mitral annulus: 24 hr after heart valve implantation
(Medtronic-Hall Valve, Minneapolis, MN)

34. ECC: CPB, ECMO,
Hemodialysis
Plasmapheresis
Extracorporeal Circuit for Blood Supply to Brain and other organs, when Heart and Lung are
stopped/Bypasses for Repair and Oxygen is supplied by Artificial Lung

35. Open Heart Surgery-ECC: Roller Pumps (4)-Arterial Filter

36. Mitral and Aortic Heart valve replacement (Starr-Edwards)
38-year old antiques Going Strong-73 year-old woman.
Thrombus on Pericardial Tissue heart valve in Calf
and young patients calcifies.
SE Mech
Ball-in-a-
Cage Valves

37. Calf (Holstein) Model for Tissue Heart Valve (Pericardium-
Sweet heart piece) Calcification
Both Aortic and mitral valve prostheses
calcified after 2 years (10 yr old boy at Mayo
Clinic)
Tissue engineering for spontaneous endothelial cell coverage of pericardial tissue
heart valve (explant from a calf at 60 days). Leaflets were conjugated with
Aminodiphosphonate and assembled at Shiley, Inc. (Dewanjee ASAIO 32: 24,1986)

38. Mapping of regional platelet thrombi on five segments of CABG
and enhancing of graft patency from 75% to 95% with aspirin-
Persantine therapy (Dewanjee et al. Circ 69: 350, 1984)
Quantitation of Universal Parameter for Platelet-
Fibrinogen Organization in Thrombus
CABG Patency by Platelet-inhibitors
(Dewanjee et al. Circulation 69:350, 1984)

39. MRI (1.5 Tesla, Picker Inc., Univ. of Miami, Radiology) of Pig Brain Swelling after
Cardiopulmonary Bypass (~3 hr) Higher TNFα during CPB

40. Cholesterol Deposition on Canine CABG (Dewanjee 1982):
Why we should use Statin Early after Surgery or Vessel
Wall Injury!

41. Mathematical Models for the Calculation of Human
Platelet Survival Times. Dewanjee MK, et. al. Mayo
Clinic Proc 61: 327-336, 1986.

43. Schematic representation of a platelet showing the different platelet organelles.
Besides the membrane systems, i.e., Open Canalicular System (OCS) and Dense Tubular System
(DTS), and Mitochondria, the three specific granules are easily identified. Dense granules (d –G,
CaPO4) are the smallest with an intense opaque dense core surrounded by a clear space.
Platelets provide a rich sources for a rapid access for a variety of growth factors

44. IV Infusion of In-111 tagged PMN Neutrophils in
a Pig Model: Transient Margination-Lung
LUNG
LIVER
SPLEEN

53. Hello Michael and Chris,
As I walk around the Bldg. 10 South entry, I was intrigued by your impressive assembly of
cardiovascular prostheses (CVPs), their history of developments and the heart lung-machine used
to implant the CVPs. My mother, a pious Hindu woman told me I have no right to kill animals,
especially holy cows, I used to evaluate the calcification of tissue heart valves, unless I solve the
puzzle of arterial thrombi. I am proud to keep the promise I made during her visit in 1980.
I was lucky to face the challenge of measurement of thrombi and emboli in animal models and
patients for the last 25 years (1976-2000) working with best cardiologists, thoracic surgeons,
pathologists, hematologists and pharmacologists at Mayo Clinic, Univ. of Miami, FL and UIUC
Urbana-Champaign, IL.
Dr. Nina Braunwald's student, Dr. Jerry Kaiser helped to me set up the Cardiovascular Surgery Lab
at Miami (1987-1996), after I left Mayo Clinic.
I hope, you could use some of figures, I developed in collaboration withe the bioengineers at
Baxter, Medtronics and Bjork-Shiley to improve blood flow, deliver oxygen and reduce thrombi.
The corporations are very generous to provide with hundreds of heart valves, circuits for heart-
lung machine and drugs, gratis to resolve their problems and patients.
If you have any question, I will be glad to assist.
Thanks. Mrinal