Upload
others
View
1
Download
0
Embed Size (px)
Citation preview
The benefits of MiECC on the human endothelium
Dr. Winkler Bernhard
Consultant Cardiac Surgery
Department of Cardiac Surgery
University Hospital Berne
Universitätsklinik für Herz- und Gefässchirurgie
2
Universitätsklinik für Herz- und Gefässchirurgie
• activation of blood elements
• vasoactive substances und endotoxines
• body fluid balance, hemodilution
• activation of coagulation
• embolisation and thrombus formation
• adsorption of serum proteins
Influence on the endothelium: direct vs indirect
Negative effects of cardio pulmonary
bypass (CPB) or standard
extracorporeal circulation (ECC)
4
Universitätsklinik für Herz- und Gefässchirurgie
• contact system
CPB: Activation of blood elements
Edmunds HL. Inflammatory Response to CPB. Ann Thorac Surg 1998;66:S12-6
Systemic
proinflammatory
response
coagulation
disorder
5
Universitätsklinik für Herz- und Gefässchirurgie
• complement system• activated by classical pathway via F XIIa, alternative pathway
activated by C3b;
• C5a directly activates Nc, leads to cell lysis
• C3a negative effect on myocardial contractility
• C3a, 4a, 5a increase capillary permeability, release of Histamin:
vasodilation, bronchospasm
CPB: Activation of blood elements
main proinflammatory stimulus
associated with creation of free
oxygen radicals and significant
morbidity [1][1] Edmunds LH Jr. Why CPB makes patients sick, in Karp RB et al. (eds): Advances in
Cardiac Surgery, Baltimore, Mosby-Year Book, Inc 1995:131-67
6
Universitätsklinik für Herz- und Gefässchirurgie
• Platelets
• activated by Thrombin, Adrenalin, plateled activating factor
– release of inflammatory mediators
• Serotonin, TXA2, Hydrolase, Proteinase
– activation of coagulation
– depletion by adsorption, aggregation, dilution
CPB: Activation of blood elements
Increased capillary
permeability, vasomotor tone,
Nc attraction
Increased bleeding risk
7
Universitätsklinik für Herz- und Gefässchirurgie
• Monocytes
– release IL-8, IL-6 und IL-1 during and after CPB
• Endothelial cells
– release t-PA, Prostacyclin, Endothelin 1 and PAF
– activate fibrinolysis and platelets
CPB: Activation of blood elements
systemic proinflammatory response
vasoconstriction, coagulation disorders
8
Universitätsklinik für Herz- und Gefässchirurgie
Function of the Endothelium
Barrier function:
the endothelium acts as a semi-selective barrier, controlling transit of
cells into and out of the bloodstream
Excessive or prolonged increases in permeability of the endothelial
monolayer, as in cases of chronic inflammation, may lead to tissue
edema.
Thrombosis and fibrinolisis:
The endothelium normally provides a non-thrombogenic surface
because it contains, for example, heparan sulfate which acts as cofactor
for activating antithrombin (a protease that inactivates several factors in
the coagulation cascade)
9
Universitätsklinik für Herz- und Gefässchirurgie
The Endothelium-nearly an organ
Vascoconstriction and Vasodilatation, and hence the control
of blood pressure
Repair of damaged or diseased organs via an injection of
blood vessel cells
Angiopioetin-2 secretion: works with VEGF to facilitate cell
proliferation and migration of endothelial cells
Formation of new blood vessels- Angiogenesis
11
Universitätsklinik für Herz- und Gefässchirurgie
Stimuli
• In the absence of pro-angiogenic stimuli, endothelial cells (ECs) are
retained in a quiescent state.
• In addition, EC homeostasis is maintained by low-level autocrine
vascular endothelial growth factor A (VEGFA) signalling124.
• During angiogenesis, high levels of exogenous pro-angiogenic factors
(such as VEGFA and VEGFC) and of VEGF receptor 2 (VEGFR2) or
VEGFR3 signalling select 'tip cells' (TCs) for sprouting.
• TC sprouting behaviour is facilitated by the vascular endothelial
cadherin-mediated loosening of EC–EC junctions, matrix
metalloproteinase-mediated degradation of extracellular matrix (ECM)
and the detachment of pericytes .
12
Universitätsklinik für Herz- und Gefässchirurgie
Endothelial repair: CEC, EPC- adventitial stem cells
14
Universitätsklinik für Herz- und Gefässchirurgie
CEC, EPC,EC,SMC…?
• Detachment of endothelial cells may represent serious
injury of the endothelium after cardiopulmonary bypass.
• In diabetic patients, smokers,after myocardial infarction the
number of CEC ( circulation endothelial cells) can be used
as a measure to quantify and detect the grade of vascular
injury/damage
• Difference between conventional or minimized circuit ?
15
Universitätsklinik für Herz- und Gefässchirurgie
How to study CEC
Circulating endothelial cells can be isolated from peripheral blood
samples at specific time points:
• Sample I: preoperatively before onset of CPB to acquire
baseline cell number
• Sample II: 30 minutes after initiation of CPB
• Sample III: 12 hours postoperatively
• Sample IV: 24 hours postoperatively
• Sample V: 48h after CPB initiation
• Sample VI: 72 after CPB
16
Universitätsklinik für Herz- und Gefässchirurgie
CEC detection
• Parameters:
–von Willebrand Factor (vWF)
–Soluble Thrombomodulin (sTM)
–Circulating Endothelial Cell (CEC): magnetic beads,
sorting, FACS
–Progenitor/ EC detection:/ FACS
–CD 34
–CD 309
–CD 31 bright cells
17
Universitätsklinik für Herz- und Gefässchirurgie
Possible Solutions through using a MIECC
• Minimized Cardiopulmonary Bypass Circuit / Priming
• Rotary Pump / Hydrophobe mini-Oxygenator
• Cristalloide Single-Shot Cardioplegia: Cardioplexol®
• Reduction of blood-air interface: Cardiosmart®
18
Universitätsklinik für Herz- und Gefässchirurgie
Literature I
The endothelial damage, the granulocyte sequestration, and
its activation are much lower since the artificial surface is
smaller *
*P. Massoudy et al.
Reduction of pro-inflammatory cytokine levels and
cellular adhesion in CABG procedures with separated
pulmonary and systemic extracorporeal circulation
without an oxygenator Eur J Cardiothorac Surg, 2000, pp.
729–736
19
Universitätsklinik für Herz- und Gefässchirurgie
Literature II
• Quantification of circulating endothelial cells and perioperative
outcome in less invasive coronary surgery: Are Off-pump
procedures superior than minimized extracorporeal circulation?
• Conceptional advantages of closed-minimised-CPB-systems
(ROCsafe™) result in morbidity and mortality comparable with OPCAB
procedures. MiniHLM therefore minimizes CPB-related systemic and
organ injury as demonstrated by low CEC-values which indicates intact
endothelial integrity.
*T. Witwer et al. Thorac cardiovasc Surg 2014; 62 - OP4
20
Universitätsklinik für Herz- und Gefässchirurgie
Skrabal, A. Liebold et al JVCTS 2006
• 20 patients , elective coronary bypass grafting were randomly assigned to
either the minimal extracorporeal circulation system or the standard
cardiopulmonary bypass circuit
• Ten healthy volunteers served as controls.
• Circulating endothelial cells per milliliter of full blood were perioperatively
determined by immunomagnetic cell separation technique. Endothelial plasma
markers were measured by enzyme-linked immunosorbent assay.
Preoperative circulating endothelial cell numbers did not differ between the
experimental groups, but were significantly higher than in the healthy controls
(18.6 ± 5.6 vs 7.2 ± 3.8, P < .001) ( cardiovascular risk factors..)
21
Universitätsklinik für Herz- und Gefässchirurgie
Skrabal, A. Liebold et al JVCTS 2006
• At 6 hours, circulating endothelial cell numbers increased significantly
compared with baseline in both experimental groups and peaked at 12 hours
after cardiopulmonary bypass initiation, each time with significantly lower
values in the minimal extracorporeal circulation group (6 hours: 44.0 ± 9.9 vs
29.6 ± 9.8, P = .007; 12 hours: 48.1 ± 6.8 vs 31.8 ± 7.1, P < .001)
• Likewise, von Willebrand factor and soluble thrombomodulin postoperatively
increased in both groups with a tendency toward lower levels in the minimal
extracorporeal circulation group.
22
Universitätsklinik für Herz- und Gefässchirurgie
Conclusions
CECs are more accurate in detecting the intrinsic
endothelial damage.
Patients with cardiovascular disease not only have
a higher CEC baseline ( more damage-more
renewal); additional damage is caused by the
standard CPB
The MiECC system may be less injurious to
endothelium than the standard CPB.
Call for large study??