Best Practice & Research Clinical Anaesthesiology 30 (2016) 257e269

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Best Practice & Research Clinical

Anaesthesiology
journal homepage: www.elsevier.com/locate/bean

The pathophysiology of aortic cross-clamping

Martin Zammert, MD, Director of Vascular Anesthesia,
Attending Anesthesiologist *,
Simon Gelman, MD PhD, Professor of Anesthesia
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard
Medical School, Boston, MA, USA

Keywords:
During open aortic surgery, interrupting the blood flow through
aortic cross-clamping
the aorta by applying a cross-clamp is often a key step to allow for
ischemia-reperfusion injury
blood shift surgical repair.
postconditioning As a consequence, ischemia is induced in parts of the body distal to
the clamp site. This significant alteration in the blood flow is
almost always associated with hemodynamic changes. Upon
release of the cross-clamp, the blood flow is restored, triggering an
ischemia-reperfusion response, leading to many pathophysiolog-
ical processes such as inflammation, humoral changes, and
metabolite circulation that could lead to injury in many organ
systems and may significantly influence the postoperative
outcome.
It is therefore important to understand these processes and how
they can be treated in order to allow for safe surgical aortic repairs
while ensuring the best possible outcomes.
© 2016 Elsevier Ltd. All rights reserved.

The time of temporary cross-clamping of the aorta and consecutively removing the clamp and
restoring the blood flow to the part of the body distal to the clamp site are among the most critical steps
for the anesthesiologist during surgery involving the aorta.
Open surgical procedures of the thoracoabdominal aorta carry the highest mortality rate among
elective procedures, with a reported overall 30-day mortality ranging from 8% to 35% [1].

* Corresponding author. Brigham and Women's Hospital, Department of Anesthesiology, Perioperative and Pain Medicine, 75
Francis Street, Boston, MA 02115, USA.
E-mail address: mzammert@partners.org (M. Zammert).

http://dx.doi.org/10.1016/j.bpa.2016.07.006
1521-6896/© 2016 Elsevier Ltd. All rights reserved.
258 M. Zammert, S. Gelman / Best Practice & Research Clinical Anaesthesiology 30 (2016) 257e269

Understanding the various effects of the temporary occlusion of the aorta is important to appropriately
manage the patient during this critical phase of the operation.

Hemodynamic changes during aortic cross-clamping

The changes that follow the application of a cross-clamp on the aorta depend to a degree on the
location of the clamp. While some hemodynamic changes are similar when a cross-clamp is applied to
either the abdominal aorta or the thoracic aorta, the changes in some hemodynamic parameters may
be different.
After applying a clamp on the aorta, an increase in the arterial blood pressure and systemic vascular
resistance (SVR) is almost uniformly observed. The increase in the arterial blood pressure is greater if
the thoracic aorta is clamped than with the clamping of the abdominal aorta. The heart rate does not
often significantly change in either circumstance [2,3].
Numerous studies have been performed in an attempt to clarify the specific changes in the cardiac
output, preload, and filling pressures that follow the application of an aortic cross-clamp.
Stokland and coworkers investigated the changes in the blood flow during aortic clamping in a
canine model. They occluded the aorta and the vena cava at different levels, while examining the left
ventricular distention by measuring the myocardial fiber length. During occlusion of the thoracic aorta,
they observed an increase in the preload and ultimately the blood pressure. However, when the
inferior vena cava (IVC) was also occluded at the diaphragmatic level, this increase in preload as well as
the increase in blood pressure was not observed. This suggests that the blood flow might shift from the
splanchnic vasculature into the IVC, leading to the observed increase in the preload and blood pressure
[4].
The reason for this drainage of blood from the splanchnic system is in part due to the recoil of the
splanchnic vasculature once the transmural pressure decreases below the natural recoil of the venous
system, leading to a collapse of the respective venous system. This drainage of blood into the IVC will
consequently increase the preload, which by the FrankeStarling mechanism allows the heart to
maintain or even increase the stroke volume and cardiac output.
Stokland and coworkers also observed that the blood flow through the superior vena cava (SVC)
almost doubled during the clamping of the descending thoracic aorta, while the blood flow through the
IVC decreased by almost 90%, indicating an even more complex shift in the blood flow toward areas
above the aortic cross-clamp [4].
Gelman et al. found similar shifts in blood volume during clamping of the aorta at the level of the
diaphragm. In their canine model, the activity of the Tc99m-labeled plasma albumin increased by
8e38% in areas proximal to the clamp such as the brain, heart, deltoid muscle, and lungs. This increase
in blood volume was however not observed during suprarenal aortic clamping. They concluded that
the blood flow could shift from capacitance vessels distal to the occlusion toward areas proximal to the
cross-clamp [5].
In addition, the application of an aortic cross-clamp increases the release of catecholamines and
angiotensin (the mechanism will be explained later). The increase in these vasoactive substances may
lead to a constriction of arterioles and venules, which in turn may contribute to the shift in the blood
flow toward the parts of the body proximal to the aortic clamp [6,7].
If the cross-clamp is applied to the infraceliac aorta, the data on changes in the preload and cardiac
output are inconclusive. Stokland performed clamping of the abdominal aorta and selective clamping
of the lower IVC and selective veins, and demonstrated that during occlusion of the abdominal aorta,
the blood flow shifts from the nonsplanchnic venous system into the IVC, leading to an increase in the
preload and the blood pressure [8].
However, some data suggest a decrease in the cardiac output [9], while other data suggest that it
remains the same [10]. The reasons for this inconsistent data may be that the blood flow may also shift
from the nonsplanchnic vasculature into the splanchnic vasculature, which may lead to a decrease in
preload and cardiac output rather than an increase.
While it is interesting to know how the cardiac output is affected by clamping of the aorta per se, in
a clinical operative scenario, the changes in the cardiac output will also be influenced to a significant
degree by the presence or absence of surgical bleeding, anesthetic technique, and active fluid
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management by the anesthesiologist as well as by regular medication taken by the patient, such as
beta-blockers and calcium channel blockers.
Changes in hemodynamic variables such as the end-systolic left ventricular area, ejection fraction,
and filling pressures, when assessed by transesophageal echocardiography, are minimal during
infrarenal aortic cross-clamping [11]. Left ventricular wall motion abnormalities are usually not
observed during infrarenal clamping; however, they do occur in 33% of the time during suprarenal
clamping [11].
In the same study, Roizen and colleagues found that during supraceliac aortic cross-clamping, filling
pressures may increase by 40%, while end-diastolic and end-systolic areas can increase by 28% and 70%,
respectively, when assessed by transesophageal echocardiography. Left ventricular wall motion ab-
normalities were observed in 92% of the time during supraceliac clamping according to this study. The
clinical significance of these observed echocardiographic changes however is unclear.
Given the increase in the preload and afterload during thoracic aortic clamping, the heart itself will
have to adapt to these sudden changes. As early as 1912, Anrep observed that sudden aortic occlusion
lead to left ventricular dilatation, which was followed by partial recovery despite sustaining high blood
pressure levels [12]. Since then, other studies have confirmed this observation that despite continuing
elevated left ventricular systolic blood pressure, both end-diastolic volume and pressure returned to
the normal level, suggesting an increase in inotropy [13]. The sudden increase in arterial blood pressure
and left ventricular pressure may lead to acute compression of subendocardial blood vessels and
subsequent ischemia. This may cause a decrease in myocardial contractility. It is presumed that
vascular autoregulation can regulate subendocardial blood distribution and increase the blood flow to
the affected areas, which in turn increases the otherwise compromised contractility of the heart
[14,15]. This effect was termed the “Anrep effect” [16].
This however does not apply to patients with concomitant coronary artery disease (CAD). In pa-
tients with CAD, the pulmonary capillary wedge pressure remains increased while the cardiac index
remains decreased after applying a cross-clamp on the aorta. This might indicate that in this patient
population, the ability of the subendocardial tissue to adapt to ischemia by the mechanism of vascular
autoregulation may be compromised, thus leading to the decrease in the contractility of the heart [17].
As most patients undergoing aortic surgery have CAD, this is an important consideration and could
explain left ventricular decompensation during aortic clamping in these patients.
Vasodilators such as nitroglycerin may increase the cardiac output by decreasing the afterload and
preload and by increasing coronary perfusion and thus facilitating the Anrep effect [18] (Figs. 1, 2).

Fig. 1. Hemodynamic changes during supraceliac aortic clamping.

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Fig. 2. Hemodynamic changes during infraceliac aortic clamping.

In patients with occlusive disease of the aorta, the hemodynamic responses to aortic cross-clamping
are less pronounced than in patients with aneurysmal disease. In a study by Johnston and coworkers,
the changes in stroke volume and SVR correlated with the degree of aortic collateral vascularization.
With a higher degree of collateral vasculature, the changes in stroke volume and SVR were less pro-
found than in patients with less or no collateral blood flow [19].
Given these changes in blood flow, increased vascular permeability, etc., fluid management is a key
component of the management of these patients during open aortic repair. Fluid management in
general has gained importance in any major surgery during the last decade. Markers such as pulse
pressure variation (PPV) have been used as a guide to fluid administration. However, Biais et al. have
concluded that PPV is unable to predict fluid responsiveness during the time of infrarenal aortic cross-
clamping. In their pig model, the PPV significantly increased during the time of cross-clamping, but
fluid administration did not increase the stroke volume [20]. The reason for this could be the fact that
the blood flow shifts from the infrasplanchnic to the splanchnic vasculature.
The aortic pressure distal to the occlusion is significantly decreased and depends on the aortic
pressure proximal to the clamp site [21]. The perfusion to the tissue and organs distal to the aortic
cross-clamp depends on collateral vasculature and even more on perfusion pressure rather than on
cardiac output [21]. The clinical significance of these findings is that in order to maintain at least some
blood flow to the tissues and organs below the aortic clamp site, the aortic pressure proximal to the
clamp should be kept as high as the heart can tolerate to minimize ischemic injury to those organs.
Oxygen consumption decreases in areas distal to the level of the aortic cross-clamp, simply because
of the lack of oxygen supply. However, interestingly, the oxygen uptake in the muscular tissue in areas
proximal to the thoracic aortic cross-clamp, such as the deltoid muscle, also decreases [22]. The reason
for this is unknown, but as this effect starts immediately after the cross-clamp is applied, mechanisms
other than the accumulation of anaerobic metabolites may cause this effect. Arterio-venous shunting
above the clamp and an increase in sympathetic discharge that leads to a decrease in the capillary
nutritive blood flow may contribute to this phenomenon of cross-clamp-adapted oxygen consumption
[23,24].
The duration of aortic occlusion itself is an important factor. With increased duration of aortic cross-
clamping, SVR gradually increases and the cardiac output may decrease over time regardless of the
initial increase [25]. Fluid shifts from the intravascular to the interstitial compartment due to increased
pressure gradients and subsequent intravascular volume loss as well as the release of vasoactive
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substances during cross-clamping have been discussed as additional causes of a decrease in the cardiac
output during ongoing aortic occlusion, but lack confirmed data.
The formation and release of inflammatory substances such as leukotriene B4 and hypoxanthine
correlate with the duration of aortic occlusion and increase with prolonged aortic clamping [26,27].
In a rat model, 60 min of intestinal ischemia showed only a moderate increase in endotoxins and
interleukin-6; however, 120 min of ischemic time resulted in a tenfold increase in cytokines and tumor
necrosis factor (TNF) [28].
From a clinical perspective, an aortic cross-clamp duration of greater than 90 min is independently
associated with a higher mortality [29].

Hemodynamic changes after unclamping

The removal of the aortic cross-clamp is consistently associated with a significant reduction in
vascular resistance and a consequent decrease in the arterial blood pressure [30,31]. The blood vessels
in the previously ischemic areas are severely dilated because of the accumulation of adenosine, lactate,
and CO2 during the time of ischemia. This increases the capacity of these blood vessels [32] to levels
above baseline, thus promoting a shift in blood flow and volume into those previously under-perfused
areas. This shift in blood flow and the increase in vascular capacity in the areas below the clamp site
may lead to central hypovolemia. Simultaneously, vasodilating compounds such as adenosine and
lactate are washed out of the previously ischemic areas into the circulation, leading to additional
vasodilatation, thus reducing blood pressure. Infusion of fluid and increase in intravascular volume
prior to the release of the aortic cross-clamp can help to attenuate the development of central hypo-
volemia and to avoid significant hypotension [33,34].
The use of vasopressors, which may be dictated clinically because of severe hypotension upon
release of the aortic cross-clamp, might actually promote this redistribution of blood volume, as the
nonischemic areas proximal to the clamp might be more reactive to vasopressors than the ischemic
and acidotic regions distal to the clamp site [35].
Reactive hyperemia is an important component of the response to aortic unclamping. This might be
explained by an induced arterial vasodilation distal to the clamp during the time of ischemia, resulting
from smooth muscle relaxation and thus facilitating higher flows in that area after removal of the aortic
clamp [32,36].
Cardiac output at that time may decrease, increase, or remain unchanged [30]. Left ventricular end-
diastolic pressure decreases and myocardial perfusion increases [30]. The blood flow in areas proximal
to the cross-clamp site reduces to levels close to the time before clamping relatively quickly [5].
The gradual release of the aortic cross-clamp and its partial or complete reapplication if significant
hypotension develops has been recommended. This avoids the abrupt changes in vascular resistance
and the shift in blood flow and volume, thus attenuating the development of central hypovolemia and
hypotension. The release of vasoactive and cardiodepressant metabolites from the ischemic areas will
also be less abrupt. In addition, the production of oxygen-free radicals is reduced if the clamp is
removed slowly [37]. This concept is known as postconditioning (Fig. 3).

Humoral effects during aortic cross-clamping

Acidosis

Metabolic acidosis and increased lactate levels develop in the ischemic areas distal to the aortic
cross-clamp [38]. The degree of acidosis and increase in the lactate concentration depend on the
duration of aortic clamping and the underlying disease of the patient. In occlusive disease, the
development of acidosis is less profound than in aneurysmal disease. This results probably from the
development of collateral vessels in patients with occlusive disease, which enables better distal
perfusion after the application of the cross-clamp.
Many investigators have suggested that metabolic acidosis and ischemic metabolites greatly expand
the vasculature in the areas distal to the clamp, thus contributing to the hypotension observed after
unclamping the aorta. The administration of sodium bicarbonate to correct the present acidosis
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Fig. 3. Hemodynamic changes after unclamping the aorta.

however does not affect the degree of post-unclamping hypotension [33]. This might be due to the
correction of acidosis in the blood rather than in the tissue, including the arterial walls. Unclamping of
the aorta also leads to a transient increase in CO2 washout as well as increased CO2 production due to
an increase in oxygen consumption in the now reperfused tissues, which can aggravate both vasodi-
latation and hypotension [39,40].
The decrease in the intramuscular pH distal to the clamp site and in the pH of the femoral venous
blood persists long after the blood flow to those areas is restored [41,42]. This is indicative of severe
metabolic derangement and cellular damage induced by aortic cross-clamping.

Renineangiotensin system

Renin and angiotensin levels are increased during aortic cross-clamping [35,43]. During suprarenal
clamping, these changes are easily explained by the reduced perfusion pressure in the afferent arte-
rioles. During infrarenal clamping, the cause for the observed increase in renin and angiotensin con-
centrations is less clear.
In animal studies, where some of the animals were pretreated with angiotensin-converting enzyme
inhibitors, the hypertension that developed after the clamping of the aorta was less profound than in
the control animals, suggesting that the release of renin and angiotensin may play an important role in
the development of increased blood pressure during aortic clamping [25]. The increase in the con-
centration of these vasoactive substances may last longer than 6 h after unclamping of the aorta;
however, this does not correlate with postoperative hypertension [44].
The clinical significance of these increased hormone levels remains unclear as the hemodynamic
changes during application and after release of the aortic cross-clamp are influenced by many factors.

Sympathetic nervous system and catecholamines

Cross-clamping of the thoracic aorta leads to an increase in the circulating epinephrine and
norepinephrine levels [6,7]. A similar increase is also noted during cross-clamping of the abdominal
aorta, but to a lesser degree.
Interestingly, epinephrine release increases predominantly after the application of the cross-clamp,
while norepinephrine mainly increases after the release of the cross-clamp [7].
The etiology for this increase in catecholamine release is considered to be multifactorial. Sympa-
thetic reflexes influenced by hypotension combined with direct ischemic excitatory stimuli of the
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spinal cord and the adrenal medulla play an important role in the release of hormones of the sym-
pathetic system, leading to an increase in the blood pressure [45].

Reactive oxygen species

Ischemia-reperfusion leads to changes in the muscular mitochondria and to the production of

reactive oxygen species (ROS) [46]. The occurrence of ROS during ischemia is an ongoing debate. Guillot
and coworkers examined the production of ROS in a rat model, measuring the ROS levels after
clamping the aorta and inducing ischemia for 3 h. The ROS levels were measured after 3 h of aortic
clamping, after 10 min of reperfusion, and after 2 h of reperfusion. They demonstrated that ischemia
alone leads to an increase in ROS production. After 10 min of reperfusion, the ROS level decreased,
suggesting that muscle antioxidant capacities were active and efficacious during the first 10 min of
reperfusion. Interestingly, the levels subsequently increased again after 2 h, showing a biphasic pattern
of increase in ROS in ischemia-reperfusion injury [47].
During ischemia, the metabolism of adenosine triphosphate produces adenosine, hypoxanthine,
xanthine oxidase, purines, and free oxygen radicals [48,49].
The concentration of hypoxanthine in particular increased threefold in humans after infrarenal
aortic clamping, because of high levels of hypoxanthine in femoral venous blood [26]. Hypoxanthine
can cause cellular damage during reperfusion by producing cytotoxic ROS that lead to tissue damage
[48,50].
Decreasing or delaying the oxygen delivery during reperfusion (postconditioning) has been shown
to reduce the extent of ischemia-reperfusion injury in animal models [51]. Initial reperfusion with
deoxygenated blood showed a decrease in post-ischemic microvascular injury in a dog model [52].
Recent studies in a pig model have shown improved antioxidant capacity with hypoxic reperfusion, but
they were unable to show a clinical improvement in end-organ function [53].

Phosphate

Some patients undergoing abdominal aortic surgery will demonstrate significant hypo-
phosphatemia postoperatively, in particular 48 h after the end of the procedure [54]. This might in part
be explained by an increase in phosphate compound synthesis after restoration of blood flow, leading
to a shift in phosphate from the extracellular to the intracellular compartment. The role of urinary
excretion of phosphate in ischemia-reperfusion scenarios is currently unknown. In the clinical setting,
phosphate levels should therefore be checked on a regular basis at least until 48 h postoperatively and
restored when needed.

Prostaglandins, platelets, neutrophils, and complement system

Prostaglandin and thromboxane concentrations are elevated during aortic surgery [55,56]. Pros-
tacyclin is released even before the application of the aortic cross-clamp due to mesenteric manipu-
lation [57,58], while thromboxane concentration in the plasma increases after clamping of the aorta
[58].
Some studies found that the release of these substances and their vasodilating effects may attenuate
the hypertension observed during aortic clamping, and they considered this to be a compensatory
mechanism [55].
Other studies have linked the release of thromboxane in particular to a decrease in cardiac
contractility during aortic clamping [59]. Aspirin may attenuate these cardiodepressive effects [58],
and this might be the reason for improved hemodynamic stability around the time of aortic cross-
clamping because of the broad use of aspirin in patients with aortic disease.
Lymphocyte counts decrease, while leukocyte and neutrophil counts increase after unclamping of
the aorta in patients undergoing aortobifemoral bypass surgery [60]. The increase in leukocyte and
neutrophil count is due to the development of an inflammatory response during ischemia-reperfusion
injury, while the numbers of lymphocyte in the circulation decrease due to entrapment of these cells in
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end organs such as the lungs. The clinical implications of this are mentioned in a paragraph below that
discusses pulmonary dysfunction after aortic surgery.
During abdominal aortic surgery, an increase in the concentrations of anaphylatoxins C3a and C5a
has been observed in particular during the time of aortic cross-clamping. The increase in the con-
centrations of these anaphylatoxins lead to an increase in the mean airway pressure, pulmonary artery
pressure, and pulmonary vascular resistance [61]. These anaphylatoxins can also cause cardiac
dysfunction [62].

Endotoxins, cytokines, and other mediators

During ischemia triggered by aortic clamping, endotoxins and cytokines such as TNF and
Interleukin-6 are released [28].
It is a common belief that the release of these substances plays a substantial role in the observed
hemodynamic changes. This belief, however, when tested does not always hold up. The role of en-
dotoxins after aortic cross-clamping is quite unclear. The temporary decrease or even full cessation of
the blood flow to the intestines or the reperfusion upon the release of the cross-clamp may lead to an
increase in intestinal permeability. This increase is followed by an increase in the blood concentration
of endotoxins [63], which by itself can trigger the release of interleukin-6 [64] and other inflammatory
mediators. While some of these substances do not cause adverse effects, TNF has been associated with
acute lung injury after acute intestinal ischemia and reperfusion [28].

Effects of aortic cross-clamping on organ systems

Lungs

Respiratory complications are among the most common complications in patients after undergoing
aortic surgery. Many factors associated with major thoracoabdominal or just abdominal surgery, such
as mechanical ventilation, laparotomy, atelectasis, and fluid shifts, contribute to the high rate of pul-
monary complications. However, some physiologic phenomena observed during cross-clamping of the
aorta might specifically contribute to the high rate of pulmonary complications. An increase in the
pulmonary vascular resistance has been observed frequently during and particularly after cross-
clamping of the thoracic aorta [65]. This might at least in part be explained by the increase in the
blood volume circulating through the pulmonary vasculature that is associated with clamping of the
thoracic aorta.
Pulmonary dysfunction after aortic clamping can also be attributed to the release of cells and
compounds during reperfusion that are subsequently entrapped in the lungs [66,67]. As mentioned
above thromboxane is also released because of ischemia during aortic clamping. Thromboxane and
leukocyte may accumulate in the pulmonary tissue and, in combination with the increase in com-
plement C3a and C5 activity after aortic clamping, lead to inflammatory processes and increase in
microvascular permeability in the lungs [68,69], which can lead to noncardiogenic pulmonary edema
[70]. TNF has also been associated with acute lung injury after acute intestinal ischemia and reper-
fusion [28].
Dextran, heparin, pentastarches, and mannitol have been tested to avoid microparticle aggregation
in the lungs, with some success. This approach has been shown to attenuate reperfusion-related
pulmonary complications mostly in animal models and in few human studies [65,71e73], but to
date, no convincing clinical trial is known to us that would support routine use of these approaches.

Kidneys

Injury to the kidneys is observed quite frequently after surgery of the aorta that involves suprarenal
and infrarenal aortic cross-clamping. Cross-clamping the thoracic aorta leads to an 85e94% decrease in
renal blood flow, glomerular filtration rate, and urine output [74,75].
In patients undergoing procedures requiring suprarenal clamping, the incidence of transient
postoperative renal dysfunction is 28e35%, while infrarenal clamping has an incidence of 10% [76,77].
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Renal failure requiring at least transient if not permanent dialysis is as frequent in suprarenal as it is
during infrarenal cross-clamping with an incidence of 3% and 2%, respectively [76].
The etiology of renal failure after aortic surgery is almost always acute tubular necrosis induced by
an ischemia-reperfusion insult associated with aortic cross-clamping [78].
Effects of neutrophil activation and release of mediators seem to contribute significantly to the
occurrence of renal dysfunction. In an animal model, renal blood flow and glomerular filtration rate
returned to levels above the baseline almost immediately after removal of the renal artery clamp [79],
whereas these levels remained low for a few hours after the release of the thoracic aortic clamp. The
degree of decrease in renal perfusion does not correlate with levels of the cardiac output or mean
arterial blood pressure [80] at that time and does not necessarily correlate with the incidence of
postoperative renal dysfunction either [81].
Siegmund and coworkers discovered in an animal model that the kidneys seemed to respond
differently to ischemia and reperfusion than other organs did [82]. After the release of the cross-clamp
and reinstitution of the blood flow to the organs below the clamp, hyperemia and increase in oxygen
delivery was observed in the gut, although this was not the case in the renal tissue. In the kidneys, both
oxygen delivery and renal cortical oxygenation remained low. This indicates that the kidneys in
particular respond differently to ischemia and reperfusion and that oxygen deprivation may continue
despite reinstitution of the blood flow.
The renineangiotensin system affects the renal blood flow during aortic clamping. Mainly, angio-
tensin II will increase the renal vascular resistance and sodium absorption directly by causing
constriction of the vas afferens and indirectly by increasing aldosterone production.
The decrease in renal function during the time of severely reduced blood flow to the kidney can be
seen as an energy conserving and a protective compensatory mechanism of the kidneys.
Clinical strategies to protect renal function during aortic surgery are discussed in chapter 5 of this
edition.

Spinal cord

The blood flow to the spinal cord may be compromised during surgery involving the descending
aorta. During the time of aortic cross-clamping, the spinal cord perfusion relies on collateral blood flow.
The artery of Adamkewicz is one of the most distal feeding arteries to the spinal cord, and if this artery
derives from that part of the aorta affected by the placement of the cross-clamp or repair itself, then the
spinal cord is at the greatest risk for ischemia.
Like other organs affected by aortic cross-clamping, the degree of injury inflicted on the spinal cord
correlates with the duration of the limited blood flow.
Further information on the effects of aortic cross-clamping on the spinal cord and clinical recom-
mendation for spinal cord protection during aortic surgery will be discussed in chapter 4 of this edition.

Intestine

Depending on the location of aortic cross-clamping, the intestine may be at risk for ischemic injury.
In particular, supramesenteric/supraceliac cross-clamping can lead to a significant reduction in blood
flow to the gut.
As part of the open aortic aneurysm repair, the inferior mesenteric artery (IMA) and the hypogastric
artery are often sacrificed [83], putting the patient at risk of developing colorectal ischemia. The
incidence of colorectal ischemia is 2.8e4.5% during elective cases [84,85] and up to 17% during
emergent open aortic repairs [85]. The severity can range from ulcerations and superficial necrosis to
transmural gangrene of the colon and rectum. Perioperative mortality of colorectal ischemia can be as
high as 31% [84].
In addition to the ligation of the IMA and the hypogastric artery, occlusive disease of the femoral
arteries or the hypogastric artery are risk factors for developing colorectal ischemia. Patients with
ruptured aortic aneurysm and preoperative shock also have an increased risk of developing colorectal
ischemia. Measurement of the IMA stump pressure has been suggested to assess the need of IMA
reconstruction [86], although it is generally recommended to reconstruct the IMA whenever possible.
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Intestinal tonometry measuring intraluminal PCO2 as a surrogate of mucosal CO2 is a reliable

predictor for the occurrence of intestinal ischemia and can be used intraoperatively. In a study by
Schiedler et al., patients in whom an intestinal mucosal pH of less than 6.99 was observed were at risk
of developing mild ischemic colitis, while patients with mucosal pH less than 6.86 developed severe
ischemic colitis [87].
Furthermore, temporary interruption of the blood flow to the gut puts the intestine at risk of
developing ischemia-reperfusion injury [88], thus contributing to the overall inflammatory processes
that occur after aortic cross-clamping.

Summary

The temporary occlusion of the aorta and the subsequent reinstitution of blood flow to previously
ischemic areas are the most critical steps during open aortic repair. The occlusion of the aorta will
increase afterload and arterial blood pressure. Cross-clamping of the supraceliac aorta leads to blood
volume shifts resulting in an increase in preload and cardiac output. Clamping of the infraceliac aorta
leads to less predictable shifts in blood volume and changes in cardiac output.During aortic cross
clamping, many vasoactive substances and mediators are released further altering blood flow and
hemodynamic parameters. Release of the aortic cross-clamp is followed by shifts in blood volume as
well as the release of vasodilating substances such as lactate, adenosine, and CO2, leading to central
hypovolemia and hypotension. Reinstitution of blood flow after unclamping also triggers an ischemia-
reperfusion response.The complex hemodynamic, humoral and inflammatory changes occurring
during aortic clamping and after unclamping of the aorta can ultimate contribute to frequently
observed postoperative complications like pulmonary dysfunction and acute kidney injury.

Practice points

 To avoid overloading the heart during aortic clamping, fluid administration before aortic
clamping should be kept to a minimum.
 Blood pressure during aortic clamping should be kept as high as the heart can tolerate to
maintain collateral perfusion to areas distal to the aortic cross-clamp.
 To attenuate hypotension after unclamping, the clamp should be removed slowly from the
aortic cross-clamp. A fluid bolus and vasopressors should be administered as well.
 Slow and gradual removal of the aortic cross-clamp and reperfusion with normo-oxygenated
rather than hyper-oxygenated blood may help reduce the severity of ischemia-reperfusion
injury.

Research agenda

 While the mechanisms of ischemia-reperfusion injury are relatively well understood, further
research on the therapy to reduce ischemia-reperfusion injury is needed. Recent discovery of
the resolution of inflammation as an active process and the role of resolvins in these pro-
cesses is one of the most exciting discoveries in the area of inflammation and ischemia-
reperfusion injury [89,90]. A first attempt to study the role of resolvins in the inflammatory
response to aortic cross-clamping in humans was performed in our institution [91]. The
research direction seems to be promising and fruitful.
 Larger studies to research the effects of postconditioning on ischemia-reperfusion injury are
needed to assess its clinical usefulness.
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Conflict of interest statement

None.

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