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The impact of ischaemia–reperfusion on the blood vessel
Maximilien J. Gourdin
a
, Bernard Bree
b
and Marc De Kock
b
Ischaemia significantly affects the cellular homeostasis
(sodium and calcium overload, intracellular acidosis,
swelling, cytoskeleton injuries, mitochondrial
hypercalcaemia and others). If reperfusion of an organ in
ischaemia is essential for its viability and its functional
recovery, the arrival of blood oxygen will cause a series of
lesions; this is known as the phenomenon of ischaemia–
reperfusion. Vasomotricity and the endothelial functions
are significantly affected by it. Endothelium-dependent
vasodilatation is more affected by ischaemia–reperfusion
injuries than vasoconstriction and endothelial-
independent vasodilatation. Reactive oxygen species and
tumour necrosis factor-a seem to play a major role in this
perturbation. Reperfusion also induces an important
inflammatory response, characterized by a massive
production of free radicals and by the activation of the
complement and leucocyte neutrophils. A narrow
interaction between activated endothelium and neutrophils
will result in a significant concentration of neutrophils
activated in the interstitium, where they release many
oxygen radicals and many kinds of proteases, which
destroy cells and extracellular matrix. This transfer of
neutrophils from the intravascular bed to the intestitium
involves several families of proteins such as selectins
(P-selectin and L-selectin), integrines (intercellular
adhesion molecule-1) and immunoglobulins (platelet–
endothelial cell adhesion molecule-1). Last, oxidative
stress, the production of cytokines and the secondary
mitochondrial lesions that occur with reperfusion will
induce apoptosis on the level of the parenchyma and the
vascular structures. According to the stage of the vascular
system considered (small arteries, capillaries or
postcapillary veins), the repercussions of ischaemia–
reperfusion are identical, but the clinical pictures differ. The
proinflammatory state induced by reperfusion continues
for several days and can affect the patient’s prognosis. Eur J
Anaesthesiol 26:537–547 Q 2009 European Society of
Anaesthesiology.
European Journal of Anaesthesiology 2009, 26:537–547
a
Department of Anaesthesiology, Universite ´ Catholique de Louvain, University
Hospital of Mont Godinne, Yvoir and
b
Department of Anaesthesiology, Universite ´
Catholique de Louvain, University Hospital Saint-Luc, Brussels, Belgium
Correspondence to Maximilien J. Gourdin, MD, Department of Anaesthesiology,
Universite ´ Catholique de Louvain, University Hospital of Mont Godinne, Avenue
Dr Therrasse 1, 5530 Yvoir, Belgium
Tel: +32 81 422111 x 3917; fax: +32 81 423920;
e-mail: maximilien.gourdin@uclouvain.be
Received 26 March 2008 Revised 30 June 2008
Accepted 3 October 2008
Introduction
The reperfusion of an organ in ischaemia is essential for its
viability and its functional recovery. But there is a flip side
to this coin, the arrival of blood oxygen will cause a series of
lesions; this is known as the phenomenon of ischaemia–
reperfusion (I/R). Histologically, the restoration of an
adequate blood flow to liver or intestines after 3h of
ischaemia followed by 1h of reperfusion presents more
parenchymatous or mucous membrane necroses than
the same organ subjected to 4h of ischaemia alone [1,2].
The arterial clamping/unclamping in vascular surgery, the
use of a tourniquet in orthopaedic surgery, cardiac surgery
with or without extracorporeal circulation, transplant
surgery, haemorrhagic shocks, septicaemia and low
blood flow states are only some examples which illustrate
daily I/R in clinical practice in the operating theatre.
I/R generates an important local inflammatory reaction
which affects mainly the organ concerned but can also
affect two other organs. In orthopaedic surgery, the use of
the tourniquet on the lower limbs affects both the lung
and liver [3–5]. A small intestine I/R induces apoptotic
and necrotic parenchymatous lesions in pulmonary, renal
and cardiac endothelium [6]. Organs with a high capillary
density such as the lungs are more sensitive to I/R lesions.
A remote I/R such as that of the splanchnic bed or a lower
limb in orthopaedic surgery can induce an acute lung
injury [6]. Often, these repercussions remain subclinical
but can generate a systemic inflammatory response syn-
drome or even multiorgan failure and lead to the death of
the patient [6].
The vascular system and particularly the endothelium are
very sensitive to I/R injuries. The endothelial cells have
multiple vital duties; they control vascular tonicity and
local blood flow, modulate coagulation and inflammation,
intervene in the immune system, control the transfer of
micro and macromolecules towards the interstitial region,
convert prohormones into active hormones (angiotensin
II) and intervene in the formation of new blood vessels. It is
thus vital to preserve them. In the heart, the reperfusion-
induced endothelial injuries contribute to myocardial
depression [7,8]. The effects of I/R on the endothelium
can go from the sideration of endothelial function
to necrosis.
The importance and the frequency of the I/R phenom-
enon in clinical practice make its physiopathology of
interest to anaesthesiologists. This review proposes to
present to clinicians the various stages and mechanisms
Review 537
0265-0215 ß 2009 Copyright European Society of Anaesthesiology DOI:10.1097/EJA.0b013e328324b7c2