Inflammatory Responses to Cardiopulmonary Bypass 1.pdf

Inflammatory responses after CPB

1. Inflammator
y
Responses
to Cardiopulmonary Bypass
By sittisard saikaew
chiangrai Rrachanukroh
Hospital

2. Intro to Imflammatory Responses
Inflammation is the body's response to tissue injury caused by factors
like pathogens or cell death from ischemia. This process is a crucial defense
mechanism designed to eliminate foreign agents and remove damaged cells.
While beneficial, inflammation can also be harmful if it is excessive or becomes a
long-term, chronic process. The inflammatory process involves vascular changes,
the migration of white blood cells, and systemic effects on the whole body.
•Vascular Changes : Alterations in blood vessel caliber result in
increased blood flow to the injured area.
•Increased Permeability : The structure of small blood vessels
changes, allowing plasma proteins and white blood cells to leak out.
•Leukocyte Emigration: White blood cells move from the
circulation to the site of injury to eliminate the offending agents.

3. Stimuli for Acute Inflammation
Several factors can trigger acute inflammation
•Infections and microbial toxins.
•Trauma and physical injury.
•Physical and chemical agents like heat, cold, or
radiation.
•Tissue necrosis (cell death).
•Foreign bodies.
•Immune reactions, such as hypersensitivity.

4. Overview of immunolgy
1.Innate immune system :
The First Line of Defense at location. Its response is non-specific.
respond : immediately
2.Adaptive Immune System :
It has the remarkable ability to recognize and remember specific pathogens
respond : Specific and Memory-Driven, Wait away from infection
3.Complement system : a cascade of systemic physiological changes, with
inflammation being a central component.

5. Innate Immune System:
The First Line of Defense
1.Physical and Chemical Barriers : The skin and mucous membranes,
respiratory, gastronitestinal, urinary. Chemical barriers include the acidic
environment of the stomach(HCL) and enzymes Lysozyme in tears and saliva
lactic acid in vagina
2.Cellular Defenses : If pathogens breach the physical and chemical barriers
•Phagocytes : These cells, such as neutrophils and macrophages.
•Natural Killer (NK) Cells : These cells can recognize and kill virus-infected
cells and some tumor cells.
3.Inflammation : a cascade of systemic physiological changes. Recuit cell
neutropil, monocyte and macrophage, vascular permeability, mast cell, clotting
system, kinin system

6. Acute Phase response
systemic inflammatory response
Cytokines

7. Acute Phase response
systemic inflammatory response
Cytokines

8. Acute Phase response
systemic inflammatory response
Cytokines

9. The Complement System
A Bridge Between Innate and Adaptive Immunity
Classical Pathway: Activated by antibodies that have bound to antigens.
Alternative Pathway : Activated directly by the surface of some pathogens
Lectin Pathway : Activated when a protein called mannan-binding lectin
binds
1.Opsonization: C3b Complement proteins coat the surface of pathogens, C
reactive protein(CRP)
2.Inflammation: C3a , C5a (anaphylatoxins) Complement proteins can attract
other immune cells to the site of infection
3.Direct Killing of Pathogens: Some complement proteins can assemble to
form a "membrane attack complex" (MAC) C5b

10. Complement System
Complement proteins C1-C9
Complement Cascade

11. Complement System
Opsonization
Opsonins is complex molecules
Attach to pathogens
Help Macrophages and neutrophel with phagocytosis

12. Adaptive Immune System
Specific and Memory-Driven
1.B Lymphocytes (B cells) : B cells differentiate into plasma cells that produce
antibodies. Antibodies are proteins that can bind to antigens and neutralize
pathogens or mark them for destruction by other immune cells.
Plasma cell
Memory B cell
2.T Lymphocytes (T cells) :
Helper T cells (Th cells) : These cells are the "generals" of the adaptive immune
response.
Cytotoxic T cells (Tc cells) : These cells are the "soldiers" that directly kill
infected cells.
3.Immunological Memory : A key feature of the adaptive immune system is its
ability to "remember" pathogens it has encountered before. these memory cells
can mount a much faster and stronger immune response

13. Adaptive Immune System

14. Adaptive Immune System
Cytotoxix T Cell
Fas/FasL (Death Receptor)
Perforin/Granzyme

15. Adaptive Immune System
B Cell

16. Key Points to Remember
1.High Rates of Illness and Death After Major Surgery: Despite
advances in medical technology, significant illness (morbidity) and death
(mortality) are still common after major operations.
2.Post-Surgery Complications Affect Multiple Organs: When
complications arise, they often involve several organ systems at once,
suggesting a body-wide (systemic) problem rather than a localized one.
3.Excessive Inflammation is a Likely Cause: It is hypothesized that an
excessive systemic inflammatory response to the trauma of surgery leads to
postoperative organ dysfunction.
4.No Proven Treatment Exists: Currently, there are no proven treatments
or interventions from large, randomized clinical trials that can effectively
reduce this inflammation to prevent illness and death in patients

17. Introduction
Definingthe Problem: SIRS vs. SIRAB
1.SIRS (Systemic Inflammatory Response Syndrome): A clinical syndrome
defined by criteria like abnormal temperature, heart rate, respiratory rate, and WBC
count.
2.The Problem in CardiacSurgery: Nearly every patient meets SIRS
criteriapost-CPB, making the definition non-specific.
3.SIRAB (Systemic Inflammatory Response After Bypass): A more precise
term acknowledging that the inflammation is multifactorial.
•Sterile inflammation in CPB surgical trauma, ischemia-reperfusion injury,
intercellular cytokines, Endotoxemia
•DAMPs (Damage associate molagular particle) high mobility group box 1
(HMGB1), heat shock proteins (HSPs), cell-free DNA

18. Causes and Mechanisms of Systemic
Inflammation
1.It has been proposed that an exaggerated systemic proinflammatory
response to surgical trauma is the root cause of many complications, from organ
dysfunction to death..
2.However, the exact causes and clinical importance of this response after heart
surgery are not fully understood.
3.This condition is a complex, multifactorial process that severely affects both
injured and healthy tissues.
4.The main triggers are believed to be:
a.Tissue Injury: The direct trauma from the surgery itself.
b.Endotoxemia: The presence of endotoxins (components of bacterial cell walls) in the
blood.
c.Cardiopulmonary Bypass (CPB): The contact of blood with the foreign
surfaces of the heart-lung machine circuit

19. The "Multifactorial Hit" of SIRAB
Contact Activation
Blood meets the artificial CPB
circuit surface.
Endotoxemia
"Leaky gut" from splanchnic
hypoperfusionSurgical Trauma
The incision, sternotomy,
and tissue handling,
DAMPs.
CPB Duration
and postoperative morbidity
and mortality.Non-Physiologic State
Hypothermia, hemodilution,
non-pulsatile flow.
Ischemia-Reperfusion
Injury
Aortic cross-clampingand
reperfusion.

20. Cardiopulmo
nary Bypass

immune System
Activation
Complement , Cytokines , Coagulation , Fibrinolysis
Cellular immune system
Contact activation
Tissue injuly, Ischemia -
reperfusion Endotoxin
SIRAB
Initiating
Factors

21. The Initiating
Events The
Initial Spark:
Contact
Activation
This is the primary, immediate trigger for the inflammatory
cascade.
It occurs the moment blood leaves the body and touches
the non-endothelialized, artificial surfaces of the CPB circuit
(tubing, oxygenator, reservoir, suction).
Endothelial Activation
Red Blood, Cell Leukocytes, Monocytes
Platelests, Coagulation system

22. Inhibitory properties of endothelial cells
Inhibition of platelet function and
coagulation
by several endothelial molecules and
factors and the targeted coagulation factors
are shown. Endothelial cells (ECs) express
nitric oxide (NO), prostacyclin (PGI2), and
ectonucleoside triphosphate
diphosphohydrolase-1 (E-NTPDase1), which
inhibit platelet adhesion and aggregation.
Heparin-like molekules (Hep) expressed on
endothelial surface serve as a cofactor for
antithrombin III (ATIII) inactivating several
coagulation factors. ECs express tissue
factor pathway inhibitor (TFPI), which limits
the action of tissue factor (TF) and inhibits
excessive TF-mediated activation of
coagulation factors VII and X.
Thrombomodulin (TM) binds thrombin
activating protein C and degrades factor Va
and VIIIa. Activation of fibrinolysis by
endothelial tissue plasminogen activator (t-
PA) and urokinase-type plasminogen
activator (u-PA) and their inhibition by
plasminogen activator inhibitor (PAI-1) is
depicted. PLG plasminogen

23. The artificial surface activates
Factor XII ,XI, Prekallikrein, Kininogen HMWK.
ActivatedFactorXIIa simultaneously triggers three major humoralcascades:
Thrombin & Fibrin XIa --> Intrinsic Coagulation Pathway XIa
Bradykinin Kallikrein --> Kinin System
Plasmin kallikerin --> Fibrinolytic System
Complemen system Plasmin -->C1 C3 Classis pathway (endotoxin, Protamine), alternate pathway;
C3a and C5a (Anaphylatoxins) Powerful chemoattractants for neutrophils
and monocytes. Activate mastcells and neutrophils. Increase vascular permeability.
Cascade Amplification Chemokines and Neutrophil Mediated injury
prevent by coating surface system
The Contact System
Cascade Factor XII
(Hagaman factor)

24. The Contact System Cascade

25. The non-physiologic environment of CPB
causes significantdamage and activation of key blood cells:
Red Blood Cells
Vascular Endothelium
Leukocytes (Neutrophils, Monocytes)
Platelets
The Cellular Response: An Overview

26. Red Blood Cells
Mechanical Shear Stress from pumps and tubing damages the RBC
membrane
•RBC Deformability: Normal red blood cells are highly flexible and can
deform
•Shear Stress Damage: In the CPB circuit, especially in roller pumps
or even centrifugal pumps and in areas of stenosis or tubing bends, high
shear stress is generated that can damage the RBC membrane
•Membrane Attack Complex ,MAC(C5b-9): causing the cell to lyse
(hemolysis) and release hemoglobin.
•Free Hemoglobin Toxicity:
•Scavenges Nitric Oxide (NO)
•Oxidative Stress
•Renal Toxicity
•Increased Oncotic Pressure/Viscosity
•Hemodilution and Aggregation: endothelial cells and trigger
inflammation.
•Endothelial Activation: The injury of red blood cells and the release of
various substances can directly activate endothelial cells

27. Vascular Endothelium
•Endothelium: The Gatekeeper Under normal conditions, it maintains balance,
prevents blood clotting, controls permeability, and inhibits inflammation.
•"Physiologic Trespass": During CPB and cardiac surgery: there is a
"trespass" upon the body's normal state, causing the endothelium to switch from a
"quiescent" state to an "activated" and pro-inflammatory state.
•Key Activators of Endothelium during CPB:
•Cytokines (IL-1β, TNF-α): Released from activated immune cells (e.g.,
macrophages, monocytes).
•Thrombin : From the activated coagulation cascade. PAF platelet activating
factor
•C5a : A potent anaphylatoxin from complement activation.
•Lipopolysaccharide (Endotoxin): Endotoxin may leak from the intestinal wall
into the bloodstream during CPB (bacterial translocation) due to splanchnic
hypoperfusion.
•Upregulation of Adhesion Molecules: This is the key mechanism that
allows leukocytes to adhere to the blood vessel wall :

28. Cellular Events: Leukocyte extravasation and
phagocytosis
01
03
Margination and
Rolling As blood flow slows,
leukocytes move to the vessel walls
Transmigration
leukocytes squeeze between the
endothelial cells to exit the blood vessel.
02
04
Adhesion
Leukocytes adhere firmly to the
endothelial cells lining the blood vessels.
Chemotaxis
After exiting the vessel, leukocytes
migrate toward the site of injury,
guided by chemical signals.
The Role of Leukocytes : The movement of leukocytes (white blood
cells) from blood vessels into the injured tissue is a critical event called
extravasation. This process occurs in several steps

29. Leukocyte adhesion and transmigraton
Leukocyte Adhesion
cascade
Adhesion molecules :
CPB
Tissue injuly,
histamine,
thrombin, PAF
Activated
Endothelium
Selectins : E, P, L selection
Immunoglobulin family :
ICAM 1, VCAM-1
Intergrins : LFA-1, VLA-4
Mucin link gycoprotein :
Chemotaxis : Creat actin
move to injury cell ;
Chemotactic stimuli : C5a,
Cytokine IL-8, PAF,
Leukotriene B
4
inhibit selectin, intergrin,
cytokine
Leukocyte adhesive Plug :
microcirculatory impairment,
ischemic reperfusion injury

30. Phagocytosis
Phagocytosis :
Recognition and attachment:
Opsonin
Engulfment :
Killing and Degradation
O
2 reactive oxygen
species(RO),
bacteicidal permeability
protein
Release of leukocyte Preducts and
leukocyte inducede tissue injury :
Lysolomal enzymes , Reactive
oxygen intermediates, Proteases ,elastase
Amplificaton during CPB:
Effector cells of Tissue Damage: ARDS,
AKI, Myocardial dysfunciton
Therapeutic Targets:
Monocyte Pro inflamamatoy, anti
inflammaty IL10, TGF B

31. Platelets Cardiopulmonary bypass (CPB) is associated with a temporary decrease in
platelet function and
number, which can impair post-operative hemostasis
•Platelets: More Than Just Clotting: Platelets are not only involved in
hemostasis but are also crucial cells in inflammatory and immune processes.
•CPB Impact on Platelets: "Platelet Dysfunction"
•Thrombocytopenia (low platelet count): 30-70%
•Hemodilution: From the priming solution.
•Consumption/Destruction: From contact with artificial surfaces in the
CPB circuit, shear stress from the pump, and mechanical destruction.
•Sequestration: Platelets may be sequestered in the liver or spleen.
•Functional Defect:
•Reduced Reactivity: Platelets that have gone through CPB may not
respond as well to agonists, a condition known as "platelet exhaustion".
•α-granule Release: P-selectin and platelet factor 4 (PF4) are released.
P-selectin on the surface of activated platelets binds to leukocytes.
•Bleeding Post-CPB: This thrombocytopenia and functional defect are major
causes of abnormal postoperative bleeding in patients, especially if the CPB
time is long.

32. Normal Platelet Function
(Briefly)
Normal Platelet Function (Briefly):
Adhesion: When the endothelium is damaged,
platelets adhere to the subendothelium via von
Willebrand Factor (vWF), which links GpIb on the
platelet to collagen.
Activation: Adhesion or contact with agonists (e.g.,
thrombin, ADP, collagen) activates platelets, causing
them to change shape (becoming spherical with
pseudopods) and release substances from their
granules.
Aggregation: Activated platelets express the
GpIIb/IIIa receptor, which binds to fibrinogen, causing
platelets to clump together (platelet plug).
Release Reaction: Various substances are
released, such as ADP, serotonin, and Thromboxane
A2 (TXA2). TXA2 causes vasoconstriction and further
stimulates other platelets.

33. Platelets Cardiopulmonary bypass (CPB) is associated with a temporary decrease in
platelet function and
number, which can impair post-operative hemostasis
Platelet-Leukocyte Aggregates (PLAs) : The Pro-inflammatory Duo
•This is a key mechanism directly linking platelets to inflammation.
•Activated platelets express P-selectin on their cell surface. P-selectin
binds to PSGL-1 (P-selectin glycoprotein ligand-1)
•Consequences of PLA formation:
•Enhanced Leukocyte Activation: Platelets in PLAs can "super-activate"
the attached leukocytes, causing them to release more inflammatory
substances.
•Cytokine Release from Monocytes: secrete IL-1β, IL-8, and MCP-1
•Induction of Tissue Factor (TF): P-selectin can also stimulate
monocytes to express Tissue Factor, a key initiator of the extrinsic
pathway of the coagulation cascade, leading to the generation of thrombin
and fibrin. This interplay where inflammation triggers thrombosis and vice
versa is called thromboinflammation or immunothrombosis, a key
mechanism in the pathogenesis of many diseases, including
complications from CPB.
•In summary, during CPB, platelets not only decrease in number and function,
increasing the risk of bleeding, but are also actively stimulated to promote a
systemic inflammatory response through the formation of PLAs and the
activation of other white blood cells.

34. Coagulation System The coagulation cascade can be
activated by both
the intrinsic and extrinsic pathways
Coagulation Pathways & CPB :
•Intrinsic Pathway: With the artificial (non-endothelial) surfaces ,
Factor XII.
•Extrinsic Pathway: Especially from Tissue Factor (TF) from injured
tissue, cardiotomy suction
•Common Pathway: Prothrombin to Thrombin, and Thrombin
converts Fibrinogen to Fibrin
•Simultaneous Fibrinolysis : In CPB,Plasmin activated, both systems
are heavily and simultaneously activated, creating a complex state.
•Thrombin: More than just clotting :
•Endothelial activation: (e.g., selectins), attracting white blood cells.
•Platelet activation: A very strong platelet agonist.
•Leukocyte activation: Can activate white blood cells directly or
indirectly.
•PARs (Protease-Activated Receptors): Thrombin, Factor Xa, and the Factor
VIIa-TF complex can activate various cells (endothelium, platelets, leukocytes, smooth muscle
cells) via PARs (especially PAR-1 for thrombin), leading to many biological responses related to
inflammation and tissue repair.

35. Coagulation System
CPB-induced Fibrinolysis & Bleeding :
Excessive activation of the fibrinolytic system by Factor XIIa and
Kallikrein during CPB can lead to:
•Increased Bleeding : Excessive clot breakdown makes
postoperative bleeding more likely.
•Platelet Dysfunction: Fibrin Degradation Products (FDPs) and
Plasmin itself may interfere with platelet function, particularly
adhesion via GpIb and aggregation via GpIIb/IIIa, contributing to a
complex coagulopathy after CPB.

36. Several mechanisms:
Classical Pathway: antigen-antibody complexes, Potamine, Contact activation
Alternative Pathway: Artificial surfaces of the CPB circuit (considered "non-self").
Lectin Pathway: May be activated by mannose-binding lectin that binds to carbohydrates on
certain surfaces.
Key Functions & Products:
Inflammation: C3a and C5a (called anaphylatoxins) are very potent inflammatory mediators.
They cause mast cells to release histamine, increase vascular permeability,
are strong chemoattractants
Opsonization: C3b (and iC3b), acts as a "tag" (opsonin) for phagocytes
(e.g., macrophages, neutrophils) to more easily recognize and engulf them.
Cell Lysis (Membrane Damage): C5b-9 (Membrane Attack Complex - MAC) assembles
into
a pore that perforates the target cell membrane (e.g., red blood cells, bacteria),
causing the cell to lyse and die.and to lysis. Contributes to hemolysis of fragile RBCs.
Complement System The complement system comprises
one of the most prominent immune mechanisms involved in the inflammatory
process, and it is activated by CPB

37. Amplification Cascade:
Complement operates as an enzyme cascade.
Cardiotomy Suction and Tissue Factor:
Tissue Factor from tissue injury. trigger the extrinsic pathway also potently activate the
complement system, significantly worsening SIRAB.
Modern View of Complement:
It's not to the MAC but a complex "network" with "hubs" like C3 and C5 that serve as
connection points to many other systems, coagulation, fibrinolysis, and adaptive immunity.
Therapeutic Target:
Because complement plays a key role in driving inflammation in CPB, there have been efforts
to develop drugs to inhibit this system (e.g., C1 esterase inhibitor, C5 inhibitors) to reduce SIRS
in cardiac surgery patients, but clinical outcomes still require further study.
Complement System

38. Endotoxemia in CPB
Systemic Inflammatory Response After Bypass
Endotoxin (Lipopolysaccharide - LPS): Is a component of the cell wall of gram-negative
bacteria.
Source: During CPB, splanchnic hypoperfusion (reduced blood flow to abdominal
organs),This allows endotoxin from bacteria in the intestine to translocate (leak) into the
bloodstream more easily.
Potent Inflammatory Stimulus: Endotoxin is a very potent inflammatory stimulus.
Specifically, it binds to Toll-like receptor 4 (TLR4) on the surface of macrophages
and monocytes, causing these cells to become highly activated
and secrete massive amounts of Tumor Necrosis Factor-alpha (TNF-α)
and other cytokines.
Findings from Rodent Model and Their Implication: TNF-α

39. IMMUNE RESPONSE AFTER
CARDIOPULMONARY BYPASS
Both cellular and humoral components of the
adaptive immune system
undergo changes in both function and number after CPB.
This section will examine the effects of CPB on adaptive immunity in general

40. Immuno deficiency and
Cardiopulmonary Bypass
The duration of CPB is associated with postoperative infection
•Adaptive Immunity Impairment: CPB "suppresses" adaptive immunity
•CPB Duration and Infection Risk: the longer the CPB time, This is a
combined result of immunosuppression, greater tissue injury, and increased
opportunity for pathogens to enter the body.
•Breakdown of Host Defenses: The body normally has a balance in
defending against pathogens, but CPB can disrupt this balance:
•Humoral immunity depression: Levels of immunoglobulins and
complement decrease, leading to poorer opsonization
•Cell-mediated immunity depression: The function of T-cells and other
cells (e.g., NK cells) is reduced.
•Opportunistic Infections: When overall immunity is weakened, especially
in patients with pre-existing complications like renal failure or low cardiac output.
•Sepsis-Related Organ Failure: Sepsis and Multisystem Organ Failure
(MSOF)

41. Humoral Immunity Serum immunoglobulin and
complement levels change
significantly during CPB
•Immunoglobulin (Antibody) Levels:
•IgG, IgM, IgA decrease:
•IgE: The fact that IgE does not change is perhaps allergies and parasites
•Complement Consumption: which adversely affects opsonization and direct
pathogen destruction.
•Leukocyte Dysfunction (Beyond Numbers):
•Reduced Chemotaxis: The ability of neutrophils to move to the site of infection is
reduced.
•Impaired Phagocytosis: The ability to "eat" pathogens or foreign substances is
reduced.
•B-Cell Changes: Data on B-cell numbers are inconsistent, but importantly, B-cell
"function" in producing antibodies (IgG, IgM, IgA) is clearly reduced when stimulated
with a mitogen (a substance that stimulates lymphocyte division) in the laboratory.
•Protein Denaturation: Denatured proteins may clump together as
microaggregates, which can be harmful to the microcirculation.

42. IMMUNE RESPONSE AFTER CARDIOPULMONARY
BYPASS
Mast Cells, Paneth Cells, and Gut I/R Injury :
Gut as a "Motor" of Inflammation: The intestine is an organ highly sensitive
to ischemia, which often occurs during CPB (splanchnic hypoperfusion).
When blood flow is restored (reperfusion), severe injury and inflammation
occur in the intestine, which can have systemic effects (gut-lung axis, gut-
brain axis).
Mast Cells: These are immune cells resident in tissues., they release a
large number of inflammatory mediators (histamine, proteases, leukotrienes, prostaglandins,
cytokines).
Paneth Cells: These are specialized epithelial cells located at the
base of crypts in the small intestine. They play a role in antimicrobial
defense by secreting antimicrobial peptides, but in the context of I/R injury,
they can also secrete IL-17, a pro-inflammatory cytokine
Clinical Relevance: Gut injury after CPB can lead to complications
such as bacterial translocation, endotoxemia, and exacerbated SIRS.
Understanding the
role of these cells may lead to targeted therapies to protect the intestine.

43. Natural Killer (NK) Cells:
•Eliminating virus-infected cells and cancer cells without prior specific activation (non-specific
killing).
•The reduction in the number and function of NK cells after CPB further increases the patient's
risk of infection, especially viral infections, and may affect the control of abnormal cells.
Reticuloendothelial System (RES) / Mononuclear Phagocyte System (MPS):
•It consists of phagocytic cells (mainly macrophages) in the liver (Kupffer cells), spleen, lungs
(alveolar macrophages), and lymph nodes or spleen (sinus histiocytes).
•"Garbage Collector" of the Body: It performs the critical function of "cleaning up" foreign
substances, dead cells, denatured proteins, microparticles, and pathogens from the bloodstream.
•RES Dysfunction in CPB: The generation of a large number of microparticles by CPB (e.g., from cell
destruction, denatured proteins) and the contact of blood with artificial surfaces can cause the RES to
become "overwhelmed" or "saturated." This reduces its efficiency in clearing other foreign substances
and pathogens, allowing pathogens or endotoxins that enter the bloodstream to persist longer and further
stimulate systemic inflammation.that someone important said and can make the reader get inspired.”
IMMUNE RESPONSE AFTER
CARDIOPULMONARY BYPASS

44. Pharmacologic Manipulation
Attempts to use drugs to suppress the inflammatory response in
cardiac surgery
to prevent the formation of the
Membrane Attack Complex (MAC) and
C5a.
anti-inflammatory agents :
dexamethasone, found no significant
reduction in mortality or improvement
(pediatric patients or those at high risk
for an exaggerated inflammatory
response)
inhibits the opening of the
Mitochondrial Permeability Transition
Pore (MPTP), reduction in cardiac
troponin I
Pexelizumab
(Anti-C5 Complement Inhibitor):

Corticosteroid
s :
Cyclosporine :

45. Mechanical Manipulation
Ultrafiltration (UF)
Modified Ultrafiltration
(MUF)
Hemoperfusion:
MUF is the filtration of blood
after CPB to remove excess
water
(to correct hemodilution,
reduce tissue edema) and may
help remove some
inflammatory mediators from
the body.
Leukocyte-Depleting
Filters:
Rationale: To remove
white blood cells
(especially neutrophils),
which are key agents in
tissue damage, from the
blood before it is returned
to the patient.
Pulsatile vs.
Nonpulsatile
Perfusion:
The Debate: This has
been a topic of debate for
decades. The theory is
that pulsatile flow
(mimicking the heart's
contraction) should be
better for microcirculation
and organ function than
nonpulsatile flow
(continuous flow).

46. Mechanical Manipulation
Heparin-Bonded
Circuits:
Rationale: Coating the
surfaces of the CPB
circuit (tubing, oxygenator,
filter) with heparin makes
the surface more
"biocompatible," reducing
the activation of the
contact activation system,
complement, and
platelets.
Minimized Cardiopulmonary Bypass (Mini-CPB) Circuits:
Concept: This involves "miniaturizing" the CPB circuit as much as
possible to reduce the adverse effects of blood contact with
artificial surfaces and hemodilution.
Reduced priming volume:
Reduced surface area:
Closed system:
Elimination of cardiotomy suction (often):

47. CONCLUSIONS
In conclusion, despite numerous pharmacological
and mechanical efforts to reduce inflammation from CPB,
there is no "magic bullet" or single method that can
completely eliminate inflammation and demonstrate clear
clinical benefits in all aspects.
Understanding the fundamental mechanisms of
inflammation remains crucial for developing new
strategies. Meanwhile, best clinical practices (e.g.,
minimizing CPB duration, maintaining optimal temperature,
ensuring good blood pressure and perfusion, and careful
blood management) remain the cornerstone of mitigating
the effects of CPB.

48. RISK FACTORS
30
%
30
%
20
%
10
%
50
%
25
%
AnimiaAUTOIMMUNE
THYROIDITIS
ARDH ,CKDHT, Old AgeTYPE 1
DIABETES
DOWN
SYNDROME

49. THANK
S!
D